Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study.


Journal

Brain stimulation
ISSN: 1876-4754
Titre abrégé: Brain Stimul
Pays: United States
ID NLM: 101465726

Informations de publication

Date de publication:
Historique:
received: 02 04 2019
revised: 08 05 2020
accepted: 16 06 2020
pubmed: 26 6 2020
medline: 23 3 2021
entrez: 26 6 2020
Statut: ppublish

Résumé

Prefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia. /Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity. We enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition. Of the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004). Subjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.

Sections du résumé

BACKGROUND
Prefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia.
OBJECTIVE
/Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity.
METHODS
We enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition.
RESULTS
Of the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004).
CONCLUSIONS
Subjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.

Identifiants

pubmed: 32585355
pii: S1935-861X(20)30135-2
doi: 10.1016/j.brs.2020.06.017
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1467-1475

Informations de copyright

Copyright © 2020. Published by Elsevier Inc.

Auteurs

Ryan D Webler (RD)

University of Minnesota, Department of Psychology, USA.

Carmen Hamady (C)

American University of Beirut, Department of Psychiatry, USA.

Chris Molnar (C)

Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina, USA.

Kevin Johnson (K)

Johnson and Johnson, Fort Washington, PA, USA.

Leo Bonilha (L)

Neurology Department, USA.

Berry S Anderson (BS)

College of Nursing, Medical University of South Carolina, USA.

Claartje Bruin (C)

American University of Beirut, Department of Psychiatry, USA.

Daryl E Bohning (DE)

Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina, USA.

Mark S George (MS)

Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

Ziad Nahas (Z)

American University of Beirut, Department of Psychiatry, USA; University of Minnesota, Department of Psychiatry, USA. Electronic address: znahas@umn.edu.

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