Cortical thickness in cocaine users: relationship to resting functional connectivity and cocaine use

Poster Presentation: no. 3092INTRODUCTION: In rats, cocaine alters dendritic morphology (1), a determinant of cortical thickness (CT). In humans, addiction vulnerability traits such as anxiety and impulsivity relate to CT (2, 3). In human cocaine users, CT differences have been noted (e.g.,(4)) but little has been done to elucidate network functioning related to these differences. Numerous studies have also noted resting state functional connectivity (rsFC) differences in cocaine users (5, 6); however, how these may relate to structural differences is unknown. We identify cortical thickness differences in cocaine users, then probe relationships to rsFC and use characteristics in order to ...postprin

Resting state functional connectivity in addiction: drug abuse and reward dysregulation

INTRODUCTION: With the advent of advanced neuroimaging, strides have been made towards better understanding the cognitive elements necessary for task processing. Resting state functional connectivity assessments using functional magnetic resonance imaging has allowed patient assessments of underlying neural networks in patient populations with variable constraints. Drug addiction, a chronically relapsing disorder, presents many variable constraints. Cellular and molecular changes in neural reward pathway of drug addicted patient populations have advanced, but circuit-level alterations with reward deficits are yet to be completely understood. Resting state functional connectivity investigations in patient populations that use illicit drugs are seen to have repercussions on neural networks. OBJECTIVE: Assess and compare reward-network resting state functional connectivity investigations in patient populations with illicit drug use. METHODS: A meta-analysis of several resting state functional connectivity studies. Patient populations for each study contained an experimental group of drug users with a group of non-drug using controls to assess changes in resting state functional connectivity of the reward network. Studies utilized Diagnostic and Statistical Manuel of Mental disorders, 4th edition, as the basis of diagnosing drug dependence and abuse. A 3 Tesla MRI scanner was utilized to assess the reward pathway of the drug abuse in all experiments with the exception of one group using a 4 Tesla scanner. Band-pass temporal filtering from roughly 0.01 Hz to 0.1 Hz on residual signals was used to obtain low-frequency fluctuations needed for resting state connectivity analyses. Correlation maps were created by computing the correlation coefficients between the blood oxygen level dependent time course from the seed regions and from all other brain voxels. Regions of interest were chosen based on data from databases or previous studies. RESULTS: Four papers found widespread reductions in the connectivity of multiple reward pathway components. Results of these studies are consistent with perspectives suggesting that transition from drug use to addiction is driven by reduced functioning of reward systems and concurrently increased activation of anti-reward systems. Two studies suggested an increase in reward pathway of drug use, suggesting enhanced connectivity within reward and motivation circuits may be interpreted in the perspective of altered incentive salience for drugs and drug-associated stimuli. CONCLUSION: At early stage of experimental data in this field, data interpretation necessitates caution. Small sample sizes, heterogeneous subject groups and variable experimental paradigms may have lead to opposing findings. With certainty, chronic drug use was found to alter reward pathway in patient populations

Altered functional connectivity within the central reward network in overweight and obese women.

Background/objectivesNeuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/methodsFifty healthy, premenopausal women, 19 overweight and obese (high BMI=26-38 kg m(-2)) and 31 lean (BMI=19-25 kg m(-2)) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.ResultsGMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.ConclusionsOverweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors

Drug polyconsumption is associated with increased synchronization of brain electrical-activity at rest and in a counting task

Drug abusers typically consume not just one but several types of drugs, starting from alcohol and marijuana consumption, and then dramatically lapsing into addiction to harder drugs, such as cocaine, heroin, or amphetamine. The brain of drug abusers presents various structural and neurophysiological abnormalities, some of which may predate drug consumption onset. However, how these changes translate into modifications in functional brain connectivity is still poorly understood. To characterize functional connectivity patterns, we recorded Electroencephalogram (EEG) activity from 21 detoxified drug abusers and 20 age-matched control subjects performing a simple counting task and at rest activity. To evaluate the cortical brain connectivity network we applied the Synchronization Likelihood algorithm. The results showed that drug abusers had higher synchronization levels at low frequencies, mainly in the θ band (4–8 Hz) between frontal and posterior cortical regions. During the counting task, patients showed increased synchronization in the β (14–35 Hz), and γ (35–45 Hz) frequency bands, in fronto-posterior and interhemispheric temporal regions. Taken together 'slow-down' at rest and task-related 'over-exertion' could indicate that the brain of drug abusers is suffering from a premature form of ageing. Future studies will clarify whether this condition can be reversed following prolonged periods of abstinence

A model for classification based on the functional connectivity pattern dynamics of the brain

—Synchronized spontaneous low frequency fluctuations of the so called BOLD signal, as measured by functional Magnetic Resonance Imaging (fMRI), are known to represent the functional connections of different brain areas. Dynamic Time Warping (DTW) distance can be used as a similarity measure between BOLD signals of brain regions as an alternative of the traditionally used correlation coefficient and the usage of the DTW algorithm has further advantages: beside the DTW distance, the algorithm generates the warping path, i.e. the time-delay function between the compared two time-series. In this paper, we propose to use the relative length of the warping path as classification feature and demonstrate that the warping path itself carries important information when classifying patients according to cannabis addiction. We discuss biomedical relevance of our findings as well

Sex Differences in Resting State Brain Function of Cigarette Smokers and Links to Nicotine Dependence

Sex – a marker of biological and social individual differences – matters for drug use, particularly for cigarette smoking, which is the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task, is important for understanding cigarette smoking, as it has been shown to differentiate between smokers and non-smokers. But, it is unclear whether and how sex influences the link between resting state brain function and smoking behavior. In this study, we demonstrate that sex is indeed associated with resting state connectivity in cigarette smokers, and that sex moderates the link between resting state connectivity and self-reported nicotine dependence. Using functional magnetic resonance imaging and behavioral data from 50 adult daily smokers (23 women), we found that women had greater connectivity than men within the default mode network, and that increased connectivity within the reward network was related to increased nicotine tolerance in women but to decreased nicotine tolerance in men. Findings highlight the importance of sex-related individual differences reflected in resting state connectivity for understanding the etiology and treatment of substance use problems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/123046/1/Beltz, Berenbaum, Wilson. Sex differences in Resting State brain function of cigarette smokers and links to nicotine dependence..pd

Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using$^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence

Volume and Connectivity of the Ventral Tegmental Area are Linked to Neurocognitive Signatures of Alzheimer's Disease in Humans

Background: There is an urgent need to identify the earliest biological changes within the neuropathological cascade of Alzheimer’s disease (AD) processes. Recent findings in a murine model of AD showed significant preclinical loss of dopaminergic neurons in the ventral tegmental area (VTA), accompanied by reduced hippocampal innervation and declining memory. It is unknown if these observations can be translated in humans. Objective: We tested the hypothesis that VTA volume is associated with the typical clinical markers of AD in a cohort of patients and healthy controls. Methods: Structural and resting state functional MRI scans, and neuropsychological scores were acquired for 51 healthy adults, 30 patients with a diagnosis of mild cognitive impairment, and 29 patients with a diagnosis of AD dementia. VTA volume was quantified together with other control nuclei. The association between nuclei volume, hippocampal size, memory performance, and linguistic-executive skills was tested. The effect of VTA functional connectivity was also tested. Results: VTA size, but not of control nuclei, yielded a strong association with both hippocampal size and memory competence (but not linguistic-executive performance), and this was particularly strong in healthy adults. In addition, functional connectivity between the VTA and hippocampus was significantly associated with both markers of AD. Conclusion: Diminished dopaminergic VTA activity may be crucial for the earliest pathological features of AD and might suggest new strategies for early treatment. Memory encoding processes may represent cognitive operations susceptible to VTA neurodegeneration