Working Memory-Related Effective Connectivity in Huntington’s Disease Patients

Jacob Lahr; Lora Minkova; Sarah J Tabrizi; Julie C Stout; Stefan Klöppel; Elisa Scheller; TrackOn-HD Investigators

doi:10.3389/fneur.2018.00370

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Working Memory-Related Effective Connectivity in Huntington’s Disease Patients

Journal article

Open access

Peer reviewed

Working Memory-Related Effective Connectivity in Huntington’s Disease Patients

Jacob Lahr, Lora Minkova, Sarah J Tabrizi, Julie C Stout, Stefan Klöppel, Elisa Scheller and TrackOn-HD Investigators

Frontiers in neurology, Vol.9, pp.370-370

06/04/2018

DOI: 10.3389/fneur.2018.00370

PMCID: PMC5994408

PMID: 29915555

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https://doi.org/10.3389/fneur.2018.00370View

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Abstract

Huntington’s disease (HD) is a genetically caused neurodegenerative disorder characterized by heterogeneous motor, psychiatric, and cognitive symptoms. Although motor symptoms may be the most prominent presentation, cognitive symptoms such as memory deficits and executive dysfunction typically co-occur. We used functional magnetic resonance imaging (fMRI) and task fMRI-based dynamic causal modeling (DCM) to evaluate HD-related changes in the neural network underlying working memory (WM). Sixty-four pre-symptomatic HD mutation carriers (preHD), 20 patients with early manifest HD symptoms (earlyHD), and 83 healthy control subjects performed an n -back fMRI task with two levels of WM load. Effective connectivity was assessed in five predefined regions of interest, comprising bilateral inferior parietal cortex, left anterior cingulate cortex, and bilateral dorsolateral prefrontal cortex. HD mutation carriers performed less accurately and more slowly at high WM load compared with the control group. While between-group comparisons of brain activation did not reveal differential recruitment of the cortical WM network in mutation carriers, comparisons of brain connectivity as identified with DCM revealed a number of group differences across the whole WM network. Most strikingly, we observed decreasing connectivity from several regions toward right dorsolateral prefrontal cortex (rDLPFC) in preHD and even more so in earlyHD. The deterioration in rDLPFC connectivity complements results from previous studies and might mirror beginning cortical neural decline at premanifest and early manifest stages of HD. We were able to characterize effective connectivity in a WM network of HD mutation carriers yielding further insight into patterns of cognitive decline and accompanying neural deterioration.

Neuroscience

cluster analysis

dynamic causal modelling

effective connectivity

functional magnetic resonance

Huntington’s disease

n-back

working memory

Details

Title: Subtitle: Working Memory-Related Effective Connectivity in Huntington’s Disease Patients
Creators: Jacob Lahr
Lora Minkova
Sarah J Tabrizi
Julie C Stout
Stefan Klöppel
Elisa Scheller
TrackOn-HD Investigators
Contributors: Hans J Johnson (Contributor) - University of Iowa, Electrical and Computer Engineering
Resource Type: Journal article
Publication Details: Frontiers in neurology, Vol.9, pp.370-370
DOI: 10.3389/fneur.2018.00370
PMID: 29915555
PMCID: PMC5994408
NLM abbreviation: Front Neurol
ISSN: 1664-2295
eISSN: 1664-2295
Publisher: Frontiers Media S.A
Language: English
Date published: 06/04/2018
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Psychiatry; The Iowa Institute for Biomedical Imaging; The Iowa Initiative for Artificial Intelligence; Iowa Informatics Initiative
Record Identifier: 9984221628502771

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