Reduced Frontal Lobe Activity in Subjects With High Impulsivity and Alcoholism

Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 02/2007; 31(1):156-65. DOI: 10.1111/j.1530-0277.2006.00277.x
Source: PubMed


Impulsivity is an important characteristic of many psychiatric disorders, including substance-related disorders. These disinhibitory disorders have a similar underlying genetic diathesis, with each disorder representing a different expression of the same underlying genetic liability. This study assessed whether there is a relationship between impulsivity and alcohol dependence, and their correlations with P3 (P300) amplitude, a proposed endophenotype of alcoholism.
Healthy control subjects (n=58) and subjects with DSM-IV diagnosis of alcohol dependence (n=57) were assessed with a visual oddball task. Event-Related Potentials (ERPs) were recorded from 61 scalp electrodes and P3 amplitudes measured. Barratt Impulsiveness Scale (BIS), version 11, was used to evaluate impulsivity. Source localization of P3 was computed using low-resolution brain electromagnetic tomography (LORETA).
Alcoholic subjects manifested reductions in target P3 amplitudes (p<0.0001). Using LORETA, significantly reduced activation was mapped in the cingulate, medial, and superior frontal regions in alcoholic subjects and highly impulsive subjects. Alcoholic subjects had significantly higher scores on the BIS (p<0.0001) than nonalcoholic individuals. There were significant negative correlations between total scores on BIS and P3 amplitude (r=-0.274, p=0.003, on Pz; r=-0.250, p=0.007, on Cz).
Our results demonstrate a strong frontal focus of reduced activation during processing of visual targets in alcoholic subjects and individuals with higher impulsivity. The findings suggest that impulsivity may be an important factor that underlies the pathogenesis of alcohol dependence. Studies are underway to examine the relationship between impulsivity and ERPs in offspring of alcoholic subjects, and to identify genes associated with the underlying predisposition involved in disinhibitory disorders.

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    • "Alcohol dependent patients display poor performance on PFC-dependent tasks and this is correlated with reduced power of delta frequency EEG measurements of frontal cortical function (Kamarajan et al., 2004; Chen et al., 2007). In addition, the sleep efficiency and time spent in slow-wave sleep are reduced in rodent models of dependence (Veatch, 2006). "
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    ABSTRACT: Chronic use of alcohol is associated with structural and functional alterations in brain areas that subserve cognitive processes. Of particular importance is the prefrontal cortex (PFC) that is involved in higher order behaviors such as decision making, risk assessment and judgment. Understanding the mechanisms that underlie alcohol's effects on PFC function is important for developing strategies to overcome the cognitive deficits that may predispose individuals to relapse. Our previous studies showed that acutely applied ethanol inhibits network activity in slices of prefrontal cortex and that exogenous and endogenous cannabinoids modulate up-state dynamics. In the present study, we examined the effects of repeated alcohol exposure on cannabinoid regulation of up-states in slice cultures of the prefrontal cortex. Compared to controls, up-state duration, but not amplitude was enhanced when measured 4 days after a 10 day ethanol exposure (44 mM ethanol; equivalent to 0.2% blood ethanol). Administration of the CB1 agonist WIN 55,212-2 enhanced the amplitude of up-states in control cultures but not in those treated previously with ethanol. This lack of effect occurred in the absence of any noticeable change in CB1 receptor protein expression. Chronic ethanol treatment and withdrawal also blunted WIN's inhibition of electrically evoked GABA IPSCs in layer II/III pyramidal neurons but not those in layer V/VI. WIN inhibited the amplitude of spontaneous GABA IPSCs in both layers and the magnitude of this effect was not altered by ethanol treatment. However, in layer V/VI neurons, WIN's effect on sIPSC frequency was greater in ethanol treated cultures. WIN also inhibited electrically evoked NMDA EPSCs in both layer II/III and V/VI neurons but this action was unaffected by ethanol treatment and withdrawal. Overall, these results suggest that ethanol's down-regulation of cannabinoid signaling results in altered network activity in the prefrontal cortex.
    Frontiers in Integrative Neuroscience 07/2014; 8:58. DOI:10.3389/fnint.2014.00058
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    • "Deficient inhibitory control in trait impulsivity has not been consistently supported on the basis of previous N2 and P3 findings. However, a reduced P3 amplitude in impulsive participants was a general result of former studies using various tasks (Chen et al., 2007; De Pascalis et al., 2004; Russo et al., 2008). This was interpreted either as an outcome of ineffective allocation of the available attentional resources, or as a consequence of attenuated physiological arousal. "
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    ABSTRACT: Impaired inhibitory control is one of the still debated underlying mechanisms of trait impulsivity. The Cognitive Energetic Model accounts for the role of energetic factors mediating task performance. The aim of the present study was to compare inhibitory control functions of adults with high and low impulsivity by using a modified Eriksen flanker task. Adults were classified as impulsive (n = 15) and control (n = 15) participants based on the Barratt Impulsiveness Scale. Flanker trials had three levels of required effort manipulated by visual degradation. We analyzed RT, accuracy, and ERPs time-locked to the flanker stimuli. Reaction time of impulsive participants was generally slower than that of controls’, but accuracy was similar across groups. N2c showed that monitoring of response conflict was modulated by task requirements independent of impulsivity. The P3 latency was delayed in the impulsive group indicating slower stimulus evaluation. The P3 amplitude was reduced in the control group for moderately degraded incongruent trials suggesting that the attentional resources were employed less. The Lateralized Readiness Potential (LRP) peaked later in the impulsive group irrespective of experimental effects. The amplitude of the positive-going LRP recorded in the incongruent condition was comparable across groups, but the latency was delayed partly supporting a stronger susceptibility to stimulus interference of impulsive participants. Their delayed incongruent negative-going LRP reflected a weaker response inhibition and a slower correct response organization. In conclusion, impaired inhibitory functions in impulsivity could not be unequivocally demonstrated, but we found a generalized lapse of motor activation.
    International journal of psychophysiology: official journal of the International Organization of Psychophysiology 04/2014; 92(1). DOI:10.1016/j.ijpsycho.2014.01.008 · 2.88 Impact Factor
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    • "Irrespective of the direction of causality, dysregulated sensitivity to reward has been shown in drug-addicted individuals. For example, using functional magnetic resonance imaging (fMRI), we reported a compromised cortical sensitivity to monetary reward on a sustained attention task in individuals with cocaine use disorders (CUD) (Goldstein et al., 2007a); similar results have since been reported in alcoholics (Chen et al., 2007) and pathological gamblers (de Ruiter et al., 2009). "
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    ABSTRACT: Recent studies suggest that drug-addicted individuals have a dampened cortical response to non-drug rewards. However, it remains unclear whether recency of drug use impacts this impairment. Therefore, in this event-related potential study, recency of cocaine use was objectively determined by measuring cocaine in urine on study day. Thirty-five individuals with current cocaine use disorder [CUD: 21 testing positive (CUD+) and 14 testing negative (CUD-) for cocaine in urine] and 23 healthy controls completed a sustained attention task with graded monetary incentives (0¢, 1¢ and 45¢). Unlike in controls, in both CUD subgroups P300 amplitude was not modulated by the varying amounts of money and the CUD- showed the most severe impairment as documented by the lowest P300 amplitudes and task accuracy. Moreover, while recency of drug use was associated with better accuracy and higher P300 amplitudes, chronic drug use was associated with lower sensitivity to money. These results extend our previous findings of decreased sustained sensitivity to monetary reward in CUD+ to recently abstaining individuals, where level of impairment was most severe. Taken together, these results support the self-medication hypothesis, where CUD may be self-administering cocaine to avoid or compensate for underlying cognitive and emotional difficulties albeit with a long-term detrimental effect on sensitivity to non-drug reward.
    07/2012; 203(1):75-82. DOI:10.1016/j.pscychresns.2012.01.001
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