___ Neurological Disorders: Addiction ___

Addiction - Brain Regions and their Dysfunctions

Addiction "We conclude that there are at least two underlying types of dysfunction where emotional signals (somatic markers) turn in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action." S "Drug abusers present significant alterations in extensive areas of the cortex (especially in the frontal and temporal cortex), subcortex (amygdala, hippocampus and insular cortex) and basal regions (striatum). These alterations are associated with abnormal patterns of activation during cognitive memory tasks, inhibition and decision-making." S "In patients with alcohol dependence, VBM (Voxel-based morphometry) of GM (gray matter) revealed a significant decrease in density in the precentral gyrus, middle frontal gyrus, insular cortex, dorsal hippocampus, anterior thalamus and cerebellum compared with controls. Reduced density of WM (white matter) was found in the periventricular area, pons and cerebellar pedunculi." S "Smoking abstinence state (vs satiety) was associated with increased cerebral blood flow (CBF) in ACC/ medial OFC and left OFC. Abstinence-induced cravings to smoke were predicted by CBF increases (abstinence minus satiety) in the right OFC, right DLPFC, occipital cortex, ACC, ventral striatum/nucleus accumbens, thalamus, amygdala, bilateral hippocampus, left caudate, and right insula." S
Affected Region	Dysfunctions
Insular lobe	"... insular hypocretin transmission plays a permissive role in the motivational properties of nicotine, and therefore may be a key neurobiological substrate necessary for maintaining tobacco addiction in human smokers." S Increase in the neuronal activity in the insular cortex during craving S "... the interoceptive system, which provides information about the subject's internal state and is integrated in the insular cortex, and not the subcortical ventral striatum, is the critical neural substrate for reward-related processes." S
Orbitofrontal Cortex	Increased cerebral blood flow (CBF) in medial OFC and left OFC in smoking abstinence; CBF increases in the right OFC S
Medial PFC	"... greater abstinence-induced craving was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision making. These findings suggest that drug abstinence can increase the salience of conditioned cues, which is consistent with incentive-motivation models of addiction." S "Basolateral amygdala (BLA) neurons provide a major excitatory input to mPFC-layer V pyramidal neurons. Under stressful conditions, commonly associated with chronic cocaine abuse, altered BLA-to-mPFC synaptic transmission could lead to defective emotional information processing and decision making within the mPFC and result in misguided and inappropriate behaviors." S
Dorsolateral PFC	Abstinence-induced cravings to smoke were predicted by CBF increases in the right dorsolateral prefrontal cortex S
Temporal lobe	Anterior temporal lobe: more active during exposure to cigarette-related cues S
Hippocampus	Increased cerebral blood flow (CBF) during smoking abstinence (bilateral) S
Amygdala	Increased cerebral blood flow (CBF) during smoking abstinence S Long term upregulation of CRF(1) receptors in the amygdala following a history of alcohol dependence S Serotonergic regulation in the amygdala is defected especially in type 2 alcoholics S
Anterior Cingulate Cortex	The OFC modulates the value of rewards by regulating the magnitude of dopamine increases in the ventral striatum, and disruption of this regulation may underlie the decreased sensitivity to rewards in addicted subjects S Increased cerebral blood flow (CBF) during smoking abstinence S 23-day abstinent "cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC" during performance of a modified version of the Stroop Task S "In contrast to previous findings on abstinent alcohol-dependent patients, nicotine craving seems to be maintained by a region-specific shift in D(2)/D(3) (dopamine 2/ 3) receptor availabilities, with higher availability within the ventral striatum but lower availability within the ACC and inferior temporal cortex." S
Posterior Cingulate Cortex	"Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues." S
Striatum	Ventral: Increased cerebral blood flow (CBF) during smoking abstinence S "Similar to other types of substance abuse, nicotine dependence is associated with low availability of dorsal striatal D(2)/D(3) (dopamine) receptors." S "The OFC modulates the value of rewards by regulating the magnitude of dopamine increases in the ventral striatum and disruption of this regulation may underlie the decreased sensitivity to rewards in addicted subjects." S
Caudate nucleus	Left: Increased cerebral blood flow (CBF) during smoking abstinence S Markedly increased dynorphin immunoreactivity in caudate (+92%), and decreased caudate neurotensin (-49%) of human chronic cocaine users as predicted by animal findings S
Globus pallidus	Markedly increased dynorphin levels in the ventral pallidum (+346%) of human chronic cocaine users as predicted by animal findings S Blockade of the ventral globus pallidus leads to a loss of drug cravings and alcohol-induced euphoria S
Nucleus accumbens	Increased cerebral blood flow (CBF) during smoking abstinence S PFC regulates the value of rewards by modulating dopamine increases in nucleus accumbens and this regulation is disrupted in addicted subjects S
Putamen	Increased dynorphin (+75%) in putamen S
Thalamus	Increased cerebral blood flow (CBF) during smoking abstinence S
Hypothalamus	Serotonergic regulation in the hypothalamus is defected especially in type 2 alcoholics S
Mammillary body	Alcoholism is associated with mammillary body tissue volume loss S
Substantia nigra	Focal MR imaging signal-intensity changes in the substantia nigra, locus ceruleus, and other selected nerve tracts and nuclei in a child exposed prenatally to cocaine and other drugs S Increased MCP-1 (monocyte chemoattractant protein 1) concentration in ventral tegmental area, substantia nigra, hippocampus and amygdala of alcoholic brains S
Cerebellum	Alcoholism is associated with cerebellar tissue volume loss S
Pons	The mammalian mesopontine tegmentum (MPT) is a master regulator of nicotinic dopaminergic signalling in the brain, including for nicotine addiction S

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