Causal network localization of brain stimulation targets for trait anxiety
Poster No:
131
Submission Type:
Abstract Submission
Authors:
Shan Siddiqi1, Julian Klingbeil2, Ian Kratter3, Daniel Blumberger4, Mark George5, Jordan Grafman6, Alvaro Pascual-Leone7, R. Mark Richardson8, Pratik Talati9, Fidel Vila-Rodriguez10, Jonathan Downar4
Institutions:
1Harvard Medical School/Brigham and Women’s Hospital, boston, MA, 2University of Leipzig, Leipzig, Germany, 3Stanford University, Palo Alto, CA, 4University of Toronto, Toronto, Ontario, 5Medical University of South Carolina, Charleston, SC, 6Northwestern University, Chicago, IL, 7Harvard Medical School, Boston, MA, 8Massachusetts General Hospital, Harvard Medical School, Boston, MA, 9Massachusetts General Hospital, Boston, MA, 10University of British Columbia, Vancouver, BC
First Author:
Co-Author(s):
Introduction:
Transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) can treat some neuropsychiatric disorders, this approach has only been used to optimize existing targets, not to identify novel targets. Lesions have been used to map causal circuitry and optimize stimulation targets for various disorders such as depression, Parkinson's, addiction, and epilepsy. However, no clear brain stimulation targets are available for anxiety. Here, we use convergent causal data to derive and validate brain stimulation targets for anxiety.
Methods:
Across seven datasets (n=936), we mapped circuitry connected to lesion sites and stimulation sites that selectively modify anxiety, independently of depression. First, we mapped the normative connectivity (using a normative human connectome database) of 111 heterogeneous TMS sites and compared it to TMS-induced change in anxiety, yielding a map of connectivity of stimulation sites that relieve anxiety. Next, we used a similar analysis to map the connectivity of 451 lesions that modify anxiety. Next, in 300 TMS patients who were all navigated to the same coordinate, we mapped individualized connectivity of TMS sites that selectively modified anxiety. We combined this information into a common brain circuit, and used this circuit to predict anxiety changes after DBS for Parkinson's disease in 74 patients with heterogeneous DBS sites.
Results:
Lesions (n=451) and TMS sites (n=111) that modify anxiety mapped to a common normative brain circuit (p=0.01). In an independent dataset (n=300), individualized TMS site connectivity to this circuit predicted anxiety change (p=0.02). Subthalamic DBS sites overlapping the circuit caused more anxiety (n=74, p=0.006), thus demonstrating a network-level effect, as the circuit was derived without any subthalamic sites. The circuit was specific to trait versus state anxiety in datasets that measured both (p=0.003). The analyses converged on a target in the right superior frontal gyrus.
Conclusions:
We derived and validated a novel brain stimulation target for trait anxiety. More broadly, this illustrates a pathway for discovering novel circuit-based targets across neuropsychiatric disorders.
Brain Stimulation:
Deep Brain Stimulation 2
Non-invasive Magnetic/TMS
TMS 1
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Keywords:
Anxiety
FUNCTIONAL MRI
Psychiatric Disorders
Transcranial Magnetic Stimulation (TMS)
Other - Deep brain stimulation
1|2Indicates the priority used for review
Provide references using author date format
S. H. Siddiqi et al., Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease. Nature human behaviour 5, 1707-1716 (2021).
S. H. Siddiqi et al., Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation. The American journal of psychiatry 177, 435-446 (2020).
S. A. Eisenstein et al., Functional anatomy of subthalamic nucleus stimulation in Parkinson disease. Ann Neurol 76, 279-295 (2014).