Journal article
Disruption of response inhibition circuits in prodromal Huntington disease
Cortex, Vol.58, pp.72-85
09/2014
DOI: 10.1016/j.cortex.2014.04.018
PMCID: PMC4227536
PMID: 24959703
Abstract
Cognitive changes in the prodromal phase of Huntington disease (prHD) are found in multiple domains, yet their neural bases are not well understood. One component process that supports cognition is inhibitory control. In the present fMRI study, we examined brain circuits involved in response inhibition in 65 prHD participants and 36 gene-negative (NEG) controls using the stop signal task (SST). PrHD participants were subdivided into three groups (LOW, MEDIUM, HIGH) based on their CAG-Age Product (CAP) score, an index of genetic exposure and a proxy for expected time to diagnosis. Poorer response inhibition (stop signal duration) correlated with CAP scores. When response inhibition was successful, activation of the classic frontal inhibitory-network was normal in prHD, yet stepwise reductions in activation with proximity to diagnosis were found in the posterior ventral attention network (inferior parietal and temporal cortices). Failures in response inhibition in prHD were related to changes in inhibition centers (supplementary motor area (SMA)/anterior cingulate and inferior frontal cortex/insula) and ventral attention networks, where activation decreased with proximity to diagnosis. The LOW group showed evidence of early compensatory activation (hyperactivation) of right-hemisphere inhibition and attention reorienting centers, despite an absence of cortical atrophy or deficits on tests of executive functioning. Moreover, greater activation for failed than successful inhibitions in an ipsilateral motor-control network was found in the control group, whereas such differences were markedly attenuated in all prHD groups. The results were not related to changes in cortical volume and thickness, which did not differ among the groups. However, greater hypoactivation of classic right-hemisphere inhibition centers [inferior frontal gyrus (IFG)/insula, SMA/anterior cingulate cortex (ACC)] during inhibition failures correlated with greater globus pallidus atrophy. These results are the first to demonstrate that response inhibition in prHD is associated with altered functioning in brain networks that govern inhibition, attention, and motor control.
Details
- Title: Subtitle
- Disruption of response inhibition circuits in prodromal Huntington disease
- Creators
- Julia A Rao - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USADeborah L Harrington - VA San Diego Healthcare System, San Diego, CA, USASally Durgerian - Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USAChristine Reece - Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, Cleveland, OH, USALyla Mourany - Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, Cleveland, OH, USAKatherine Koenig - Imaging Institute, Cleveland Clinic, Cleveland, OH, USAMark J Lowe - Imaging Institute, Cleveland Clinic, Cleveland, OH, USAVincent A Magnotta - Carver College of Medicine, The University of Iowa, Iowa City, IA, USAJeffrey D Long - Carver College of Medicine, The University of Iowa, Iowa City, IA, USAHans J Johnson - Carver College of Medicine, The University of Iowa, Iowa City, IA, USAJane S Paulsen - Carver College of Medicine, The University of Iowa, Iowa City, IA, USAStephen M Rao - Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA
- Resource Type
- Journal article
- Publication Details
- Cortex, Vol.58, pp.72-85
- DOI
- 10.1016/j.cortex.2014.04.018
- PMID
- 24959703
- PMCID
- PMC4227536
- NLM abbreviation
- Cortex
- ISSN
- 0010-9452
- eISSN
- 1973-8102
- Publisher
- Elsevier BV
- Language
- English
- Date published
- 09/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Biostatistics
- Record Identifier
- 9984066139602771
Metrics
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