Ketamine’s modulation of cerebro-cerebellar circuitry during response inhibition in major depression

NeuroImage: Clinical

Ashish K. Sahib¹  Katherine L. Narr²  Joana R.A. Loureiro³  Randall Espinoza³  Benjamin Wade³  Amber Leaver³  Gerhard Hellemann³  Shantanu Joshi³  Megha Vasavada³  Roger P. Woods⁴  Eliza Congdon⁴  Antoni Kubicki⁵ 

[1] Corresponding author at: 635 Charles E Young Drive South Suite 225, Los Angeles, CA 90095-7334, USA.;Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA;Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA;Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA;Northwestern University, Chicago, IL, USA;

关键词: Ketamine;    Cerebellum;    Large-scale networks;    Response-inhibition;    PPI;   

DOI  :  

来源: DOAJ

【 摘 要 】

Patients with major depressive disorder (MDD) exhibit impaired control of cognitive and emotional systems, including deficient response selection and inhibition. Though these deficits are typically attributed to abnormal communication between macro-scale cortical networks, altered communication with the cerebellum also plays an important role. Yet, how the circuitry between the cerebellum and large-scale functional networks impact treatment outcome in MDD is not understood. We thus examined how ketamine, which elicits rapid therapeutic effects in MDD, modulates cerebro-cerebellar circuitry during response-inhibition using a functional imaging NoGo/Go task in MDD patients (N = 46, mean age: 39.2, 38.1% female) receiving four ketamine infusions, and healthy controls (N = 32, mean age:35.2, 71.4% female). We fitted psychophysiological-interaction (PPI) models for a functionally-derived cerebellar-seed and extracted average PPI in three target functional networks, frontoparietal (FPN), sensory-motor (SMN) and salience (SN) networks. Time and remission status were then evaluated for each of the networks and their network-nodes. Follow-up tests examined whether PPI-connectivity differed between patient remitter/non-remitters and controls. Results showed significant decreases in PPI-connectivity after ketamine between the cerebellum and FPN (p < 0.001) and SMN networks (p = 0.008) in remitters only (N = 20). However, ketamine-related changes in PPI-connectivity between the cerebellum and the SN (p = 0.003) did not vary with remitter status. Cerebellar-FPN, -SN PPI values at baseline were also associated with treatment outcome. Using novel methodology to quantify the functional coupling of cerebro-cerebellar circuitry during response-inhibition, our findings highlight that these loops play distinct roles in treatment response and could potentially serve as novel biomarkers for fast-acting antidepressant therapies in MDD.

【 授权许可】

Unknown