The gray matter structural connectome and its relationship to alcohol relapse: Reconnecting for recovery.

Gray matter (GM) atrophy associated with alcohol use disorders (AUD) affects predominantly the frontal lobes. Less is known how frontal lobe GM loss affects GM loss in other regions and how it influences drinking behavior or relapse after treatment. The profile similarity index (PSI) combined with graph analysis allows to assess how GM loss in one region affects GM loss in regions connected to it, ie, GM connectivity. The PSI was used to describe the pattern of GM connectivity in 21 light drinkers (LDs) and in 54 individuals with AUD (ALC) early in abstinence. Effects of abstinence and relapse were determined in a subgroup of 36 participants after 3 months. Compared with LD, GM losses within the extended brain reward system (eBRS) at 1-month abstinence were similar between abstainers (ABST) and relapsers (REL), but REL had also GM losses outside the eBRS. Lower GM connectivities in ventro-striatal/hypothalamic and dorsolateral prefrontal regions and thalami were present in both ABST and REL. Between-networks connectivity loss of the eBRS in ABST was confined to prefrontal regions. About 3 months later, the GM volume and connectivity losses had resolved in ABST, and insula connectivity was increased compared with LD. GM losses and GM connectivity losses in REL were unchanged. Overall, prolonged abstinence was associated with a normalization of within-eBRS connectivity and a reconnection of eBRS structures with other networks. The re-formation of structural connectivities within and across networks appears critical for cognitive-behavioral functioning related to the capacity to maintain abstinence after outpatient treatment

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

Resting-state abnormalities in heroin-dependent individuals

Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games

Acute and chronic effects of betel quid chewing on brain functional connectivity

Background: The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dependence, is not clear. Methods: In this observational study, functional magnetic resonance imaging in a resting-state was performed in 24 male betel quid-dependent chewers and 28 male controls prior to and promptly after betel quid chewing. Network-based statistics were employed to determine significant differences in functional connectivity between brain networks for both acute effects and in long-term betel users versus controls. A support vector machine was employed for pattern classification analysis. Results: Before chewing betel quid, higher functional connectivity in betel quid-dependent chewers than in controls was found between the temporal, parietal and frontal brain regions (right medial orbitofrontal cortex, right lateral orbital frontal cortex, right angular gyrus, bilateral inferior temporal gyrus, superior parietal gyrus, and right medial superior frontal gyrus). In controls, the effect of betel quid chewing was significantly increased functional connectivity between the subcortical regions (caudate, putamen, pallidum, and thalamus), and the visual cortex (superior occipital gyrus and right middle occipital gyrus). Conclusion: These findings show that individuals who chronically use betel quid have higher functional connectivity than controls of the orbitofrontal cortex, and inferior temporal and angular gyri. Acute effects of betel quid are to increase the functional connectivity of some visual cortical areas (which may relate to the acute symptoms) and the basal ganglia and thalamus

Reduced executive and default network functional connectivity in cigarette smokers

Altered functional connectivity has been associated with acute and chronic nicotine use. Connectivity alterations, specifically in the right and left executive control networks (RECN/LECN) and the default mode network (DMN), may contribute to the addiction cycle. The objective of this study was to determine if executive control network (ECN) and DMN connectivity is different between non‐smokers and smokers and whether reductions in connectivity are related to chronic cigarette use. The RECN, LECN, and DMN were identified in resting state functional magnetic resonance imaging data in 650 subjects. Analyses tested for group differences in network connectivity strength, controlling for age and alcohol use. There was a significant group effect on LECN and DMN connectivity strength with smokers (n = 452) having lower network strengths than non‐smokers (n = 198). Smokers had lower connectivity than non‐smokers associated with key network hubs: the dorsolateral prefrontal cortex, and parietal nodes within ECNs. Further, ECN connectivity strength was negatively associated with pack years of cigarette use. Our data suggest that chronic nicotine use negatively impacts functional connectivity within control networks that may contribute to the difficulty smokers have in quitting. Hum Brain Mapp 36:872–882, 2015. © 2014 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110754/1/hbm22672.pd

Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications”,

Drug addiction encompasses a relapsing cycle of intoxication, bingeing, withdrawal and craving that results in excessive drug use despite adverse consequences (FIG. 1). Drugs that are abused by humans increase dopamine in the reward circuit and this is believed to underlie their rewarding effects. Therefore, most clinical studies in addiction have focused on the midbrain dopamine areas (the ventral tegmental area and substantia nigra) and the basal ganglia structures to which they project (the ventral striatum, where the nucleus accumbens is located, and the dorsal striatum), which are known to be involved in reward, conditioning and habit formation On the basis of imaging findings and emerging preclinical studies 5,6 , we proposed 10 years ago that disrupted function of the PFC leads to a syndrome of impaired response inhibition and salience attribution (iRISA) in addiction Here we review imaging studies into the role of the PFC in addiction from the past decade, integrating them into the iRISA model with the aim to gain a greater understanding of the dysfunction of the PFC in addiction. Specifically, this is the first systematic evaluation of the role of distinct regions within the functionally heterogeneous PFC in the neuropsychological mechanisms that putatively underlie the relapsing cycle of addiction. We review positron emission tomography (PET) and functional MRI (fMRI) studies focusing on regions of the PFC that have been implicated in addiction. These include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) (see R E V I E W S Non-contingent administration Administration of a certain drug that is not dependent on the subject's behaviour. Fixed-rate self-administration Self-administration of a certain drug on a ratio between drug delivery and behaviour that is fixed by an experimenter (for example, after emission of a certain number of responses or after a certain time has elapsed following the previous response). into the executive function of the PFC we refer the reader to other reviews Direct effects of drug exposure Here, we review studies that assessed the effects of stimulant and non-stimulant drugs on PFC activity 18 Fluorodyoxyglucose PET (PET FDG) study, administration of the stimulant drug methylphenidate (MPH) to active cocaine users increased whole-brain glucose metabolism 14 . Here, the left lateral OFC showed greater metabolism in response to unexpected than to expected MPH; the opposite pattern to that of the BOLD effect in the above study 13 possibly reflects the different temporal sensitivity of the imaging modalities (see below). Stimulant drugs also increase PFC activity in laboratory animals. For example, regional cerebral blood flow (rCBF) in drug-naive rhesus monkeys increased in DLPFC after non-contingent administration and in ACC during a simple fixed-rate self-administration of cocain

Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions

BACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. METHODS: Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. RESULTS: Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. CONCLUSIONS: Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions

Functional Organization of the Human Brain: How We See, Feel, and Decide.

The human brain is responsible for constructing how we perceive, think, and act in the world around us. The organization of these functions is intricately distributed throughout the brain. Here, I discuss how functional magnetic resonance imaging (fMRI) was employed to understand three broad questions: how do we see, feel, and decide? First, high-resolution fMRI was used to measure the polar angle representation of saccadic eye movements in the superior colliculus. We found that eye movements along the superior-inferior visual field are mapped across the medial-lateral anatomy of a subcortical midbrain structure, the superior colliculus (SC). This result is consistent with the topography in monkey SC. Second, we measured the empathic responses of the brain as people watched a hand get painfully stabbed with a needle. We found that if the hand was labeled as belonging to the same religion as the observer, the empathic neural response was heightened, creating a strong ingroup bias that could not be readily manipulated. Third, we measured brain activity in individuals as they made free decisions (i.e., choosing randomly which of two buttons to press) and found the activity within fronto-thalamic networks to be significantly decreased compared to being instructed (forced) to press a particular button. I also summarize findings from several other projects ranging from addiction therapies to decoding visual imagination to how corporations are represented as people. Together, these approaches illustrate how functional neuroimaging can be used to understand the organization of the human brain

Neuroplastic and cognitive impairment in substance use disorders: a therapeutic potential of cognitive stimulation

Author manuscriptDrug addiction is a chronic and relapsing disorder in which repeated drug exposure compromises brain neuroplasticity. Brain areas normally involved in learning and goal- directed behaviors become corrupted, which may lead to cognitive deficits that coexist with other addiction symptoms and predict a worse treatment outcome. New learning experiences that are not motivated by drugs may improve both cognitive deficits and drug-induced symptoms by promoting adaptive neuroplastic changes that could alleviate or reverse those involved in addiction. The present review will focus on whether potentiating healthy cognitive function, either by formal cognitive training or non-drug related environmental experiences, could exert beneficial effects in the therapeutics of addiction. Although additional studies are needed, the available clinical and preclinical evidence suggests that cognitive stimulation may provide a valuable adjuvant intervention in drug addiction.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-founded by the European Research Development Fund-AEI/FEDER, UE- (PSI2015-73156-JIN to E.C.O.; PSI2017-82604R to L.J.S.), Red de Trastornos Adictivos (RD16/0017/0001 to F.R.F.), Plan Nacional sobre Drogas, Ministerio de Sanidad, Servicios Sociales e Igualdad (PNSD2015/047 to J.S.) and the University of Málaga (Plan Propio 2017 – ‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to P.S.P). Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of Economy, Industry and Competitiveness (code: FJCI-2015-23925). Author D.L.G.M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (code: FPU13/04819). Authors J.S., A.S. and F.J.P. hold ‘Miguel Servet’ grants (codes: CPII17/00024, CP14/00173 and CP14/00212, respectively) from the National System of Health-Instituto de Salud Carlos- III co-funded by FEDER, UE. Author E.C.O. holds a ‘Jóvenes Investigadores’ grant (code: PSI2015-73156-JIN) from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-funded by FEDER, UE