Neuroscience
Yesterday, the New York Times magazine had an article on a new, extremely experimental treatment for depression: deep brain stimulation (DBS) in the ventral portion of the anterior cingulate cortex, in Brodmann's area 25. This procedure, which involves implanting electrodes deep into the brain, has been tested on 12 patients who failed to respond to multiple antidepressant medications and electroconvulsive therapy (8 of them responded to DBS). It works using the same sort of device used in deep brain stimulation for Parkinson's disease, which has been remarkably successful.
A preliminary report on the results was published last year in Neuron.
However, statements like these make one a bit concerned about the ethics involved:
It's a good article (by David Dobbs), but as usual, someone in the popular press had to come up with a ridiculous title:
- Broaden Trial Of Dbs For Treatment-resistant Depression Halted By The Fda
Webpage for the BROADEN™ study formerly run by St. Jude Medical It's become mainstream these days to say that psychiatric disorders are neural circuit disorders. You can even read all about it in the New York Times! Cognitive training and neuromodulation...
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- Modern Tract-tracing For Historical Psychosurgery
Figure 3 (Schoene-Bake et al., 2010). Intersection of connectivity maps of Anterior Capsulotomy (red), Anterior Cingulotomy (blue), and Subcaudate Tractotomy (green) tracking results. Overlap of AC and ACT shown with magenta, AC and SCT in yellow, and...
- Good News/bad News Update On Nucleus Accumbens Dbs For Treatment-resistant Depression
Taken from Fig. 1 (Bewernick et al., 2009). Hamilton Depression Rating Scale (PDF) over time. Two and a half years ago, The Neurocritic wrote about the very early results of deep brain stimulation (DBS) in the nucleus accumbens for severe, refractory...
- ...but My Subgenual Cingulate Is Sad
In the previous post, The Neurocritic discussed an article in Nature in which greater activity in the rostral anterior cingulate cortex (rACC) was associated with optimism1 (Sharot et al., 2007). "But wait!" you might say, "what about the sad cingulate?"...
Neuroscience
The Sad Cingulate
Yesterday, the New York Times magazine had an article on a new, extremely experimental treatment for depression: deep brain stimulation (DBS) in the ventral portion of the anterior cingulate cortex, in Brodmann's area 25. This procedure, which involves implanting electrodes deep into the brain, has been tested on 12 patients who failed to respond to multiple antidepressant medications and electroconvulsive therapy (8 of them responded to DBS). It works using the same sort of device used in deep brain stimulation for Parkinson's disease, which has been remarkably successful.
A preliminary report on the results was published last year in Neuron.
Deep Brain Stimulation for Treatment-Resistant DepressionBut why stimulate area 25 in depression? Previous neuroimaging studies by Mayberg and colleagues showed that this region is overactive in depression. This excessive activity is dampened in those who respond to SSRIs but remains elevated in those who don't respond to the meds:
Helen S. Mayberg, Andres M. Lozano, Valerie Voon, Heather E. McNeely, David Seminowicz, Clement Hamani, Jason M. Schwalb, and Sidney H. Kennedy
Neuron, Vol 45, 651-660, 03 March 2005
Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.
Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes.It's a dramatic next step to propose DBS to "turn off" area 25, but at least it's more grounded in the scientific literature than older forms of psychosurgery. Although by no means a trivial operation, DBS doesn't cause permanent damage in the manner of the old-school ablations.
Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA.
Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response.
Biol Psychiatry. 2000 Oct 15;48(8):830-43.
However, statements like these make one a bit concerned about the ethics involved:
The expectations for the Toronto team's D.B.S. study were accordingly modest. When I later asked Mayberg's collaborator Dr. Andres Lozano, the neurosurgeon who performed the operations, what he had expected, he replied, "Nothing."
. . .It would be really unethical to conduct a controlled treatment trial with a stimulator implanted in some other portion of the brain. The Neuron paper, however, did report on the use of "sham" stimulation (0.0 volts) in area 25 during a blinded, DBS discontinuation period (which seems a reasonable control, given the ethical considerations).
Mayberg, who speaks of a "paradigm shift," notes that she developed the trial to evaluate not a treatment but a hypothesis.
It's a good article (by David Dobbs), but as usual, someone in the popular press had to come up with a ridiculous title:
A Depression Switch?If it were so simple!
- Broaden Trial Of Dbs For Treatment-resistant Depression Halted By The Fda
Webpage for the BROADEN™ study formerly run by St. Jude Medical It's become mainstream these days to say that psychiatric disorders are neural circuit disorders. You can even read all about it in the New York Times! Cognitive training and neuromodulation...
- Deep Brain Stimulation For Bipolar Depression
The Melancholia of Kirsten Dunst and Lars von Trier “Gray wool, clinging to my legs, it's heavy to carry along” The disastrous wedding reception of the severely depressed Justine precedes the end of the world, depicted as a highly stylized and...
- Modern Tract-tracing For Historical Psychosurgery
Figure 3 (Schoene-Bake et al., 2010). Intersection of connectivity maps of Anterior Capsulotomy (red), Anterior Cingulotomy (blue), and Subcaudate Tractotomy (green) tracking results. Overlap of AC and ACT shown with magenta, AC and SCT in yellow, and...
- Good News/bad News Update On Nucleus Accumbens Dbs For Treatment-resistant Depression
Taken from Fig. 1 (Bewernick et al., 2009). Hamilton Depression Rating Scale (PDF) over time. Two and a half years ago, The Neurocritic wrote about the very early results of deep brain stimulation (DBS) in the nucleus accumbens for severe, refractory...
- ...but My Subgenual Cingulate Is Sad
In the previous post, The Neurocritic discussed an article in Nature in which greater activity in the rostral anterior cingulate cortex (rACC) was associated with optimism1 (Sharot et al., 2007). "But wait!" you might say, "what about the sad cingulate?"...