Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity

Abstract

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders.

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“…Furthermore, the use of electric field modeling techniques is paving the way for predicting the spread and distribution of the magnetic field in the brain tissue based on the orientation of the coil relative to the spatial distribution of the neurons being stimulated [43]. Lastly, the use of EEG allows for measurement of brain activity with high temporal resolution, potentially allowing for "closed loop stimulation" that delivers stimulation based on the detection of spontaneous or cue-induced symptoms related to the disorder being targeted [44]. In light of the mixed and inconsistent results found in this review, the use of these novel techniques represent promising avenues for improving clinical outcomes.…”