Development of a novel rodent rapid serial visual presentation task reveals dissociable effects of stimulant versus nonstimulant treatments on attentional processes.

The rapid serial visual presentation (RSVP) task and continuous performance tasks (CPT) are used to assess attentional impairments in patients with psychiatric and neurological conditions. This study developed a novel touchscreen task for rats based on the structure of a human RSVP task and used pharmacological manipulations to investigate their effects on different performance measures. Normal animals were trained to respond to a target image and withhold responding to distractor images presented within a continuous sequence. In a second version of the task, a false-alarm image was included, so performance could be assessed relative to two types of nontarget distractors. The effects of acute administration of stimulant and nonstimulant treatments for ADHD (amphetamine and atomoxetine) were tested in both tasks. Methylphenidate, ketamine, and nicotine were tested in the first task only. Amphetamine made animals more impulsive and decreased overall accuracy but increased accuracy when the target was presented early in the image sequence. Atomoxetine improved accuracy overall with a specific reduction in false-alarm responses and a shift in the attentional curve reflecting improved accuracy for targets later in the image sequence. However, atomoxetine also slowed responding and increased omissions. Ketamine, nicotine, and methylphenidate had no specific effects at the doses tested. These results suggest that stimulant versus nonstimulant treatments have different effects on attention and impulsive behaviour in this rat version of an RSVP task. These results also suggest that RSVP-like tasks have the potential to be used to study attention in rodents.

Visual similarity effects in immediate serial recall and (sometimes) in immediate serial recognition.

Words that sound dissimilar are recalled better than otherwise comparable words that sound similar on both immediate serial recall and immediate serial recognition tests, the so-called acoustic similarity effect. Although studies using immediate serial recall have shown an analogous visual similarity effect, in which words that look dissimilar are recalled better than words that look similar, this effect has not been examined in immediate serial recognition. We derived a prediction from the Feature Model that a visual similarity effect will be observed in immediate serial recognition only when the items are acoustically dissimilar; the model predicts no effect when the items are acoustically similar. Experiments 1 and 2 used visually dissimilar and visually similar stimuli that were all acoustically similar and replicated the visual similarity effect in serial recall but revealed no effect in serial recognition. Experiments 3 and 4 used a second set of stimuli that were acoustically dissimilar and found a visual similarity effect in both serial recall and serial recognition. The experiments confirm the Feature Model's predictions and add to earlier findings that the two tests, serial recall and serial recognition, may show quite different results because the two tests are not as similar as previously thought.

Aprendizaje serial de secuencias basadas en la posición y dimensión de sus componentes / Serial learning of sequences based on the position and dimension of its components

El objetivo de esta investigación fue evaluar el aprendizaje serial empleando el método de recuerdo de secuencias de tres componentes. Uno de los componentes de las secuencias fue la posición mientras los otros dos variaron en propiedad dimensional: colores y/o números. El Experimento 1 evaluó las diferencias en el aprendizaje y recuerdo de una secuencia de colores o números. Los resultados mostraron que la secuencia de números se aprendió más rápido que la de colores. El Experimento 2 buscó aislar el efecto del aprendizaje inicial de la secuencia de posiciones sobre el aprendizaje y recuerdo posterior de una secuencia de colores o números superpuesta a la secuencia de posiciones ya aprendida. Los resultados mostraron que aprender inicialmente la secuencia de posiciones facilitó el aprendizaje de los componentes posteriores de la secuencia. El análisis se orienta a la identificación de un gradiente de posición como factor explicativo del aprendizaje de este tipo de secuencias; además se propone la existencia de un efecto de la dimensión de los componentes de las secuencias en su aprendizaje y recuerdo. Finalmente, se analizan las funciones atípicas obtenidas en las curvas de posición serial de los dos experimentos

Serial learning was evaluated using the recall method. Three-component sequences were used. One of the components was the position of the element, while the other two varied in the dimensional property: colors or numbers. Experiment 1 evaluated differences in learning and remembering a sequence of colors or numbers. The results showed the numerical sequence was learned faster than the colors sequence; Experiment 2 isolate the effect of initial learning of positions on learning and subsequent recall of superimposed sequences of colors or numbers. The results showed that learn the positions facilitated the learning of sequence. The analysis identified a position gradient as an explanatory factor of sequence learning; We also discuss about the item dimension effect on learning and recall sequences. Finally, the atypical serial position curves obtain were analyzed

FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia.

We recruited 14 unmedicated patients with Kraepelinian schizophrenia (12 men and 2 women; mean age = 47 years old), 27 non-Kraepelinian patients (21 men and 6 women; mean age = 36.4 years old) and a group of 56 age- and sex-matched healthy volunteers. FDG positron emission tomography and MRI scans were coregistered for both voxel-by-voxel statistical mapping and stereotaxic regions of interest analysis. While both Kraepelinian and non-Kraepelinian patients showed equally lower uptake than healthy volunteers in the frontal lobe, the temporal lobes (Brodmann areas 20 and 21) showed significantly greater decreases in Kraepelinian than in non-Kraepelinian patients. Kraepelinian patients had lower FDG uptake in parietal regions 39 and 40, especially in the right hemisphere, while non-Kraepelinian patients had similar reductions in the left. Only non-Kraepelinian patients had lower caudate FDG uptake than healthy volunteers. While both patient groups had lower uptake than healthy volunteers in the medial dorsal nucleus of the thalamus, Kraepelinian patients alone had higher uptake in the ventral nuclei of the thalamus. Kraepelinian patients also showed higher metabolic rates in white matter. Our results are consistent with other studies indicating that Kraepelinian schizophrenia is a subgroup of schizophrenia, characterized by temporal and right parietal deficits and normal rather than reduced caudate uptake. It suggests that Kraepelinian schizophrenia may be more primarily characterized by FDG uptake decreased in both the frontal and temporal lobes, while non-Kraepelinian schizophrenia may have deficits more limited to the frontal lobe. This is consistent with some neuropsychological and prognosis reports of disordered sensory information processing in Kraepelinian schizophrenia in addition to deficits in frontal lobe executive functions shared with the non-Kraepelinian subtype.

Learned together, extinguished apart: reducing fear to complex stimuli.

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window attenuates fear responding and prevents the return of fear in pure tone Pavlovian fear conditioning. Here we sought to examine whether this effect also applies to a more complex fear memory. First, we show that after fear conditioning to the simultaneous presentation of a tone and a light (T+L) coterminating with a shock, the compound memory that ensues is more resistant to fear extinction than simple tone-shock pairings. Next, we demonstrate that the compound memory can be disrupted by interrupting the reconsolidation of the two individual components using a sequential retrieval+extinction paradigm, provided the stronger compound component is retrieved first. These findings provide insight into how compound memories are encoded, and could have important implications for PTSD treatment.

Effects of aging and dopamine genotypes on the emergence of explicit memory during sequence learning.

The striatum and medial temporal lobe play important roles in implicit and explicit memory, respectively. Furthermore, recent studies have linked striatal dopamine modulation to both implicit as well as explicit sequence learning and suggested a potential role of the striatum in the emergence of explicit memory during sequence learning. With respect to aging, previous findings indicated that implicit memory is less impaired than explicit memory in older adults and that genetic effects on cognition are magnified by aging. To understand the links between these findings, we investigated effects of aging and genotypes relevant for striatal dopamine on the implicit and explicit components of sequence learning. Reaction time (RT) and error data from 80 younger (20-30 years) and 70 older adults (60-71 years) during a serial reaction time task showed that age differences in learning-related reduction of RTs emerged gradually over the course of learning. Verbal recall and measures derived from the process-dissociation procedure revealed that younger adults acquired more explicit memory about the sequence than older adults, potentially causing age differences in RT gains in later stages of learning. Of specific interest, polymorphisms of the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32, rs907094) and dopamine transporter (DAT, VNTR) genes showed interactive effects on overall RTs and verbal recall of the sequence in older but not in younger adults. Together our findings show that variations in genotypes relevant for dopamine functions are associated more with aging-related impairments in the explicit than the implicit component of sequence learning, providing support for theories emphasizing the role of dopaminergic modulation in cognitive aging and the magnification of genetic effects in human aging.

Pre-treatment with the mGlu2/3 receptor agonist LY379268 attenuates DOI-induced impulsive responding and regional c-Fos protein expression.

RATIONALE: Overactivation of serotonin (5-hydroxytryptamine, 5-HT)(2A) receptors causes impulsivity and attentional deficits. Since 5-HT(2A) receptors are known to entertain antagonistic interactions with metabotropic glutamate (mGlu)2/3 receptors, this interaction may provide an alternative target for a novel class of antipsychotics. OBJECTIVES/METHODS: The study characterizes interactions between 5-HT(2A) and mGlu2/3 receptors implicated in impulse control. Hooded Lister rats were trained in a 5-choice serial reaction time task (5-CSRTT) and treated with the 5-HT(2A/2C) receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride (DOI, 0.1 mg/kg) and the mGlu2/3 receptor agonist LY379268 (1 mg/kg). In addition, associated drug-induced changes in neuronal activity were assessed via c-Fos immunoreactivity (Fos IR), and co-localization of c-Fos and GABAergic markers was detected using double immunofluorescence labeling. RESULTS: Systemic DOI caused impulsive overresponding that was attenuated in animals pre-treated with LY379268. LY379268 itself had no significant effect on the rats' performance in the 5-CSRTT. DOI enhanced Fos IR within fronto-cortical and limbic brain structures, and this effect was blocked by LY379268 pre-treatment. Double immunofluorescence labeling showed a specific co-localization of DOI-elicited Fos IR with GABAergic (GAD(67)-positive) cells lacking the calcium-binding protein parvalbumin while LY379268 increased Fos IR in GABAergic and non-GABAergic cells. CONCLUSION: Our results suggest that impulsivity is possibly due to a primary increase in Glu transmission mediated via 5-HT(2A) receptor activation. Thus, mGlu2/3 receptor agonists might have some potential for treating motor impulsivity-related impairments while their cognitive enhancing effects were not confirmed in this study.

Hippocampal involvement in the acquisition of relational associations, but not in the expression of a transitive inference task in mice.

The hippocampus (HC) has been suggested to play a role in transitive inference (TI) on an ordered sequence of stimuli. However, it has remained unclear whether HC is involved in the expression of TI, or rather contributes to TI through its role in the acquisition of the sequence of elements (Frank, Rudy, & O'Reilly, 2003). Presently, the authors compared the effects of excitotoxic dorsal HC lesions in C57BL mice that received surgery before or after they were trained to discriminate between pairs of visual stimuli. Performance on a subsequent TI task was worse in mice with pretraining lesions than in those with posttraining lesions, which showed similar performance to shams without lesions. This indicates that HC is not involved in the expression of TI, but may merely help to acquire the underlying representations required for TI.

5-HT4 receptor agonism in the five-choice serial reaction time task.

5-HT4 agonists are currently being developed for the treatment of Alzheimer's disease and have previously been demonstrated to improve cognitive performance in a variety of tests but none that specifically test attention. Here we characterise the 5-HT4 partial agonist SL65.0155 compared to the reference drug, nicotine, in a test that is used to measure attention in rats, the five-choice serial reaction time task (5CSRTT). SL65.0155 (0.1 or 1 mg/kg s.c) and nicotine (0.2 mg/kg s.c.) were tested in protocols using fixed or variable stimulus durations. SL65.0155 improved performance by virtue of reducing incorrect responses and increasing % correct trials. Perseverative responses were reduced by SL65.0155, and latency during incorrect trials was increased following treatment with 0.1 mg/kg SL65.0155. Nicotine, as previously reported, improved performance in several parameters in the 5CSRTT, including response latencies, errors of omission and correct responses in both the baseline and variable stimulus protocol. These data suggest 5-HT4 agonists may have beneficial effects on attention and thereby may be useful for the treatment of cognitive deficits.

Effects of semantic relations, repetition of words, and list length in word list recall of Alzheimer's patients / Efeitos da relação semântica, repetição de palavras e extensão das listas na recordação de pacientes com doença de Alzheimer

INTRODUCTION: Semantic relations among words and repetition enhance free recall, but it is unknown if these facilitating factors are effective in dementia. METHOD: Alzheimer's patients (MILD-Alz, MOD-Alz) were compared to healthy elderly. Fifteen-word lists were read out to the subjects. In four sets of lists the words in intermediary input positions were semantically related or not, or the midlist words were repeated, or they were repeated and semantically related. RESULTS: The usual third peak of recall of semantically related words was not observed in MOD-Alz, repetition of words did not increase recall of the patients, and the combination of relatedness and repetition benefited only MID-Alz. In a second experiment, with related or unrelated midlist words, and list length shortened from 15 to 9 words, semantic facilitation was observed in mild and moderate Alzheimer´s patients, although diminished compared to controls. CONCLUSION: Progression of dementia turns facilitating factors of recall less effective.

INTRODUÇÃO: Relacionamento semântico e repetição facilitam a recordação livre mas não se sabe se esses fatores continuam efetivos na demência. MÉTODO: O desempenho de pacientes com doença de Alzheimer (MILD-Alz e MOD-Alz) foi comparado com o de idosos sadios na recordação livre de listas de 15 palavras, utilizando quatro diferentes conjuntos de listas que continham ou não palavras relacionadas nas posições intermediárias, palavras repetidas, ou ainda palavras repetidas e semanticamente relacionadas. RESULTADOS: O terceiro pico usual na recordação das palavras semanticamente relacionadas não foi observado em MOD-Alz; a repetição não aumentou a recordação dos pacientes; a combinação de relacionamento e repetição beneficiou apenas MILD-Alz. Em outro experimento, com palavras intermediárias relacionadas ou não, e em que a extensão das listas foi reduzida para 9 palavras, observou-se facilitação semântica em MILD-Alz e MOD-Alz. CONCLUSÃO: A progressão da demência diminui a eficácia de fatores facilitadores da recordação.

Adolescent exposure to nicotine impairs adult serial pattern learning in rats.

In the present study investigating the effects of adolescent nicotine exposure on adult serial pattern learning, adolescent rats received daily i.p. injections of either 1.0 mg/kg nicotine or saline for 5 days per week for 5 weeks beginning on postnatal day 25 (P25), then were allowed 35 days drug free. Rats then began training on P95 as adults on a 24-element serial pattern composed of eight 3-element chunks. Adolescent exposure to 1.0 mg/kg nicotine produced persistent retardation of learning for the first element of each 3-element chunk of the pattern, that is, for chunk boundary elements, and transient retardation of learning for elements 2 and 3 of each chunk of the pattern, that is, for the within-chunk elements. Deficits at chunk boundaries were interpreted as deficits of phrasing cue discrimination learning whereas deficits for learning responses for elements within-chunks (elements 2 and 3 of chunks) were interpreted as deficits of rule learning. These results indicate that the effects of adolescent nicotine exposure on adult learning and cognitive capacity deserve further scrutiny.

Smokers' brains compute, but ignore, a fictive error signal in a sequential investment task.

Addicted individuals pursue substances of abuse even in the clear presence of positive outcomes that may be foregone and negative outcomes that may occur. Computational models of addiction depict the addicted state as a feature of a valuation disease, where drug-induced reward prediction error signals steer decisions toward continued drug use. Related models admit the possibility that valuation and choice are also directed by 'fictive' outcomes (outcomes that have not been experienced) that possess their own detectable error signals. We hypothesize that, in addiction, anomalies in these fictive error signals contribute to the diminished influence of potential consequences. Using a simple investment game and functional magnetic resonance imaging in chronic cigarette smokers, we measured neural and behavioral responses to error signals derived from actual experience and from fictive outcomes. In nonsmokers, both fictive and experiential error signals predicted subjects' choices and possessed distinct neural correlates. In chronic smokers, choices were not guided by error signals derived from what might have happened, despite ongoing and robust neural correlates of these fictive errors. These data provide human neuroimaging support for computational models of addiction and suggest the addition of fictive learning signals to reinforcement learning accounts of drug dependence.

Dorsal hippocampus, CA3, and CA1 lesions disrupt temporal sequence completion.

An experiment was designed to evaluate effects of dorsal hippocampus, dorsal CA3a,b, dorsal CA1, and control lesions on performance of a temporal sequence task. Rats were trained on a sequential learning task involving six spatial locations on a radial 8-arm maze. After initial training followed by surgery, it was found that all lesioned animals were able to remember the sequence. To test temporal sequence completion, rats were started at different positions in the sequence and expected to complete the remainder of the sequence. The results indicate that control rats had no difficulty completing the sequence, regardless of starting point. In contrast, rats with dorsal hippocampus and dorsal CA3a,b lesions made errors by always returning to the first position in the sequence, regardless of which start position was used, whereas rats with dorsal CA1 lesions made random errors in the process of completing the sequence and did not appear to remember the serial order of the spatial sequence. This suggests that the dorsal hippocampus, and specifically the dorsal CA3 in conjunction with CA1, may be involved in temporal pattern completion processes.

Is short-term memory involved in decision making? Evidence from a short-term memory patient.

It is reasonable to suggest that working memory (WM; Baddeley & Hitch, 1974) is involved in decision making, as decision making is dependent on the ability to remember and update past choices and outcomes. However, contradictory results have been reported in the literature concerning the role of two of its components, namely the central executive and the phonological loop. In order to investigate the role of these components in the decision-making process, we tested a patient with intact central executive but impaired phonological loop on a laboratory decision-making task involving hypothetical gambles (gambling task, GT). When tested in a no-load condition (simple keypress task), her performance was not significantly different from that of matched controls. We also verified whether her performance would be affected differently by memory-load when compared with control subjects. The memory task (holding a string of letters in memory) loaded WM without incurring number-number interference. When the memory-load was imposed during the GT, both the patient and the controls showed a decline in performance, but the strategy they adopted differed. Possible explanations are discussed. In conclusion, our results suggest that the phonological loop is not directly involved in decision making.

Strain specificity and cholinergic modulation of visuospatial attention in three inbred mouse strains.

The tremendous increase in the use of mouse inbred strains and mutant mice to study the molecular basis of psychiatric disorders urges for a better understanding of attentional performance in mice. To this aim, we investigated possible strain differences in performance and cholinergic modulation of visuospatial attention in three widely used mouse inbred strains (129S2/SvHsd, C57BL/6JOlaHsd and DBA/2OlaHsd) in the five-choice serial reaction time task. Results indicated that after extended training, performance of 129S2/SvHsd mice was superior to that of C57BL/6JOlaHsd and DBA/2OlaHsd mice in terms of attention, omission errors, inhibitory control and latencies to correct choice. Increasing the attentional load resulted in comparable decrements in attention in all strains and inhibitory control impairments that were most pronounced in DBA/2OlaHsd mice. Further pharmacological evaluation indicated that all strains showed attentional impairments after treatment with the muscarinic and nicotinic antagonists scopolamine and mecamylamine, respectively. 129S2/SvHsd mice were less sensitive, whereas DBA/2OlaHsd mice appeared more sensitive to the detrimental effects of mecamylamine. In addition, subchronic, but not acute, nicotine treatment slightly improved attentional performance in all strains to the same extent. In conclusion, our data indicate strain specificity with particularly good performance of 129S2/SvHsd mice and strong cholinergic involvement in visuospatial attention in mice.

Attentional performance of (C57BL/6Jx129Sv)F2 mice in the five-choice serial reaction time task.

Impaired attention is evident in several neurological and psychiatric disorders. In the present study, attentional capabilities were measured in the operant five-choice serial reaction time task (5-CSRTT) in male (C57BL/6Jx129Sv)F2 hybrid (B6129F2) mice. Main aims were to validate and standardize the test in these mice: to setup procedures, measure potential beneficial effects of sub-chronic nicotine in degraded versions of the 5-CSRTT (by decreasing stimulus duration, inducing white noise and making the stimuli unpredictable) and study disruptive effects of additional administration of the muscarinic antagonist scopolamine. During the baseline pre-nicotine sessions, the B6129F2 mice attained a very good performance in the test (95% accuracy). As stimulus duration was reduced from 2 s to 1 s, response accuracy of the mice decreased. Mice treated with nicotine (0.16 mg/kg) attained significantly higher response accuracy and had a lower percentage of incorrect responses in comparison with the solvent-treated animals. No further beneficial effects of nicotine were found. Reduced response accuracy was also obtained when stimulus duration was reduced from 1 s to 0.5 s and when a variable intertrial interval was introduced. Noise interpolation between trials did not impair performance. Finally, scopolamine (0.16 mg/kg) disrupted attentional functioning. Although most studies have been performed in rats, these results add to the existing evidence that the 5-CSRTT can also be used to assess attentional performance in mice. This offers the opportunity to test transgenic and knockout mice with similar background as the B6129F2 as animal models of psychiatric and neurological diseases.

A new mathematical model for assessment of memorization dynamics.

A new memory model is proposed based on regression analysis and exponential- shaped learning curves. The efficacy of the model is tested with several types of experiments including food aversion in snails, maze learning in rats and memory tests for adults and children. The model is also tested on drug abusers and alcoholics. The results of goodness of fit tests indicate that our model can accurately be used to predict the memory dynamics of diverse experiments and populations. The model can also be used to predict both group and individual performance. The application of the model to detect memory impairment is discussed, as are limitations.

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.

Deficits in a sustained attention task following nicotine withdrawal in rats.

OBJECTIVE: Behavioural consequences of spontaneous and antagonist-precipitated withdrawal from nicotine upon performance of rats were compared alongside non-nicotinic antagonists in the 5-choice serial reaction time task (5-CSRTT). METHODS: Male hooded Lister rats were trained to detect and respond to brief flashes of light presented every 15 s in one of five holes until a stable level of performance was achieved. RESULTS: Surgical removal of osmotic minipumps from rats having received nicotine (3.16 mg/kg per day base SC) chronically for 7 days produced marked deficits in performance. Compared to saline-treated controls, deficits were apparent 10 h and 16 h following nicotine abstinence; the percentage of omission errors increased concomitantly with modest decreases in response accuracy. Tests conducted 34 h and 106 h post-withdrawal indicated a progressive and complete recovery in attention performance, respectively. In another experiment, following the exposure to the same nicotine regime, administration of the competitive nicotine receptor antagonist dihydro-beta-erythroidine precipitated immediate deficits in performance that were greater than those observed in saline-treated subjects. Methyllycaconitine, an alpha(7) nicotinic receptor antagonist failed to precipitate attention deficits in nicotine-treated rats. Tests with SCH23390 and raclopride produced impairments that were similar in profile to nicotine withdrawal contrasting with non-specific effects of dizocilpine. CONCLUSIONS: These results provide evidence of a cognitive impairment resulting from nicotine deprivation in rodents. Specifically, blockade of D(1) receptors by SCH23390 produced decrements in performance that were qualitatively similar but greater in magnitude to the alterations observed following nicotine withdrawal. Overall, assessing nicotine withdrawal in the 5-CSRTT presents an animal model that exhibits robust construct and face validity.

Frontal deficits in alcoholism: an ERP study.

Alcoholism is a major health problem afflicting people all over the world. Understanding the neural substrates of this addictive disorder may provide the basis for effective interventions. So-called "executive processes" play a role in cognitive functions like attention and working memory, and appear to be disrupted in alcoholism (Noel et al., 2001). Event related potentials (ERPs) provide an excellent, minimally invasive technique for exploring these neural deficits. The current study used the P300 in number sequencing task (modified version of the Petries & Milner, 1982) requiring working memory to compare a group of patients with alcoholism and frontal lobe lesions to patients with subcortical lesions and normal controls to assess the relationship of alcoholism to frontal lobe damage. The ERP paradigm was a Number Sequencing task. Electrophysiological results indicate that the frontal lesion group had significant P300 amplitude reduction and a similar trend for alcohol dependent group but not the subcortical group compared to the normal controls.