Partial recovery of alcohol dependence-related deficits in sleep evoked potentials following 12 months of abstinence.

Stimuli presented during sleep can produce an evoked EEG delta wave referred to as a K-complex. These responses occur when large numbers of cortical cells burst fire in a synchronized manner. Large amplitude synchronized scalp responses require that the CNS contain large numbers of healthy neurons that are interconnected with highly functional white matter pathways. The P2, N550, and P900 components of the evoked K-complex are sensitive measures of normal healthy brain aging, showing a decrease in amplitude with age. N550 and P900 amplitudes are also reduced in recently detoxified alcoholics, most dramatically over frontal scalp regions. The present study tested the hypothesis that the amplitude of K-complex related evoked potential components would increase with prolonged abstinence. Fifteen alcoholics (12 men) were studied twice, separated by a 12 month period, during which time they were followed with monthly phone calls. Subjects were aged between 38 and 60 years at their first study. They had on average a 29.3 ± 6.7 year drinking history and had been abstinent for between 54 and 405 days at initial testing. Evoked K-complexes were identified in the EEG and averaged to enable measurement of the P2, N550 and P900 peaks. Data were collected from seven scalp sites (FP1, FP2, Fz, FCz, Cz, CPz, and Pz). N550 and P900 amplitudes were significantly higher after 12 months of abstinence and an improvement of at least 5 µV occurred in 12 of the 15 subjects. N550 and P900 also showed highly significant site by night interactions with the largest increases occurring over prefrontal and frontal sites. The data indicate that the sleep evoked response may provide a sensitive marker of brain recovery with abstinence from alcohol.

Independent contributions of cortical gray matter, aging, sex and alcoholism to K-complex amplitude evoked during sleep.

STUDY OBJECTIVES: The amplitude of the N550 component derived from the averaged evoked K-complex decreases with normal aging and with alcoholism. The study was designed to determine whether these declines are related to the extent of cortical or subcortical shrinkage. SETTING: Research sleep laboratory and MR imaging facility PARTICIPANTS: 26 abstinent long-term alcoholic men, 14 abstinent long-term alcoholic women, 18 control men, and 22 control women. MEASUREMENTS AND RESULTS: MRI data collected at 3T were analyzed from alcoholic and control men and women previously reported to have significantly different evoked delta activity during sleep. Segmented and parcellated MRI data collected at 3T were compared between these groups and evaluated for correlation with evoked K-complex amplitude measured at FP1, Fz, FCz, Cz, CPz, and Pz. Cortical gray matter and regional subcortical tissue volumes entered as predictors into stepwise multiple regression identified cortical gray matter as a unique significant predictor of evoked K-complex at all sites. Age added independent variance at 5 of the 6 sites, while alcoholism and sex added independent variance at frontal sites only. CONCLUSIONS: These data support recent intracranial studies showing cortical generation of K-complexes by indicating that cortical, but not subcortical volume contributes to K-complex amplitude. Establishing the extent of the relation between cortical volume and K-complex amplitude provides a mechanistic understanding of sleep compromise clinically relevant to normal aging, alcoholism, and likely other conditions affecting cortical volume and integrity.

Developmental change in regional brain structure over 7 months in early adolescence: comparison of approaches for longitudinal atlas-based parcellation.

Early adolescence is a time of rapid change in neuroanatomy and sexual development. Precision in tracking changes in brain morphology with structural MRI requires image segmentation with minimal error. Here, we compared two approaches to achieve segmentation by image registration with an atlas to quantify regional brain structural development over a 7-month interval in normal, early adolescent boys and girls. Adolescents were scanned twice (average interval=7.3 months), yielding adequate data for analysis in 16 boys (baseline age 10.9 to 13.9 years; Tanner Stage=1 to 4) and 12 girls (baseline age=11.2 to 13.7 years; Tanner Stage=3 to 4). Brain volumes were derived from T1-weighted (SPGR) images and dual-echo Fast Spin-Echo (FSE) images collected on a GE 3T scanner with an 8-channel phased-array head coil and analyzed by registration-based parcellation using the SRI24 atlas. The "independent" method required two inter-subject registrations: both baseline (MRI 1) to atlas and follow-up (MRI 2) to the atlas. The "sequential" method required one inter-subject registration, which was MRI 1 to the atlas, and one intra-subject registration, which was MRI 2 to MRI 1. Gray matter/white matter/CSF were segmented in both MRI-1 and MRI-2 using FSL FAST with tissue priors also based on the SRI24 atlas. Gray matter volumes were derived for 10 cortical regions, gray+white matter volumes for 5 subcortical structures, and CSF volumes for 4 ventricular regions and the cortical sulci. Across the 15 tissue regions, the coefficient of variation (CV) of change scores across individuals was significantly lower for the sequential method (CV=3.02), requiring only one inter-subject registration, than for the independent method (CV=9.43), requiring two inter-subject registrations. Volume change based on the sequential method revealed that total supratentorial and CSF volumes increased, while cortical gray matter volumes declined significantly (p<0.01) in anterior (lateral and medial frontal, anterior cingulate, precuneus, and parietal) but not posterior (occipital, calcarine) cortical regions. These volume changes occurred in all boys and girls who advanced a step in Tanner staging. Subcortical structures did not show consistent changes. Thus, longitudinal MRI assessment using robust registration methods is sufficiently sensitive to identify significant regional brain changes over a 7-month interval in boys and girls in early adolescence. Increasing the temporal resolution of the retest interval in longitudinal developmental studies could increase accuracy in timing of peak growth of regional brain tissue and refine our understanding of the neural mechanisms underlying the dynamic changes in brain structure throughout adolescence.

Electrophysiological evidence of enhanced performance monitoring in recently abstinent alcoholic men.

RATIONALE: Chronic alcoholism is associated with mild to moderate cognitive impairment. Under certain conditions, impairment can be ameliorated by invoking compensatory processes. OBJECTIVE: To identify electrophysiological mechanisms of such compensation that would be required to resolve response conflict. METHODS: 14 abstinent alcoholic men and 14 similarly aged control men performed a variation of the Eriksen flanker task during an electroencephalography (EEG) recording to examine whether alcoholics could achieve and maintain control-level performance and whether EEG markers could identify evidence for the action of compensatory processes in the alcoholics. Monitoring processes engaged following a response were indexed by the correct related negativity (CRN) and error related negativity (ERN), two medial-frontal negative event-related potentials. RESULTS: The alcoholics were able to perform at control levels on accuracy and reaction time (RT). Alcoholics generated larger ERN amplitudes following incorrect responses and larger CRNs following correct responses than controls. Both groups showed evidence of post-error slowing. Larger CRN amplitudes in the alcoholics were related to longer RTs. Also observed in the alcoholics was an association between smaller CRN amplitudes and length of sobriety, suggesting a normalization of monitoring activity with extended abstinence. CONCLUSIONS: To the extent that greater amplitude of these electrophysiological markers of performance monitoring indexes greater resource allocation and performance compensation, the larger amplitudes observed in the alcoholic than control group support the view that elevated performance monitoring enables abstinent alcoholics to overcome response conflict, as was evident in their control-level performance.

Lapses in a prefrontal-extrastriate preparatory attention network predict mistakes.

Mistakes are common to all forms of behavior but there is disagreement about what causes errors. We recorded electrophysiological and behavioral measures in a letter discrimination task to examine whether deficits in preparatory attention predicted subsequent response errors. Error trials were characterized by decreased frontal-central preparatory attention event-related potentials (ERPs) prior to stimulus presentation and decreased extrastriate sensory ERPs during visual processing. These findings indicate that transient lapses in a prefrontal-extrastriate preparatory attention network can lead to response errors.