Optimal Functional Connectivity Pattern Predicts Acute Auditory Hallucination Suppression in Schizophrenia after Substantia Nigra Pars Reticulata Deep Brain Stimulation

Saturday, May 4, 2024

3:31 PM – 3:33 PM CT

Location: S405b

Presenting Author(s)

Min Jae Kim, BS (he/him/his)

MD/PhD Candidate
Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania
Philadelphia, PA, US

Co-Author(s)

WA

William Anderson, PhD,MD

Professor
Department of Neurosurgery, Johns Hopkins School of Medicine
Baltimore, Maryland, United States
AB

Ankur Butala, MD

Assistant Professor
Department of Neurology, Johns Hopkins School of Medicine, United States
NC

Nicola Cascella, MD

Assistant Professor
Department of Psychiatry, Johns Hopkins School of Medicine, United States
KC

Ki Sueng Choi, PhD

Professor of Radiology
Mount Sinai Health System, United States
MF

Marin Figee, MD, PhD

Professor of Psychiatry
Mount Sinai Health System, United States
KM

Kelly Mills, MD

Associate Professor
Department of Neurology, Johns Hopkins School of Medicine, United States
YS

Yousef Salimpour, PhD

Assistant Professor
Department of Neurosurgery, Johns Hopkins School of Medicine, United States
AS

Akira Sawa, MD,PhD

Professor
Department of Psychiatry, Johns Hopkins School of Medicine, United States
DS

David Schretlen, PhD

Professor
Department of Psychiatry, Johns Hopkins School of Medicine, United States

Disclosure(s):

Min Jae Kim, BS: No financial relationships to disclose

Introduction: Deep brain stimulation (DBS) of substantia nigra pars reticulata (SNpr) is being explored for treatment-resistant schizophrenia (trSZ). Targeting the SNpr was proposed for auditory-verbal hallucinations (AVH) in trSZ based on its connectivity with medial dorsal nucleus of thalamus and superior temporal gyrus. However, mechanisms of SNpr-DBS in suppressing AVH through network-level modulation are not yet known. Understanding underlying circuitries engaged after clinically effective DBS can help better optimize surgical targeting and stimulation parameters. In this study, we determined the functional connectomic map of effective SNr-DBS for AVH in trSZ patients.

Methods: Three trSZ patients who underwent bilateral SNpr-DBS were evaluated. After 1-month follow-up, each patient underwent a monopolar review where different active electrode contacts and stimulation amplitude were surveyed, followed by Likert scale report of AVH severity at respective stimulation conditions. Based on each stimulation parameter, volumes of tissue activated (VTA) were produced and seeded into a normative functional connectome to produce functional connectivity (FC) profiles. FC profiles were then regressed against baseline-normalized AVH scores to produce a voxel-wise T-map. Finally, based on clinically optimal DBS settings at 1-month follow-up, FC profiles of three patients were compared with T-map.

Results: From a monopolar review across three patients, 47 left and 39 right VTAs were produced across the dorsal-ventral axis of bilateral SNpr. T-map produced from 86 FC profiles yielded a whole-brain map representing regions with FC associated with AVH reduction. These regions included right medial dorsal nucleus of thalamus (t=-2.05, p=0.04), right IFG pars orbitalis (t=-2.07,p=0.04), and bilateral superior ACC and anterior OFC. Furthermore, FC profiles produced from clinically optimized settings from three patients were spatially very similar to inverted T-map (r=0.56 for patient 1, r=0.39 for patient 2, r=0.54 for patient 3), suggesting that our T-map delineates a therapeutically optimal FC pattern.

Conclusion : We have identified an optimal connectivity pattern associated with acute suppression of AVH symptoms in trSZ patients. This finding can inform prospective programming sessions to refine stimulation parameters in SNpr and augment long-term clinical benefits.