Evidence for abnormal cortical functional connectivity during working memory in schizophrenia

Topic: Brain proteins, microglia and lab models

Objective Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is further suggested by theoretical formulations and neurochemical and neuroanatomical data. The authors applied to schizophrenia a recently available functional neuroimaging analytic method that permits characterization of cooperative action on the systems level. Method Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baseline task during positron emission tomography. "Functional connectivity" patterns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. Results More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects. Expression of this pattern perfectly separated all patient scans from comparison scans, thus showing promise as a trait marker. This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort. An additional 19% of variance corresponded to the pattern activated by the working memory task. Expression of this pattern was more variable in patients during working memory but not the control condition, suggesting inability to sustain a task-adequate neural network, consistent with the disconnection hypothesis. Conclusions Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal interactions showed promise as a trait marker and may be useful for future investigations.

Key findings

• Results More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects.
• This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort.

Why it matters

In this small imaging study, a pattern of brain activity separated all schizophrenia patient scans from comparison scans and was validated in a new cohort. It concerns schizophrenia and a possible trait marker, not Alzheimer's disease treatment, cure or prevention.

Study details

• Evidence strengthModerate

Read the original

• DOI: 10.1176/appi.ajp.158.11.1809
• PubMed: 11691686
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{meyerlindenberg2001-11691686,
  author  = {Meyer-Lindenberg, A. and Poline, J. B. and Kohn, P. D. and Holt, J. L. and Egan, M. F. and Weinberger, D. R. and Berman, K. F.},
  title   = {{Evidence for abnormal cortical functional connectivity during working memory in schizophrenia}},
  journal = {The American journal of psychiatry},
  year    = {2001},
  doi     = {10.1176/appi.ajp.158.11.1809},
  pmid    = {11691686},
  url     = {https://doi.org/10.1176/appi.ajp.158.11.1809}
}

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