Reduced interhemispheric resting state functional connectivity in cocaine addiction - PubMed (original) (raw)

Reduced interhemispheric resting state functional connectivity in cocaine addiction

Clare Kelly et al. Biol Psychiatry. 2011.

Abstract

Background: Models of cocaine addiction emphasize the role of disrupted frontal circuitry supporting cognitive control processes. However, addiction-related alterations in functional interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. We examined interhemispheric resting-state functional connectivity (RSFC) in cocaine dependence using a recently validated approach, voxel-mirrored homotopic connectivity.

Methods: We compared interhemispheric RSFC between 25 adults (aged 35.0 ± 8.8) meeting DSM-IV criteria for cocaine dependence within the past 12 months but currently abstaining (>2 weeks) from cocaine and 24 healthy comparisons (35.1 ± 7.5), group-matched on age, sex, education, and employment status.

Results: We observed reduced prefrontal interhemispheric RSFC in cocaine-dependent participants relative to control subjects. Further analyses demonstrated a striking cocaine-dependence-related reduction in interhemispheric RSFC among nodes of the dorsal attention network, comprising bilateral lateral frontal, medial premotor, and posterior parietal areas. Further, within the cocaine-dependent group, RSFC within the dorsal attention network was associated with self-reported attentional lapses.

Conclusions: Our findings provide further evidence of an association between chronic exposure to cocaine and disruptions within large-scale brain circuitry supporting cognitive control. We did not detect group differences in diffusion tensor imaging measures, suggesting that alterations in the brain's functional architecture associated with cocaine exposure can be observed in the absence of detectable abnormalities in the white matter microstructure supporting that architecture.

Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

Financial Disclosures

All authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1

Figure 1. Voxel-Mirrored Homotopic Connectivity (VMHC)

A. Group-level VMHC for the control and cocaine-dependent groups (Z>2.3, cluster-level p<0.05, corrected; images are axial slices at z = 5; 28; and 51). Although there is only one correlation for each pair of homotopic voxels, results are projected on to both hemispheres, to minimize confusion regarding the laterality of the results. B. Cross-scan consistency of mean VMHC values across the IFS area exhibiting significant group differences in the primary VMHC analysis (i.e., the area shown in Figure 1C; controls: r=0.495, p<0.05; cocaine: r=0.587, p<0.01; all participants: r=0.69; p<0.0001). See Supplement for full details of the within-sample replication analysis. C. Inferior frontal sulcus (IFS) area for which the control group exhibited significantly stronger VMHC than the cocaine-dependent group (Z>2.3, cluster-level p<0.05, corrected). D. In recognition of the fact that non-independence in voxel-wise analyses of group differences necessarily provides inflated estimates of effect sizes (–91), the plots show mean VMHC values across the IFS area exhibiting significant group differences in the primary VMHC analysis (shown in B) computed on the basis of the secondary scan (Scan 2) data. The group difference in VMHC for the secondary scan is significant (controls mean Scan 2 VMHC=0.38±0.10, cocaine mean Scan 2 VMHC=0.26±0.09; t(2,38)=4.13, p<0.001).

Figure 2

Figure 2. Cocaine-dependent participants exhibit reduced interhemispheric, but not intrahemispheric RSFC within the Dorsal Attention Network (DAN)

We tested for group differences in intrahemispheric (e.g., right IFS and right IPL), heterotopic interhemispheric (e.g., right IFS and left IPL) and homotopic interhemispheric (e.g., right and left IFS) RSFC between all pairs of 16 DAN nodes. Relative to controls, the cocaine-dependent group exhibited reduced homotopic (controls mean=0.45±0.11; cocaine mean=0.39±0.09; t(2,47)=2.66, p<0.05) and heterotopic (controls mean=0.16±0.07; cocaine mean=0.11±0.07; t(2,47)=2.68, p<0.05) interhemispheric RSFC, but not reduced intrahemispheric RSFC (controls left-left mean=0.25±0.07; cocaine left-left mean=0.23±0.08; t(2,47)=0.76, p=0.45; controls right-right mean=0.25±0.1; cocaine right-right mean=0.21±0.08; t(2,47)=1.44, p=0.16). Abbreviations: R: Right; L: Left; antIFS: anterior inferior frontal sulcus; midIFC: middle IFS; postIFS: posterior IFS; preSMA: presupplementary motor area; FEF: frontal eye fields; MT: middle temporal area; IPS: intraparietal sulcus.

Figure 3

Figure 3. ROI-based and voxel-wise brain/behavior relationships

A. Interhemispheric RSFC (i.e., VMHC) within a 4mm-radius sphere centered on the peak of the group difference in VMHC correlated with self-reported cognitive failures, as measured by the Cognitive Failures Questionnaire (CFQ; r=−0.43, _n_=23, p<0.05). Cocaine-dependent participants with the weakest prefrontal interhemispheric RSFC reported experiencing more frequent attentional failures. This relationship remained significant after adjusting for cocaine withdrawal symptoms (as measured by the Cocaine Selective Severity Assessment – CSSA: r=−0.66, p<0.001). B. Voxel-wise analyses revealed relationships between right IFS RSFC and self-reported cognitive failures. Shown in green is the medial/superior lateral premotor area whose RSFC with right IFS exhibited a negative relationship with the CFQ. Cocaine-dependent participants with the weakest RSFC between these two areas reported experiencing more frequent attentional failures. Axial slices (z = 5; 28; and 51) are displayed according to neurological convention (right is right).

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