Cocaine Use May Cause Alterations in Brain Regions Involved in Decisionmaking

AbstractSingle photon emission tomography (SPECT) is the prototypical tool for measuring cerebral blood flow (CBF) in discrete areas of the brain. Compared with when a male ‘crack’ cocaine user received placebo, oral cocaine (1mg/kg) ingestion was associated with non-uniformity of overall CBF with hypoperfusion of discrete brain regions, particularly of the frontal, temporo-parietal, basal ganglia, and thalamic areas. While these results should be viewed as preliminary, they do suggest that oral cocaine use may be associated with CBF abnormalities in ‘crack’ users.

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Motor Timing as a Predictor of Attention, Working Memory and Impulsivity in Alcohol and/or Cocaine Use Disorders

Timing & Time Perception ◽

10.1163/22134468-bja10001 ◽

2020 ◽

pp. 1-25

Author(s):

S.Y. Young ◽

J.J.M. van Hoof ◽

M. Kidd ◽

S. Seedat

Keyword(s):

Working Memory ◽

Alcohol Use Disorder ◽

Brain Regions ◽

Motor Timing ◽

Motor Tasks ◽

Cognitive Demands ◽

Cocaine Use ◽

Neurotoxic Effects ◽

Millisecond Timing ◽

The Brain

In recent years, there has been a growing interest in neuropsychological deficits in patients with Cocaine Use Disorder (CUD) and Alcohol Use Disorder (AUD). Besides deficits in working memory (WM), impulsivity and attention, chronic alcohol and cocaine use have neurotoxic effects on frontostriatal areas in the brain. Individuals with deficits in these brain regions experience motor-timing deficits. It is unclear whether observed temporal processing deficits, in fact, reflect increased sustained attention or WM demands (which are required by timing tasks), or whether motor-timing deficits reflect some other process. The main questions of this were: (i) Can attention and WM be explained by motor-timing performance, and (ii), is impulsivity related to motor timing performance, in an inpatient SUD population? The study sample consisted of 74 abstinent patients who completed selected neuropsychological and motor-timing tasks. No significant correlation was found between performance on motor tasks and impulsivity. With regard to visual and auditory WM, motor timing was a significant predictor but only under conditions that required increased cognitive demands. Motor-timing performance contributed to a small portion of the variance in attention, but only for spatial abilities and only at increased cognitive demands. These preliminary findings suggest that, in line with the literature, millisecond timing engages other cognitive functions, but only minimally. As such motor timing should be regarded as a separate neurocognitive concomitant. Impulsivity was not associated with millisecond motor timing. More research is needed to further investigate these preliminary findings.

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Motor Timing as a Predictor of Attention, Working Memory and Impulsivity in Alcohol and/or Cocaine Use Disorders

Timing & Time Perception ◽

10.1163/22134468-20201156 ◽

2020 ◽

Vol 8 (2) ◽

pp. 192-216

Author(s):

S.Y. Young ◽

J.J.M. van Hoof ◽

M. Kidd ◽

S. Seedat

Keyword(s):

Working Memory ◽

Alcohol Use Disorder ◽

Brain Regions ◽

Motor Timing ◽

Motor Tasks ◽

Cognitive Demands ◽

Cocaine Use ◽

Neurotoxic Effects ◽

Millisecond Timing ◽

The Brain

In recent years, there has been a growing interest in neuropsychological deficits in patients with Cocaine Use Disorder (CUD) and Alcohol Use Disorder (AUD). Besides deficits in working memory (WM), impulsivity and attention, chronic alcohol and cocaine use have neurotoxic effects on frontostriatal areas in the brain. Individuals with deficits in these brain regions experience motor-timing deficits. It is unclear whether observed temporal processing deficits, in fact, reflect increased sustained attention or WM demands (which are required by timing tasks), or whether motor-timing deficits reflect some other process. The main questions of this were: (i) Can attention and WM be explained by motor-timing performance, and (ii), is impulsivity related to motor timing performance, in an inpatient SUD population? The study sample consisted of 74 abstinent patients who completed selected neuropsychological and motor-timing tasks. No significant correlation was found between performance on motor tasks and impulsivity. With regard to visual and auditory WM, motor timing was a significant predictor but only under conditions that required increased cognitive demands. Motor-timing performance contributed to a small portion of the variance in attention, but only for spatial abilities and only at increased cognitive demands. These preliminary findings suggest that, in line with the literature, millisecond timing engages other cognitive functions, but only minimally. As such motor timing should be regarded as a separate neurocognitive concomitant. Impulsivity was not associated with millisecond motor timing. More research is needed to further investigate these preliminary findings.

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Ibrutinib as a potential therapeutic for cocaine use disorder

Translational Psychiatry ◽

10.1038/s41398-021-01737-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Spencer B. Huggett ◽

Jeffrey S. Hatfield ◽

Joshua D. Walters ◽

John E. McGeary ◽

Justine W. Welsh ◽

...

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Public Health Problem ◽

Brain Regions ◽

Cocaine Exposure ◽

Self Administration ◽

Cocaine Use ◽

Potential Therapeutics

AbstractCocaine use presents a worldwide public health problem with high socioeconomic cost. No current pharmacologic treatments are available for cocaine use disorder (CUD) or cocaine toxicity. To explore pharmaceutical treatments for tthis disorder and its sequelae we analyzed gene expression data from post-mortem brain tissue of individuals with CUD who died from cocaine-related causes with matched cocaine-free controls (n = 71, Mage = 39.9, 100% male, 49% with CUD, 3 samples/brain regions). To match molecular signatures from brain pathology with potential therapeutics, we leveraged the L1000 database honing in on neuronal mRNA profiles of 825 repurposable compounds (e.g., FDA approved). We identified 16 compounds that were negatively associated with CUD gene expression patterns across all brain regions (padj < 0.05), all of which outperformed current targets undergoing clinical trials for CUD (all padj > 0.05). An additional 43 compounds were positively associated with CUD expression. We performed an in silico follow-up potential therapeutics using independent transcriptome-wide in vitro (neuronal cocaine exposure; n = 18) and in vivo (mouse cocaine self-administration; n = 12–15) datasets to prioritize candidates for experimental validation. Among these medications, ibrutinib was consistently linked with the molecular profiles of both neuronal cocaine exposure and mouse cocaine self-administration. We assessed the therapeutic efficacy of ibrutinib using the Drosophila melanogaster model. Ibrutinib reduced cocaine-induced startle response and cocaine-induced seizures (n = 61–142 per group; sex: 51% female), despite increasing cocaine consumption. Our results suggest that ibrutinib could be used for the treatment of cocaine use disorder.

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Brain multimodal co-alterations related to delay discounting: a multimodal MRI fusion analysis in persons with and without cocaine use disorder

BMC Neuroscience ◽

10.1186/s12868-021-00654-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Christina S. Meade ◽

Xiang Li ◽

Sheri L. Towe ◽

Ryan P. Bell ◽

Vince D. Calhoun ◽

...

Keyword(s):

Delay Discounting ◽

Gray Matter Volume ◽

Dorsal Striatum ◽

Occipital Lobe ◽

Component Analysis ◽

Brain Regions ◽

Multimodal Fusion ◽

Cocaine Use ◽

Diffusion Weighted Images ◽

Brain Structure And Function

Abstract Background Delay discounting has been proposed as a behavioral marker of substance use disorders. Innovative analytic approaches that integrate information from multiple neuroimaging modalities can provide new insights into the complex effects of drug use on the brain. This study implemented a supervised multimodal fusion approach to reveal neural networks associated with delay discounting that distinguish persons with and without cocaine use disorder (CUD). Methods Adults with (n = 35) and without (n = 37) CUD completed a magnetic resonance imaging (MRI) scan to acquire high-resolution anatomical, resting-state functional, and diffusion-weighted images. Pre-computed features from each data modality included whole-brain voxel-wise maps for gray matter volume, fractional anisotropy, and regional homogeneity, respectively. With delay discounting as the reference, multimodal canonical component analysis plus joint independent component analysis was used to identify co-alterations in brain structure and function. Results The sample was 58% male and 78% African–American. As expected, participants with CUD had higher delay discounting compared to those without CUD. One joint component was identified that correlated with delay discounting across all modalities, involving regions in the thalamus, dorsal striatum, frontopolar cortex, occipital lobe, and corpus callosum. The components were negatively correlated with delay discounting, such that weaker loadings were associated with higher discounting. The component loadings were lower in persons with CUD, meaning the component was expressed less strongly. Conclusions Our findings reveal structural and functional co-alterations linked to delay discounting, particularly in brain regions involved in reward salience, executive control, and visual attention and connecting white matter tracts. Importantly, these multimodal networks were weaker in persons with CUD, indicating less cognitive control that may contribute to impulsive behaviors.

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Neurite orientation dispersion and density imaging in cocaine use disorder

10.1101/2020.10.28.20221911 ◽

2020 ◽

Author(s):

Jalil Rasgado-Toledo ◽

Apurva Shah ◽

Madhura Ingalhalikar ◽

Eduardo A. Garza-Villarreal

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Compartment Model ◽

Brain Regions ◽

Impulsive Behavior ◽

Cross Sectional ◽

Cocaine Use ◽

Psychiatric Severity ◽

Clinical Measures ◽

And Diffusion

AbstractCocaine use disorder (CUD) is characterized by compulsive searching for cocaine that produces cognitive deficits, including lack of inhibition and decision-making. Several studies have shown that cocaine users exhibit brain volume and diffusion-based white-matter alterations in a wide variety of brain regions. However, the non-specificity of standard volumetric and diffusion-tensor methods to detect structural micropathology may lead to wrong conclusions. To better understand microstructural pathology in CUD, we analyzed 60 CUD participants (3 female) and 43 non-CUD controls (HC; 2 female) retrospectively from our cross-sectional Mexican SUD neuroimaging dataset (SUDMEX-CONN), using multi-shell diffusion-weighted imaging and the neurite orientation dispersion and density imaging (NODDI) analysis whose aims to more accurately model micro-structural pathology. We used Viso values of NODDI that employ a three-compartment model in white (WM) and gray-matter (GM). These values were correlated with clinical measures, including psychiatric severity status, impulsive behavior and pattern of cocaine and tobacco use in the CUD group. As hypothesized, we found higher whole-brain microstructural pathology in WM and GM in CUD patients than controls. ROI analysis revealed higher Viso-NODDI values in superior longitudinal fasciculus, cingulum, hippocampus cingulum, forceps minor and Uncinate fasciculus, as well as in frontal and parieto-temporal GM structures. Correlations between significant ROIs showed a dependency of impulsivity and years of cocaine consumption over Viso-NODDI. However, we did not find correlations with psychopathology measures. Overall, microstructural pathology seems to be present in CUD both in gray and white-matter, however their clinical relevance remains questionable.

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Synaptic organization of the gustatory NST

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100168487 ◽

1994 ◽

Vol 52 ◽

pp. 150-151

Author(s):

M. C. Whitehead

Keyword(s):

Central Nervous System ◽

Dendritic Spines ◽

Fundamental Problem ◽

Cell Types ◽

Brain Regions ◽

Excitatory Synapses ◽

Solitary Tract ◽

Synaptic Organization ◽

Synaptic Junctions ◽

Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

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Suspect Cocaine Use in Patients With Chest Pain

Pediatric News ◽

10.1016/s0031-398x(07)70104-2 ◽

2007 ◽

Vol 41 (2) ◽

pp. 41

Author(s):

SHERRY BOSCHERT

Keyword(s):

Chest Pain ◽

Cocaine Use

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Musical Anhedonia

Zeitschrift für Neuropsychologie ◽

10.1024/1016-264x/a000292 ◽

2020 ◽

Vol 31 (2) ◽

pp. 62-68

Author(s):

Sara E. Holm ◽

Alexander Schmidt ◽

Christoph J. Ploner

Keyword(s):

Quality Of Life ◽

Nucleus Accumbens ◽

Brain Damage ◽

Parietal Cortex ◽

Neurological Disorders ◽

Brain Regions ◽

Precise Information ◽

Exact Localization ◽

High Prevalence

Abstract. Some people, although they are perfectly healthy and happy, cannot enjoy music. These individuals have musical anhedonia, a condition which can be congenital or may occur after focal brain damage. To date, only a few cases of acquired musical anhedonia have been reported in the literature with lesions of the temporo-parietal cortex being particularly important. Even less literature exists on congenital musical anhedonia, in which impaired connectivity of temporal brain regions with the Nucleus accumbens is implicated. Nonetheless, there is no precise information on the prevalence, causes or exact localization of both congenital and acquired musical anhedonia. However, the frequent involvement of temporo-parietal brain regions in neurological disorders such as stroke suggest the possibility of a high prevalence of this disorder, which leads to a considerable reduction in the quality of life.

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Serotonergic Genes and Suicidality

Crisis ◽

10.1027//0227-5910.22.2.54 ◽

2001 ◽

Vol 22 (2) ◽

pp. 54-60 ◽

Cited By ~ 42

Author(s):

Lisheng Du ◽

Gabor Faludi ◽

Miklos Palkovits ◽

David Bakish ◽

Pavel D. Hrdina

Keyword(s):

Suicidal Ideation ◽

Suicidal Behavior ◽

Tryptophan Hydroxylase ◽

Association Studies ◽

Receptor Gene ◽

Brain Regions ◽

Depressive Illness ◽

Control Group ◽

Serotonergic Activity ◽

Completed Suicide

Summary: Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of depressive illness and suicidal behavior. Studies have shown that the number of brain and platelet serotonin transporter binding sites are reduced in patients with depression and in suicide victims, and that the density of 5-HT2A receptors is increased in brain regions of depressed in suicide victims and in platelets of depressed suicidal patients. Genes that code for proteins, such as tryptophan hydroxylase, 5-HT transporter, and 5-HT2A receptor, involved in regulating serotonergic neurotransmission, have thus been major candidate genes for association studies of suicide and suicidal behavior. Recent studies by our group and by others have shown that genetic variations in the serotonin-system-related genes might be associated with suicidal ideation and completed suicide. We have shown that the 102 C allele in 5-HT2A receptor gene was significantly associated with suicidal ideation (χ2 = 8.5, p < .005) in depressed patients. Patients with a 102 C/C genotype had a significantly higher mean HAMD item #3 score (indication of suicidal ideation) than T/C or T/T genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression and not with depression itself. We also found that the 5-HT transporter gene S/L polymorphism was significantly associated with completed suicide. The frequency of the L/L genotype in depressed suicide victims was almost double of that found in control group (48.6% vs. 26.2%). The odds ratio for the L allele was 2.1 (95% CI 1.2-3.7). The association between polymorphism in serotonergic genes and suicidality supports the hypothesis that genetic factors can modulate suicide risk by influencing serotonergic activity.

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