Impaired spatial dynamic functional network connectivity and neurophysiological correlates in functional stroke mimics

Abstract

The present study investigated spatial dynamic functional network connectivity (dFNC) in patients with functional hemiparesis (i.e., functional stroke mimics, FSM). The aim of this work was to assess dynamic brain states, which represent distinct dFNC patterns that reoccur in time and across subjects. Resting-state fMRI data were collected from 15 patients with FSM (mean age=42.3±9.4, female=80%) and 52 age-matched healthy controls (HC, mean age=42.1±8.6, female=73%). Each patient underwent a resting-state functional MRI scan for spatial dFNC evaluation and transcranial magnetic stimulation protocols for indirect assessment of GABAergic and glutamatergic transmission. We considered three dynamic brain networks, i.e., the somatomotor network (SMN), the default mode network (DMN) and the salience network (SN), each summarized into four distinct recurring spatial configurations. Compared to HC, patients with FSM showed significant decreased dwell time, e.g. the time each individual spends in each spatial state of each network, in state 2 of the SMN (HC vs. FSM, 13.5±27.1 vs. 1.9±4.1, p=0.034). Conversely, as compared to HC, FSM spent more time in state 1 of the DMN (10.8±14.9 vs. 27.3±38.9, p=0.033) and in state 3 of the SN (23.1±23.0 vs. 38.8±38.2, p=0.001). We found a significant correlation between the dwell time of impaired functional state of the SMN and measures of GABAergic neurotransmission (r=0.581, p=0.037). Specifically, longer impaired dwell time was associated with greater GABAergic inhibition. These findings demonstrate that FSM present altered functional brain network dynamics, which correlate with measures of GABAergic neurotransmission. Both dFNC and GABAergic neurotransmission may serve as potential targets for future intervention strategies.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

05.19.2015, #NP1965

Funding Statement

No external fundings have been used in this work.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The local ethics committee of the Brescia Hospital approved the present study (05.19.2015, #NP1965).

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All study data, including study design, protocol, statistical analysis plan, and results are available from the corresponding author, upon reasonable request.

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