TY - JOUR
T1 - Subgenual cingulate connectivity and hippocampal activation are related to MST therapeutic and adverse effects
AU - Hadas, Itay
AU - Zomorrodi, Reza
AU - Hill, Aron T.
AU - Sun, Yinming
AU - Fitzgerald, Paul B.
AU - Blumberger, Daniel M.
AU - Daskalakis, Zafiris J.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Here we combine transcranial magnetic stimulation with electroencephalography (TMS-EEG) to evaluate the effects of MST on connectivity and activation between the DLPFC, the SGC and hippocampus (Hipp) in patients with TRD. The TMS-EEG was collected from 31 TRD patients prior to and after an MST treatment trial. Through TMS-EEG methodology we evaluated significant current scattering (SCS) as an index of effective connectivity between the SGC and left DLPFC. Significant current density (SCD) was used to assess activity at the level of the Hipp. The SCS between the SGC and DLPFC was reduced after the course of MST (p < 0.036). The DLPFC-SGC effective connectivity reduction correlated with the changes in Hamilton depression score pre-to-post treatment (R = 0.46; p < 0.031). The SCD localized to the Hipp was reduced after the course of MST (p < 0.015), and the SCD change was correlated with montreal cognitive assessment (MOCA) scores pre-post the course of MST (R = −0.59; p < 0.026). Our findings suggest that MST treatment is associated with SGC-DLPFC connectivity reduction and that changes to cognition are associated with Hipp activation reduction. These findings demonstrate two distinct processes which drive efficacy and side effects separately, and might eventually aid in delineating physiological TRD targets in clinical settings.
AB - Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Here we combine transcranial magnetic stimulation with electroencephalography (TMS-EEG) to evaluate the effects of MST on connectivity and activation between the DLPFC, the SGC and hippocampus (Hipp) in patients with TRD. The TMS-EEG was collected from 31 TRD patients prior to and after an MST treatment trial. Through TMS-EEG methodology we evaluated significant current scattering (SCS) as an index of effective connectivity between the SGC and left DLPFC. Significant current density (SCD) was used to assess activity at the level of the Hipp. The SCS between the SGC and DLPFC was reduced after the course of MST (p < 0.036). The DLPFC-SGC effective connectivity reduction correlated with the changes in Hamilton depression score pre-to-post treatment (R = 0.46; p < 0.031). The SCD localized to the Hipp was reduced after the course of MST (p < 0.015), and the SCD change was correlated with montreal cognitive assessment (MOCA) scores pre-post the course of MST (R = −0.59; p < 0.026). Our findings suggest that MST treatment is associated with SGC-DLPFC connectivity reduction and that changes to cognition are associated with Hipp activation reduction. These findings demonstrate two distinct processes which drive efficacy and side effects separately, and might eventually aid in delineating physiological TRD targets in clinical settings.
UR - http://www.scopus.com/inward/record.url?scp=85095775919&partnerID=8YFLogxK
U2 - 10.1038/s41398-020-01042-7
DO - 10.1038/s41398-020-01042-7
M3 - Article
C2 - 33173028
AN - SCOPUS:85095775919
SN - 2158-3188
VL - 10
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 392
ER -