Intracranial neural biomarkers of psychiatric symptoms and their utility for guiding neuromodulation therapy: a systematic review.

The quest to develop and improve neuromodulatory therapies for treatment-resistant psychiatric disorders has been fueled by the discovery of intracranial neural biomarkers of symptom dimensions. These neural correlates shed light on the underlying neurophysiology of the disorder and may even be useful in guiding therapy delivery. This systematic review summarizes recent efforts in this field relating neural activity to behavior and symptomatology. For years, the majority of these neurobehavioral relationships had been studied in the hospital or clinic environment. Recent technological advances in implanted neuromodulation devices that permit not only stimulation, but also intracranial neural recording have enabled this research to move into natural settings, recording for longer periods of time in the real world. We review this combined literature to identify neurobehavioral relationships that show commonalities across these different recording strategies and environments. We also discuss potential ways to use this information for guiding neuromodulation therapy. The success of "closed loop" stimulation strategies for movement disorders and epilepsy has led to interest in exploring similar approaches for psychiatric disorders. Such efforts, however, need to consider the disorder-specific time constant relating changes in a neural biomarker to changes in symptoms and behavior. This relationship likely differs between Parkinson's disease and depression, OCD, or addiction. We interpret the results of our systematic review in this light to offer suggestions for future closed-loop or "clinician in the loop" implementations to inform the next generation of neuromodulatory therapies.