Cerebral gray matter volumes and low-frequency fluctuation of BOLD signals in cocaine dependence: duration of use and gender difference

Abstract

Background: Magnetic resonance imaging has provided a wealth of information on altered brain activations and structures in individuals addicted to cocaine. However, few studies have considered the influence of age and alcohol use on these changes.

Methods: We examined gray matter volume with voxel based morphometry (VBM) and low frequency fluctuation (LFF) of BOLD signals as a measure of cerebral activity of 84 cocaine dependent (CD) and 86 healthy control (HC) subjects. We performed a covariance analysis to account for the effects of age and years of alcohol use.

Results: Compared to HC, CD individuals showed decreased gray matter (GM) volumes in frontal and temporal cortices, middle/posterior cingulate cortex, and the cerebellum, at p<0.05, corrected for multiple comparisons. The GM volume of the bilateral superior frontal gyri (SFG) and cingulate cortices were negatively correlated with years of cocaine use, with women showing a steeper loss in the right SFG in association with duration of use. In contrast, the right ventral putamen showed increased GM volume in CD as compared to HC individuals. Compared to HC, CD individuals showed increased fractional amplitude of LFF (fALFF) in the thalamus, with no significant overlap with regions showing GM volume loss.

Conclusions: These results suggested that chronic cocaine use is associated with distinct changes in cerebral structure and activity that can be captured by GM volume and fALFF of BOLD signals.

Keywords: Cerebral morphometry; Gender difference; Low-frequency fluctuation; Prefrontal; Stimulant; Thalamus.

Figure 1

Voxel based morphometry: analysis of covariance comparing cocaine dependent (CD) and healthy control (HC) participants, with age and years of alcohol use as covariates. (A) The results were examined at voxel p<0.05, corrected for family-wise error (FWE) of multiple comparisons. Compared to HC, CD showed gray matter (GM) volume loss in multiple cortical regions, including the temporal cortex, middle and posterior cingulate cortex, superior frontal cortices, and the cerebellum. Conversely, no brain regions showed greater GM volume in CD, as compared to HC, at this threshold. (B) The same contrast examined at voxel p<0.0001, and cluster p<0.05, FWE corrected. In addition to decreased GM volume in the cortical regions and cerebellum, CD also showed increased GM volume in the right ventral putamen, compared to HC (Table 2A). Color bars represent voxel T value. Neurological orientation: R=right.

Figure 1

Voxel based morphometry: analysis of covariance comparing cocaine dependent (CD) and healthy control (HC) participants, with age and years of alcohol use as covariates. (A) The results were examined at voxel p<0.05, corrected for family-wise error (FWE) of multiple comparisons. Compared to HC, CD showed gray matter (GM) volume loss in multiple cortical regions, including the temporal cortex, middle and posterior cingulate cortex, superior frontal cortices, and the cerebellum. Conversely, no brain regions showed greater GM volume in CD, as compared to HC, at this threshold. (B) The same contrast examined at voxel p<0.0001, and cluster p<0.05, FWE corrected. In addition to decreased GM volume in the cortical regions and cerebellum, CD also showed increased GM volume in the right ventral putamen, compared to HC (Table 2A). Color bars represent voxel T value. Neurological orientation: R=right.

Figure 2

Gender difference in the correlation of GM volume with years of cocaine use in the cocaine dependent group, for the three regions of interest. Compared to men, women showed a steeper decline in GM volume of the right superior frontal gyrus with the duration of use (p<0.016, test of difference in slope; Zar, 1999).

Figure 3

Differences in fractional amplitude of low frequency fluctuation (fALFF) of BOLD signals between CD and HC participants. (A) At voxel p<0.05, corrected for family-wise error (FWE) of multiple comparisons, a single cluster in the thalamus showed decreased fALFF in CD, as compared to HC. (B) The same contrast examined at voxel p<0.0001 and cluster p<0.05, FWE corrected, identified additional differences (Table 2B). Color bars represent voxel T value. Neurological orientation: R=right.

Figure 3

Differences in fractional amplitude of low frequency fluctuation (fALFF) of BOLD signals between CD and HC participants. (A) At voxel p<0.05, corrected for family-wise error (FWE) of multiple comparisons, a single cluster in the thalamus showed decreased fALFF in CD, as compared to HC. (B) The same contrast examined at voxel p<0.0001 and cluster p<0.05, FWE corrected, identified additional differences (Table 2B). Color bars represent voxel T value. Neurological orientation: R=right.