Working memory fMRI activation in cocaine-dependent subjects: Association with treatment response

Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, 1300 Moursund, Houston, TX 77030, United States.
Psychiatry Research (Impact Factor: 2.47). 02/2010; 181(3):174-82. DOI: 10.1016/j.pscychresns.2009.11.003
Source: PubMed


Functional magnetic resonance imaging (fMRI) studies of early abstinence cocaine users offer information about the state of the brain when most cocaine users seek treatment. This study examined the relationship between pretreatment brain function and subsequent treatment response in 19 treatment-seeking early abstinence cocaine-dependent (CD) subjects. These subjects and 14 non-drug-using control subjects underwent fMRI while performing a working memory task with three levels of difficulty. CD subjects were then randomized to treatment studies. Results showed CD subjects had significantly lower (random effects, corrected for multiple comparisons) brain activation in caudate, putamen, cingulate gyrus, middle and superior frontal gyri, inferior frontal gyrus pars triangularis and pars opercularis, precentral gyrus, and thalamus compared with non-drug-using controls. Within CD subjects, thalamic activation significantly correlated with treatment response. This study shows CD subjects in early abstinence have alterations of brain function in frontal, striatal, and thalamic brain regions known to be part of a circuit associated with motor control, reward, and cognition. Subjects with pretreatment thalamic deactivation showed the poorest treatment response, possibly related to thalamic involvement in mesocortical and mesolimbic dopamine projections.

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    • "One possible mechanism underlying this difference is an impairment of working memory in cocaine addiction. Indeed, many previous studies have shown impaired working memory as a result of chronic exposure to cocaine (Albein-Urios et al., 2012; Fisk et al., 2011; Jovanovski et al., 2005; Kalapatapu et al., 2011; Kalechstein et al., 2013; Kubler et al., 2005; Lundqvist, 2005; Moeller et al., 2010; Porter et al., 2011; Rosselli and Ardila, 1996; Tau et al., 2013; Tomasi et al., 2007; Vonmoos et al., 2013). Since chronic cocaine use compromises cerebral structures critical for working memory and the extent of the structural deficits is related to years of drug use (Ide et al., 2014), more research is needed to confirm a lack of association between altered sequential effect and drug use. "
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    ABSTRACT: Cocaine dependence is associated with cognitive control deficits. Here, we apply a Bayesian model of stop-signal task (SST) performance to further characterize these deficits in a theory-driven framework. A "sequential effect" is commonly observed in SST: encounters with a stop trial tend to prolong reaction time (RT) on subsequent go trials. The Bayesian model accounts for this by assuming that each stop/go trial increases/decreases the subject's belief about the likelihood of encountering a subsequent stop trial, P(stop), and that P(stop) strategically modulates RT accordingly. Parameters of the model were individually fit, and compared between cocaine-dependent (CD, n=51) and healthy control (HC, n=57) groups, matched in age and gender and both demonstrating a significant sequential effect (p<0.05). Model-free measures of sequential effect, post-error slowing (PES) and post-stop slowing (PSS), were also compared across groups. By comparing individually fit Bayesian model parameters, CD were found to utilize a smaller time window of past experiences to anticipate P(stop) (p<0.003), as well as showing less behavioral adjustment in response to P(stop) (p<0.015). PES (p=0.19) and PSS (p=0.14) did not show group differences and were less correlated with the Bayesian account of sequential effect in CD than in HC. Cocaine dependence is associated with the utilization of less contextual information to anticipate future events and decreased behavioral adaptation in response to changes in such anticipation. These findings constitute a novel contribution by providing a computationally more refined and statistically more sensitive account of altered cognitive control in cocaine addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Drug and alcohol dependence 04/2015; 151. DOI:10.1016/j.drugalcdep.2015.03.021 · 3.42 Impact Factor
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    • "The age range in the present study is consistent with the average age of cocaine-dependent subjects who were seeking treatment in Houston (see Schmitz et al., 2012 for example ). The age range in the present study is also consistent with our other research (e.g., Moeller et al., 2010), and previous studies (e.g., Xu et al., 2010) published by other groups. "
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    ABSTRACT: Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microstructural organization of white matter (WM), and the most consistent DTI finding regarding cocaine-related WM alterations is in the corpus callosum (CC). WM injury has also been observed in subjects with traumatic brain injury (TBI), including in the CC. We used DTI to test if the WM microstructure is relatively more impaired in cocaine-dependent subjects who had suffered a mild TBI (mTBI). Fractional anisotropy (FA), which reflects the degree of alignment of cellular structures within fiber tracts and their structural integrity, was compared across cocaine-dependent subjects with mTBI (COCTBI group, n=9), matched cocaine-dependent subjects without TBI (COC group, n=12), and matched healthy controls (CTL group, n=12). The COCTBI group had significantly lower FA in the genu, body, and splenium of CC, than the CTL group whenever the education was controlled or not. The COC group had significantly lower FA in the left and right anterior corona radiata than the CTL group only when the education was controlled. There was no significant difference in FA between the COC and COCTBI groups. Cocaine dependence (or mTBI) related WM impairments in the CC were not detectable in this small subject sample. The significant finding in the CC suggests that the concurrence of cocaine dependence and mTBI might result in more severe damage to the CC, which could even be detected in small sample size. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Drug and alcohol dependence 03/2015; 151. DOI:10.1016/j.drugalcdep.2015.03.015 · 3.42 Impact Factor
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    • "In addition to reductions in ACC activation, current and former female cocaine users in our study showed reduced activation in left dorsomedial PFC (BA9), right dorsolateral PFC (BA9), and right anterior PFC (BA10) during recognition . This is consistent with cocaine-dependent individuals demonstrating reduced PFC activation during working memory tasks (Moeller et al. 2010). However, our pattern of findings might be particular to females, given previous evidence for sex differences (Wetherington 2007). "
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    ABSTRACT: Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-infected women. Three groups of HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study were compared: current users of crack cocaine (n = 10), former users of cocaine (n = 11), and women who had never used cocaine (n = 9). Participants underwent functional magnetic resonance imaging during a verbal memory task and completed a neuropsychological test of verbal memory. On the neuropsychological test, current crack users performed significantly worse than other groups on semantic clustering, a measure of strategic encoding, p < 0.05. During encoding, activation in left anterior cingulate cortex (ACC) was lower in current and former cocaine users compared to never users. During recognition, activation in bilateral PFC, specifically left dorsal medial PFC and bilateral dorsolateral PFC, was lower in current and former users compared to women who had never used cocaine. Lower activation in left dorsolateral PFC was correlated with worse performance on the recognition task, p < 0.05. The verbal learning and memory deficits associated with cocaine use in women with HIV may be partially accounted for by alterations in ACC and PFC function.
    Journal of NeuroVirology 04/2014; 20(4). DOI:10.1007/s13365-014-0250-x · 2.60 Impact Factor
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