Projects

Transcranial magnetic stimulation (TMS) is increasingly being applied to effectively treat mental illness, however efforts to quantify the effects of TMS on the network architecture of the brain have largely been limited in scope and tied to specific neurologic and psychiatric disorders. The objective of the current work is to build and validate a whole-brain, domain-general model of brain connectivity changes following TMS, based on physical models of the current distribution at the cortex. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will provide direct evidence that brain connectivity changes following neuromodulatory TMS vary as a function of the current density at the cortex, which can be used to predict psychiatric symptom change following neuromodulatory TMS.

Given the overall lack of treatment adherence/efficacy, side effects of drugs, and the substantial burden of anxiety disorders on the individual and on the national healthcare system, there is a critical need for mechanistic research into the CNS mechanisms that underlie these disorders. Accordingly, the objective of this grant is to use noninvasive neuromodulation to causally identify the key neural mechanisms that mediate the cognitive symptoms of anxiety. This project is relevant to public health because it has the potential to lead to novel repetitive transcranial magnetic stimulation treatments for pathological anxiety.

Despite the high prevalence of anxiety disorders, it has been nearly two decades since the most recent first-line pharmacological treatment of anxiety was introduced to the market. Accordingly, there is a critical need for novel second-line treatments for anxiety disorders, developed out of a mechanistic understanding of the neurobiological underpinnings of these disorders. In this project, I will stimulate either the right dorsolateral prefrontal cortex or the right intraparietal sulcus with single TMS pulses, while measuring brain activity with functional magnetic resonance imaging (fMRI) during threat of unpredictable shock. This research is significant because upon completion, we expect to have direct evidence for a causal role of FPN imbalance in anxiety regulation, complete with evidence of target engagement through simultaneous TMS/fMRI.

Neuromodulation is a promising avenue for novel anxiety treatment; however, neuromodulatory treatments for depression, which are thought to normalize frontal connections with the subgenual anterior cingulate cortex are likely not optimal for anxiety patients, who have abnormal functioning in regions associated with fear and attention control. Therefore the objective of this grant is to determine the extent to which a round of intensive low-frequency repetitive transcranial magnetic stimulation (rTMS) designed to attenuate hyperactivity in an anxiety-specific parietal cortex hub can reduce bottom-up process related to anxiety expression and attentional orienting to salient environmental stimuli in generalized anxiety patients. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will yield direct evidence that rTMS induces lasting changes in parietal cortex activity, and that these changes reduce anxiety and anxiety-related deficits in attention control, which could be used to develop future clinical trials to treat clinical anxiety.

Hypervigilance may be a shared mechanism connecting elevated anxiety and impaired attention control; however, we have a critical gap in our understanding of the mechanisms that underly hypervigilance. Therefore, the objective of this work is to use causal neuromodulation to up and downregulate activity in the intraparietal sulcus (IPS) and measure the effect of this neuromodulation on anxiety and attention control. PUBLIC HEALTH RELEVANCE: This work is significant because it will provide direct, mechanistic evidence linking IPS to increased hypervigilance, which could provide a foundation for future work aimed at understanding how attention deficits emerge in anxiety disorders.