Biomedical subjects

George Fein

Publications and source records attributed to George Fein.

17 recordsLinked to original sources

PubMed2006

Sub-diagnostic psychiatric comorbidity in alcoholics.

BACKGROUND: Psychiatric comorbidity in alcohol use disorders is clearly established, however most studies ignore data on psychiatric symptom counts that do not meet criteria for a diagnosis. We examined psychiatric symptom counts and psychological measures in the domains of anxiety, mood and externalizing pathology in 48 long-term abstinent alcoholics (LTAA) compared to 48 age/gender comparable light/non-drinking controls (NC). METHODS: Continuous measures of pathology (i.e., symptoms counts and psychological assessments) in each domain were compared between groups for: (1) all study participants, (2) excluding individuals with a lifetime psychiatric diagnosis in the domain, and (3) excluding individuals with a current psychiatric diagnosis in the domain. RESULTS: Psychiatric symptom counts and psychological pathology were greater in LTAA than NC. The differences between groups on these measures were not reduced by removal of individuals with lifetime or current diagnoses. CONCLUSIONS: The bulk of the difference between LTAA and NC in psychiatric illness was carried by sub-diagnostic psychopathology. In comparison to the limited view provided by using only symptomatology that meets criteria for a diagnosis, the use of continuous measures of psychiatric symptomatology and psychological abnormality yields a much more accurate picture of psychiatric illness co-occurring with alcoholism.

Alcoholism↗

PubMed2006

Brain atrophy in long-term abstinent alcoholics who demonstrate impairment on a simulated gambling task.

We recently demonstrated impairment on the Simulated Gambling Task (SGT) in long-term abstinent alcoholics (AbsAlc). Brain regions that have been shown to be necessary for intact SGT performance are the ventromedial prefrontal cortex (VMPFC) and the amygdala; patients with VMPFC or amygdalar damage demonstrate SGT impairments similar to those of substance abusing populations. We examined these brain regions, using T1-weighted MRIs, in the 101 participants from our previous study using voxel-based morphometry (VBM). VBM was performed using a modification we developed [Fein, G., Landman, B., Tran, H., Barakos, J., Moon, K., Di Sclafani, V., Shumway, R., 2006. Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs. Neuroimage] of Baron's procedure, [], in which we use skull-stripped images as input. We also restricted the analysis to a ROI consisting of the amygdala and VMPFC as defined by the Talairach Daemon resource. Compared to the controls, the AbsAlc participants had significant foci of reduced gray matter density within the amygdala. Thus, SGT decision-making deficits are associated with reduced gray matter in the amygdala, a brain region previously implicated in similar decision-making impairments in neurological samples. This structurally based abnormality may be the result of long-term alcohol abuse or dependence, or it may reflect a pre-existing factor that predisposes one to severe alcoholism. From an image analysis perspective, this work demonstrates the increased sensitivity that results from using skull-stripped inputs and from restricting the analysis to a ROI. Without both of these methodological advances, no statistically significant finding would have been forthcoming from this work.

Adult↗

PubMed2006

Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs.

A major attraction of voxel-based morphometry (VBM) is that it allows researchers to explore large datasets with minimal human intervention. However, the validity and sensitivity of the Statistical Parametric Mapping (SPM2) approach to VBM are the subject of considerable debate. We visually inspected the SPM2 gray matter segmentations for 101 research participants and found a gross inclusion of non-brain tissue surrounding the entire brain as gray matter in five subjects and focal areas bordering the brain in which non-brain tissue was classified as gray matter in many other subjects. We also found many areas in which the cortical gray matter was incorrectly excluded from the segmentation of the brain. The major source of these errors was the misregistration of individual brain images with the reference T1-weighted brain template. These errors could be eliminated if SPM2 operated on images from which non-brain tissues (scalp, skull, and meninges) are removed (brain-extracted images). We developed a modified SPM2 processing pipeline that used brain-extracted images as inputs to test this hypothesis. We describe the modifications to the SPM2 pipeline that allow analysis of brain-extracted inputs. Using brain-extracted inputs eliminated the non-brain matter inclusions and the cortical gray matter exclusions noted above, reducing the residual mean square errors (RMSEs, the error term of the SPM2 statistical analyses) by over 30%. We show how this reduction in the RMSEs profoundly affects power analyses. SPM2 analyses of brain-extracted images may require sample sizes only half as great as analyses of non-brain-extracted images.

Adult↗

PubMed2006

Normal performance on a simulated gambling task in treatment-naive alcohol-dependent individuals.

BACKGROUND: Research suggests that substance abusers make more disadvantageous decisions on the simulated gambling task (SGT); such decisions are associated with deviance proneness and antisocial symptoms. This study examines decision making on the SGT in young adults with alcohol dependence who are treatment-naive (TxN). METHODS: A total of 116 subjects (58 controls, 58 TxNs) were tested on the SGT, where participants choose cards from 4 different decks that vary in terms of the magnitude of the immediate gain (large/small) and the magnitude of long-term loss (larger/smaller). Participants were also assessed on measures of externalizing symptoms, personality traits reflecting social deviance, neuropsychological function, and the density of the family history of alcoholism. RESULTS: Treatment-naïves did not differ from controls on measures of SGT decision making. Simulated gambling task performance was not associated with externalizing symptoms, social deviance proneness, or a familial density of alcoholism. Although TxNs had higher levels of externalizing symptoms, social deviance, and familial density of alcoholism compared with controls, these variables were only modestly elevated compared with previous samples of long-term abstinent alcohol-dependent individuals who showed decision-making deficits on the SGT. CONCLUSIONS: The results suggest that our sample of young adult TxN adults with alcohol dependence do not have global deficits in decision making as measured by the SGT, and that their poor decisions regarding their alcohol consumption are more specific to drinking.

Adult↗

PubMed2006

Cognitive performance in long-term abstinent alcoholic individuals.

BACKGROUND: There are few investigations of the potential recovery of neurocognitive function in chronic alcoholic samples after very-long-term abstinence. The current study examined cognitive abilities in middle-aged (mean age 46.8 years), long-term abstinent alcoholic individuals (LTAA). Twenty-five LTAA men and 23 LTAA women abstinent for an average of 6.7 years were compared with an equal number of gender and age-comparable normal controls (NC). We examined the association of neurocognitive variables with age, duration of abstinence, alcohol use measures, and the density of a family history of problem drinking. METHODS: Long-term abstinent alcoholic individuals and NC underwent comprehensive neuropsychological assessment. Performance was measured in the following 9 domains: abstraction/cognitive flexibility, attention, auditory working memory, immediate memory, delayed memory, psychomotor function, reaction time, spatial processing, and verbal skills. RESULTS: Long-term abstinent alcoholic individuals performed similarly to NC, except for deficits in the spatial processing domain. The spatial processing results must be interpreted with caution because of multiple comparison issues; however, spatial processing deficits are among the impairments most often reported in abstinent alcoholic individuals. None of the cognitive measures were associated with length of abstinence, any alcohol use variable, or family history measure. CONCLUSIONS: Very-long-term abstinence resolves most neurocognitive deficits associated with alcoholism, except for the suggestion of lingering deficits in spatial processing.

Adult↗

PubMed2006

Visual P300s in long-term abstinent chronic alcoholics.

BACKGROUND: Evidence of reduced P3b amplitudes in chronic alcoholics and individuals at risk for developing alcoholism suggest that the P3b may be an endophenotypic marker for alcoholism. If this is the case, then long-term abstinent alcoholics (LTAAs) should exhibit reduced P3b amplitudes. Thus far, P3b studies on chronic alcoholics have focused primarily on samples with relatively short-term abstinence (less than 15 months). This study examines the amplitude and latency of the P3b and P3a event-related brain electrical components in LTAAs compared with normal controls (NCs) and whether these measures are related to alcohol use and other subject variables. METHODS: Electroencephalographs (EEGs) were recorded on 48 LTAAs (mean abstinence=6.7 years) compared with 48 age-matched and gender-matched NCs during a visual P300 experiment consisting of standard, target, and rare nontarget conditions. This paradigm elicited the P3b (target condition) and the P3a (rare nontarget condition) components. RESULTS: Long-term abstinent alcoholics had reduced P3b amplitudes and increased P3b latencies in comparison with NCs. Long-term abstinent alcoholics also exhibited delayed P3a components, but no P3a amplitude reductions. Alcohol use variables, a family history of alcohol problems, and the duration of alcohol abstinence were not associated with any amplitude or latency variables. CONCLUSIONS: Even after very prolonged abstinence, reduced P3b amplitudes are present in chronic alcoholics and are not associated with any family history or alcohol use variables. These results provide equivocal support for reduced P3b amplitude being an endophenotypic marker for alcoholism, but are also consistent with P3b being affected by a threshold of alcohol abuse, with the effect not resolving over long periods of abstinence.

Adult↗

PubMed2005

Treated and treatment-naive alcoholics come from different populations.

In most research on alcoholism, convenience samples of individuals who have been in some type of treatment are used. Berkson's fallacy results when the associations found in studies of select samples are incorrectly presumed to apply to all alcoholics (i.e., including untreated alcoholics in the general population). In the current study, we examined whether treated and untreated alcoholics have similar early alcohol use histories by comparing abstinent alcoholics (treated and sober at least 6 months) with treatment-naive alcoholics (active drinkers). We studied 14 pairs of women and 25 pairs of men matched on the age at which they first met criteria for heavy alcohol use (women, 80 drinks per month; men, 100 drinks per month). The timeline follow-back interview method was used to gather retrospective alcohol use information. Alcohol dose and duration of use were subsequently computed for two intervals: (1) time between the person's first drink and date at which the person met criteria for heavy drinking and (2) period between when criteria for heavy drinking were met and current age of the treatment-naive person from each pair. During the period before the matching "heavy drinking" criteria were met, alcohol dose did not differ between groups. In the period after criteria for heavy alcohol use were met, in comparison with treatment-naive alcoholics, the treated alcoholics had higher average and peak alcohol doses. We rejected the hypothesis that the treatment-naive alcoholics and the treated alcoholics have similar alcohol use trajectories over time, with the treatment-naive sample simply being observed earlier in its alcohol use histories. Instead, we concluded that the two groups come from different populations with regard to alcohol use. In fact, the treated alcoholics had alcohol doses more than 50% higher than those of treatment-naive alcoholics in the years just after they began drinking heavily. This finding supports the suggestion that results from studies of alcoholics in treatment or after treatment (i.e., most studies of alcoholics) cannot be generalized to untreated individuals (who make up the majority of alcoholics).

Adult↗

PubMed2005

EEG spectral changes in treatment-naive, actively drinking alcoholics.

BACKGROUND: The current study examines the EEG spectra of actively drinking, treatment-naive alcoholics (TxNAs). METHODS: EEGs were gathered on 51 TxNAs and age- and sex-matched controls during closed-eyes conditions. Participants were excluded for lifetime diagnoses of psychiatric or substance abuse disorders. Power for the theta to high beta bands was examined across midline electrodes. RESULTS: The TxNA sample exhibited a nexus of disinhibited traits associated with the vulnerability to alcoholism and had developed alcohol dependence but no other diagnosable psychiatric or substance abuse disorders. The TxNAs evidenced higher power for all EEG bands compared with controls. The magnitude and anterior-posterior extent of the group differences varied across bands. Within TxNA, EEG power was negatively correlated with average and peak alcohol drinking duration dose. CONCLUSIONS: Increased EEG power across the theta to high beta bands distinguishes TxNAs without comorbid diagnoses from controls. These effects varied across bands in magnitude and spatial extent, suggesting different effects for the different EEG spectral generators. The authors hypothesize that the increased power in these individuals is a trait difference associated with the inherited nexus of disinhibited traits and its manifestation in alcoholism. Based on the strong negative correlations with alcohol use variables, the authors speculate that decreases in EEG power are a morbid effect of long-term alcohol abuse. They acknowledge that this hypothesized effect of alcohol abuse on EEG power is opposite to the increased EEG power that they hypothesize is associated with alcoholism and its inherited nexus of disinhibited traits. An implication of this model is that with continuing alcohol abuse, the increased EEG power in TxNAs will eventually be overpowered by the effects of long-term severe alcohol abuse. This model predicts that in very long-term alcoholics, EEG power would be equal to or lower than that of age- and sex-comparable controls.

Adult↗

PubMed2005

Treated and treatment-naive alcoholics come from different populations.

Adult↗

PubMed2004

Controlling for premorbid brain size in imaging studies: T1-derived cranium scaling factor vs. T2-derived intracranial vault volume.

Intracranial vault (ICV) volume, obtained from T2-weighted magnetic resonance imaging (MRI), is generally used to estimate premorbid brain size in imaging studies. T1-weighted sequences lack the signal characteristics for ICV measurements [they have poor contrast at the outer boundary of sulcal cranium scaling factor (CSF)] but are valuable in imaging studies due to their excellent gray vs. white matter contrast. Smith et al. [NeuroImage 17 (2002) 479] suggested a T1-derived cranium scaling factor as an alternative control variable for premorbid brain size in cross-sectional studies. This index, which is computed using the SIENAX software, is a scaling factor comparing an individual's skull to a template skull derived from the Montreal Neurological Institute (MNI) average of 152 T1 studies (the MNI152). SIENAX computes coarsely defined estimates for the individual and MNI skulls rather than well-defined volumes. To test how well this approach would work as a control variable for premorbid brain size in cross-sectional studies, we compared the T1-derived cranium scaling factor to T2-derived ICV measurements in a sample of 92 individuals: 39 white males, 22 white females, and 31 African-American males, with an age range of 26-78 years. The correlation between T1- and T2-derived variables was 0.94 and did not differ across subject groups. The T1-derived cranium scaling factor accounted for a statistically significant portion (87%) of the variance of the T2-derived ICV measure and thus is a good surrogate for ICV measurement of premorbid brain size as a reference measure in MRI atrophy studies. Furthermore, neither race, sex, nor age accounted for any additional variance in ICV, indicating that neither race-, gender-, nor age-associated cranial bone thickness effects were present in this data set.

Adult↗

PubMed2004

Cerebral reserve capacity: implications for alcohol and drug abuse.

Cerebral reserve capacity (or functional reserve) refers to the brain's ability to maintain function when confronted by degenerative processes. Functional reserve can be estimated by several associated measures, including premorbid brain size, premorbid IQ, and level of education attained. There is accumulating evidence that the magnitude of reserve capacity is important in determining the onset and progression of the clinical manifestations of neurodegenerative brain diseases. Normal aging also whittles away at this cerebral reserve, and there may be a consequent unmasking of morbid effects that was not clinically evident when this compensatory reserve was sufficient. We review the evidence supporting this model for a number of degenerative brain processes, including Alzheimer's disease, presenile dementia, HIV dementia, aging, and chronic (multiyear) substance abuse. The concept of cerebral functional reserve has important implications for alcohol and drug abuse morbidity. First, given the high genetic contribution to substance abuse, there is an increased likelihood that the parents of substance abusers were substance abusers themselves. Substance abuse during pregnancy can inhibit brain growth, resulting in reduced brain size and reduced reserve capacity (and therefore less ability to compensate for loss of function later in life). Second, substance abuse is often coupled with poverty, and both substance abuse and poverty are associated with some of the same conditions that reduce brain growth. Finally, we comment on the most important public health implication of the cerebral reserve capacity model (vis-à-vis addiction).

Alcoholism↗

PubMed2004

Mismatch negativity: no difference between controls and abstinent alcoholics.

BACKGROUND: A number of studies have examined the amplitude of the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. The current study examined MMN in alcoholics abstinent an average of 6.7 years (with a minimum of six months abstinence) compared to controls. This study examined the association of MMN with alcoholism family history density, with indices of the presence and severity of externalizing disorders (a risk-factor for alcoholism), and with alcohol use variables. METHODS: Electroencephalograms were gathered on 76 subjects (38 controls, 38 abstinent alcoholics) during a nonattending mismatch negativity experiment. Measures of alcoholism family history density, disinhibited personality traits, and antisocial symptoms served as measures of risk-factors known to be associated with a genetic liability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. RESULTS: There were no differences in MMN amplitude or latency between controls and abstinent alcoholics. There also were no significant associations between MMN measures and the measures of risk for alcoholism or with the severity of alcohol use or duration of abstinence. CONCLUSIONS: The results suggest that MMN is neither affected in chronic alcoholics nor associated with alcoholism vulnerability, and thus does not reflect a trait marker of alcoholism or alcoholism risk. The current results do not address effects on MMN of acute alcohol ingestion or withdrawal from alcohol.

Adult↗

PubMed2004

Mismatch negativity: no difference between treatment-naive alcoholics and controls.

BACKGROUND: Several studies have examined the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. This study examined MMN in actively drinking treatment-naive alcohol-dependent individuals. This study examined the association of MMN with risk factors for alcoholism, postalcohol withdrawal hyperexcitability, and alcohol use variables. METHODS: Electroencephalograms were gathered on 84 subjects (42 controls and 42 treatment-naive alcohol-dependent individuals) during a nonattending MMN experiment. Alcoholism family history density, the number of externalizing disorder symptoms, and psychological indices of deviance proneness served as measures of risk factors associated with the vulnerability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. RESULTS: There were no differences in the MMN integral, amplitude, or latency between control and treatment-naive alcohol-dependent subjects. There also were no significant associations of MMN measures with any of the measures of alcoholism vulnerability, with any of the alcohol use variables, or with the prevalence or severity of symptoms of postalcohol withdrawal hyperexcitability. CONCLUSIONS: Although there is a strong association between alcohol abuse and symptoms of disinhibition and deviance proneness, the MMN response does not offer any direct physiological evidence of this phenomenon.

Adult↗

PubMed2002

Prefrontal cortical volume reduction associated with frontal cortex function deficit in 6-week abstinent crack-cocaine dependent men.

BACKGROUND: This study examined regional cortical volumes in 6-week abstinent men dependent on crack-cocaine only (Cr) or on both crack-cocaine and alcohol (CrA). Our goal was to test the a priori hypothesis of prefrontal cortical volume reduction, along with associated impairments in frontal mediated functions, and to look for differences between the Cr and CrA groups. METHODS: Structural magnetic resonance imaging (MRI) of the brain and neuropsychological assessment were performed on 17 6-week abstinent Cr subjects, 29 six-week abstinent CrA subjects, and 20 normal controls. Cortical volume was quantified in the prefrontal, parietal, temporal and occipital regions. RESULTS: Cr and CrA subjects showed comparable reductions in prefrontal gray matter volume compared to controls; this reduction was negatively associated with performance impairments in the executive function domain. CONCLUSIONS: Dependence on Cr (with or without concomitant alcohol dependence) was associated with reduced prefrontal cortical volume. Cr dependence with concomitant alcohol dependence was not associated with greater prefrontal volume reductions than Cr dependence alone. The existence of these findings at 6-week abstinence indicates that they are not a result of acute cocaine or alcohol exposure. The association of reduced prefrontal cortical volume with cognitive impairments in frontal cortex mediated abilities suggests that this reduced cerebral volume has functional consequences.

Adult↗

PubMed2002

Neuropsychological performance of individuals dependent on crack-cocaine, or crack-cocaine and alcohol, at 6 weeks and 6 months of abstinence.

BACKGROUND: Little data exist on the neuropsychological effects of crack-cocaine dependence or crack-cocaine and alcohol dependence. This study examined cognitive function in abstinent crack dependent and crack and alcohol dependent individuals at 6 weeks and 6 months abstinence. METHODS: a comprehensive neuropsychological battery, including the MicroCog computerized assessment, was administered to 20 abstinent crack dependent subjects, 37 abstinent crack and alcohol dependent subjects, and 29 normal controls. Depression was examined as a covariate, and the association between substance use variables and neuropsychological performance was examined. RESULTS: the two substance dependent groups had similar neuropsychological profiles at 6 weeks abstinent, with both groups exhibiting significant cognitive impairment in a wide range of functions compared to controls. The substance dependent groups were still impaired significantly at 6 months of abstinence. Only mild effects of depression on neuropsychological performance were observed. CONCLUSIONS: crack dependence and crack and alcohol dependence may lead to severe and persistent neuropsychological deficits over a wide range of domains. The strongest predictor of brain damage associated with substance dependence in this sample was dose (particularly quantity and duration of peak dose).

Adult↗

PubMed2002

Alpha2-noradrenergic effects on ERP and behavioral indices of auditory information processing.

Norepinephrine is believed to modulate CNS processing of environmental signals. However, its specific role in stimulus evaluation processes has not been delineated. We examined the effects of the alpha2 noradrenergic agents, clonidine and yohimbine, on ERP and performance measures of auditory information processing. Ten healthy participants performed a three-tone target detection experiment, receiving either placebo, 0.2 mg clonidine, or 30 mg yohimbine, in a double-blind randomized design. The principal locus of action of the noradrenergic agents occurred between 100 and 200 ms poststimulus. P200 latency was sped by yohimbine and slowed by clonidine, and the frontal P3a was shifted in tandem. Components related to target detection (N250 and P3b) were unaffected. The results suggest that norepinephrine modulates CNS mechanisms of selective attention to infrequent stimuli. This may be relevant for patients with schizophrenia, a subset of whom exhibit selective abnormalities of these same ERP components. Our results offer a possible link between these two sets of findings, suggesting that some patients with schizophrenia may have dysfunctional noradrenergic systems.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2002

N400 event-related potential reduction indexes: early central nervous system impairment in HIV.

We examined event-related potential (ERP) measures of priming in a lexical decision task in which two-thirds of the words were presented as sequential antonym pairs. HIV-1+ subjects were divided into cognitively normal and cognitively impaired subgroups on the basis of a neuropsychological battery. Cognitively impaired HIV-1+ subjects showed reduced priming, associated with reduced N400 ERP component amplitudes, suggesting that the processing of linguistic stimuli in these patients may involve reduced activation of semantic networks. Cognitively normal HIV-1+ subjects showed a reduction in N400 amplitude, but no reduction in performance, suggesting that some reduction in neural signal may occur earlier in the course of HIV-1 central nervous system disease than behavioral priming deficit. As the known neurological deficit in HIV-1 disease is primarily in the basal ganglia and periventricular white matter, we propose that a functional disconnection of subcortical and frontal structures from posterior cortical structures underlies this reduction in semantic activation.

AIDS Dementia Complex↗