1 00:00:05,160 --> 00:00:09,639 Speaker 1: What is depression and why are brains so easily able 2 00:00:09,680 --> 00:00:14,640 Speaker 1: to slip into it? Is depression detectable in animals? And 3 00:00:14,720 --> 00:00:17,000 Speaker 1: when we look across the animal kingdom do we see 4 00:00:17,239 --> 00:00:21,079 Speaker 1: options beyond fight or flight? And what does any of 5 00:00:21,120 --> 00:00:25,560 Speaker 1: this have to do with measuring depression medications in city 6 00:00:25,600 --> 00:00:29,560 Speaker 1: water supplies, or reward pathways in the brain, or the 7 00:00:29,600 --> 00:00:33,920 Speaker 1: prevalence of tuberculosis or zapping the head with magnetic stimulation. 8 00:00:37,280 --> 00:00:39,879 Speaker 2: Welcome to Inner Cosmos with me David Eagleman. 9 00:00:40,000 --> 00:00:42,960 Speaker 1: I'm a neuroscientist and an author at Stanford and in 10 00:00:43,000 --> 00:00:47,199 Speaker 1: these episodes we sail deeply into our three pound universe 11 00:00:47,520 --> 00:00:51,000 Speaker 1: to understand why and how our lives look the way 12 00:00:51,000 --> 00:01:04,320 Speaker 1: they do. Today's episode is about depression. We are going 13 00:01:04,360 --> 00:01:07,080 Speaker 1: to dive into the science behind it and we'll see 14 00:01:07,360 --> 00:01:09,200 Speaker 1: what new solutions are. 15 00:01:09,000 --> 00:01:12,760 Speaker 2: On the horizon. So let me start by assuming way out. 16 00:01:13,360 --> 00:01:17,039 Speaker 1: What fascinates me is not just what the brain can 17 00:01:17,080 --> 00:01:21,560 Speaker 1: accomplish in terms of our normal functioning, but also one 18 00:01:21,640 --> 00:01:25,200 Speaker 1: can't help but notice the fragility of the brain. 19 00:01:25,319 --> 00:01:28,160 Speaker 2: I mean, just think about how easy it is to 20 00:01:28,280 --> 00:01:30,800 Speaker 2: lose consciousness when you hit your head. 21 00:01:30,880 --> 00:01:35,160 Speaker 1: Or think about what happens when you drink alcohol and 22 00:01:35,240 --> 00:01:39,000 Speaker 1: your perception and your decision making changes, or you don't 23 00:01:39,040 --> 00:01:41,760 Speaker 1: get enough sleep, and how you behave and how you 24 00:01:41,840 --> 00:01:44,960 Speaker 1: decide these can become a little different. Or when you're 25 00:01:45,120 --> 00:01:48,840 Speaker 1: angry and you act differently, or if you consume psychedelic 26 00:01:48,920 --> 00:01:53,480 Speaker 1: drugs and your conscious experience changes entirely. What all this 27 00:01:53,760 --> 00:01:56,440 Speaker 1: tells us, I think, is that it's very easy for 28 00:01:56,520 --> 00:02:00,680 Speaker 1: the system to get knocked off its normal pathway. And 29 00:02:00,720 --> 00:02:03,919 Speaker 1: what's clear is that the brain puts an enormous amount 30 00:02:03,960 --> 00:02:10,480 Speaker 1: of effort into trying to stay operating in the normal range. Now, 31 00:02:10,520 --> 00:02:15,760 Speaker 1: given this context, one area that's fascinating and of massive 32 00:02:15,880 --> 00:02:18,560 Speaker 1: social importance is depression. 33 00:02:19,240 --> 00:02:21,120 Speaker 2: This is a mood disorder. 34 00:02:21,160 --> 00:02:24,120 Speaker 1: It affects how you feel, how you think, how you 35 00:02:24,440 --> 00:02:28,200 Speaker 1: handle your daily tasks, how you eat and sleep. People 36 00:02:28,240 --> 00:02:40,359 Speaker 1: with depression feel persistently sad. They often feel empty or anxious, pessimistic, hopeless, worthless, helpless, 37 00:02:40,800 --> 00:02:43,760 Speaker 1: and they lose interest in the things that used to 38 00:02:43,800 --> 00:02:47,520 Speaker 1: bring them joy. They're slowed down in all the aspects 39 00:02:47,560 --> 00:02:52,240 Speaker 1: of their life, and often there are thoughts of suicide. Now, 40 00:02:52,400 --> 00:02:55,720 Speaker 1: almost everyone has had someone in their life who has 41 00:02:55,720 --> 00:02:59,280 Speaker 1: suffered depression at some point, whether that's recognized or not. 42 00:03:00,160 --> 00:03:05,120 Speaker 1: And generally everyone's first intuition when they have a friend 43 00:03:05,240 --> 00:03:08,640 Speaker 1: or a loved one who becomes depressed is to talk 44 00:03:08,680 --> 00:03:11,840 Speaker 1: them out of it, to say, hey, things are okay, 45 00:03:12,440 --> 00:03:14,840 Speaker 1: snap out of it, look at the bright side. And 46 00:03:14,880 --> 00:03:18,360 Speaker 1: eventually you might be tempted to say, come on, just 47 00:03:18,600 --> 00:03:23,320 Speaker 1: toughen up. But the important lesson from centuries of psychiatry 48 00:03:23,320 --> 00:03:26,800 Speaker 1: and more recently neuroscience is that it's not so easy. 49 00:03:27,040 --> 00:03:30,680 Speaker 1: It's a physical problem. And that's why we talk about 50 00:03:31,120 --> 00:03:35,160 Speaker 1: mental illness nowadays exactly as we talk about a physical 51 00:03:35,480 --> 00:03:40,040 Speaker 1: illness like COVID or a broken leg, and that understanding 52 00:03:40,520 --> 00:03:45,360 Speaker 1: opens the door to different approaches, because a physical problem 53 00:03:45,920 --> 00:03:52,080 Speaker 1: invites physical solutions. Now, my father was a psychiatrist, and 54 00:03:52,200 --> 00:03:55,720 Speaker 1: he was always impressed that he could have a patient 55 00:03:56,080 --> 00:03:59,760 Speaker 1: who would be suffering from clinical depression and would lose 56 00:03:59,800 --> 00:04:02,240 Speaker 1: his job and maybe lose his spouse, and my father 57 00:04:02,320 --> 00:04:06,240 Speaker 1: can make a prescription like let's say prozac, and that 58 00:04:06,400 --> 00:04:09,640 Speaker 1: patient often could get out of bed again and then 59 00:04:09,680 --> 00:04:13,160 Speaker 1: get his job back and win his spouse back. Now, 60 00:04:13,200 --> 00:04:15,720 Speaker 1: how do we understand this, Well, it's an issue that 61 00:04:15,760 --> 00:04:18,120 Speaker 1: I talk about a lot, which is that we are 62 00:04:18,240 --> 00:04:21,840 Speaker 1: made up of small pieces and parts, And the thing 63 00:04:21,880 --> 00:04:25,520 Speaker 1: to appreciate is that you are the sum total of 64 00:04:25,560 --> 00:04:26,679 Speaker 1: all those pieces and parts. 65 00:04:26,720 --> 00:04:27,760 Speaker 2: Whatever is going on. 66 00:04:28,160 --> 00:04:32,839 Speaker 1: At this microscopic level is you and your mood and 67 00:04:32,880 --> 00:04:37,200 Speaker 1: your behavior. Now, why would anybody think that crazy statement 68 00:04:37,279 --> 00:04:40,280 Speaker 1: is true. Well, there are many things that we see 69 00:04:40,279 --> 00:04:43,360 Speaker 1: in the clinics every day which teach us this lesson. 70 00:04:43,920 --> 00:04:46,960 Speaker 1: People can get damage to their brains and they can 71 00:04:47,000 --> 00:04:50,440 Speaker 1: no longer understand how to use a mirror, or they 72 00:04:50,480 --> 00:04:54,080 Speaker 1: can no longer name furry animals, or they can no 73 00:04:54,160 --> 00:04:59,560 Speaker 1: longer see colors, or understand speech, or understand music or 74 00:04:59,720 --> 00:05:02,480 Speaker 1: any We have a million other things that we think 75 00:05:02,560 --> 00:05:05,400 Speaker 1: should just come for free in the world. Now, what 76 00:05:05,480 --> 00:05:09,320 Speaker 1: this exposes is that these are functions of the brain, 77 00:05:09,560 --> 00:05:12,200 Speaker 1: and even if a little bit of the brain is damaged, 78 00:05:12,680 --> 00:05:16,800 Speaker 1: then you can't perform that function anymore. Now, many of 79 00:05:16,839 --> 00:05:20,039 Speaker 1: the sorts of brain damage that you'll read about in 80 00:05:20,160 --> 00:05:22,440 Speaker 1: an exciting book about the brain, these are things that 81 00:05:22,880 --> 00:05:27,080 Speaker 1: most people won't see in their lifetimes. They won't know 82 00:05:27,279 --> 00:05:30,560 Speaker 1: any friend or relative who has these issues because they 83 00:05:30,600 --> 00:05:34,560 Speaker 1: are rare things to happen, and they usually involve damage 84 00:05:34,560 --> 00:05:37,840 Speaker 1: to a region of the brain from a tumor or 85 00:05:37,880 --> 00:05:41,159 Speaker 1: a stroke or a traumatic brain injury, and those things 86 00:05:41,240 --> 00:05:44,919 Speaker 1: represent big changes in the city of the brain, like 87 00:05:45,279 --> 00:05:48,400 Speaker 1: an entire block of New York City falling in an earthquake. 88 00:05:49,320 --> 00:05:51,760 Speaker 1: But there are much more subtle things that happen in 89 00:05:51,760 --> 00:05:54,480 Speaker 1: the brain as well, and these are changes that have 90 00:05:54,560 --> 00:05:57,760 Speaker 1: to do with the way the system runs, with its 91 00:05:58,080 --> 00:06:02,360 Speaker 1: tens of billions of neurons and trillions of synaptic connections. 92 00:06:03,080 --> 00:06:06,240 Speaker 1: So to return to the city analogy, imagine that instead 93 00:06:06,240 --> 00:06:09,480 Speaker 1: of big damage that you can see, the city still 94 00:06:09,839 --> 00:06:13,200 Speaker 1: looks the same, but parts of it are operating very 95 00:06:13,440 --> 00:06:18,960 Speaker 1: subtly differently. So the playwrights have all quit, and the 96 00:06:19,000 --> 00:06:23,440 Speaker 1: city planners have stopped planning, and the coffee shops are 97 00:06:23,440 --> 00:06:27,760 Speaker 1: closing two hours earlier, and all of this stuff impedes 98 00:06:27,880 --> 00:06:32,119 Speaker 1: the city's ability to thrive and be an active, well 99 00:06:32,200 --> 00:06:36,520 Speaker 1: functioning place for innovation and tourism. But it's all very subtle, 100 00:06:37,240 --> 00:06:39,919 Speaker 1: and if you looked at this from a drone flying 101 00:06:39,960 --> 00:06:42,640 Speaker 1: over the city, you really wouldn't see much of a difference. 102 00:06:42,760 --> 00:06:47,159 Speaker 1: It's small stuff that's happening at a small level, but 103 00:06:47,720 --> 00:06:52,520 Speaker 1: it changes the way that the city operates. And again, 104 00:06:52,880 --> 00:06:56,520 Speaker 1: who you are and how you see, the world comes 105 00:06:56,560 --> 00:06:59,760 Speaker 1: from the way that the city of your brain is operating. 106 00:07:00,200 --> 00:07:03,120 Speaker 1: In other words, the sum total of what's happening under 107 00:07:03,120 --> 00:07:07,000 Speaker 1: the hood your biology. And I think the reason this 108 00:07:07,120 --> 00:07:11,400 Speaker 1: is surprising is because we tend to think of ourselves 109 00:07:11,440 --> 00:07:15,360 Speaker 1: as being removed from our biology. You are separate from 110 00:07:15,440 --> 00:07:21,080 Speaker 1: it or able to ride above it. So if you've 111 00:07:21,160 --> 00:07:24,760 Speaker 1: ever known someone with depression, or had depression yourself, you 112 00:07:24,800 --> 00:07:27,640 Speaker 1: will know that you can't just say hey, come on, 113 00:07:27,880 --> 00:07:31,240 Speaker 1: cheer up, snap out of it. That doesn't suffice to 114 00:07:31,520 --> 00:07:37,280 Speaker 1: change the biology. And one of the most pervasive and 115 00:07:37,480 --> 00:07:41,960 Speaker 1: societally important examples of these kind of subtle changes to 116 00:07:42,040 --> 00:07:46,200 Speaker 1: the brain is with depression. And so for this episode, 117 00:07:46,600 --> 00:07:49,800 Speaker 1: I decided to call my colleague Jonathan Downer, who is 118 00:07:50,120 --> 00:07:54,920 Speaker 1: an incredibly insightful and empathic observer of the brain. He 119 00:07:54,960 --> 00:07:58,400 Speaker 1: has an MD and specializes in psychiatry, and he also 120 00:07:58,440 --> 00:08:02,040 Speaker 1: has a PhD in neurosci and one of his areas 121 00:08:02,040 --> 00:08:06,280 Speaker 1: of expertise is depression. And as it turns out, Jonathan 122 00:08:06,280 --> 00:08:10,160 Speaker 1: and I wrote a textbook together on cognitive neuroscience called 123 00:08:10,200 --> 00:08:13,560 Speaker 1: Brain and Behavior, and this is the textbook used at 124 00:08:13,600 --> 00:08:17,400 Speaker 1: Stanford and at universities worldwide. And the textbook covers a 125 00:08:17,400 --> 00:08:20,080 Speaker 1: lot of ground, but for today, I just want to 126 00:08:20,200 --> 00:08:23,840 Speaker 1: zoom in on depression. So I rang him up to 127 00:08:23,880 --> 00:08:26,559 Speaker 1: get his perspective on this issue that is not only 128 00:08:27,000 --> 00:08:32,679 Speaker 1: neuroscientifically important and fascinating, but also, unlike the strange deficits 129 00:08:32,679 --> 00:08:35,520 Speaker 1: that you might see only in a textbook, you almost 130 00:08:35,559 --> 00:08:38,920 Speaker 1: certainly know someone with depression, perhaps someone close to you, 131 00:08:39,080 --> 00:08:40,120 Speaker 1: or perhaps yourself. 132 00:08:40,480 --> 00:08:43,640 Speaker 2: It's a shockingly common challenge. 133 00:08:43,960 --> 00:08:52,079 Speaker 1: So let's dive in to understand it. So, Jonathan, how 134 00:08:52,080 --> 00:08:54,600 Speaker 1: did you get interested in studying depression? 135 00:08:55,800 --> 00:08:58,920 Speaker 3: Well, it's a bit of an interesting story, David. You'd 136 00:08:58,920 --> 00:09:01,559 Speaker 3: have to go back about years too. When I was 137 00:09:01,600 --> 00:09:04,880 Speaker 3: a graduate student over at the Toronto Western Hospital. That 138 00:09:05,040 --> 00:09:08,120 Speaker 3: is a hospital that has a i guess a major 139 00:09:08,240 --> 00:09:12,720 Speaker 3: neurosurgical unit where they perform surgeries where they implant deep 140 00:09:12,720 --> 00:09:15,920 Speaker 3: brain stimulators, which are a bit like brain pacemakers, into 141 00:09:15,920 --> 00:09:18,840 Speaker 3: the brains of people with Parkinson's disease and other kinds 142 00:09:18,840 --> 00:09:22,400 Speaker 3: of neurological disorders. And in a round two thousand and two, 143 00:09:22,520 --> 00:09:25,160 Speaker 3: a patient came in who was a middle aged woman 144 00:09:25,240 --> 00:09:28,720 Speaker 3: who had previously suffered from depression but no longer. She 145 00:09:28,840 --> 00:09:31,120 Speaker 3: was coming in to have the deep brain stimulators implanted 146 00:09:31,240 --> 00:09:34,439 Speaker 3: for her Parkinson's disease. They implanted the electrodes, one on 147 00:09:34,440 --> 00:09:37,320 Speaker 3: one side and one on the other, and during the 148 00:09:37,320 --> 00:09:39,520 Speaker 3: surgery they turned them on to make sure that they 149 00:09:39,559 --> 00:09:43,000 Speaker 3: are succeeding in reducing the person's hand tremors or the 150 00:09:43,040 --> 00:09:45,880 Speaker 3: other tremors in their body that they're trying to have treated. 151 00:09:46,600 --> 00:09:48,800 Speaker 3: What was interesting is when they turned on the one 152 00:09:48,840 --> 00:09:52,200 Speaker 3: on one side, the opposite hands started to reduce in 153 00:09:52,240 --> 00:09:54,240 Speaker 3: its tremor and the tremor went away, which is exactly 154 00:09:54,320 --> 00:09:57,040 Speaker 3: what they expected to happen. On the other side, there 155 00:09:57,080 --> 00:09:59,040 Speaker 3: was something very strange happened as soon as they turned 156 00:09:59,080 --> 00:10:01,920 Speaker 3: it on. Nothing Hahigh up into her tremor whatsoever, and 157 00:10:01,960 --> 00:10:08,840 Speaker 3: instead she descended instantly into a deep despairing re experiencing 158 00:10:08,880 --> 00:10:11,920 Speaker 3: of her depression. It kicked him within seconds, and she 159 00:10:12,000 --> 00:10:14,280 Speaker 3: described it as a deep down, bad feeling in the 160 00:10:14,280 --> 00:10:17,360 Speaker 3: pit of my stomach. I wanted to cry, but I couldn't. 161 00:10:18,040 --> 00:10:19,559 Speaker 3: Someone could have come in to shoot me and I 162 00:10:19,559 --> 00:10:23,199 Speaker 3: wouldn't have cared. I couldn't have cared less. No, immediately 163 00:10:23,240 --> 00:10:26,680 Speaker 3: they turned the switch off again, and surprisingly, within seconds, 164 00:10:26,720 --> 00:10:29,920 Speaker 3: the sadness lifted again and they found themselves in a 165 00:10:30,000 --> 00:10:33,320 Speaker 3: very weird situation where every time they turned on this current, 166 00:10:33,480 --> 00:10:36,920 Speaker 3: the person would descend immediately within a few seconds into sadness, 167 00:10:37,240 --> 00:10:39,320 Speaker 3: and then every time they turned it off she would 168 00:10:39,440 --> 00:10:41,640 Speaker 3: be able to emerge within a few seconds. Again, it 169 00:10:41,679 --> 00:10:43,920 Speaker 3: was literally sadness the flip of the switch. 170 00:10:45,120 --> 00:10:45,400 Speaker 2: Wow. 171 00:10:45,440 --> 00:10:48,679 Speaker 1: And so that's what's got you started in researching that. 172 00:10:49,400 --> 00:10:50,400 Speaker 2: So that's exactly it. 173 00:10:50,440 --> 00:10:53,760 Speaker 3: So at the time I was doing my PhD using 174 00:10:53,760 --> 00:10:57,000 Speaker 3: a technology called functional functional MRI, which I'm sure you've 175 00:10:57,000 --> 00:11:00,559 Speaker 3: talked about on the podcast before, which is a way 176 00:11:00,600 --> 00:11:03,240 Speaker 3: of using MRI scanners to look at the brain activity 177 00:11:03,400 --> 00:11:06,280 Speaker 3: of people as various things happen. So the neuros versions 178 00:11:06,480 --> 00:11:09,120 Speaker 3: wanted to understand what was going on, So we went 179 00:11:09,160 --> 00:11:11,720 Speaker 3: down to where the functional MRIs were being done and 180 00:11:12,559 --> 00:11:14,599 Speaker 3: they turned on and off one of the switches on 181 00:11:14,640 --> 00:11:16,720 Speaker 3: the one side that affected the tremor, and they were 182 00:11:16,760 --> 00:11:19,400 Speaker 3: able to show a particular brain pathway that was affected 183 00:11:19,600 --> 00:11:21,960 Speaker 3: controlling the motor circuits of the brain, which was the 184 00:11:21,960 --> 00:11:25,319 Speaker 3: intended effect. On the other hemisphere, though the electrode was 185 00:11:25,360 --> 00:11:27,600 Speaker 3: just a few millimeters off and as a result, it 186 00:11:27,800 --> 00:11:30,840 Speaker 3: landed on some other pathways that projected out to a 187 00:11:30,840 --> 00:11:33,520 Speaker 3: completely different part of the front lobes, and every time 188 00:11:33,520 --> 00:11:35,679 Speaker 3: they turned on and off this part of the frontal lobes, 189 00:11:35,720 --> 00:11:38,640 Speaker 3: the person would instantly going out of the sadness. That 190 00:11:38,679 --> 00:11:40,400 Speaker 3: was happy news of the patient because they were able 191 00:11:40,440 --> 00:11:43,360 Speaker 3: to reposition the electrodes so that both electrodes did the 192 00:11:43,400 --> 00:11:47,120 Speaker 3: appropriate thing. But it got us thinking about what this 193 00:11:47,160 --> 00:11:50,240 Speaker 3: really meant about depression. All these theories at the time 194 00:11:50,320 --> 00:11:53,000 Speaker 3: that depression might be a chemical imbalance or this or that, 195 00:11:53,520 --> 00:11:55,360 Speaker 3: we really saw it very directly that there was a 196 00:11:55,440 --> 00:11:58,640 Speaker 3: question of the activity of the brain and that within seconds, 197 00:11:58,920 --> 00:12:01,680 Speaker 3: one pattern of activity the brain led to sadness, and 198 00:12:01,720 --> 00:12:04,120 Speaker 3: within seconds, if that padding of activity could somehow be 199 00:12:04,160 --> 00:12:07,280 Speaker 3: turned off, then the person's sadness would go away. And 200 00:12:07,360 --> 00:12:09,959 Speaker 3: that really got us thinking about whether we might start 201 00:12:10,000 --> 00:12:12,719 Speaker 3: being able to use things like brain stimulation to understand 202 00:12:13,240 --> 00:12:15,760 Speaker 3: what depression was about in the brain, and maybe even 203 00:12:15,760 --> 00:12:17,560 Speaker 3: to come up with a new generation of treatments that 204 00:12:17,600 --> 00:12:20,400 Speaker 3: work better than the medications and therapy of the time. 205 00:12:20,720 --> 00:12:22,800 Speaker 2: Okay, terrific, So we'll talk about that. 206 00:12:23,520 --> 00:12:26,720 Speaker 1: Let's start with you, can you define depression clinical depression? 207 00:12:27,679 --> 00:12:27,959 Speaker 2: Sure? 208 00:12:28,320 --> 00:12:31,280 Speaker 3: So, there are standardized definitions of depression that involve a 209 00:12:31,320 --> 00:12:33,960 Speaker 3: series of symptoms, the core of which is sad or 210 00:12:34,000 --> 00:12:36,880 Speaker 3: depressed mood most of the day most days, and the 211 00:12:36,920 --> 00:12:39,480 Speaker 3: second of which is a thing called anhedonia, which is 212 00:12:39,520 --> 00:12:42,559 Speaker 3: the inability to enjoy things or experience pleasure, a loss 213 00:12:42,559 --> 00:12:44,760 Speaker 3: of motivation, a loss of joy, a loss of the 214 00:12:44,800 --> 00:12:48,280 Speaker 3: brain's reward functions. In addition to that, there are some 215 00:12:48,360 --> 00:12:51,200 Speaker 3: standard symptoms that go along with that. Commonly, people will 216 00:12:51,280 --> 00:12:54,640 Speaker 3: have disturbances in their sleep or appetite, trouble with concentration, 217 00:12:55,480 --> 00:12:58,080 Speaker 3: They may have difficulty with their energy and fatigue levels, 218 00:12:58,760 --> 00:13:01,200 Speaker 3: and there are thoughts that come along of self harm 219 00:13:01,200 --> 00:13:03,880 Speaker 3: and suicide that there are obviously the most concerning parts 220 00:13:04,240 --> 00:13:07,640 Speaker 3: about the depression. So that's the standard sort of diagnostic 221 00:13:07,679 --> 00:13:11,160 Speaker 3: approach by which we determine whether somebody has been entering 222 00:13:11,200 --> 00:13:14,600 Speaker 3: into a period of depression. It's unfortunately, really common. At 223 00:13:14,640 --> 00:13:17,320 Speaker 3: any given time in North America, about five percent of 224 00:13:17,320 --> 00:13:20,600 Speaker 3: people are in the middle of a depressive episode, and 225 00:13:20,760 --> 00:13:23,440 Speaker 3: at least ten percent of people, perhaps more these days, 226 00:13:23,520 --> 00:13:25,800 Speaker 3: are going to go through an episode of depression at 227 00:13:25,880 --> 00:13:29,280 Speaker 3: some point in their lifetimes. Almost everybody will have somebody 228 00:13:29,400 --> 00:13:32,160 Speaker 3: they know who has been through depression or is going 229 00:13:32,200 --> 00:13:34,200 Speaker 3: through depression or will go through depression. 230 00:13:34,520 --> 00:13:36,040 Speaker 1: So one of the things I want to talk about 231 00:13:36,080 --> 00:13:38,960 Speaker 1: is why this happens, What it is about the wiring 232 00:13:39,040 --> 00:13:41,520 Speaker 1: of the human brain that allows us to slip so 233 00:13:41,640 --> 00:13:43,960 Speaker 1: easily into that mode. 234 00:13:44,640 --> 00:13:45,600 Speaker 2: What are your thoughts on that. 235 00:13:46,440 --> 00:13:50,520 Speaker 3: It's a really fascinating question, And I think to answer that, 236 00:13:50,600 --> 00:13:52,320 Speaker 3: what we found is you can get a lot of 237 00:13:52,320 --> 00:13:54,800 Speaker 3: the clue to that looking at evolution or a biology, 238 00:13:55,360 --> 00:13:57,640 Speaker 3: because humans are not, by no means the only animals 239 00:13:57,640 --> 00:13:59,480 Speaker 3: that can go into it a spare like syndrome, I 240 00:13:59,480 --> 00:14:01,920 Speaker 3: mean depression. Most of us who have pets, and most 241 00:14:01,920 --> 00:14:05,240 Speaker 3: of us of animals who have seen situations where animals 242 00:14:05,240 --> 00:14:07,520 Speaker 3: can drop into a despair and stop eating and stop 243 00:14:07,559 --> 00:14:09,720 Speaker 3: sleeping and do all the same things and don't enjoy 244 00:14:09,760 --> 00:14:12,600 Speaker 3: the things they normally would. Something that looks a bit 245 00:14:12,640 --> 00:14:16,079 Speaker 3: like depression is detectable in dogs and cats and elephants 246 00:14:16,200 --> 00:14:19,680 Speaker 3: and zoo animals, and even in things like zebrafish, which 247 00:14:19,680 --> 00:14:23,600 Speaker 3: are tiny little vertebrates. So evolution seems to have put 248 00:14:23,640 --> 00:14:26,720 Speaker 3: a depression like mode there, you know, a very long 249 00:14:26,760 --> 00:14:28,920 Speaker 3: time ago, and it's one of the oldest circuits in 250 00:14:28,960 --> 00:14:32,440 Speaker 3: the brain. When we look at the circuitry that drives depression. 251 00:14:32,440 --> 00:14:35,160 Speaker 3: What we find is it falls into a bigger category 252 00:14:35,240 --> 00:14:38,160 Speaker 3: of circuits that help the brain to defend against threats. 253 00:14:38,920 --> 00:14:41,000 Speaker 3: And in a nutshell, for every living thing, whether you're 254 00:14:41,000 --> 00:14:43,440 Speaker 3: a fish or a raccoon or a human, there are 255 00:14:44,000 --> 00:14:46,080 Speaker 3: sort of four main categories of things you can do 256 00:14:46,120 --> 00:14:47,840 Speaker 3: if a threat comes along. So let's say you're a 257 00:14:47,840 --> 00:14:50,520 Speaker 3: fish swimming along and a shark shows up. The first 258 00:14:50,520 --> 00:14:52,800 Speaker 3: thing you can do is you can freeze and hope 259 00:14:52,800 --> 00:14:55,120 Speaker 3: the shark doesn't see you, So that's freeze mode. If 260 00:14:55,120 --> 00:14:56,880 Speaker 3: the shark sees you and starts chasing you, then you 261 00:14:56,920 --> 00:14:58,480 Speaker 3: have to go beyond freeze. You have to go into 262 00:14:58,480 --> 00:15:01,000 Speaker 3: this sort of the flight mode would be the escape mode, 263 00:15:01,880 --> 00:15:04,440 Speaker 3: and if the shark corners you. We've all seen that. 264 00:15:04,440 --> 00:15:06,240 Speaker 3: There are animals, you know, if you happen to get 265 00:15:06,240 --> 00:15:09,320 Speaker 3: a possum or a raccoon in your garage, there usually 266 00:15:09,360 --> 00:15:11,160 Speaker 3: will run away, But of course if they get cornered 267 00:15:11,160 --> 00:15:12,640 Speaker 3: and they feel like there's no way out, they will 268 00:15:12,680 --> 00:15:15,760 Speaker 3: fight very fiercely, and lots of animals do that. So 269 00:15:15,920 --> 00:15:18,920 Speaker 3: there is this third mode called fight. But the brain 270 00:15:19,000 --> 00:15:21,840 Speaker 3: needs a fourth mode to deal with situations that are unwinnable. 271 00:15:22,040 --> 00:15:25,640 Speaker 3: Sometimes you've tried freezing, you've tried fleeing, you've tried fighting. 272 00:15:26,000 --> 00:15:27,720 Speaker 3: But if at some point the brain decides you're not 273 00:15:27,760 --> 00:15:29,640 Speaker 3: going to win this fight and there's no running away, 274 00:15:29,680 --> 00:15:32,239 Speaker 3: there's no escaping, and you can't just ignore the problem, 275 00:15:32,600 --> 00:15:35,080 Speaker 3: the brain taps into a fourth mode that I'll call fold. 276 00:15:35,400 --> 00:15:38,520 Speaker 3: There's a passive threat defense mode where the instincts are 277 00:15:38,520 --> 00:15:41,440 Speaker 3: all about losing your confidence, running home and hiding in 278 00:15:41,480 --> 00:15:43,720 Speaker 3: your burrow and keeping your head down and hoping that 279 00:15:43,880 --> 00:15:47,440 Speaker 3: something changes. This is the mode that is turned on 280 00:15:47,480 --> 00:15:49,960 Speaker 3: when people are fighting off in illness or a major injury. 281 00:15:50,040 --> 00:15:51,720 Speaker 3: So if they have surgery or if they're fighting off 282 00:15:51,720 --> 00:15:53,680 Speaker 3: in illness. Some people will actually have a drop in 283 00:15:53,720 --> 00:15:55,960 Speaker 3: their mood when they have an immunization as their immune 284 00:15:55,960 --> 00:15:59,080 Speaker 3: system fires up to sort of to deal with the infection. 285 00:16:00,080 --> 00:16:02,480 Speaker 3: In any situation where the brain decides that it needs 286 00:16:02,480 --> 00:16:06,240 Speaker 3: to be hiding doubt in recovery and recovering and keeping 287 00:16:06,240 --> 00:16:08,800 Speaker 3: its head down, it will go into this fold mode. 288 00:16:09,840 --> 00:16:12,160 Speaker 3: Now that may be necessary to keep you out of 289 00:16:12,240 --> 00:16:15,160 Speaker 3: danger until the threat goes away, or at least hopefully 290 00:16:15,200 --> 00:16:17,920 Speaker 3: until the threat goes away. But the problem that comes 291 00:16:17,960 --> 00:16:20,840 Speaker 3: up in depression is when this becomes a self perpetuating 292 00:16:20,880 --> 00:16:24,280 Speaker 3: process and the circuits that drive fold mode, which is 293 00:16:24,320 --> 00:16:27,400 Speaker 3: a normal and useful defense mechanism for the threats we 294 00:16:27,440 --> 00:16:30,040 Speaker 3: can't win against. If those circuits get stuck in an 295 00:16:30,040 --> 00:16:32,560 Speaker 3: infinite feedback loop and just keep going and going, then 296 00:16:32,560 --> 00:16:34,720 Speaker 3: the person may still be stuck in depression weeks later, 297 00:16:34,960 --> 00:16:36,680 Speaker 3: months later, maybe even years later. 298 00:16:37,640 --> 00:16:40,640 Speaker 1: You once give me an example of falling off a 299 00:16:40,760 --> 00:16:42,800 Speaker 1: ship in the middle of the night to illustrate this 300 00:16:42,880 --> 00:16:43,520 Speaker 1: fold mode. 301 00:16:44,360 --> 00:16:46,400 Speaker 3: Yeah, so I wanted to. That's actually a great point. 302 00:16:47,120 --> 00:16:50,920 Speaker 3: So there are situations where we're we're going into this 303 00:16:51,000 --> 00:16:54,040 Speaker 3: mode is really useful, and every once in a while 304 00:16:54,080 --> 00:16:56,000 Speaker 3: we're reading the news about somebody who falls off the 305 00:16:56,000 --> 00:16:57,360 Speaker 3: back of a ship in the middle of the night 306 00:16:57,400 --> 00:17:00,440 Speaker 3: and then miraculously gets rescued in the morning. Now, if 307 00:17:00,440 --> 00:17:01,800 Speaker 3: you or I fell off the back of a ship 308 00:17:01,800 --> 00:17:03,120 Speaker 3: in the middle of the night, like a cruise ship 309 00:17:03,200 --> 00:17:05,520 Speaker 3: or something, we'd probably swim after the ship for a 310 00:17:05,560 --> 00:17:08,199 Speaker 3: while and scream for help and try and attract his attention. 311 00:17:08,280 --> 00:17:09,800 Speaker 3: But if it was really clear that the ship was 312 00:17:09,840 --> 00:17:11,600 Speaker 3: sailing away and no one could hear us, and we're 313 00:17:11,920 --> 00:17:14,520 Speaker 3: stuck in the middle of the sea, I mean we're 314 00:17:14,560 --> 00:17:16,640 Speaker 3: in a really bad situation. It's really risky, and this 315 00:17:16,680 --> 00:17:18,600 Speaker 3: is probably not going to work out well. But our 316 00:17:18,640 --> 00:17:23,000 Speaker 3: best chance of survival is actually to fold, to curl 317 00:17:23,040 --> 00:17:25,239 Speaker 3: up into a ball and just wait and save your 318 00:17:25,320 --> 00:17:28,480 Speaker 3: energy and hope that something about the situation changes, hope 319 00:17:28,520 --> 00:17:31,560 Speaker 3: you get rescued. That mode is the same mode that 320 00:17:31,560 --> 00:17:34,119 Speaker 3: we talk about when we talk about depression, and in fact, 321 00:17:34,800 --> 00:17:38,439 Speaker 3: when pharmaceutical companies are developing new medications for depression, one 322 00:17:38,480 --> 00:17:40,560 Speaker 3: of the ways that they'll do animal testing to see 323 00:17:40,560 --> 00:17:43,200 Speaker 3: if the molecule helps depression is whether a thing called 324 00:17:43,200 --> 00:17:46,399 Speaker 3: the forced swim test, and the forced swim test, the animal, 325 00:17:46,440 --> 00:17:49,640 Speaker 3: like the mouse or whatever, is placed inside an air 326 00:17:50,040 --> 00:17:51,800 Speaker 3: a little beaker where they have to swim around and 327 00:17:51,840 --> 00:17:54,240 Speaker 3: there's nothing to stand on. Now, mice are quite good swimmers, 328 00:17:54,240 --> 00:17:56,200 Speaker 3: and they're also quite good floaters, so they'll swim and 329 00:17:56,240 --> 00:17:59,000 Speaker 3: swim around, and eventually, at some point they'll realize that 330 00:17:59,040 --> 00:18:00,760 Speaker 3: they're not going to get out of this situation, and 331 00:18:00,760 --> 00:18:02,520 Speaker 3: so they stop swimming around and they just give up 332 00:18:02,520 --> 00:18:05,800 Speaker 3: and float. And at that point the experimenter will stop 333 00:18:05,800 --> 00:18:08,080 Speaker 3: the stop watch and see how many minutes that took. 334 00:18:08,520 --> 00:18:11,760 Speaker 3: What's interesting is that there are breeds of mice who 335 00:18:11,760 --> 00:18:13,680 Speaker 3: are prone to depression and prone to this are giving 336 00:18:13,720 --> 00:18:18,000 Speaker 3: up quickly, and most antidepressants, when the mice are on 337 00:18:18,040 --> 00:18:20,920 Speaker 3: the antidepressant still actually swim for a lot longer before 338 00:18:21,000 --> 00:18:24,000 Speaker 3: giving up. And so this forced swim tests, which is 339 00:18:24,040 --> 00:18:26,119 Speaker 3: really a way of tapping into how long before the 340 00:18:26,160 --> 00:18:29,040 Speaker 3: animal switches into this mode of folding and giving up 341 00:18:29,080 --> 00:18:33,560 Speaker 3: and waiting for something to change. That approach is a 342 00:18:33,720 --> 00:18:36,240 Speaker 3: long standing and standard way that people have searched for 343 00:18:36,880 --> 00:18:40,440 Speaker 3: new antidepressant medications over the last several decades. 344 00:18:40,880 --> 00:18:41,760 Speaker 2: Okay, terrific. 345 00:18:41,920 --> 00:18:46,240 Speaker 1: And so when we look at depression in this country 346 00:18:46,640 --> 00:18:51,080 Speaker 1: or around the world, what are the rates of depression? Like, 347 00:18:51,160 --> 00:18:52,920 Speaker 1: are things going up or down? 348 00:18:54,000 --> 00:18:57,520 Speaker 3: Yeah, so it's unfortunate that, I mean, the encouraging thing 349 00:18:57,560 --> 00:19:00,240 Speaker 3: over the last few decades is that compared to say, 350 00:19:00,280 --> 00:19:02,760 Speaker 3: the nineteen eighties and the nineteen nineties when I started 351 00:19:02,800 --> 00:19:05,600 Speaker 3: doing brain imaging research, there's a lot less stigma around 352 00:19:05,640 --> 00:19:08,240 Speaker 3: mental health than there was, and that that's certainly very encouraging. 353 00:19:08,520 --> 00:19:10,880 Speaker 3: There are a lot more people seeking treatment than before, 354 00:19:11,320 --> 00:19:15,800 Speaker 3: and people are seeking treatments with medications and with psychotherapy 355 00:19:15,960 --> 00:19:18,560 Speaker 3: more more than ever. The problem is that this hasn't 356 00:19:18,640 --> 00:19:21,480 Speaker 3: changed the numbers at all. So despite the fact that 357 00:19:21,520 --> 00:19:24,080 Speaker 3: there's less stigma, despite the fact that people are coming 358 00:19:24,080 --> 00:19:27,080 Speaker 3: forward and taking antidepressants, and that in fact, antidepressants are 359 00:19:27,080 --> 00:19:29,760 Speaker 3: being used in sex quantities that they can be detected 360 00:19:29,880 --> 00:19:34,719 Speaker 3: with spectroscopes in the water supplies of cities and so on, 361 00:19:34,800 --> 00:19:36,320 Speaker 3: so they'll actually be able to go and they can 362 00:19:36,359 --> 00:19:40,960 Speaker 3: detect trace amounts of all these medications in city water supplies. 363 00:19:41,680 --> 00:19:44,800 Speaker 3: Despite all of this, the prevalence of depression and of 364 00:19:44,840 --> 00:19:48,520 Speaker 3: suicidal acts and suicidality has not gone down at all, 365 00:19:48,920 --> 00:19:53,199 Speaker 3: And in certain populations like younger folks under age twenty 366 00:19:53,240 --> 00:19:55,960 Speaker 3: and in the early twenties, the numbers for depression, anxiety, 367 00:19:55,960 --> 00:19:59,040 Speaker 3: and suicidality are going up rather than down. So we 368 00:19:59,119 --> 00:20:02,359 Speaker 3: definitely need to put the search on to understand how 369 00:20:02,400 --> 00:20:04,600 Speaker 3: depression works in the brain and really develop a new 370 00:20:04,680 --> 00:20:07,520 Speaker 3: generation of treatments because what we're having right now is 371 00:20:07,520 --> 00:20:08,480 Speaker 3: not moving the needle. 372 00:20:08,760 --> 00:20:10,600 Speaker 2: Why do you suppose the numbers are going up? 373 00:20:12,080 --> 00:20:14,719 Speaker 3: There are a lot of different possibilities for why that is. 374 00:20:15,680 --> 00:20:17,880 Speaker 3: I think we could probably have a whole other podcast 375 00:20:18,000 --> 00:20:20,840 Speaker 3: on what that is. In a nutshell, there are more 376 00:20:21,000 --> 00:20:23,480 Speaker 3: there seem to be more situations where people feel like 377 00:20:23,520 --> 00:20:26,280 Speaker 3: the fight is unwinnable. When I see that numbers for 378 00:20:26,320 --> 00:20:28,959 Speaker 3: depression and suicidality going up, it's sort of an index 379 00:20:28,960 --> 00:20:31,320 Speaker 3: of number of people who feel like they are losing 380 00:20:31,359 --> 00:20:34,000 Speaker 3: it life and that there's no way out for them. 381 00:20:34,320 --> 00:20:36,600 Speaker 3: So it is a bit of a barometer of social 382 00:20:36,600 --> 00:20:39,560 Speaker 3: health in that way. Some people have also attributed to 383 00:20:39,920 --> 00:20:42,640 Speaker 3: increased stressors around social media use and so on, and 384 00:20:42,680 --> 00:20:45,240 Speaker 3: some people have even attributed to things like changes in 385 00:20:45,240 --> 00:20:48,120 Speaker 3: the composition of the bacteria that live within our guts, 386 00:20:48,400 --> 00:20:51,240 Speaker 3: some of which appear to have a protective effect against depressions. 387 00:20:51,280 --> 00:20:53,760 Speaker 3: So there are a lot of theories out there, but 388 00:20:53,760 --> 00:20:55,800 Speaker 3: I wouldn't say anyone has solved the mysteries of what 389 00:20:55,840 --> 00:20:58,640 Speaker 3: it is. There are lots of people posing everything from 390 00:20:58,680 --> 00:21:03,919 Speaker 3: social factors to psychological factors to biological factors like literally 391 00:21:03,960 --> 00:21:16,320 Speaker 3: write down to the bacteria in a person's gut. 392 00:21:23,400 --> 00:21:26,280 Speaker 1: So what do you think about the pharmaceutical treatments for depression? 393 00:21:27,000 --> 00:21:30,040 Speaker 2: Are they are they useful? Are they neutral? 394 00:21:30,720 --> 00:21:32,760 Speaker 3: Well, I would say that I can give you what 395 00:21:32,800 --> 00:21:35,360 Speaker 3: the numbers say. So if a person comes into their 396 00:21:35,359 --> 00:21:38,240 Speaker 3: family doctor with an episode of depression and they try 397 00:21:38,280 --> 00:21:41,320 Speaker 3: an antidepressant. There was a famous study about fifteen years 398 00:21:41,359 --> 00:21:43,879 Speaker 3: ago called star d Let out of the University of 399 00:21:43,960 --> 00:21:48,639 Speaker 3: Texas Southwestern and they found that about two thirds of 400 00:21:48,680 --> 00:21:53,720 Speaker 3: people could get to remission from depression after trying one 401 00:21:53,760 --> 00:21:57,320 Speaker 3: medication or two medications, or three medications or four medications 402 00:21:57,359 --> 00:22:00,000 Speaker 3: one after the other. But the numbers really drop precipit 403 00:22:00,320 --> 00:22:02,480 Speaker 3: so about one third of people would get better trying 404 00:22:02,480 --> 00:22:05,080 Speaker 3: the first medication they ever tried, only about one third 405 00:22:05,359 --> 00:22:07,119 Speaker 3: about a quarter of people would get better on the 406 00:22:07,119 --> 00:22:10,080 Speaker 3: second medication they tried. But by the time you've tried 407 00:22:10,080 --> 00:22:12,480 Speaker 3: two medications without success, the third and the fourth one 408 00:22:12,480 --> 00:22:16,159 Speaker 3: are down to, you know, around eight to twelve percent 409 00:22:16,200 --> 00:22:20,320 Speaker 3: success rates, not particularly high at all. So we're unfortunately 410 00:22:20,320 --> 00:22:22,760 Speaker 3: the situation where the medications tend to work by fairly 411 00:22:22,760 --> 00:22:26,120 Speaker 3: similar mechanisms in terms of boosting serotonin levels or boosting 412 00:22:26,520 --> 00:22:29,439 Speaker 3: nor at inefferent levels or dobamine levels and so on 413 00:22:29,800 --> 00:22:32,600 Speaker 3: and so. Yes, you try to influence the person's oppression 414 00:22:32,600 --> 00:22:35,720 Speaker 3: by influencing these neurotransmitters in the brain, but at least 415 00:22:35,800 --> 00:22:37,920 Speaker 3: one third of people don't get any benefit from them, 416 00:22:37,960 --> 00:22:41,560 Speaker 3: and unfortunately a lot of people relapse and a very 417 00:22:41,640 --> 00:22:44,000 Speaker 3: large percentage of people. About twenty five percent of people 418 00:22:44,040 --> 00:22:47,439 Speaker 3: stop taking medications early because of side effects. So I 419 00:22:47,480 --> 00:22:50,840 Speaker 3: don't want to run down medications because the upside is that, 420 00:22:51,240 --> 00:22:53,359 Speaker 3: you know, it's in some ways, it's quite remarkable that 421 00:22:53,400 --> 00:22:55,920 Speaker 3: you can take somebody who's despairing about where their life 422 00:22:56,000 --> 00:22:57,960 Speaker 3: is going, and all you ask them to do is 423 00:22:58,040 --> 00:23:00,280 Speaker 3: take ten seconds out of their day to take a 424 00:23:00,359 --> 00:23:03,119 Speaker 3: serotonin boosting medication or an or an effort in boosting 425 00:23:03,160 --> 00:23:06,159 Speaker 3: medication just at bedtime with their toothbrush, And it is 426 00:23:06,200 --> 00:23:08,520 Speaker 3: quite remarkable that just by doing that one little thing, 427 00:23:08,600 --> 00:23:11,399 Speaker 3: a certain percentity of people will emerge from depressed, dispar 428 00:23:11,480 --> 00:23:13,680 Speaker 3: and suicidality and be able to face the world again. 429 00:23:14,160 --> 00:23:16,080 Speaker 3: So that's the upside of it. The downside is that 430 00:23:16,119 --> 00:23:18,200 Speaker 3: there's also a very large number of people who don't 431 00:23:18,200 --> 00:23:20,320 Speaker 3: get better on the medications, and a very large number 432 00:23:20,320 --> 00:23:22,040 Speaker 3: of people who can't tolerate the medications. 433 00:23:22,200 --> 00:23:25,560 Speaker 1: So tell me about recent breakthroughs that are understanding. 434 00:23:26,880 --> 00:23:29,639 Speaker 3: So we're in what I would argue is actually one 435 00:23:29,680 --> 00:23:33,239 Speaker 3: of the most exciting periods of discovery within all of 436 00:23:33,920 --> 00:23:37,000 Speaker 3: within all of medicine, so psychiatry and in particular a 437 00:23:37,000 --> 00:23:41,199 Speaker 3: field called interventional psychiatry is now looking at all the 438 00:23:41,800 --> 00:23:45,119 Speaker 3: traditional disorders like depression, anxiety, and so on in terms 439 00:23:45,160 --> 00:23:48,520 Speaker 3: of brain circuitry and in terms of brain function, and 440 00:23:48,640 --> 00:23:51,400 Speaker 3: thanks to twenty five years of brain imaging research, we're 441 00:23:51,400 --> 00:23:54,639 Speaker 3: actually starting to get really lovely maps of where stuff 442 00:23:54,680 --> 00:23:57,440 Speaker 3: happens in the brain and what brain circuits are involved 443 00:23:57,480 --> 00:24:02,879 Speaker 3: in depression, anxiety, OCD, post traumatic stress disorder, or eating disorders, 444 00:24:03,200 --> 00:24:08,520 Speaker 3: pretty much most of the major categories of mental health disorders. 445 00:24:08,840 --> 00:24:10,920 Speaker 3: We are starting to get really great maps of what 446 00:24:11,040 --> 00:24:13,400 Speaker 3: areas of the brain are affected in them. The thing 447 00:24:13,440 --> 00:24:16,679 Speaker 3: that's making that knowledge useful is that we're also starting 448 00:24:16,720 --> 00:24:19,680 Speaker 3: to really take advantage now of a new generation of 449 00:24:20,440 --> 00:24:24,560 Speaker 3: brain stimulation treatments inspired by the kinds of cases that 450 00:24:24,600 --> 00:24:27,040 Speaker 3: I told you about at the beginning of our conversation, 451 00:24:27,840 --> 00:24:31,200 Speaker 3: which can go into those circuits which may be overactive 452 00:24:31,440 --> 00:24:35,360 Speaker 3: or underactive, and can actually stimulate them and reset them 453 00:24:35,400 --> 00:24:39,480 Speaker 3: back to their normal pattern of activity. So these new 454 00:24:39,520 --> 00:24:43,119 Speaker 3: generation of treatments are brain stimulation treatments, and what's important 455 00:24:43,160 --> 00:24:46,560 Speaker 3: about them is they're anatomically precise. Some of them, as 456 00:24:46,560 --> 00:24:51,680 Speaker 3: I mentioned before, involve implantable devices like deep brain stimulators, 457 00:24:51,920 --> 00:24:54,400 Speaker 3: and for the last twenty years, people have been pioneering 458 00:24:54,440 --> 00:24:56,199 Speaker 3: and starting to come up with ways that they can 459 00:24:56,200 --> 00:24:59,280 Speaker 3: actually implant little pacemakers in the brains of people who 460 00:24:59,320 --> 00:25:02,520 Speaker 3: have very serious forms of depression where nothing has worked, 461 00:25:03,040 --> 00:25:06,479 Speaker 3: and these deep brain stimulators have caused quite remarkable ability 462 00:25:06,480 --> 00:25:08,560 Speaker 3: of people that could turn around and immerge from their depression. 463 00:25:09,200 --> 00:25:10,800 Speaker 3: But of course we also have the issue that not 464 00:25:10,840 --> 00:25:13,160 Speaker 3: everybody wants to have a pacemaker and plant in their brain, 465 00:25:13,200 --> 00:25:16,159 Speaker 3: and so it would be really really useful if they 466 00:25:16,200 --> 00:25:19,879 Speaker 3: could undergo a different form of treatment that was non invasive. 467 00:25:20,359 --> 00:25:22,359 Speaker 3: And so the other kind of treatment that's really taking 468 00:25:22,359 --> 00:25:25,639 Speaker 3: off right now involves a treatment approved by the FDA 469 00:25:25,880 --> 00:25:30,560 Speaker 3: in two thousand and eight called transcranial magnetic stimulation. Transcranial 470 00:25:30,600 --> 00:25:36,359 Speaker 3: magnetic stimulation involves using a powerful focus magnetic pulse generator 471 00:25:37,080 --> 00:25:39,000 Speaker 3: placed it looks like a little ping pong paddle. It's 472 00:25:39,000 --> 00:25:41,680 Speaker 3: sort of placed against the scalp. You place it over 473 00:25:41,720 --> 00:25:44,480 Speaker 3: the target circuit that you want to stimulate, and with 474 00:25:44,560 --> 00:25:48,080 Speaker 3: the magnetic pulses you're able to actually stimulate and activate 475 00:25:48,119 --> 00:25:51,240 Speaker 3: target circuits in the brain without needing any surgery. They're 476 00:25:51,320 --> 00:25:53,640 Speaker 3: quite powerful, so even though they're magnetic pulses. These are 477 00:25:53,640 --> 00:25:56,760 Speaker 3: not fridge magnets. Like if you were to place this 478 00:25:56,960 --> 00:26:00,560 Speaker 3: paddle over the precise spot on your brain that moves 479 00:26:00,600 --> 00:26:03,760 Speaker 3: your thumb, and I were to press the button and 480 00:26:03,840 --> 00:26:06,120 Speaker 3: cause a couple of little pulses, you would actually see 481 00:26:06,520 --> 00:26:09,240 Speaker 3: your thumb or your hand move with every single pulse. 482 00:26:10,040 --> 00:26:12,280 Speaker 3: So these are ways of actually stimulating target reagions in 483 00:26:12,320 --> 00:26:15,280 Speaker 3: the brain. And by stimulating them over and over again 484 00:26:15,359 --> 00:26:18,280 Speaker 3: hundreds of times a day, you can gradually strengthen the 485 00:26:18,280 --> 00:26:22,200 Speaker 3: connections in areas of the brain that require strengthening, or 486 00:26:22,320 --> 00:26:24,840 Speaker 3: you can reduce the strength of the connections and areas 487 00:26:24,880 --> 00:26:28,400 Speaker 3: that I guess are over connected. And with these two approaches, 488 00:26:28,440 --> 00:26:30,679 Speaker 3: you can try to return the brain or reset the 489 00:26:30,680 --> 00:26:34,560 Speaker 3: brain back to its normal pattern of activity that occurs 490 00:26:34,600 --> 00:26:38,400 Speaker 3: when they are not in this mode of despair and folding. 491 00:26:39,119 --> 00:26:42,920 Speaker 1: And how is this figured out? About which brain areas 492 00:26:43,040 --> 00:26:43,720 Speaker 1: to zap. 493 00:26:44,840 --> 00:26:48,000 Speaker 3: So the work on this began all the way back 494 00:26:48,000 --> 00:26:50,560 Speaker 3: in the nineteen eighties when they started using pet scanners, 495 00:26:51,000 --> 00:26:54,240 Speaker 3: which inject a radioactive dye to look at the metabolism 496 00:26:54,320 --> 00:26:56,879 Speaker 3: of the brain, and they were able to compare the 497 00:26:56,880 --> 00:27:00,760 Speaker 3: brain activity of people with depression people who are not 498 00:27:00,800 --> 00:27:03,680 Speaker 3: in depression, and so the first maps of these came 499 00:27:03,680 --> 00:27:06,280 Speaker 3: out in the late nineteen eighties and early nineteen nineties, 500 00:27:06,320 --> 00:27:09,240 Speaker 3: and they pinpointed a set of areas in the frontal 501 00:27:09,280 --> 00:27:11,800 Speaker 3: lobes and also elsewhere in the brain that seemed to 502 00:27:11,800 --> 00:27:16,320 Speaker 3: be consistently underactive in people with depression. They also pinpointed 503 00:27:16,680 --> 00:27:20,000 Speaker 3: areas of the brain that were consistently overactive in people 504 00:27:20,040 --> 00:27:23,000 Speaker 3: with depression. Those ones appear to be deeper in and 505 00:27:23,040 --> 00:27:25,480 Speaker 3: this led to a new generation of treatments where people 506 00:27:25,600 --> 00:27:29,919 Speaker 3: use the transcranial magnetic stimulation devices to target the frontal 507 00:27:29,920 --> 00:27:32,760 Speaker 3: lobe areas near the surface because the magnetic pulses could 508 00:27:32,760 --> 00:27:35,600 Speaker 3: read them. They also went to the surgeons and began 509 00:27:35,720 --> 00:27:39,240 Speaker 3: using the deep brain stimulator electrodes, which despite their name 510 00:27:39,400 --> 00:27:42,639 Speaker 3: as stimulators, can actually be used to inhibit and disrupt 511 00:27:42,960 --> 00:27:45,720 Speaker 3: areas of the brain that are overactive, and so they 512 00:27:45,720 --> 00:27:47,679 Speaker 3: were able to implant these in the areas of the 513 00:27:47,680 --> 00:27:51,000 Speaker 3: brain that were deeper and overactive in depression and use 514 00:27:51,040 --> 00:27:53,520 Speaker 3: them to reset their activity. 515 00:27:53,680 --> 00:27:57,840 Speaker 1: So I recently did an episode on how brains simulate 516 00:27:57,920 --> 00:28:00,240 Speaker 1: the future. This is one of the main jobs of 517 00:28:00,240 --> 00:28:02,040 Speaker 1: brains is to simulate and. 518 00:28:02,000 --> 00:28:03,760 Speaker 2: Evaluate possible futures. 519 00:28:04,000 --> 00:28:07,440 Speaker 1: What's your interpretation of what happens when somebody is depressed 520 00:28:07,480 --> 00:28:10,800 Speaker 1: in terms of the futures that they are simulating. 521 00:28:11,600 --> 00:28:15,720 Speaker 3: So that's a fascinating question, and I think there actually 522 00:28:15,760 --> 00:28:18,040 Speaker 3: are some really lovely brain imaging studies that were done 523 00:28:18,040 --> 00:28:22,040 Speaker 3: on this about ten years ago, led by Adam Gazzale 524 00:28:22,280 --> 00:28:25,399 Speaker 3: and some other folks over at UCSF. What they noticed 525 00:28:25,560 --> 00:28:28,480 Speaker 3: was that perhaps in your discussion you talked about a 526 00:28:29,000 --> 00:28:31,760 Speaker 3: network of areas in the brain called the default mode network. 527 00:28:32,640 --> 00:28:35,439 Speaker 3: The default mode network is named that because it seems 528 00:28:35,440 --> 00:28:37,159 Speaker 3: to be one of the most you know, it's the 529 00:28:37,200 --> 00:28:38,840 Speaker 3: area of the brain that is on by default when 530 00:28:38,840 --> 00:28:40,720 Speaker 3: we're not doing anything else. So if you or I 531 00:28:41,000 --> 00:28:43,080 Speaker 3: were sitting in a room quietly and there's nothing going on, 532 00:28:43,200 --> 00:28:45,840 Speaker 3: our default mode network turns on. And as we've all 533 00:28:45,880 --> 00:28:48,640 Speaker 3: experienced that involved what happens in our minds is our 534 00:28:48,640 --> 00:28:50,720 Speaker 3: brains start thinking about the past and thinking about the 535 00:28:50,720 --> 00:28:53,520 Speaker 3: future and making plans and thinking about what may take place. 536 00:28:53,920 --> 00:28:56,040 Speaker 3: There are two pathways by which we do that. There's 537 00:28:56,080 --> 00:28:59,000 Speaker 3: a so called reward pathway where our brain thinks about 538 00:28:59,000 --> 00:29:01,880 Speaker 3: opportunities and things we might start to want or desire 539 00:29:02,000 --> 00:29:03,720 Speaker 3: to get us up out of our seats and get going. 540 00:29:04,200 --> 00:29:08,160 Speaker 3: But there's also a second pathway called the non reward pathway, 541 00:29:08,360 --> 00:29:11,720 Speaker 3: whose job it is entirely to think about non rewarding outcomes. 542 00:29:11,760 --> 00:29:14,120 Speaker 3: Things could go wrong, fires I have to put out 543 00:29:14,160 --> 00:29:16,320 Speaker 3: problems in my life, things that I should be motivated 544 00:29:16,320 --> 00:29:18,800 Speaker 3: to go and sort out. And we need both of 545 00:29:18,800 --> 00:29:20,920 Speaker 3: those to work in balance. So we both need the 546 00:29:20,960 --> 00:29:24,240 Speaker 3: ability to come up with ideas for opportunities and things 547 00:29:24,240 --> 00:29:26,600 Speaker 3: that we desire to do, but we also need to 548 00:29:26,600 --> 00:29:29,800 Speaker 3: be guided by all the problems in life, all the 549 00:29:29,840 --> 00:29:32,160 Speaker 3: things that we really need to be motivated to take 550 00:29:32,160 --> 00:29:35,040 Speaker 3: care of. And with a balance between those two, we 551 00:29:35,080 --> 00:29:37,320 Speaker 3: can both pursue opportunities in the future, and we can 552 00:29:37,360 --> 00:29:41,920 Speaker 3: also avoid threats and problems and resolve them. The problem 553 00:29:41,920 --> 00:29:45,040 Speaker 3: and depression occurs when this so called non reward pathway, 554 00:29:45,120 --> 00:29:48,040 Speaker 3: whose whole job is to think about all negative consequences, 555 00:29:48,080 --> 00:29:50,440 Speaker 3: things that are going wrong, things that could screw up, 556 00:29:51,120 --> 00:29:54,600 Speaker 3: It can get trapped into sort of self perpetuating feedback loop. 557 00:29:54,720 --> 00:29:56,960 Speaker 3: So the circuit in the brain is arranged as a 558 00:29:56,960 --> 00:29:59,720 Speaker 3: bit of a loop from the frontal lobes going down 559 00:29:59,760 --> 00:30:03,600 Speaker 3: into the reward and motivational structures of the brain and 560 00:30:04,600 --> 00:30:07,120 Speaker 3: as if it gets stuck in a loop. What happens 561 00:30:07,200 --> 00:30:10,080 Speaker 3: is the person experience is just finding that even though 562 00:30:10,120 --> 00:30:12,040 Speaker 3: there maybe ninety nine things that are going well in 563 00:30:12,040 --> 00:30:15,240 Speaker 3: the person's life, their brain will find the one thing 564 00:30:15,400 --> 00:30:17,280 Speaker 3: that's going wrong and it will get stuck on it, 565 00:30:17,320 --> 00:30:19,040 Speaker 3: and it will just loop on it over and over 566 00:30:19,080 --> 00:30:21,560 Speaker 3: and over again. I think most of us know somebody 567 00:30:21,760 --> 00:30:24,440 Speaker 3: as family, friends, colleagues, maybe even ourselves who tend to 568 00:30:24,480 --> 00:30:26,320 Speaker 3: do that, who are always really good at spotting the 569 00:30:26,360 --> 00:30:29,040 Speaker 3: one problem and getting stuck on it. But in depression 570 00:30:29,040 --> 00:30:31,560 Speaker 3: it becomes true to a pathological extent where they get 571 00:30:31,600 --> 00:30:33,680 Speaker 3: so stuck on it that even with effort, they cannot 572 00:30:33,720 --> 00:30:38,520 Speaker 3: pull themselves out of the negative circle of thoughts, which 573 00:30:38,560 --> 00:30:42,480 Speaker 3: we call by the technical term ruminations. So in depression, 574 00:30:43,440 --> 00:30:45,880 Speaker 3: this non reward pathway has gotten stuck in a loop, 575 00:30:45,920 --> 00:30:48,760 Speaker 3: and what the person experiences is an endless circle of 576 00:30:48,840 --> 00:30:52,920 Speaker 3: ruminations and self criticism and thoughts about all the possible 577 00:30:52,960 --> 00:30:55,200 Speaker 3: futures that will go wrong and all the past things 578 00:30:55,240 --> 00:30:57,800 Speaker 3: that have gone wrong. And it just becomes very difficult 579 00:30:57,840 --> 00:30:59,880 Speaker 3: to pull yourself out of this even when you need to. 580 00:31:00,200 --> 00:31:04,520 Speaker 1: And so what is the transcranial magnetic stimulation doing when 581 00:31:04,560 --> 00:31:08,280 Speaker 1: you are hitting a particular area, is it giving a 582 00:31:08,440 --> 00:31:11,920 Speaker 1: second bite at the apple for that area to rewire? 583 00:31:12,480 --> 00:31:15,160 Speaker 1: Is it simply making the area more plastic so that 584 00:31:15,200 --> 00:31:18,640 Speaker 1: it has an opportunity to wire up in a more 585 00:31:18,640 --> 00:31:20,080 Speaker 1: beneficial way the next time around. 586 00:31:20,920 --> 00:31:23,560 Speaker 3: So I'll give you our best guess as to what's 587 00:31:23,600 --> 00:31:26,320 Speaker 3: happening right now. As with many things in psychiatry, we 588 00:31:26,400 --> 00:31:29,240 Speaker 3: discovered that these things worked long before we actually figured 589 00:31:29,240 --> 00:31:33,520 Speaker 3: out why they worked. But the original areas of the 590 00:31:33,520 --> 00:31:36,720 Speaker 3: brain that we stimulated were targeted because they just seem 591 00:31:36,760 --> 00:31:38,920 Speaker 3: to be underactive in depression. So the theory was, look, 592 00:31:38,960 --> 00:31:41,760 Speaker 3: they're underactive, let's use this brain stimulator. Let's stimulate them, 593 00:31:41,800 --> 00:31:43,760 Speaker 3: let's turn them back on, and then all will be well. 594 00:31:44,480 --> 00:31:46,760 Speaker 3: Later on, we discovered that what these areas really seem 595 00:31:46,800 --> 00:31:50,640 Speaker 3: to be associated with is courage and resilience. In other words, 596 00:31:50,720 --> 00:31:54,440 Speaker 3: people who happened just by chance to have more gray 597 00:31:54,480 --> 00:31:57,280 Speaker 3: matter or more gray matter in these areas, they're more 598 00:31:57,280 --> 00:32:00,760 Speaker 3: resilient distress. They have better ability to cope. These brain 599 00:32:00,800 --> 00:32:04,000 Speaker 3: areas in the frontal lobes are engaged every time we 600 00:32:04,080 --> 00:32:06,520 Speaker 3: do a thing called cognitive control, which is our ability 601 00:32:06,520 --> 00:32:09,000 Speaker 3: to self regulate our thoughts and our behaviors and emotions. 602 00:32:09,600 --> 00:32:12,240 Speaker 3: In fact, for those of you who've tried MINDFULSS meditation, 603 00:32:12,280 --> 00:32:14,280 Speaker 3: if you've ever sat in a chair and tried to 604 00:32:14,280 --> 00:32:17,360 Speaker 3: not ruminate and tried to focus on your breathing. Every 605 00:32:17,400 --> 00:32:20,280 Speaker 3: time you notice that your mind is wandering, and you 606 00:32:20,360 --> 00:32:23,200 Speaker 3: shut down the ruminations and come back to your breathing again, 607 00:32:23,520 --> 00:32:26,080 Speaker 3: you turn on this network of areas. It looks like 608 00:32:26,120 --> 00:32:28,320 Speaker 3: what we're doing with TMS is actually not so much 609 00:32:28,400 --> 00:32:31,640 Speaker 3: pushing happiness into the brain or pulling anxiety out, but 610 00:32:31,680 --> 00:32:35,920 Speaker 3: more generally strengthening the very same network that is activated 611 00:32:35,960 --> 00:32:39,160 Speaker 3: when you do mindfulness meditation. And so when I talk 612 00:32:39,280 --> 00:32:41,920 Speaker 3: to patients about what it's like for them after the 613 00:32:42,080 --> 00:32:44,680 Speaker 3: TMS has worked, they talk a lot about how something 614 00:32:44,720 --> 00:32:46,960 Speaker 3: stressful happen this week, and normally it would have ruined 615 00:32:47,000 --> 00:32:49,040 Speaker 3: my whole week, but I noticed that I just got 616 00:32:49,080 --> 00:32:50,959 Speaker 3: over it. I kind of thought about it and realized 617 00:32:50,960 --> 00:32:52,760 Speaker 3: it wasn't as bad as and I was able to 618 00:32:52,840 --> 00:32:55,600 Speaker 3: kind of cope with it. They describe it as having 619 00:32:55,640 --> 00:32:58,400 Speaker 3: more coping capacity, And so it looks like the effects 620 00:32:58,400 --> 00:33:01,040 Speaker 3: of TMS on depression, at least with the standard areas, 621 00:33:01,080 --> 00:33:03,800 Speaker 3: might be somewhat indirect You're not so much pushing happiness 622 00:33:03,800 --> 00:33:07,080 Speaker 3: in or taking anxiety out, but you are strengthening a 623 00:33:07,120 --> 00:33:10,240 Speaker 3: sort of mental muscle for cognitive control. And as a result, 624 00:33:10,360 --> 00:33:13,760 Speaker 3: people just generally get better at self regulating their thoughts 625 00:33:13,800 --> 00:33:16,320 Speaker 3: and behaviors and emotions, and they can cope with more stress, 626 00:33:16,720 --> 00:33:18,960 Speaker 3: so things don't feel quite as defeating, things don't look 627 00:33:19,000 --> 00:33:19,520 Speaker 3: quite as bad. 628 00:33:20,760 --> 00:33:24,120 Speaker 1: I've been sort of playing with a different interpretation slightly 629 00:33:24,160 --> 00:33:28,600 Speaker 1: about it, which is that you are, to phrase it colloquially, 630 00:33:28,640 --> 00:33:32,120 Speaker 1: you're sort of loosening up a network that has found 631 00:33:32,200 --> 00:33:37,880 Speaker 1: itself getting into a particular way, a particular structure, and 632 00:33:37,920 --> 00:33:41,520 Speaker 1: what you're doing is reintroducing plasticity to that area so 633 00:33:41,680 --> 00:33:45,560 Speaker 1: that you have a chance of things running correctly through there. 634 00:33:45,960 --> 00:33:50,200 Speaker 1: And with TMS, as we know, sometimes the first treatment 635 00:33:50,400 --> 00:33:53,840 Speaker 1: doesn't work, but the second treatment does. My view on 636 00:33:53,880 --> 00:33:57,080 Speaker 1: that is that it's possible that after the first time, 637 00:33:57,480 --> 00:34:04,240 Speaker 1: the system reconverges into to some pathological wiring, and then 638 00:34:04,280 --> 00:34:06,240 Speaker 1: you know, if you do it again, you're getting another 639 00:34:06,400 --> 00:34:09,920 Speaker 1: chance to have it find better wiring. 640 00:34:10,960 --> 00:34:11,160 Speaker 2: Yeah. 641 00:34:11,280 --> 00:34:13,359 Speaker 3: I'm really glad you brought that up, because I think 642 00:34:13,400 --> 00:34:16,040 Speaker 3: that actually lines up really well with a very recent 643 00:34:16,080 --> 00:34:21,440 Speaker 3: discovery that's still quite new about what is happening for 644 00:34:21,520 --> 00:34:25,200 Speaker 3: people who are trying a second form of OURTMS that 645 00:34:25,600 --> 00:34:27,759 Speaker 3: kicks in when the first one doesn't work. So when 646 00:34:27,800 --> 00:34:33,040 Speaker 3: I start rTMS, repetitive transcranial magnetic stimulation, it's effectively TMS 647 00:34:33,080 --> 00:34:35,839 Speaker 3: treatment but using these repetitive pulses. So some people will 648 00:34:35,840 --> 00:34:38,920 Speaker 3: call it rTMS, and some people will simply just abbreviate 649 00:34:38,920 --> 00:34:41,279 Speaker 3: it to TMS. But we're talking about using this non 650 00:34:41,320 --> 00:34:44,120 Speaker 3: invasive stimulation. So when a person goes through and does 651 00:34:44,160 --> 00:34:46,880 Speaker 3: the treatment using the standard parameters that I talked about, 652 00:34:47,160 --> 00:34:49,279 Speaker 3: sometimes it works, and yet there's a percentage of people 653 00:34:49,280 --> 00:34:52,160 Speaker 3: where it doesn't work. What we've noticed that those people 654 00:34:52,200 --> 00:34:55,480 Speaker 3: tend to have higher scales on rumination negative ruminations. A 655 00:34:55,520 --> 00:34:58,440 Speaker 3: Bad Life and a Lovely study came out by a 656 00:34:58,440 --> 00:35:00,840 Speaker 3: group led by Andy Lukter at You where he was 657 00:35:00,880 --> 00:35:04,680 Speaker 3: able to identify that these people have higher rumination scores. 658 00:35:06,239 --> 00:35:08,600 Speaker 3: They then move the coil to a different areas, so 659 00:35:08,640 --> 00:35:10,799 Speaker 3: instead of stimulating the first area that to talk about, 660 00:35:10,800 --> 00:35:13,840 Speaker 3: they go to a different brain area which actually sits 661 00:35:13,880 --> 00:35:17,000 Speaker 3: within this non reward circuit that we were talking about before, 662 00:35:17,480 --> 00:35:20,399 Speaker 3: and instead of trying to stimulate and strengthen it. Sure enough, 663 00:35:20,440 --> 00:35:22,840 Speaker 3: what they do is they try and inhibit and disrupt 664 00:35:22,880 --> 00:35:25,279 Speaker 3: the activity of this area. So they are trying to 665 00:35:25,360 --> 00:35:28,719 Speaker 3: disrupt and break up the feedback loop that they call 666 00:35:28,760 --> 00:35:32,520 Speaker 3: the non reward attractor state. It's in fact a professor 667 00:35:32,600 --> 00:35:35,280 Speaker 3: named Edmund Rolls out of Cambridge by the way just described, 668 00:35:35,320 --> 00:35:37,279 Speaker 3: He came up with a theory of depression which is 669 00:35:37,360 --> 00:35:39,200 Speaker 3: very similar to what you describe. He called it the 670 00:35:39,600 --> 00:35:43,520 Speaker 3: non reward attractor theory of depression. That non reward circuit. 671 00:35:43,880 --> 00:35:46,240 Speaker 3: The more it runs and the more it dwells on things, 672 00:35:46,280 --> 00:35:48,680 Speaker 3: the more it strengthens the connections in and of itself, 673 00:35:48,680 --> 00:35:51,920 Speaker 3: so it becomes self strengthening, self perpetuating, and you're just 674 00:35:51,960 --> 00:35:54,319 Speaker 3: going to get stuck in this so called attractor state 675 00:35:54,480 --> 00:35:56,359 Speaker 3: and not be able to get out of it. The 676 00:35:56,360 --> 00:35:59,200 Speaker 3: solution with TMS would be to put the coil over 677 00:35:59,480 --> 00:36:02,360 Speaker 3: those areas and apply some pulses of stimulation, not to 678 00:36:02,360 --> 00:36:04,440 Speaker 3: strengthen the pathway that's not what we want, but to 679 00:36:04,600 --> 00:36:08,920 Speaker 3: disrupt and weaken the connections through a neuroplasticity to the 680 00:36:08,920 --> 00:36:11,120 Speaker 3: point where the person can now pull themselves out again. 681 00:36:11,600 --> 00:36:12,600 Speaker 2: That's your interpretation. 682 00:36:12,880 --> 00:36:15,760 Speaker 1: Of what transcrinial megaing stimulation does, right. 683 00:36:15,760 --> 00:36:17,840 Speaker 3: Yeah, so we're still figuring this out. But what we 684 00:36:17,840 --> 00:36:20,120 Speaker 3: think is that for some people, when you strengthen the 685 00:36:20,160 --> 00:36:24,520 Speaker 3: first circuit and they regain their cognitive control, that circuit 686 00:36:24,520 --> 00:36:26,880 Speaker 3: is connected to the non reward circuit, so they can 687 00:36:26,920 --> 00:36:29,600 Speaker 3: then use their cognitive control to do this work themselves 688 00:36:29,600 --> 00:36:32,640 Speaker 3: of popping themselves out at this tractor state and other people, 689 00:36:32,680 --> 00:36:35,640 Speaker 3: for whatever reason, these two pathways aren't really very well connected, 690 00:36:35,680 --> 00:36:38,120 Speaker 3: so they kind of operate independently. So you strengthen the 691 00:36:38,120 --> 00:36:41,000 Speaker 3: first pathway, they get more coping capacity, but the problem 692 00:36:41,080 --> 00:36:43,960 Speaker 3: is they're still stuck in these negative terminations. Then you 693 00:36:43,960 --> 00:36:46,440 Speaker 3: bring them back again you move the stimulator over to 694 00:36:46,480 --> 00:36:49,480 Speaker 3: this other pathway. I actually had a patient who described 695 00:36:49,480 --> 00:36:51,880 Speaker 3: as saying this for your first treatment didn't work, but 696 00:36:51,920 --> 00:36:54,800 Speaker 3: the second one you gave me over this non reward pathway. 697 00:36:55,440 --> 00:36:57,640 Speaker 3: He said, I'm definitely one of those people you talked 698 00:36:57,680 --> 00:37:00,399 Speaker 3: about who always finds the one negative thing the room. 699 00:37:00,440 --> 00:37:02,879 Speaker 3: And if I see it, it's like a negative he said, 700 00:37:02,920 --> 00:37:05,640 Speaker 3: it's like an escalator. I'm forcing it on the escalator 701 00:37:05,640 --> 00:37:07,960 Speaker 3: and ride it down, down, down, all the way to 702 00:37:08,000 --> 00:37:09,839 Speaker 3: the bottom. And then I'm just stuck there. That could 703 00:37:09,840 --> 00:37:12,480 Speaker 3: be stuck there for days or weeks. And after I 704 00:37:12,520 --> 00:37:15,480 Speaker 3: finished the course of treatment, something really horrible happened, and 705 00:37:15,560 --> 00:37:17,080 Speaker 3: I thought, oh boy, here we go. I'm going to 706 00:37:17,120 --> 00:37:19,600 Speaker 3: be dragged down the escalator, and it just didn't happen. 707 00:37:19,880 --> 00:37:21,680 Speaker 3: I noticed the way he said it. 708 00:37:21,680 --> 00:37:22,279 Speaker 2: It's like I. 709 00:37:22,239 --> 00:37:24,239 Speaker 3: Walked up to the top of this escalator, I saw 710 00:37:24,280 --> 00:37:26,399 Speaker 3: where it was going, and I realized I didn't want 711 00:37:26,400 --> 00:37:28,799 Speaker 3: to go down there, and so my brain just kept going. 712 00:37:29,719 --> 00:37:32,440 Speaker 3: And I think what's interesting on the brain imaging studies, 713 00:37:32,480 --> 00:37:34,319 Speaker 3: of course, is if you scan people before and after, 714 00:37:34,360 --> 00:37:36,680 Speaker 3: what you find is exactly what you described, that the 715 00:37:36,719 --> 00:37:41,040 Speaker 3: connections between within this circuit are actually getting disrupted and weekend, 716 00:37:41,160 --> 00:37:43,719 Speaker 3: so the circuit's still there and functioning, but it's not 717 00:37:43,719 --> 00:37:47,040 Speaker 3: getting stuck in this attractor state or this loop. So 718 00:37:47,120 --> 00:37:48,640 Speaker 3: I think it actually lines up really well with the 719 00:37:48,680 --> 00:37:51,759 Speaker 3: account you just described. In the one case, plasticity being 720 00:37:51,840 --> 00:37:54,480 Speaker 3: used to strengthen the person's ability to control their thoughts. 721 00:37:54,840 --> 00:37:56,880 Speaker 3: But if that doesn't work in the other case, you 722 00:37:56,880 --> 00:37:59,360 Speaker 3: can then go directly to the area that's stuck in 723 00:37:59,400 --> 00:38:02,000 Speaker 3: a loop in the first place and use another form 724 00:38:02,040 --> 00:38:04,960 Speaker 3: of plasticity. To weaken those connections and loosen them so 725 00:38:05,040 --> 00:38:06,440 Speaker 3: the person can come out of it again. 726 00:38:24,400 --> 00:38:28,000 Speaker 1: This is very cool because originally with depression, I mean, 727 00:38:28,000 --> 00:38:30,240 Speaker 1: I think it's always been this way historically, that people, 728 00:38:30,480 --> 00:38:33,000 Speaker 1: let's say loved ones who are with somebody who's depressed, 729 00:38:33,320 --> 00:38:35,399 Speaker 1: feel like, hey, we should just be able to talk 730 00:38:35,400 --> 00:38:37,080 Speaker 1: to the person out of this, just say hey, look 731 00:38:37,080 --> 00:38:38,080 Speaker 1: at the bright side and so on. 732 00:38:38,480 --> 00:38:41,120 Speaker 2: That doesn't work. And so this. 733 00:38:41,239 --> 00:38:47,319 Speaker 1: Idea of being able to help somebody buy let's say, 734 00:38:47,480 --> 00:38:49,920 Speaker 1: loosening up circuits in the brain, doing other things, you know, 735 00:38:49,960 --> 00:38:54,680 Speaker 1: getting someone out of an attractor state non invasively is 736 00:38:55,200 --> 00:38:58,680 Speaker 1: so promising. What do you predict is going to be 737 00:38:58,760 --> 00:39:02,440 Speaker 1: the field in forty years from now when you're elderly. 738 00:39:03,320 --> 00:39:06,719 Speaker 3: Oh wow, that's really interesting. I'll get to that in 739 00:39:06,719 --> 00:39:09,120 Speaker 3: a moment, but I want to just come back and 740 00:39:09,160 --> 00:39:11,040 Speaker 3: highlight that I think you've really hit the nail on 741 00:39:11,080 --> 00:39:13,719 Speaker 3: the head of this, that every one of us has 742 00:39:13,760 --> 00:39:16,520 Speaker 3: tried to talk someone who's despairing out of the respair. 743 00:39:16,560 --> 00:39:19,399 Speaker 3: We've all tried to do it, and we've all been 744 00:39:19,480 --> 00:39:21,960 Speaker 3: sort of stimied and frustrated, going, why are you fighting 745 00:39:22,040 --> 00:39:23,840 Speaker 3: us on this? Like I keep trying to tell you 746 00:39:23,880 --> 00:39:25,480 Speaker 3: all the things that are good in life and reminds 747 00:39:25,480 --> 00:39:27,040 Speaker 3: you of them, and it's almost like you want your 748 00:39:27,040 --> 00:39:29,040 Speaker 3: brain wants to just go to the one negative thing 749 00:39:29,080 --> 00:39:31,720 Speaker 3: and stuck there. You've had that experience in talking to somebody. 750 00:39:31,719 --> 00:39:34,960 Speaker 3: I'm sure we all have, and it comes back to 751 00:39:35,040 --> 00:39:38,800 Speaker 3: exactly that lesson that depression is a kind of motivated state. 752 00:39:38,880 --> 00:39:41,680 Speaker 3: It's the brain is turning this on because it thinks 753 00:39:41,680 --> 00:39:43,719 Speaker 3: that it needs to be in this survival mechanism of 754 00:39:43,760 --> 00:39:45,960 Speaker 3: just folding and giving up. It thinks that that's its 755 00:39:46,000 --> 00:39:49,000 Speaker 3: best chance of survival. And so it's a highly motivated state. 756 00:39:49,040 --> 00:39:50,759 Speaker 3: And you will not be able to talk somebody out 757 00:39:50,760 --> 00:39:55,160 Speaker 3: of it because their motivational circuitry literally has been hijacked 758 00:39:55,160 --> 00:39:58,120 Speaker 3: by the depression, and so just talking people out of 759 00:39:58,160 --> 00:40:00,120 Speaker 3: it doesn't work terribly well. But as you say, now 760 00:40:00,120 --> 00:40:04,080 Speaker 3: that we know where this motivational cirguit lives, now that 761 00:40:04,120 --> 00:40:06,879 Speaker 3: we know where this non reward circuit lives, we can 762 00:40:06,920 --> 00:40:10,040 Speaker 3: do all kinds of interventions. And you asked, what's it 763 00:40:10,080 --> 00:40:12,000 Speaker 3: going to look like in forty years. I don't think 764 00:40:12,040 --> 00:40:15,759 Speaker 3: there's going to be any one treatment that is just 765 00:40:15,920 --> 00:40:18,960 Speaker 3: universally what people use. I'll give you an example of that. 766 00:40:19,000 --> 00:40:21,520 Speaker 3: So recently, a couple of years ago, a team that 767 00:40:21,640 --> 00:40:25,600 Speaker 3: you see San Francisco, led by Catherine Scangos and colleagues. 768 00:40:26,160 --> 00:40:28,680 Speaker 3: They were able to go to this non reward circuit 769 00:40:28,680 --> 00:40:31,399 Speaker 3: in the brain that I talked about, and they took 770 00:40:31,480 --> 00:40:33,719 Speaker 3: people who had very severe depression and they did something 771 00:40:33,760 --> 00:40:36,800 Speaker 3: that I think is very kind of futuristic. First of all, 772 00:40:37,000 --> 00:40:39,600 Speaker 3: they brought them into a special monitoring ward in the 773 00:40:39,640 --> 00:40:42,680 Speaker 3: hospital and they implanted the little electrodes in their brain and 774 00:40:42,800 --> 00:40:46,200 Speaker 3: let them stay in the hospital for several days or weeks. Normally, 775 00:40:46,239 --> 00:40:48,520 Speaker 3: that's what you'll do in epilepsy patients if you were 776 00:40:48,520 --> 00:40:50,879 Speaker 3: trying to find the source of the epilepsy within the brain. 777 00:40:50,880 --> 00:40:52,799 Speaker 3: You'll put electrodes all over the brain and you'll let 778 00:40:52,840 --> 00:40:54,520 Speaker 3: them sit and you wait for them to have seizures, 779 00:40:54,520 --> 00:40:56,799 Speaker 3: and then you go back and reconstruct where they came 780 00:40:56,840 --> 00:40:59,520 Speaker 3: from so you can perform a surgery. And this guys, 781 00:40:59,520 --> 00:41:02,000 Speaker 3: they said, well, you know the folks of depression, these 782 00:41:02,000 --> 00:41:05,319 Speaker 3: folks are really depressed. They can't function, their suicidal you know, 783 00:41:05,400 --> 00:41:07,520 Speaker 3: they really need something just as drastic as this. So 784 00:41:07,520 --> 00:41:10,120 Speaker 3: they brought them in, they implanted the electrodes but instead 785 00:41:10,120 --> 00:41:12,160 Speaker 3: of waiting for seizures, they just let them have negative 786 00:41:12,160 --> 00:41:14,920 Speaker 3: thoughts and using a little app on their tablet, they 787 00:41:14,960 --> 00:41:17,480 Speaker 3: could constantly rate what their brain was thinking about, and 788 00:41:17,560 --> 00:41:20,360 Speaker 3: so you could see what kind of brain activity was 789 00:41:20,400 --> 00:41:23,040 Speaker 3: going on when they were having positive thoughts or negative thoughts. 790 00:41:23,960 --> 00:41:26,680 Speaker 3: And by doing that and using a machine learning algorithm, 791 00:41:26,760 --> 00:41:30,319 Speaker 3: they were able to detect the electrodes that showed particular 792 00:41:30,440 --> 00:41:33,600 Speaker 3: pattern of abnormal activity that was present when the brain 793 00:41:33,640 --> 00:41:36,960 Speaker 3: got sucked into those negative ruminations. When they did that, 794 00:41:37,000 --> 00:41:39,640 Speaker 3: they were then able to implant a deep brain stimulator 795 00:41:39,640 --> 00:41:42,040 Speaker 3: in that and it was a closed loop system, so 796 00:41:42,080 --> 00:41:44,480 Speaker 3: it was attached to a tiny little computer that would 797 00:41:45,360 --> 00:41:47,719 Speaker 3: that would detect when the brain had gone into this 798 00:41:47,800 --> 00:41:50,840 Speaker 3: abnormal rhythm of negative thoughts and it would just disrupt 799 00:41:50,880 --> 00:41:53,120 Speaker 3: the activity with about five or six seconds of stimulation. 800 00:41:53,200 --> 00:41:54,640 Speaker 3: So we just flip the blip the blip, just to 801 00:41:54,840 --> 00:41:56,560 Speaker 3: like when you tap on a microphone to break a 802 00:41:56,600 --> 00:41:58,920 Speaker 3: feedback loop. It was literally just tapping on that microphone 803 00:41:58,960 --> 00:42:01,680 Speaker 3: and saying, hey, stop it. We've used this approach in 804 00:42:01,719 --> 00:42:03,640 Speaker 3: the heart for a long time, so people have heart 805 00:42:03,680 --> 00:42:07,120 Speaker 3: rhythm problems, can wear things called implantable, have a surgery 806 00:42:07,160 --> 00:42:11,360 Speaker 3: to have an implantable a cardiac defibrillator, so something like 807 00:42:11,360 --> 00:42:13,520 Speaker 3: the defibrillator padals that you might see in the airport, 808 00:42:13,560 --> 00:42:15,680 Speaker 3: but this is actually implanted inside. So if their heart 809 00:42:15,680 --> 00:42:18,600 Speaker 3: ever gets stuck in an abnormal rhythm that might be fatal, 810 00:42:19,000 --> 00:42:21,960 Speaker 3: the device will automatically detect that the heart's in that 811 00:42:22,040 --> 00:42:24,239 Speaker 3: rhythm and just give a few blips to reset it. 812 00:42:24,960 --> 00:42:27,319 Speaker 3: So interestingly, they were doing the same thing in the brain, 813 00:42:27,360 --> 00:42:31,399 Speaker 3: these folks that effectively created an implantable brain defibrillator, and 814 00:42:31,440 --> 00:42:34,000 Speaker 3: so it was detecting when this abnormal pattern comes along, 815 00:42:34,160 --> 00:42:37,040 Speaker 3: they blip it for a few seconds. And there's a 816 00:42:37,080 --> 00:42:38,680 Speaker 3: lovely article in the New York Times a couple of 817 00:42:38,719 --> 00:42:40,759 Speaker 3: years ago where they interviewed the patient describe what it 818 00:42:40,800 --> 00:42:43,200 Speaker 3: was like, and they talked about it as being a 819 00:42:43,280 --> 00:42:45,600 Speaker 3: sort of you're about to get sucked down into these 820 00:42:45,640 --> 00:42:48,560 Speaker 3: negative thoughts, and she said, suddenly the rational side of 821 00:42:48,600 --> 00:42:51,680 Speaker 3: you comes on and those negative emotions can be separated 822 00:42:51,680 --> 00:42:55,040 Speaker 3: from your real situation. What was encouraging is that this 823 00:42:55,320 --> 00:42:58,279 Speaker 3: seems to this process of implanting these stimulators seems to 824 00:42:58,320 --> 00:43:01,040 Speaker 3: work even in people who have had depression for decades 825 00:43:01,080 --> 00:43:05,200 Speaker 3: and have tried every other treatment available, multiple medications, therapies, TMS, 826 00:43:05,239 --> 00:43:08,880 Speaker 3: even electric convulsive therapy, all kinds of things. So people 827 00:43:08,880 --> 00:43:11,880 Speaker 3: have really gotten nowhere with the other treatments using this 828 00:43:11,960 --> 00:43:15,200 Speaker 3: targeted intelligent approach. I think that really is sort of 829 00:43:15,200 --> 00:43:17,000 Speaker 3: the prototype of what the future looks like. 830 00:43:17,520 --> 00:43:19,799 Speaker 1: Yeah, I think one of the most amazing things about this. 831 00:43:20,520 --> 00:43:23,720 Speaker 1: Many listeners will already sort of be aware of this research, 832 00:43:23,800 --> 00:43:28,640 Speaker 1: but generally we think of ourselves and our personalities and 833 00:43:28,680 --> 00:43:32,879 Speaker 1: our thoughts and our emotions as something different from let's 834 00:43:32,880 --> 00:43:35,200 Speaker 1: say our heart and how is our heart functioning? And 835 00:43:35,239 --> 00:43:38,960 Speaker 1: you can defibrillate the heart, but the brain it feels like, well, 836 00:43:39,000 --> 00:43:41,600 Speaker 1: that's me, that's just who I am, and so on. 837 00:43:41,960 --> 00:43:45,360 Speaker 1: And it's sort of an amazing revelation that many people 838 00:43:45,400 --> 00:43:47,880 Speaker 1: have when they start seeing this sort of data to 839 00:43:48,080 --> 00:43:53,080 Speaker 1: understand that we are physical creatures, and when you do 840 00:43:53,160 --> 00:43:56,080 Speaker 1: things to change the physical structure, that changes who you 841 00:43:56,160 --> 00:43:57,000 Speaker 1: are in that moment. 842 00:43:58,280 --> 00:44:00,319 Speaker 3: I think that's spot on, And that comes back to 843 00:44:00,360 --> 00:44:02,239 Speaker 3: the story we told at the beginning of why it 844 00:44:02,320 --> 00:44:04,080 Speaker 3: was so interesting for me as a as a young 845 00:44:04,160 --> 00:44:07,960 Speaker 3: researcher that you know, at that time many years ago, 846 00:44:08,000 --> 00:44:10,640 Speaker 3: we really there were the default idea was this thing 847 00:44:10,640 --> 00:44:14,799 Speaker 3: called the serotonin bothesis of depression, where you know, serotonin 848 00:44:14,840 --> 00:44:16,480 Speaker 3: had something to do with your mood, and if your 849 00:44:16,480 --> 00:44:18,640 Speaker 3: mood was low, it was maybe because your serotonin was low. 850 00:44:18,680 --> 00:44:20,759 Speaker 3: You you know, didn't have enough serotonin in your soup. 851 00:44:21,120 --> 00:44:23,160 Speaker 3: So we should get out a serotonin shaker and we 852 00:44:23,160 --> 00:44:25,279 Speaker 3: should shake some put some more serotonin into your soup, 853 00:44:25,320 --> 00:44:27,239 Speaker 3: and that will somehow just you know, make your mood 854 00:44:27,280 --> 00:44:30,080 Speaker 3: get better. But it turns out, of course, it's not 855 00:44:30,080 --> 00:44:33,160 Speaker 3: as simple as that, the serotonin is not mood. Serotonin 856 00:44:33,200 --> 00:44:36,040 Speaker 3: in you know, in your in your GI tract will 857 00:44:36,080 --> 00:44:39,080 Speaker 3: will cause your you know, to have to have GI 858 00:44:39,120 --> 00:44:42,080 Speaker 3: emotions in the brain. Stomach can regulate nausea, and the 859 00:44:42,160 --> 00:44:44,640 Speaker 3: visual cortex it can do visual things. And so there's 860 00:44:44,840 --> 00:44:47,560 Speaker 3: no such thing as a really where mood is just 861 00:44:47,600 --> 00:44:50,000 Speaker 3: boiled down to not having enough of a molecule in place. 862 00:44:51,000 --> 00:44:53,000 Speaker 3: But when we looked at those cases, as you said, 863 00:44:53,040 --> 00:44:55,640 Speaker 3: where people who had been depressed for so long that 864 00:44:55,680 --> 00:44:57,239 Speaker 3: they thought it was just part of who they were, 865 00:44:58,160 --> 00:45:00,680 Speaker 3: they then have this experience where you literally just take 866 00:45:01,040 --> 00:45:04,560 Speaker 3: a circuit in the brain and blip it and reset it, 867 00:45:05,080 --> 00:45:07,280 Speaker 3: and the person immediately in their thoughts is no longer 868 00:45:07,320 --> 00:45:10,360 Speaker 3: getting stuck in the negative thoughts and can look past 869 00:45:10,440 --> 00:45:12,799 Speaker 3: the one thing that's going wrong to the other ninety 870 00:45:12,840 --> 00:45:15,359 Speaker 3: nine things that are going right through that clear sort 871 00:45:15,360 --> 00:45:18,000 Speaker 3: of logical way, And you're right, people do really find 872 00:45:18,000 --> 00:45:21,560 Speaker 3: it as a revelation, and people who improve on these 873 00:45:21,640 --> 00:45:24,200 Speaker 3: they often find that because they've been depressed for twenty years, 874 00:45:24,320 --> 00:45:27,239 Speaker 3: you know that they don't It can be actually quite 875 00:45:27,280 --> 00:45:28,960 Speaker 3: a lot of work to sit down with a person 876 00:45:29,000 --> 00:45:31,520 Speaker 3: and figure out how to reconstruct their life based on 877 00:45:31,560 --> 00:45:33,480 Speaker 3: the premise that they actually get up every day and 878 00:45:33,480 --> 00:45:35,399 Speaker 3: feel good and ready to do things. They have spent 879 00:45:35,480 --> 00:45:39,440 Speaker 3: twenty years building a life around disability, so it's not 880 00:45:39,520 --> 00:45:41,359 Speaker 3: something where so there often can be quite a lot 881 00:45:41,400 --> 00:45:43,040 Speaker 3: of work done over months or years to try and 882 00:45:43,080 --> 00:45:45,600 Speaker 3: figure out how the person will adapt to a life 883 00:45:45,640 --> 00:45:49,080 Speaker 3: that has hope in it. Again, Yeah, so you. 884 00:45:49,080 --> 00:45:52,480 Speaker 1: Once told me how you see the battle against depression 885 00:45:52,560 --> 00:45:55,600 Speaker 1: in the twenty first century from a historical point of view. 886 00:45:57,920 --> 00:46:00,279 Speaker 3: Yeah, so, I mean, let's come back to those we 887 00:46:00,280 --> 00:46:02,640 Speaker 3: talked about earlier on where we said that there's the 888 00:46:02,719 --> 00:46:06,160 Speaker 3: prevalence of depression over the lifetime is maybe ten percent, 889 00:46:06,239 --> 00:46:08,640 Speaker 3: and the prevalence at any given time is about five percent. 890 00:46:09,239 --> 00:46:09,439 Speaker 2: Now. 891 00:46:09,520 --> 00:46:12,520 Speaker 3: There are lots of diseases in the history of medicine 892 00:46:12,520 --> 00:46:15,640 Speaker 3: where the prevalence has come down a lot, So people 893 00:46:16,160 --> 00:46:18,120 Speaker 3: used to be a lot of people. Tuberculosis, that's come 894 00:46:18,160 --> 00:46:20,880 Speaker 3: down a lot, and we're now making progress against malaria. 895 00:46:20,920 --> 00:46:24,400 Speaker 3: We're making progress against various forms of hepatitis. We're making 896 00:46:24,440 --> 00:46:27,840 Speaker 3: progress against stomach alsers that used to sometimes be fatal 897 00:46:27,880 --> 00:46:29,680 Speaker 3: if they progress. And for each of these things we 898 00:46:29,760 --> 00:46:32,640 Speaker 3: now have effective treatments and the prevalence has come down. 899 00:46:32,680 --> 00:46:36,799 Speaker 3: Even for HIV, something that was once untreatable and uncontrollable 900 00:46:36,880 --> 00:46:39,239 Speaker 3: is now turned into something that is controllable, and that 901 00:46:39,280 --> 00:46:41,399 Speaker 3: over time we may be able to get the prevalences down. 902 00:46:42,320 --> 00:46:44,080 Speaker 3: So the dream for us, I think for the twenty 903 00:46:44,080 --> 00:46:46,520 Speaker 3: first century would view that we would like, you know, 904 00:46:46,840 --> 00:46:48,759 Speaker 3: at the end of our careers forty years from now, 905 00:46:48,760 --> 00:46:50,600 Speaker 3: as you said, we'd like to be able to look 906 00:46:50,640 --> 00:46:54,200 Speaker 3: back at the prevalence of depression and anxiety and other 907 00:46:54,280 --> 00:46:57,040 Speaker 3: mental health disorders and say, look at that we used 908 00:46:57,080 --> 00:46:59,000 Speaker 3: to be at five or ten percent, and look how 909 00:46:59,040 --> 00:47:02,640 Speaker 3: much numbers come down since then. Millions of people who 910 00:47:03,200 --> 00:47:07,000 Speaker 3: had no pathway forward now see. Depression is something that 911 00:47:07,080 --> 00:47:11,359 Speaker 3: is treatable, and employers no longer look at depression as 912 00:47:11,360 --> 00:47:14,000 Speaker 3: something that would disqualify you from being hired for a job. 913 00:47:14,400 --> 00:47:16,080 Speaker 3: Oh you have depression, that's okay and not the end 914 00:47:16,080 --> 00:47:17,680 Speaker 3: of the world. Just go in and get the course 915 00:47:17,680 --> 00:47:19,319 Speaker 3: of treatment and we'll see you. We'll see you back 916 00:47:19,320 --> 00:47:21,879 Speaker 3: in a week or two. So you know, this will 917 00:47:21,920 --> 00:47:24,080 Speaker 3: help to erode the stigma, and I think we'll really 918 00:47:24,120 --> 00:47:26,480 Speaker 3: get to see the numbers coming down on this. Are 919 00:47:26,480 --> 00:47:28,480 Speaker 3: we going to get those millions of people better with 920 00:47:28,600 --> 00:47:31,120 Speaker 3: deep brain stimulators alone? No, of course not. We're not 921 00:47:31,160 --> 00:47:33,359 Speaker 3: going to be implanting millions and millions of deep brain 922 00:47:33,400 --> 00:47:35,879 Speaker 3: stimulators and everybody, not everybody wants them and just throw 923 00:47:35,880 --> 00:47:38,759 Speaker 3: on up serasons to do that. But I think we 924 00:47:38,880 --> 00:47:42,320 Speaker 3: do have a real opportunity using the non invasive forms 925 00:47:42,320 --> 00:47:45,560 Speaker 3: of brain stimulation like TMS, which are getting you know, 926 00:47:45,800 --> 00:47:48,600 Speaker 3: very very good as well. So your colleague over at 927 00:47:49,480 --> 00:47:51,800 Speaker 3: over at Stanford are one of my good friends. Nolan 928 00:47:51,840 --> 00:47:55,880 Speaker 3: Williams was instrumental in developing a radical new form of 929 00:47:55,920 --> 00:47:59,640 Speaker 3: TMS treatment that could take a person from severe depression 930 00:47:59,680 --> 00:48:01,360 Speaker 3: on money day all the way down to being in 931 00:48:01,400 --> 00:48:05,480 Speaker 3: remission in literally five days. The secret was to do 932 00:48:05,520 --> 00:48:07,520 Speaker 3: two things. The first was not to do a treatment 933 00:48:07,560 --> 00:48:10,520 Speaker 3: once a day traditionally, but to do up to ten 934 00:48:10,520 --> 00:48:12,359 Speaker 3: treatments a day, so that a person can have thirty 935 00:48:12,400 --> 00:48:14,440 Speaker 3: or forty or fifty treatments in a week and that's 936 00:48:14,480 --> 00:48:17,439 Speaker 3: definitely enough TMS sessions to get them better. The second 937 00:48:17,480 --> 00:48:19,640 Speaker 3: part of their trick was actually performed some brain imaging 938 00:48:19,719 --> 00:48:21,719 Speaker 3: in the person so you could see what pathways to 939 00:48:21,760 --> 00:48:24,160 Speaker 3: be targeting and then fine tune and personalized where the 940 00:48:24,200 --> 00:48:27,839 Speaker 3: coil is. Through some combination of those two things, they 941 00:48:27,840 --> 00:48:30,000 Speaker 3: seem to be hitting very high success rates that are 942 00:48:30,320 --> 00:48:33,240 Speaker 3: north of fifty percent. So we have a tool now 943 00:48:33,360 --> 00:48:37,000 Speaker 3: with TMS that if you know someone who has struggled 944 00:48:37,000 --> 00:48:39,920 Speaker 3: with depression or anxiety and has not done well on 945 00:48:39,960 --> 00:48:42,879 Speaker 3: therapy or medications, that's a lot of people. They can 946 00:48:42,920 --> 00:48:45,160 Speaker 3: go anywhere in the United States right now to a 947 00:48:45,200 --> 00:48:48,000 Speaker 3: TMS clinic and they can undergo a course of transcradial 948 00:48:48,080 --> 00:48:53,400 Speaker 3: magnetic simulation. And with the most recent FD protocols, we 949 00:48:53,520 --> 00:48:55,320 Speaker 3: believe that we can get more than fifty percent of 950 00:48:55,360 --> 00:48:58,279 Speaker 3: people to remission even if nothing else has worked. So 951 00:48:58,800 --> 00:49:00,359 Speaker 3: we do think we have a tool that is now 952 00:49:00,400 --> 00:49:04,080 Speaker 3: capable of treating most people with depression and getting at 953 00:49:04,160 --> 00:49:06,439 Speaker 3: least half of them out of the depression, maybe more. 954 00:49:06,920 --> 00:49:08,880 Speaker 3: The trick is going to be to scale that. So 955 00:49:09,000 --> 00:49:11,279 Speaker 3: it's scaling up so that everyone in the country will 956 00:49:11,320 --> 00:49:13,960 Speaker 3: have access to this treatment. Once we're there, I think 957 00:49:14,000 --> 00:49:18,240 Speaker 3: we will absolutely see improvements in the prevalence in our lifetimes. 958 00:49:18,400 --> 00:49:22,080 Speaker 1: It's great, Hey, just think into one more thing, because 959 00:49:22,120 --> 00:49:25,600 Speaker 1: you'd talked I've heard you talked before about tuberculosis and 960 00:49:25,160 --> 00:49:26,960 Speaker 1: the parallel there. 961 00:49:28,400 --> 00:49:32,200 Speaker 3: Yeah, so that's an interesting thing. It is possible. I 962 00:49:32,200 --> 00:49:34,279 Speaker 3: guess that our battle against depression in the twenty first 963 00:49:34,280 --> 00:49:36,840 Speaker 3: century is really a little bit like the battle against 964 00:49:37,080 --> 00:49:40,719 Speaker 3: tuberculosis in the nineteenth and the twentieth century. One of 965 00:49:40,719 --> 00:49:45,000 Speaker 3: the pioneers of modern medicine the nineteenth century physician Sir 966 00:49:45,080 --> 00:49:48,880 Speaker 3: William Osler. He, of course saw many patients in his 967 00:49:48,920 --> 00:49:51,799 Speaker 3: career with tuberculosis coming from the poorer areas of town, 968 00:49:51,880 --> 00:49:55,200 Speaker 3: the overcrowded areas and so on, the places where living 969 00:49:55,200 --> 00:49:58,320 Speaker 3: conditions were terrible, where sanitation was terrible, and as a result, 970 00:49:58,360 --> 00:50:03,840 Speaker 3: he described tuberculosis as primarily quote a social disease with 971 00:50:03,920 --> 00:50:06,919 Speaker 3: a medical aspect. In other words, yes, we can treat 972 00:50:06,960 --> 00:50:09,960 Speaker 3: it medically, but fundamentally, tuberculosis isn't going to go away 973 00:50:10,040 --> 00:50:12,520 Speaker 3: until people have better living conditions, until you don't have 974 00:50:12,560 --> 00:50:15,279 Speaker 3: eight people living in one room, until people aren't with 975 00:50:15,320 --> 00:50:17,720 Speaker 3: bad food, and all the rest of it. So, in fact, 976 00:50:17,800 --> 00:50:21,040 Speaker 3: although tuberculosis drugs were developed in the twentieth century and 977 00:50:21,080 --> 00:50:24,160 Speaker 3: save millions of lives when they're invented, the reality is 978 00:50:24,160 --> 00:50:28,440 Speaker 3: that the rates of tuberculosis were coming down decades before 979 00:50:28,600 --> 00:50:30,720 Speaker 3: any of these drugs were ever ruled out to reach people, 980 00:50:31,480 --> 00:50:35,440 Speaker 3: and the prevalence of tuberculosis improved because people's lives improved, 981 00:50:35,600 --> 00:50:39,239 Speaker 3: you know, better food, cleaner water, less crowded living conditions, 982 00:50:39,320 --> 00:50:43,759 Speaker 3: less dire poverty, less desperation, And I think we're going 983 00:50:43,840 --> 00:50:45,680 Speaker 3: to see that a very similar thing is happening here. 984 00:50:45,680 --> 00:50:47,120 Speaker 3: It's not that we won't be able to use new 985 00:50:47,160 --> 00:50:50,400 Speaker 3: technologies like brain stimulation to pull people out of despair, 986 00:50:50,760 --> 00:50:52,960 Speaker 3: but it's also possible that a key to getting people 987 00:50:52,960 --> 00:50:55,640 Speaker 3: out of despair will be to understand depression also as 988 00:50:55,760 --> 00:50:58,799 Speaker 3: to some degree a social disease with a medical aspect. 989 00:50:59,120 --> 00:51:01,560 Speaker 3: If we go back to the idea that depression is 990 00:51:01,560 --> 00:51:03,799 Speaker 3: the thing that happens when the brain has decided it's 991 00:51:03,840 --> 00:51:05,759 Speaker 3: in a battle for survival that it is not going 992 00:51:05,800 --> 00:51:08,800 Speaker 3: to win. Then we look at the prevalence of depression 993 00:51:08,800 --> 00:51:10,520 Speaker 3: as a number of people who look around at their 994 00:51:10,560 --> 00:51:13,719 Speaker 3: lives and concluded that they are in an unwinnable situation. 995 00:51:14,600 --> 00:51:17,120 Speaker 3: And I believe in the same way that we part 996 00:51:17,120 --> 00:51:19,799 Speaker 3: of the pathway to getting people out of depression and 997 00:51:19,880 --> 00:51:23,520 Speaker 3: reducing its prevalence will be improving the conditions of people's lives. 998 00:51:23,920 --> 00:51:26,319 Speaker 3: They're the degree to which they feel secure, a degree 999 00:51:26,360 --> 00:51:27,759 Speaker 3: to which they don't feel like they're going to lose 1000 00:51:27,800 --> 00:51:30,759 Speaker 3: their housing or to be under threat of violence. The 1001 00:51:30,800 --> 00:51:34,120 Speaker 3: first places in the world to overcome depression will be 1002 00:51:34,520 --> 00:51:37,960 Speaker 3: the ones that don't just develop better technologies to reset 1003 00:51:38,000 --> 00:51:42,120 Speaker 3: the brain, but also develop stronger societies in which we 1004 00:51:42,239 --> 00:51:44,560 Speaker 3: just have fewer percentages of people who are trapped in 1005 00:51:44,600 --> 00:51:46,960 Speaker 3: fights for survival that they feel like it never seem 1006 00:51:47,000 --> 00:51:50,920 Speaker 3: to win. And I guess that's maybe. There is a 1007 00:51:51,000 --> 00:51:54,520 Speaker 3: concept which one of my colleagues introduced me to from 1008 00:51:54,520 --> 00:51:56,800 Speaker 3: the history of Judaism, and it's a lovely phrase that 1009 00:51:56,920 --> 00:51:59,359 Speaker 3: I guess really carry around with me all day. It's 1010 00:52:00,200 --> 00:52:03,759 Speaker 3: the phrase is to kun olam, and it has been 1011 00:52:03,800 --> 00:52:08,279 Speaker 3: described to me as a religious injunction to repair the world. Yeah, 1012 00:52:08,520 --> 00:52:10,240 Speaker 3: I can't. I think you and I have also discussed 1013 00:52:10,239 --> 00:52:13,960 Speaker 3: this in the past as well. Yeah, so yeah, when 1014 00:52:13,960 --> 00:52:16,000 Speaker 3: we talk about resetting the brain, I think that falls 1015 00:52:16,000 --> 00:52:18,640 Speaker 3: within the larser of battles to try and improve the 1016 00:52:18,880 --> 00:52:22,239 Speaker 3: lot of humanity and reduce the reduce despair everywhere. And 1017 00:52:23,120 --> 00:52:25,760 Speaker 3: so when I think about the pathway to takun Olam 1018 00:52:26,120 --> 00:52:29,400 Speaker 3: and what neuroscience can contribute to it, and what you 1019 00:52:29,400 --> 00:52:32,880 Speaker 3: know brain stimulation can contribute to it, I think it 1020 00:52:32,920 --> 00:52:37,160 Speaker 3: has an essential role in reducing the number of people 1021 00:52:37,239 --> 00:52:39,200 Speaker 3: who face the world in despair, and that will be 1022 00:52:39,200 --> 00:52:42,160 Speaker 3: an essential component of this much larger injunction to repair 1023 00:52:42,239 --> 00:52:43,960 Speaker 3: the world, which I think we can all relate to. 1024 00:52:48,920 --> 00:52:52,560 Speaker 1: I spend many of these episodes talking about the extraordinary 1025 00:52:52,680 --> 00:52:56,520 Speaker 1: things that the brain does well, but it's equally important 1026 00:52:56,840 --> 00:52:59,759 Speaker 1: to talk about what happens when the brain gets off, 1027 00:53:00,719 --> 00:53:04,160 Speaker 1: because some percentage of your friends and loved ones are 1028 00:53:04,200 --> 00:53:07,600 Speaker 1: going to have to battle depression at some point, and 1029 00:53:07,719 --> 00:53:11,320 Speaker 1: it might be a slightly higher percentage. 1030 00:53:10,640 --> 00:53:11,320 Speaker 2: Than you think. 1031 00:53:11,920 --> 00:53:16,520 Speaker 1: The brain is incredible, but fragile, and what we see 1032 00:53:16,760 --> 00:53:20,480 Speaker 1: from depression is that it's relatively easy for it to 1033 00:53:20,680 --> 00:53:26,680 Speaker 1: slip out of its optimal operating range. Happily, neuroscience labs 1034 00:53:26,760 --> 00:53:30,560 Speaker 1: all over the world are working to understand this, and 1035 00:53:30,719 --> 00:53:36,239 Speaker 1: researchers and companies are generating new approaches, as with transcranial 1036 00:53:36,280 --> 00:53:41,399 Speaker 1: magnetic stimulation, such that as we move forward, we will 1037 00:53:41,440 --> 00:53:46,480 Speaker 1: have increasingly better ways to get things back on track. 1038 00:53:50,520 --> 00:53:53,800 Speaker 1: Go to Eagleman dot com slash podcast for more information 1039 00:53:53,920 --> 00:53:57,160 Speaker 1: and to find further reading. Send me an email at 1040 00:53:57,239 --> 00:54:00,400 Speaker 1: podcasts at eagleman dot com with questions or discuss ession 1041 00:54:00,719 --> 00:54:03,200 Speaker 1: and I'll be making monthly episodes in which I address 1042 00:54:03,280 --> 00:54:07,319 Speaker 1: those and check out and subscribe to Inner Cosmos on 1043 00:54:07,400 --> 00:54:10,640 Speaker 1: YouTube for videos of each episode and to leave comments 1044 00:54:11,200 --> 00:54:15,480 Speaker 1: until next time. I'm David Eagleman, and this is Inner Cosmos.