White matter disruptions in male cocaine polysubstance users: Associations with severity of drug use and duration of abstinence

Son, Dana van; Wiers, Reinout W.; Catena, Andrés; Pérez-Garcı́a, Miguel; Verdejo-García, Antonio

doi:10.1016/j.drugalcdep.2016.09.023

Cited by 21 publications

(18 citation statements)

References 63 publications

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“…Further, our recordings are consistent with signals reported in primate ACC [17], and firing of single neurons in the same region of rat ACC are elevated during response conflict, as reported in humans [42]. This work is also consistent with research in humans examining cocaineinduced impairments in attention and cognitive control [50][51][52][53]. Thus, our work likely translates well to the human condition, providing additional evidence of drug-induced changes in brain and behavior at the level of single neurons [54] while controlling for confounding variables that might influence work in humans (e.g., genetics, life history, and polysubstance abuse).…”

Section: Discussionsupporting

confidence: 89%

Prior cocaine self-administration impairs attention signals in anterior cingulate cortex

Vázquez

Pribut

Burton

et al. 2019

Neuropsychopharmacol.

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Although maladaptive decision-making is a defining feature of drug abuse and addiction, we have yet to ascertain how cocaine self-administration disrupts neural signals in anterior cingulate cortex (ACC), a brain region thought to contribute to attentional control. To address this issue, rats were trained on a reward-guided decision-making task; reward value was manipulated by independently varying the size of or the delay to reward over several trial blocks. Subsequently, rats self-administered either a cocaine (experimental group) or sucrose (control) during 12 consecutive days, after which they underwent a 1-month withdrawal period. Upon completion of this period, rats performed the previously learned reward-guided decision-making task while we recorded from single neurons in ACC. We demonstrate that prior cocaine self-administration attenuates attention and attentionrelated ACC signals in an intake-dependent manner, and that changes in attention are decoupled from ACC firing. These effects likely contribute to the impaired decision-making-typified by chronic substance abuse and relapse-observed after drug use.

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Section: Discussionsupporting

confidence: 89%

Prior cocaine self-administration impairs attention signals in anterior cingulate cortex

Vázquez

Pribut

Burton

et al. 2019

Neuropsychopharmacol.

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“…Duration of cocaine use and telomere length can be considered indicators of chronicity. Previous studies have shown that severity and/or extent of cocaine use (with polysubstance use) was related to decreased WM integrity [12,72], while abstinence from cocaine was related to specific fiber tract improvements in FA value [35,73]. Associations between CUD and reductions in white matter integrity suggest allostatic shifts and possible neurotoxicity to white matter neurons [11,74,75].…”

Section: Discussionmentioning

confidence: 99%

Measures of possible allostatic load in comorbid cocaine and alcohol use disorder: Brain white matter integrity, telomere length, and anti-saccade performance

et al. 2019

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Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, resulting in changes consistent with an allostatic load model of neurocognitive impairment.The present study measured potential markers of allostatic load in individuals with comorbid cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white matter (WM), telomere length, and impulsivity/attentional bias were obtained. WM (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by the telomere to single copy gene (T/S) ratio. Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and FA were associated with years of cocaine use (R2 = 0.56 and 0.51, both p < .005) but not years of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, exploratory regression using an elastic-net model determined that more years of cocaine use, older age, larger HDDM drift rate differences and shorter telomere length were all predictive of WM as measured by RD (model R2 = 0.79). Collectively, the results provide modest support linking CUD/AUD to putative markers of allostatic load.

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“…Duration of cocaine use and telomere length can be considered indicators of chronicity. Previous studies have shown that severity and/or extent of cocaine use (with polysubstance use) was related to decreased WM integrity [12,71], while abstinence from cocaine was related to specific fiber tract improvements in FA value [35,72]. Associations between CUD and reductions in white matter integrity suggest allostatic shifts and possible neurotoxicity to white matter neurons [11,73,74].…”

Section: Discussionmentioning

confidence: 99%

Measures of Possible Allostatic Load in Comorbid Cocaine and Alcohol Use Disorder: Brain White Matter Integrity, Telomere Length, and Anti-Saccade Performance

Lane

Tannous

Mwangi

et al. 2018

Preprint

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34 Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, 35 resulting in changes consistent with an allostatic load model of neurocognitive impairment.36 The present study measured potential markers of allostatic load in individuals with comorbid 37 cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white 38 matter (WM) integrity, telomere length, and impulsivity/attentional bias were obtained. WM 39 integrity (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial 40 diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by T/S ratio.41 Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also 42 modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and 43 FA were associated with years of cocaine use (R 2 = 0.56 and 0.51, both p < .005) but not years 44 of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater 45 attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials 46 (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in 47 CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, 48 exploratory regression using an elastic-net model determined that more years of cocaine use, , 49 older age, larger HDDM drift rate differences and shorter telomere length were all predictive 50 of white matter integrity as measured by RD (model R 2 = 0.79). Collectively, the results 51 provide modest support linking CUD/AUD to putative markers of allostatic load. 52 Cocaine and Allostasis -3 53 54 Introduction 55Allostasis implies a shift in homeostatic systems in response to acute or chronic 56 stressors (e.g., allostatic load), described by McEwen as "the price the body pays for being 57 forced to adapt to adverse psychosocial or physical situations" [1]. Exposure to extreme or 58 pervasive stressors can result in pathophysiological change. Examination of allostatic load has 59 commonly focused on changes in the regulation of stress hormones and the sequelae of such 60 changes [2,3], but the concept can apply broadly to effects on many homeostatic systems.61 Nearly two decades ago, Koob and colleagues proposed allostatic models of chronic cocaine 62 and alcohol intake based on preclinical work [4-6], but only modest attention has focused on 63 the allostasic framework in studying human substance use disorders (SUD). Here, we focus on 64 the effects of chronic SUD in adults with co-morbid cocaine and alcohol use disorders [7][8][9]. 65Cocaine use disorder (CUD) with co-occurring abuse of other substances, e.g., 66 marijuana and alcohol use disorder (AUD), is the norm rather than the exception [10].67 Individuals who use only cocaine are of putative scientific importance with regard to isolating 68 individual drug effects. However, such investigations are more precisely understood using 69 preclinical models that can isolate dose-respon...

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White matter disruptions in male cocaine polysubstance users: Associations with severity of drug use and duration of abstinence

Abstract: Since the results did not survive multiple comparison-corrected thresholds, more studies are needed to confirm these indications.

Cited by 21 publications

References 63 publications

Prior cocaine self-administration impairs attention signals in anterior cingulate cortex

Prior cocaine self-administration impairs attention signals in anterior cingulate cortex

Measures of possible allostatic load in comorbid cocaine and alcohol use disorder: Brain white matter integrity, telomere length, and anti-saccade performance

Measures of Possible Allostatic Load in Comorbid Cocaine and Alcohol Use Disorder: Brain White Matter Integrity, Telomere Length, and Anti-Saccade Performance

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