By Eugene Rubin, MD, Ph.D., and Charles Zorumski, MD
Two recent articles in JAMA Psychiatry examine technologies that will likely advance psychiatric research and lead to future treatments. Noah Philip, Mascha van’t Wout-Frank, and Amanda Arulpragasam review the potential of focused ultrasound neuromodulation (FUS). Peter Manza, Charles Lynch, Joshua Siegel, and Jacqueline Clauss discuss longitudinal precision functional mapping.
Low-intensity focused ultrasound stimulation
Psychiatric conditions are increasingly understood as abnormalities in specific brain circuits. Many brain circuits associated with psychiatric symptoms involve brain structures deep inside the brain—that is, those not near the skull and below the cerebral cortex. Currently used stimulation techniques such as transcranial magnetic stimulation (TMS) and transcortical direct current stimulation (tDCS) have less influence on deep brain matter than on brain areas nearer the skull surface. Another experimental technique, deep brain stimulation, requires neurosurgical intervention and, therefore, is being developed to treat refractory psychiatric conditions.
FUS is a form of neuromodulation that can reach deep brain regions without the need for invasive procedures. Parameters of this neuromodulation technique can be adjusted to target specific brain structures and lead to reversible physiologic effects that influence the function of deep brain regions. The exact nature of the induced physiologic changes is still being elucidated, but the mechanism may involve “mechanical effects on neuronal membranes mediated through mechanosensitive ion channels, modulation of synaptic plasticity, and neurovascular coupling.” Early work suggests that such reversible changes have the potential to produce clinical improvement in a variety of psychiatric disorders. More research is required to demonstrate safety and efficacy of this technology, but this work is rapidly proceeding as summarized in a recent review article in Biological Psychiatry by Amanda Arulpragasam and colleagues. More information about this technique will be forthcoming over the next several years.
Longitudinal precision functional mapping
Several brain circuits have been identified that are involved in cognitive, motivational, attentional, and emotional functions. Defining the specific anatomic structures in these circuits has traditionally been obtained by averaging results from multiple individuals. However, the exact locations of brain regions involved in a specific circuit vary in each person. Recently, it has been shown that the precise location of circuits can be identified in single individuals, although doing so requires a major investment in imaging time. By mapping the function of an individual’s brain circuitry repeatedly over time using functional magnetic resonance imaging (fMRI) and correlating this activity with changes in symptom severity, it should be possible to better understand the relationship between symptom presentation and neural activity in specific brain regions in individual patients. Such knowledge should allow development of therapeutic approaches targeting specific brain regions in an individual. This mapping technique is called longitudinal precision functional mapping, and methods for this approach to shorten scan times are advancing rapidly.
Thoughts
If FUS is approved for human use, it will most likely be utilized to help people with severe symptoms that are not responsive to less intensive approaches such as pharmacotherapies and psychotherapies. Will FUS be more effective and safer than other stimulation techniques such as TMS? The possibility exists.
In addition, longitudinal precision functional mapping may help identify specific brain structures that could be targeted in an individual by brain stimulation techniques such as FUS.
If symptoms can be substantially ameliorated by therapeutic approaches that target specific deep brain circuits, it is likely that psychosocial and psychotherapeutic interventions will assist an individual in returning to activities involving family, friends, and work.
