Thalamic stimulation induced changes in effective connectivity.

Deep brain stimulation (DBS) is a viable treatment for a variety of neurological conditions, however, the mechanisms through which DBS modulates large-scale brain networks are unresolved. Clinical effects of DBS are observed over multiple timescales. In some conditions, such as Parkinson's disease and essential tremor, clinical improvement is observed within seconds. In many other conditions, such as epilepsy, central pain, dystonia, neuropsychiatric conditions or Tourette syndrome, the DBS related effects are believed to require neuroplasticity or reorganization and often take hours to months to observe. To optimize DBS parameters, it is therefore essential to develop electrophysiological biomarkers that characterize whether DBS settings are successfully engaging and modulating the network involved in the disease of interest. In this study, 10 individuals with drug resistant epilepsy undergoing intracranial stereotactic EEG including a thalamus electrode underwent a trial of repetitive thalamic stimulation. We evaluated thalamocortical effective connectivity using single pulse electrical stimulation, both at baseline and following a 145 Hz stimulation treatment trial. We found that when high frequency stimulation was delivered for >1.5 hours, the evoked potentials measured from remote regions were significantly reduced in amplitude and the degree of modulation was proportional to the strength of baseline connectivity. When stimulation was delivered for shorter time periods, results were more variable. These findings suggest that changes in effective connectivity in the network targeted with DBS accumulate over hours of DBS. Stimulation evoked potentials provide an electrophysiological biomarker that allows for efficient data-driven characterization of neuromodulation effects, which could enable new objective approaches for individualized DBS optimization.