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An fMRI Investigation of Cerebellar Function During Verbal Working Memory in Methadone Maintenance Patients

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Abstract

Working memory is impaired in opioid-dependent individuals, yet the neural underpinnings of working memory in this population are largely unknown. Previous studies in healthy adults have demonstrated that working memory is supported by a network of brain regions that includes a cerebro-cerebellar circuit. The cerebellum, in particular, may be important for inner speech mechanisms that assist verbal working memory. This study used functional magnetic resonance imaging to examine brain activity associated with working memory in five opioid-dependent, methadone-maintained patients and five matched, healthy controls. An item recognition task was administered in two conditions: (1) a low working memory load “match” condition in which participants determined whether target letters presented at the beginning of the trial matched a probe item, and (2) a high working memory load “manipulation” condition in which participants counted two alphabetical letters forward of each of the targets and determined whether either of these new items matched a probe item. Response times and accuracy scores were not significantly different between the groups. FMRI analyses indicated that, in association with higher working memory load (“manipulation” condition), the patient group exhibited hyperactivity in the superior and inferior cerebellum and amygdala relative to that of controls. At a more liberal statistical threshold, patients exhibited hypoactivity in the left prefrontal and medial frontal/pre-SMA regions. These results indicate that verbal working memory in opioid-dependent individuals involves a disrupted cerebro-cerebellar circuit and shed light on the neuroanatomical basis of working memory impairments in this population.

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Notes

  1. Even though the authors of each study interpreted the hyperactivity as compensatory in their respective patient groups, it should be noted that the cocaine-dependent group [21] showed behavioral deficits, whereas the opioid-dependent group [22] performed at normal levels.

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Acknowledgments

The authors would like to thank Jonathan Cooper for his assistance with scoring the data. MRI scans were obtained at the Kirby Center of the Kennedy Krieger Institute in Baltimore, MD. Parts of this research were presented at the Society for Neuroscience Annual Meeting 2009, and Organization for Human Brain Mapping Annual Meeting 2011. Funding for this study was provided by NIH grants K01 DA030442 (Marvel), K24 DA023186 (Strain), R01 MH060234 (Desmond), and the Nellie Ball Research Trust (Marvel).

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Authors and Affiliations

  1. Department of Neurology, Division of Cognitive Neuroscience, Johns Hopkins University School of Medicine, 1620 McElderry St., Reed Hall 2219, Baltimore, MD, 21205, USA

    Cherie L. Marvel, Monica L. Faulkner & John E. Desmond

  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Cherie L. Marvel, Eric C. Strain & Miriam Z. Mintzer

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  1. Cherie L. Marvel
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  2. Monica L. Faulkner
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Correspondence to Cherie L. Marvel.

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Marvel, C.L., Faulkner, M.L., Strain, E.C. et al. An fMRI Investigation of Cerebellar Function During Verbal Working Memory in Methadone Maintenance Patients. Cerebellum 11, 300–310 (2012). https://doi.org/10.1007/s12311-011-0311-0

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