A clinical trial inspired and guided by optogenetics experiments in rodents has reported positive results from targeted transcranial magnetic stimulation in patients suffering from cocaine addiction.
The specific clinical hypothesis arose directly from an experiment in rats by Chen and colleagues in 2013. Rats that compulsively sought cocaine were found to have lower activity in the prelimbic cortex than non–drug-seeking rats. When optogenetic stimulation of the prelimbic cortex was performed in compulsive rats, their cocaine-seeking behavior decreased. Terraneo and colleagues adapted this approach to the clinical setting using a technique called transcranial magnetic stimulation (TMS). This noninvasive brain stimulation modality, approved for treatment of major depression in the US and in Europe, employs strong, rapidly changing (millisecond timescale) magnetic fields arising from coiled wires positioned outside the head, which in turn induce electrical responses inside the brain.
32 cocaine-addicted individuals participated in this study. Half of the participants were randomly allocated to rTMS therapy (40 trains of pulses to DLPFC at 15 Hz, 13 min total) and the other half were allocated to a standard drug treatment (a cocktail of medications that have been used to treat symptoms of cocaine withdrawal). Participants in both groups were treated in an outpatient clinic daily for the first 5 days and subsequently once a week for 3 more weeks. After the initial month of treatment, individuals were given the option to switch to the opposite treatment arm and were followed for a further 2 months.
Although the study was brief, 69% of individuals in the rTMS-treated group remained drug-free during the initial treatment phase, compared with 19% of the control group (as tracked by urine drug tests). The rTMS group also reported significantly less cocaine craving. The difference between groups emerged early during the treatment: by day 12, 50% of the control group had already relapsed, whereas not a single member of the rTMS group had relapsed.
A conclusion of the study, concordant with the prior rodent experiments, was that stimulation of the DLPFC may suppress the compulsion of cocaine-addicted subjects to seek out cocaine, further supporting the hypothesis that DLPFC hypoactivity can be a pathophysiologic feature of the disorder. This result also lends support to the concept that the prefrontal cortex exerts top-down control over the brain’s reward circuitry through modulation of striatal dopamine signaling. Future studies using two frequently used clinical treatments (DBS and pharmacotherapy) could be combined in a principled optogenetics-guided and hypothesis-driven manner for joint benefit.
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Ferenczi E and Deisseroth K: Illuminating next-generation brain therapies. Nature Neuroscience [Epub ahead of print, Jan.18, 2016; doi: 10.1038/nn.4232].
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http://www.ncbi.nlm.nih.gov/pubmed/26780510