Depression’s Wiring Diagram
When Helen Mayberg started curing depression by stimulating a previously unknown neural junction box in a brain area called Brodmann’s area 25—discovered through 20 years of dogged research—people asked her where she was going to look next. Her reaction was, “What do you mean, Where am I going to look next? I’m going to look more closely here!”
Her closer look is now paying off. In a series of papers last year, Mayberg and several of her colleagues used diffusion tensor imaging (DTI) to reveal the neural circuitry of depression at new levels of precision. This MRI technique illuminates the connective tracts in the brain. For depression, the resulting map may allow a better understanding of what drives the disorder—and much better targeting and patient selection for treatments such as deep-brain stimulation (DBS) that seek to tweak this circuitry.
In the early 2000s Mayberg and Wayne C. Drevets, then at Washington University Medical School, separately established that area 25, which appeared to connect several brain regions involved in mood, thought and emotion, is hyperactive in depressed patients. The area’s significance was confirmed when Mayberg and her colleagues at the University of Toronto—neurosurgeon Andres Lazano and psychiatrist Sidney Kennedy—used DBS devices to bring relief to 12 out of 20 intractably depressed patients [see “Turning Off Depression,” by David Dobbs; Scientific American Mind, August/September 2006]. “That confirmed my hypothesis that area 25 is an important crossroads,” Mayberg says. “But exactly what circuits were we affecting?”
The recent papers take her much closer to answering this question. Working with fellow imaging experts Heidi Johansen-Berg and Tim Behrens of the University of Oxford and others, Mayberg used DTI to produce detailed images of area 25’s “tractography,” the layout of the white matter tracts that connect disparate brain regions. They identified five connective tracts that run through this pea-size region, carrying neural traffic among five vital areas: the amygdala, a deep-brain area that moderates fear and other emotions; the orbitofrontal and medial frontal cortices, two poorly understood areas that appear to be significant in expectation, reward processing, error assessment, learning and decision making; the hippocampus, vital to memory; and the hypothalamus, which helps to regulate stress and arousal.
The refined imaging of these tracts does more than just confirm Mayberg’s previous work identifying area 25 as a junction box. It also gives her a map that provides diagnostic and targeting information for DBS treatments of the area. As she expected, the locations of those tracts varies among individuals. “And this variation,” Mayberg says, “along with variations in the nature of different patients’ depression, probably explains why some patients respond better than others. Because the location varies, we’re not hitting all five tracts the same way in every patient.”
In a new study of 20 more patients she began at Emory University, Mayberg plans to analyze the tractography and electrode placement to see which of the tracts seems to be most essential to the treatment’s success. That investigation may reveal yet more about the nature of depression—and it might help Mayberg identify which patients will benefit from surgery so she can spare those it will not help.
Meanwhile a kind of DBS gold rush has developed as other scientists slide neuromodulators into different brain areas to try to treat depression, obsessive-compulsive disorder, eating disorders, Tourette’s syndrome, headaches and chronic pain [see “Sparking Recovery with Brain ‘Pacemakers,’ ” by Morton L. Kringelbach and Tipu Z. Aziz; Scientific American Mind, December 2008/January 2009].
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17 Comments
Add CommentI recently read a quote in a forum, it stated
Reply | Report Abuse | Link to this"it's a beautiful spring day, the sun is shining, the birds are singing, and i am stuck in a soul-stealing cubicle. If there is a drug that makes me OK with that, i don't want it".
Just a thought....
You have a choice, you can choose to be unhappy about being in the cubicle or you can choose to be happy that you are alive in the cubicle looking at the pleasant day. No drug needed, just a change in attitude. Depressed people may need help to achieve this ability. That help may be chemical, electrical or Cognitive Behavior Therapy
Reply | Report Abuse | Link to thisApologies. I neglected to say that you can also choose to walk out of the cubicle into the pleasant day. The way out is through the door. Why not use it?
Reply | Report Abuse | Link to thisObviously, you have never been seriously depressed.
Reply | Report Abuse | Link to thisas an individual who has been suffering from the ups and downs, and the drug reactions, days of tears for reasons i can only medicate, i am not ready for surgery but i am looking for a way out
Reply | Report Abuse | Link to thisas an individual who has been suffering from the ups and downs, and the drug reactions, days of tears for reasons i can only medicate, i am not ready for surgery but i am looking for a way out
Reply | Report Abuse | Link to thisas an individual who has been suffering from the ups and downs, and the drug reactions, days of tears for reasons i can only medicate, i am not ready for surgery but i am looking for a way out
Reply | Report Abuse | Link to thisas an individual who has been suffering from the ups and downs, and the drug reactions, days of tears for reasons i can only medicate, i am not ready for surgery but i am looking for a way out
Reply | Report Abuse | Link to thisas an individual who has been suffering from the ups and downs, and the drug reactions, days of tears for reasons i can only medicate, i am not ready for surgery but i am looking for a way out
Reply | Report Abuse | Link to this@iramarks - irre dude - thata alot of ups and downs
Reply | Report Abuse | Link to thisand in
ps
btw
depression is cultural
'love' is da answer
&
the only drug i recomend is herb - but hope faith placebo love emotion empathy bonding tribe gang sharing pain etc etc are the traditional words for what is at issue
beyond cbt is dbt
they dont want to tell you about nor why
i shall let you work out what why etc
or if baffled
and interested
good@gmx.co.uk
Okay..... Area 25 is base of the brain, just above the throat... up in the sinuses. I'm not a physiologist, I don't know the exact location.
Reply | Report Abuse | Link to thisBones, resonating cavities....
Whacky idea ahead ---> how effective is chanting as a means to stimulate the area?
You know you are depressed when you walk out that door into the beautiful spring day and still feel like shit.
Reply | Report Abuse | Link to thisethicspiedpiper - depression is not cultural. Depression likely hits those in individualistic cultures differently than collectivist cultures, but it is a disorder that spans the globe. Just fyi.
Reply | Report Abuse | Link to thisBrodmanns area 25 that combines neural traffic among five vital areas: hippocampus that serves as a short term memory storage, the amygdala, that moderates fear and other emotions; hypothalamus, which helps to regulate stress and arousal, and the orbitofrontal and medial frontal cortices, two poorly understood areas that serve as a long term memory storage is not a junction box but a center responsible for allocation and mapping of long term memory while it is transcribed from hippocampus to the other areas of the brain during sleep period. This area is also activated during retrieval of these memories and the fact that this area is active in people who are suffering from depression is mostly a unintended consequence of using antidepressant medication.
Reply | Report Abuse | Link to thisLet me try to explain: we all have painful memories and some peoples memories are more painful that others. These memories are formed at the times when painful events take place in our lives. Painful and scary events that affect us cause our brains to release fight of flight hormones into out bloodstream. Once released these hormones circulate in our bloodstream for a long time unless they get metabolised by physical activity like; fighting or running away.
Simply put; we get scared by an outside trigger and we deal with it by fighting or running away from the cause of our fears. In such case our brains return to normal state so when we fall asleep memories of events of the day that are stored in short term memory are transferred and stored in part of the brain that are accessible to easy retrieval. (We have a total memory recall of the event).
If for whatever reason we are unable to fight or run away from the cause of our fears and fall asleep at the end of the day still in fear for our life with amygdala on a high alert and hypothalamus still pumping out fight or flight hormones into our bloodstream, the memory of painful event gets transferred, during sleep period, from short term memory to inaccessible part of long term memory (we have no instant recall of what scared us) because we failed to cope with the threat when memory got transferred for long term storage.
High level of activity of amygdale and high activity of hypotalamus causes massive release of various neurotransmitters in our brains to better cope with the threat that we are facing, so when we fall asleep in such condition Brodmanns area 25 maps out such memories for storage with all neurotransmitters at high level (area 25 dials proverbial #999 distress call on an old telephone exchange). and as a result storage of long term memory is made in not so easily accessible brain location. Such memories are not easily accessible but also they do not easily overwritten by memories of any subsequent events. Normally we should get recall of these emotionally charged (emotionally unprocessed) memories only if and when we encounter similar scary situations when such recall is useful to our survival.
Among many other factors; illness, physical injuries, disability, lack of daylight, emotional stress caused by other peoples aggression and hostility, aging, poor nutrition, are natural causes of depression and depressive reaction to such causes serves useful function as depression causes reduction in level of physical activities allowing for recovery from illness or physical injuries and survival in hostile or harsh (seasonal depression) environment. Depression by itself as discomforting as it is rarely leads someone to commit suicide.
Now, we enter into this mix modern psychiatry and their reckless use of psychotropic substances and antidepressants.
What antidepressants of SSRI type do is bock re-uptake of neurotransmitter serotonin and allow for a build-up of the level of serotonin in the brain. Other antidepressants give a big bust to a level neurotransmitter called norepinephrine. By boosting level of neurotransmitters antidepressants increase activity of Brodmanns area 25 they crank up numbers that can be dialled on a proverbial old telephone exchange and cause that #999 distress calls from these emotionally charged (emotionally unprocessed) memories start to flood our consciousness and cause our brain do suffer emotional stress that is caused this time not so much by other peoples aggression and hostility (useful depression) but by memories past painful events reactive depression.
This starts a vicious circle more antidepressants to combat depression and as a result of boost in level of neurotransmitters more painful memories flooding conscious part of the brain causing more emotional distress and more depression until victim of such psychiatric treatment hunted by the demons of his or her painful childhood calls it quit and commits suicide.
Even without use of antidepressants sudden success in life or exposure to constant daylight can cause such a boost in levels of neurotransmitters circulating in the brain that they can trigger flood of painful and emotionally unprocessed memories and start a vicious cycle leading to a suicide.
Since this theory lays blame for suicides on psychoactive substances that are used to allegedly help people relive symptoms of depression and reduce risk of suicide no psychiatrist in US or Canada would be willing to go on the record with such theory even if they knew it because if any of them did Big Pharma would make sure that his or her psychiatric career would come to an abrupt end.
What causes area 25 to be under stimulated in the first place? Neurojunction blockages?
Reply | Report Abuse | Link to thisI am no neuro-scientist.
Reply | Report Abuse | Link to this5HT2 receptors are very important.
2009 depression theapy (for 37 million Americans on these pills) is by SSRI treatment which increases electric currents in neurotransmitter areas.
In future --protein substrates of synaptic 5HT2
regions can hopefully be rebuilt by genetic alterations.
This means that there will be no need to increase electrical
activity by SSRI's pills in said regions -- meaning proteins of synaptic cells will rebuild themselfs -- in effect pre-empting necessity of SSRI electrical inhancers.
Peace.
Not one single depressed person I know wants to take pills. But most, like I, are happy to have anything offering at least some relief. Hopefully, the next generation will have better treatments , but for now, medication is all that is keeping me alive. Crapping on meds in here is not effecting my choice of treatment options....not one little bit.
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