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

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 (fMRI) to examine brain activity associated with working memory in 5 opioid-dependent, methadone-maintained patients and 5 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.

The role of the supplementary motor area for speech and language processing

“…Recent studies, furthermore, indicate that such cortico-cerebellar mechanisms are not confined to procedural aspects in the motor domain, but also apply to higher-order cognitive functions such as working memory, lexical processing, and grammar, verb generation, and semantic discrimination (Marien et al, 2014;Keren-Happuch et al, 2014;Marvel & Desmond, 2010). As an example, working memory deficits in opioiddependent individuals seem to be caused by dysfunction of cortico-cerebellar mechanisms concomitant with hypoactivity of pre-SMA (Marvel et al, 2012). Further studies, although not explicitly investigating SMA, point to higher-order linguistic functions of corticocerebellar circuits: TMS of a lateral cerebellar site had effects on noun-to-verb priming, indicating a cerebellar role in linguistic expectancy generation (Argyropoulos & Muggleton, 2013), and a further TMS experiment with cerebellar stimulation showed effects on the processing of past tense and future as well as an interaction of verb tense with spatial information processing (Oliveri et al, 2009).…”

Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy

“…Chronic opioid exposure is associated with deficits across a range of neuropsychological domains with robust impairment in verbal working memory and cognitive impulsivity (risk taking) alongwith cognitive flexibility (verbal fluency) [85]. Recent fMRI studies demonstrate alterations in neuronal activation in brain areas associated with working memory and addiction [86] and disruption in cerebro-cerebellar circuits in opioid dependent individuals [87]. Further research is needed to determine the clinical significance of impairments in cognitive and lab based tests for daily performance in the natural environment.…”

Wpływ leczenia operacyjnego na zmiany pamięci roboczej u chorych z procesami rozrostowymi w obrębie móżdżku – opis przypadków

“…Udział móżdżku w funkcjonowaniu pamięci operacyjnej jest coraz szerzej opisywany w piśmiennictwie oraz potwierdzany w badaniach klinicznych [11,12,13,14,15,16]. Wykazano ujawniające się zaburzenia pamięci operacyjnej u pacjentów po udarach krwotocznych móżdżku, a także u chorych z guzami tej okolicy.…”