Intraindividual variability in brain activation-A novel correlate of obesity risk among female college students.

There are published data describing impairments in the brain function of adolescents or young adults who have a genetic or familial predisposition for obesity. From these descriptions, it is often assumed that the impairments are appropriately captured by a central tendency estimate and therefore consistently detectable. The present study questions this assumption and shows that the variability in brain function over the time course of a cognitive task is a better predictor of familial risk than its central tendency. Sixty-nine female young adults lacking an obese parent and 24 female young adults with an obese parent were compared on the average amplitude and inter-trial variability (ITV) in amplitude of their P300 electroencephalographic responses to rarely-occurring stimuli during a selective attention task. Simple group comparisons revealed statistically significant findings with effect sizes that were markedly greater for analyses of P300 ITV versus P300 average amplitude. It is suggested that the elevation in P300 ITV among young adults with familial risk indicates temporal instability in systems responsible for the maintenance of attention. These fluctuations may episodically disrupt their attention to satiety cues as well as other cues that influence behavior regulation.

Altered brain activation in uncomplicated pediatric obesity: The second moment is more sensitive than the first.

Traditionally, studies of the neurocognitive correlates of obesity have computed a central tendency across trials of a task to estimate the functional abilities of individual members of obese and non-obese groups. This computation assumes that the correlate is stable over time-a questionable assumption when individuals are impulsive, periodically inattentive, and capable of overcompensation following awareness of failure. The present investigation departs from the tradition by focusing on the second moment, or variability, in brain activation during a simple selective attention task. It compared 124 non-obese and 80 obese teenaged girls on the across-trial average amplitude and inter-trial variability (ITV) of a sensitive biomarker of attention, the P300 event-related electroencephalographic potential. It found that P300 ITV outperformed P300 average amplitude in differentiating the groups. Further, it found that the elevated P300 ITV among obese teenagers was associated with other indicators of impulsivity and inattention as well as slower reaction times and a trend toward more variable reaction times. Future studies should investigate the value of P300 ITV as an objective and sensitive endpoint for cognitive training focused on improving the attention skills of obese children.

Neural Responses to Signals for Behavior Change: Greater Within-Person Variability is Associated With Risk Factors for Substance Dependence.

BACKGROUND: An impaired ability to change behavior in the face of cues indicating a need for change is one means of defining risk for substance dependence. The present study used a cognitive task administered in a laboratory as a model of this process. It focused on 2 known and related correlates of risk (conduct disorder, borderline personality disorder) and examined their associations with reactivity to cues requesting a change in motor behavior. METHODS: A total of 224 teenagers, 14 to 19 years of age, performed a task during which white noise bursts were used to cue a requirement to reverse the mapping of right and left key press responses onto high- and low-frequency pure tones during a subsequent trial block. The amplitude of the P300 electroencephalographic (EEG) response to each cue was summarized by calculating its across-trial average as well as its intertrial variability (ITV). In addition, the number of motor response reversal failures (perseveration errors) was calculated. RESULTS: The ITV of the P300 response to cues for behavior change was superior to its average amplitude in revealing associations with risk: It was significantly greater among teenagers with more conduct problems and more borderline personality disorder symptoms in comparison with their less-affected peers. ITV was also positively correlated with perseveration errors. No group differences were found in P300 amplitude averaged over trials. CONCLUSIONS: The findings suggest that the measurement of intertrial variability in brain activity may be more valuable than the average level for revealing neurophysiological differences associated with impulsivity and personality risk factors for dependence. EEG measures may be particularly valuable in this context because they offer superior temporal resolution and signal-to-noise characteristics.

HIV/AIDS and an overweight body mass are associated with excessive intra-individual variability in response preparation.

Factors other than HIV/AIDS may influence the cognitive function of patients living with this disease. The present study tested the influence of a common comorbid problem-an overweight body mass. It also examined intra-task variabilities in performance and brain activation as potentially more sensitive indicators of dysfunction than their mean levels. One-hundred seventy-eight participants were recruited and categorized by HIV-1 serostatus (-/+) and body mass (BMI < 26/≥ 26 kg/m2). They performed a simple time estimation task during which response time accuracy and electroencephalographic readiness potentials were recorded. A few hours later, they completed a battery of tests measuring balance and gait. The analyses revealed an advantage of variability over the mean in differentiating groups: the presence of HIV-1 and an overweight body mass were independently and additively associated with greater variability across trials in readiness potential amplitude and response accuracy. The analysis also showed that intra-task variability in the readiness potential, but not in response accuracy, was predictive of decrements in single and tandem leg balance and gait velocity. The present findings suggest that an elevated body mass is associated with, and may contribute to, problems in brain function and motor behavior experienced by patients in the current era. The findings recommend a careful consideration of the manner in which these problems are measured. When the problems are episodic and subtle, measures of central tendency may be less than ideal.

Challenges in the Detection of Working Memory and Attention Decrements among Overweight Adolescent Girls.

BACKGROUND: The present study is unique in employing unusually difficult attention and working memory tasks to reveal subtle cognitive decrements among overweight/obese adolescents. It evaluated novel measures of background electroencephalographic (EEG) activity during one of the tasks and tested correlations of these and other measures with psychological and psychiatric predictors of obesity maintenance or progression. METHODS: Working memory and sustained attention tasks were presented to 158 female adolescents who were rated on dichotomous (body mass index percentile <85 vs. ≥85) and continuous (triceps skinfold thickness) measures of adiposity. RESULTS: The results revealed a significant association between excess adiposity and performance errors during the working memory task. During the sustained attention task, overweight/obese adolescents exhibited more EEG frontal beta power as well as greater intraindividual variability in reaction time and beta power across task periods than their normal-weight peers. Secondary analyses showed that frontal beta power during the sustained attention task was positively correlated with anxiety, panic, borderline personality features, drug abuse, and loss of control over food intake. CONCLUSIONS: The findings suggest that working memory and sustained attention decrements do exist among overweight/obese adolescent girls. The reliable detection of the decrements may depend on the difficulty of the tasks as well as the manner in which performance and brain activity are measured. Future studies should examine the relevance of these decrements to dietary education efforts and treatment response.

Visual illusions and inattention: Their association with adiposity among adolescent girls.

The Delboeuf concentric circle illusion is frequently invoked as an explanation for the hypothesized association between dinner plate size and overeating. We examined its association with adiposity among 162 girls, aged 14-18 years. We also examined the association of adiposity with neural and behavioral responses during a separate visual discrimination task. The analysis showed that girls with a body mass index percentile ≥ 85, or with greater triceps skinfold thickness, exhibited less sensitivity to the Delboeuf illusion than girls with normal adiposity. The excess adiposity group also exhibited significantly smaller electroencephalographic responses and more errors during the separate visual discrimination task. In combination, the findings from the two tasks suggest that girls with an elevated body mass are less sensitive to visual cues in their environment. The implications of these findings for weight loss education should be considered.

On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis.

BACKGROUND: As the architecture of complex traits incorporates a widening spectrum of genetic variation, analyses integrating common and rare variation are needed. Body mass index (BMI) represents a model trait, since common variation shows robust association but accounts for a fraction of the heritability. A combined analysis of single nucleotide polymorphisms (SNP) and copy number variation (CNV) was performed using 1850 European and 498 African-Americans from the Study of Addiction: Genetics and Environment. Genetic risk sum scores (GRSS) were constructed using 32 BMI-validated SNPs and aggregate-risk methods were compared: count versus weighted and proxy versus imputation. RESULTS: The weighted SNP-GRSS constructed from imputed probabilities of risk alleles performed best and was highly associated with BMI (p=4.3×10(-16)) accounting for 3% of the phenotypic variance. In addition to BMI-validated SNPs, common and rare BMI/obesity-associated CNVs were identified from the literature. Of the 84 CNVs previously reported, only 21-kilobase deletions on 16p12.3 showed evidence for association with BMI (p=0.003, frequency=16.9%), with two CNVs nominally associated with class II obesity, 1p36.1 duplications (OR=3.1, p=0.009, frequency 1.2%) and 5q13.2 deletions (OR=1.5, p=0.048, frequency 7.7%). All other CNVs, individually and in aggregate, were not associated with BMI or obesity. The combined model, including covariates, SNP-GRSS, and 16p12.3 deletion accounted for 11.5% of phenotypic variance in BMI (3.2% from genetic effects). Models significantly predicted obesity classification with maximum discriminative ability for morbid-obesity (p=3.15×10(-18)). CONCLUSION: Results show that incorporating validated effect sizes and allelic probabilities improve prediction algorithms. Although rare-CNVs did not account for significant phenotypic variation, results provide a framework for integrated analyses.

Who gains? Genetic and neurophysiological correlates of BMI gain upon college entry in women.

The present investigation examined P3 event-related electroencephalographic potentials and a short and selected list of addiction-related candidate gene single nucleotide polymorphisms (SNPs) within 84 female students, aged 18-20 yrs. The students were assigned to groups defined by the presence versus absence of a positive body mass index (BMI) change from the pre-college physical exam to the current day. Analyses revealed significantly greater P3 latencies and reduced P3 amplitudes during a response inhibition task among students who exhibited a BMI gain. BMI gain was also significantly associated with a ANKK1 SNP previously implicated in substance dependence risk. In logistic regression analyses, P3 latencies at the frontal electrode and this ANKK1 genotype correctly classified 71.1% of the students into the BMI groups. The present findings suggest that heritable indicators of impaired response inhibition can differentiate students who may be on a path toward an overweight or obese body mass.

GABRA2 genotype, impulsivity, and body mass.

BACKGROUND: The goal of this study was to test a hypothesis associating impulsivity with an elevated body mass index (BMI). METHODS: To this end, we examined associations of BMI with putative genetic, neurophysiological, psychiatric, and psychological indicators of impulsivity in 78 women and 74 men formerly dependent on alcohol or drugs. A second analysis was designed to test the replicability of the genetic findings in an independent sample of 109 women and 111 men with a similar history of substance dependence. RESULTS: The results of the first analysis showed that BMI was positively correlated with Total and Nonplanning Scale Scores on the Barratt Impulsiveness Scale and the number of childhood symptoms of Attention-Deficit/Hyperactivity Disorder in women. It was also positively correlated, in women, with a GABRA2 variant previously implicated as a risk factor for substance dependence and an objective electroencephalographic feature previously associated with GABRA2 and relapse risk. The second analysis confirmed that the correlation between BMI and the substance-dependence-associated GABRA2 genotype was reliable and sex-specific. CONCLUSIONS: We conclude that an elevated BMI is associated with genetic, neurophysiological, psychiatric, and psychological indicators of impulsivity. The sex difference may be explained by greater opportunities to eat and overeat, a preference for higher calorie foods, a longer duration of alcohol/drug abstinence, or previous pregnancies in women.

Inter-trial variability in postural control and brain activation: Effects of previous opiate abuse.

There is an abundant literature demonstrating the superiority of inter-trial variability (ITV) of reaction time over mean reaction time in the early identification of subtle cognitive processing decrements. The present study extends these ideas by examining brain activation and postural control ITV among participants with versus without a history of chronic opiate abuse. Participants enrolled in opiate abuse (n = 82) and control (n = 112) groups completed tasks that challenged selective attention and balance. During the respective tasks, the inter-trial variabilities in frontal P300a electroencephalographic responses and sway strategy scores outperformed their mean levels in differentiating the groups. The relevance of several potential alternative explanations for the differences, including premorbid conduct disorder and comorbid alcohol abuse, depression, and methadone use, was discounted via simultaneous or post hoc analyses. It appears that chronic opiate abuse has adverse CNS effects that persist into the protracted abstinence period. These effects alter the temporal stability of its response to external and internal stimuli.

Signal in the noise: Altered brain activation among adolescent alcohol users detected via the analysis of intra-individual variability1.

RATIONALE: Unlike its average level, the variability in brain activation over time or trials can capture subtle and brief disruptions likely to occur among participants with low-to-moderate levels of substance use or misuse. OBJECTIVE: The present study used this intra-individual variability measurement approach to detect neural processing differences associated with light-to-moderate use of alcohol among 14-19-year-old adolescents. METHOD: A total of 128 participants reporting any level of alcohol use during the previous 6 months and 87 participants reporting no use during this period completed intake questionnaires and interviews as well as an assessment of P300 electroencephalographic responses to novel stimuli recorded during two separate tasks. RESULTS: In addition to differing in recent alcohol use, the groups differed in nicotine and cannabis use, risk-taking behavior and conduct disorder symptoms, and P300 amplitude inter-trial variability (ITV) across both tasks. Across all participants, P300 ITV was positively correlated with a family history of depression but not with a family history of alcohol dependence. There were no group differences in P300 amplitude averaged across trials. CONCLUSIONS: Recent reports attributing brain volume or brain function differences to an effect of light-to-moderate alcohol use should be viewed with great caution. In the present analysis of brain function differences among substance-using adolescents, the group differences were small, complicated by many factors coinciding with or preceding alcohol use, and not reflected in a stable central tendency.

Interactive effects of HIV/AIDS, body mass, and substance abuse on the frontal brain: a P300 study.

In view of the rising prevalence of an overweight body mass among patients living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), clinicians must now be mindful of possible adverse outcomes resulting from the co-occurrence. The present study was designed to examine the additive and interactive effects of HIV/AIDS and an excess body mass, as well as the additional contributions of substance abuse or dependence. The dependent variable was brain function estimated by the measurement of P300 electroencephalographic potentials. P300 potentials were recorded during a task designed to elicit subcomponents with frontal (P300a) and both frontal and non-frontal (P300b) generators. Analyses revealed greater frontal P300a latencies among the 102 HIV-1 seropositive versus the 68 seronegative participants. In addition, frontal P300a latency was further increased by a synergistic interaction of HIV-1 serostatus with a body mass index (BMI)≥25 kg/m². A history of substance abuse/dependence did not alter these changes. However, it did combine with HIV/AIDS to produce a smaller P300a amplitude than was seen in participants with neither disorder. The findings suggest that white matter changes accompanying an excess BMI may exacerbate those that attend HIV/AIDS and thereby slow down frontal brain function. Substance abuse, likewise, interacts with HIV/AIDS but may impair frontal brain function via a different mechanism.

Temporal instability in brain activation: a novel paradigm for evaluating the maintenance of attention among substance dependent patients.

RATIONALE: Prior studies have demonstrated statistically significant but subtle differences in brain function between patients with a history of substance dependence (SD) and control groups. OBJECTIVES: The goal of the present study was to show that variability in brain activation over the trials of a cognitive task is more useful for revealing the putative impact of SD than analyses focusing on the amplitude of activation averaged over trials. The study also tested the additional contribution of antisocial personality disorder (ASPD)-a prevalent comorbidity that promotes both an early onset and more severe course of SD. METHODS: Two hundred eleven adults performed two selective attention tasks while P300 event-related electroencephalographic potentials were recorded. They were assigned to one of 3 mutually exclusive groups: no lifetime history of SD or ASPD (n = 67), a SD history but no ASPD (n = 68), or both SD and ASPD (n = 76). RESULTS: The major finding was a statistically significant elevation of P300 amplitude inter-trial variability (ITV) in the SD plus ASPD group in comparison to the group with neither attribute. The elevation was detected during both selective attention tasks and most prominent at electrodes sites located over the frontal brain. There were no group differences in P300 amplitude averaged over trials. CONCLUSIONS: We conclude from these findings that the ITV of P300 amplitude is an efficient and sensitive biomarker of the maintenance of attention. It is valuable for revealing group differences associated with substance dependence and ASPD. It may ultimately be valuable for detecting improvements resulting from psychostimulant treatment or other interventions, including cognitive remediation.

P300 and the stroop effect in overweight minority adolescents.

AIM: The goal was to examine the relationship between a risk factor for poor cognitive control and a health outcome of growing public significance--an excess body mass--among adolescents. METHODS: To this end, 109 adolescents aged 14-20 years were recruited and assigned to 1 of 4 groups defined by the crossing of the absence versus presence of a parental history (PH) of externalizing disorders with a body mass index (BMI) percentile (BMIP) < 85 versus > or = 85. The principal measure estimating cognitive control was the P300 event-related electroencephalographic response recorded during the Stroop task. RESULTS: The analyses revealed a synergistic interaction between BMIP rank, PH and trial type: the increase in P300 latency and the decrease in response accuracy, elicited by the presence of interfering information, were markedly greater in high-BMIP subjects with a PH of externalizing disorders than in the other subject groups. Analyses of a later component, the N450, previously associated with the Stroop interference effect, revealed no effect of BMI or PH. CONCLUSIONS: We conclude that subjects with both a PH of externalizing disorders and an excess BMI constitute a unique group that is less able to resolve cognitive conflict than others. The excessive delay in P300 evoked by conflicting response demands in these subjects may be a marker of a heritable factor that increases risk for both excess body mass and substance use disorders.

GRM8 genotype is associated with externalizing disorders and greater inter-trial variability in brain activation during a response inhibition task.

OBJECTIVE: The present investigation tested the association of a novel measure of brain activation recorded during a simple motor inhibition task with a GRM8 genetic locus implicated in risk for substance dependence. METHODS: 122 European-American adults were genotyped at rs1361995 and evaluated against DSM-IV criteria for Alcohol Dependence, Cocaine Dependence, Conduct Disorder, and Antisocial Personality Disorder. Also, their brain activity was recorded in response to rare, so-called "No-Go" stimuli presented during a continuous performance test. Brain activity was quantified with two indices: (1) the amplitude of the No-Go P300 electroencephalographic response averaged across trials; and (2) the inter-trial variability of the response. RESULTS: The absence of the minor allele at the candidate locus was associated with all of the evaluated diagnoses. In comparison to minor allele carriers, major allele homozygotes also demonstrated increased inter-trial variability in No-Go P300 response amplitude but no difference in average amplitude. CONCLUSIONS: GRM8 genotype is associated with Alcohol and Cocaine Dependence as well as personality risk factors for dependence. The association may be mediated through an inherited instability in brain function that affects cognitive control. SIGNIFICANCE: The present study focuses on a metric and brain mechanism not typically considered or theorized in studies of patients with substance use disorders.

Priming deficiency in male subjects at risk for alcoholism: the N4 during a lexical decision task.

BACKGROUND: While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics. METHOD: A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n = 23] and nonalcoholic fathers [low risk (LR) n = 28] to study whether the 2 groups differ in terms of the N4 component. Subjects were presented with 150 words and 150 nonwords. Among the words, 50 words (primed) were preceded by their antonyms (prime, n = 50), whereas the remaining 50 words were unprimed. For the analysis, N4 amplitude and latency as well as behavioral measures for the primed and unprimed words were considered. RESULTS: A significant interaction effect was observed between semantic condition and group, where HR subjects did not show N4 attenuation for primed stimuli. CONCLUSION: The lack of N4 attenuation to primed stimuli and/or inability to differentiate between primed and unprimed stimuli, without latency and reaction time being affected, suggest deficits in semantic priming, especially in semantic expectancy and/or postlexical semantic processing in HR male offspring. Further, it indicates that it might be an electrophysiological endophenotype that reflects genetic vulnerability to develop alcoholism.

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.

Evidence suggests the P3 amplitude of the event-related potential and its underlying superimposed event-related oscillations (EROs), primarily in the theta (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3-q32.1 under the peak region where we previously identified significant linkage (peak LOD = 3.5) using a genome-wide linkage scan of the same phenotype (event-related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The family-based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event-related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event-related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

The effects of HIV on P300 are moderated by familial risk for substance dependence: implications for a theory of brain reserve.

BACKGROUND: The goal of the study was to test the validity of additive versus synergistic versus underadditive versions of brain reserve theory within the context of HIV/AIDS. In addition, it tested the convergent validity of 2 operational definitions of premorbid reserve: verbal IQ (VIQ) and a family history (FH) of substance abuse or dependence. METHODS: Seventy HIV-1 seronegative and 115 HIV-1 seropositive male and female volunteers were assigned to 4 subgroups defined by the crossing of a VIQ score < versus > or = 90 with the presence versus absence of a paternal history of alcohol, cocaine, or opiate abuse or dependence. The principal dependent measure was the P300 event related brain potential elicited during the Stroop color-word interference task. RESULTS: The principal finding was an underadditive effect of FH plus HIV/AIDS on P300 area over the frontal region: FH reduced frontal scalp P300 to such a degree that the additional effects of HIV/AIDS were blunted. The alternate operational definition of brain reserve, VIQ, had no effect on P300 and did not alter the effects of HIV/AIDS. CONCLUSIONS: Familial risk for substance dependence and low VIQ compromise different aspects of brain structure and/or function and therefore differ in their relationship to HIV/AIDS and P300. Genetic differences associated with familial risk may reduce brain reserve to such a degree that the neurophysiological effects of HIV/AIDS can no longer be measured.

A family history of psychopathology modifies the decrement in cognitive control among patients with HIV/AIDS.

The present study was designed to evaluate the effect of HIV/AIDS on cognitive control and to determine if the effect is modified by familial risk for either alcohol or mood disorders. Sixty HIV-1 seropositive and 75 seronegative volunteers were assigned to four subgroups defined by the crossing of a diagnosis of alcohol dependence in the biological father with diagnoses of either major depressive disorder or bipolar disorder in the biological mother. Cognitive control was evaluated during a task in which subjects were asked, on occasion, to inhibit the impulse to respond in the same physical direction as the stimulus and instead respond in the opposite direction. Event related brain potentials and measures of task performance were recorded. The task evoked a negative shift in a late slow potential (SP) as well as an increment in reaction time when cognitive control was challenged. An important finding was an interaction between trial type, HIV/AIDS, and family history: HIV/AIDS and family history each attenuated the negative shift in the SP to such a degree that no further attenuation could be accomplished by the other. The effects of familial risk for alcohol versus mood disorders were equivalent. In conclusion, the absence of change in a late slow potential following a challenge to cognitive control may represent a marker of familial risk for both externalizing and internalizing disorders. The effects of familial risk on this slow potential are sufficiently robust as to attenuate the effects of HIV/AIDS on the probable generators of the response: the anterior cingulate and prefrontal cortex.

Inter-trial variability in brain activity as an indicator of synergistic effects of HIV-1 and drug abuse.

BACKGROUND: The objective of this investigation was to detect evidence of the synergism in the effects of HIV-1 and drug abuse on brain function that has been hypothesized but rarely shown. The investigation incorporated several noteworthy improvements in the approach. It used urine toxicology tests to exclude participants complicated by recent methadone use and illicit drug use. Also, it defined drug abuse on a scale that considered symptom severity. Most importantly, it examined inter-trial variability in brain activity as a potentially more sensitive indicator of group differences and functional impairment than the across-trial average. METHODS: 173 participants were assigned to groups defined by their HIV-1 serostatus and Drug Abuse Screening Test score (DAST < vs. > = 6). They completed a simple letter discrimination task including rare target and rare nontarget stimuli. Event-related electroencephalographic responses and key press responses were measured on each trial. During a separate assessment, posturographic measures were recorded. RESULTS: The inter-trial standard deviation of P300-like activity was superior to the mean amplitude of this activity in differentiating the groups. Unlike the mean, it revealed synergistic statistical effects of HIV and drug abuse. It also correlated significantly with static ataxia. CONCLUSIONS: Inter-trial variability in P300-like activity is a useful marker for detecting subtle and episodic disruptions in brain function. It demonstrates greater sensitivity than the mean amplitude for detecting differences across groups. Also, as a putative indicator of a disruption in the attentional monitoring of behavior, it predicts subtle impairments in gross motor function.