Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation

Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI). We investigated 10 akinetic catatonic patients in a postacute state and compared them with 10 noncatatonic postacute psychiatric controls (age-, sex-, diagnosis-, and medication-matched) and 10 healthy controls. Positive and negative pictures from the International Affective Picture System were used for emotional stimulation. FMRI measurements covered the whole frontal lobe, activation signals in various frontal cortical regions were obtained, and functional connectivity between the different prefrontal cortical regions was investigated using structural equation modeling. Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls. Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity. It is concluded that catatonic symptoms may be closely related to dysfunction in the orbitofrontal cortex and consequent alteration in the prefrontal cortical network during emotional processing. Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome in schizophrenic or affective psychosis.     

Cortical sulcal enlargement in catatonic schizophrenia: a planimetric CT study.

To determine whether patients with catatonic schizophrenia have specific alterations in brain morphology, internal (ventricles) and external (frontal, temporal, parieto-occipital) components of the cerebrospinal fluid (CSF) spaces were examined morphometrically. Planimetric measurements of computed tomographic (CT) scans from 37 patients with catatonic schizophrenia, 28 patients with hebephrenic schizophrenia, and 39 patients with paranoid schizophrenia, all diagnosed according to DSM-III-R criteria, were compared with separate age- and sex-matched non-psychiatric control groups, respectively. The areas of the frontal sulci, the parieto-occipital sulci, the inter-hemispheric fissure, and the lateral and third ventricles were measured separately for the right and left hemispheres. Catatonic patients showed significant enlargements in almost all CSF spaces, especially in the left fronto-temporal area which, in addition, correlated significantly with illness duration. Hebephrenic patients showed selective enlargements in left temporal and left/right lower frontal cortical sulci, whereas paranoid schizophrenic patients showed no enlargements but significant correlations between left temporal cortical sulcal volume and illness duration. Alterations in temporal cortical areas were present in all three sub-types of schizophrenia. In addition to temporal alterations, hebephrenic schizophrenia was characterised by lower frontal (i.e. orbitofrontal) enlargement. Catatonic schizophrenia, the most severe sub-type with regard to clinical symptomatology and brain pathology, showed fronto-parietal cortical alterations.     

Prefrontal cortical dysfunction in depression determined by Wisconsin Card Sorting Test performance.

OBJECTIVE: Neuroimaging studies have demonstrated reduced prefrontal cortical blood flow and metabolism in depression, but the neurobehavioral significance of these observations is not yet established. METHOD: The Wisconsin Card Sorting Test, a widely used neuropsychological index of prefrontal cortical function, was administered to 79 patients with major depression who had been unmedicated for at least 28 days, to 47 patients with schizophrenia who had never received antipsychotic medication, and to 61 healthy comparison subjects. RESULTS: Depressed patients demonstrated significant deficits on multiple Wisconsin Card Sorting Test measures compared with healthy individuals. These deficits were correlated with the severity of depression and were less severe than those demonstrated by patients with schizophrenia. CONCLUSIONS: These results provide neuropsychological evidence for significant prefrontal cortical dysfunction in depression.     

Neuropsychological and oculomotor correlates of spatial working memory performance in schizophrenia patients and controls.

Recent reports of spatial working memory deficits in schizophrenia provide evidence for dorsolateral prefrontal cortical (DLPFC) dysfunction. However, the question of how spatial working memory performance relates to other task impairments in schizophrenia considered reflective of frontal dysfunction, such as the Wisconsin Card Sorting Test (WCST) and smooth pursuit eye tracking, has been largely unexplored. Spatial working memory, as measured by a computerized visual-manual delayed response task (DRT), was evaluated in 42 schizophrenia patients and 54 normal controls. Subjects also completed a battery of neuropsychological and oculomotor tasks. Schizophrenia patients performed as accurately as controls on a no-delay, sensory-motor control condition, but showed a significant impairment in spatial accuracy with the addition of an 8-s delay and verbal distraction task. For the patients, working memory impairment was associated with fewer categories on the WCST, impaired eye tracking, fewer words learned on the Rey Auditory Verbal Learning Test, but not with measures of general cognitive and clinical functioning. Results suggest the presence of a sub-group of schizophrenia patients with common pathophysiology that accounts for the co-variance of several tasks implicating prefrontal dysfunction.     

Impairment in visual-spatial function in catatonia: a neuropsychological investigation.

Catatonia is a psychomotor syndrome with motor and behavioral abnormalities which may be due to alterations in fronto-parietal cortical function. We therefore investigated neuropsychological tasks (attention, executive, visual-spatial, working memory) associated with frontal and parietal cortical function. Thirteen catatonic patients, diagnosed as catatonic according to criteria by Rosebush and Bush, were compared with 13 psychiatric non-catatonic controls (matched with regard to underlying psychiatric diagnosis, age, sex, and medication), and 13 age- and sex-matched healthy controls. Catatonics showed significantly poorer performances and different neuropsychological intercorrelation patterns in visual spatial object perception (VOSPobject) than psychiatric and healthy controls. In addition, we found significant correlations between catatonic symptoms, visual-spatial abilities, and attentional measures (i.e., d2, CWI). Catatonia was characterized by specific visual-spatial deficits which are related to attentional abilities and right parietal cortical function. The data suggest attentional-motor and fronto-parietal dysfunction in catatonia, a conclusion which should be considered as preliminary, however, due to the small sample size.     

Iowa gambling task in schizophrenia: a review and new data in patients with schizophrenia and co-occurring cannabis use disorders

BACKGROUND: We reviewed previous studies comparing schizophrenia patients and healthy subjects for performance on the Iowa Gambling Task (IGT) (a laboratory task designed to measure emotion-based decision-making), and found mixed results. We hypothesize that deficits in IGT performance in schizophrenia may be more specifically related to concurrent substance use disorders. To test this hypothesis, we compared schizophrenia patients with (SCZ((+))) or without (SCZ((-))) cannabis use disorders, to healthy subjects, on measures of cognition and IGT performance. METHODS: A comprehensive battery of cognitive tests and the IGT were administered to three groups of subjects: (1) 13 subjects with DSM-IV diagnosis of schizophrenia and no concurrent substance use disorders (mean age: 28+/-12 (SD); 54% males); (2) 14 subjects with schizophrenia and concurrent cannabis use disorders (mean age: 29+/-9 (SD); 71% males); and (3) 20 healthy subjects (mean age 33+/-10 (SD); 60% males). RESULTS: Compared to the healthy group, both schizophrenia groups were cognitively more impaired, and did worse on IGT performance. There were no differences between SCZ((+)) and SCZ((-)) patients on most of the cognitive tests, and IGT performance. CONCLUSIONS: Schizophrenia patients show widespread impairments in several cognitive domains and emotion-based decision-making. These results are consistent with the evidence that schizophrenia reflects a dorsolateral and orbitofrontal/ventromedial prefrontal cortex dysfunction. More intriguing, it appears that the concurrent abuse of cannabis has no compounding effects on cognition, as well as emotion/affect-based decision-making.     

Dissociation of decisions in ambiguous and risky situations in obsessive–compulsive disorder

Patients with obsessive–compulsive disorder (OCD) often show deficits in everyday decision-making, a phenomenon which is leading to a growing research interest in neuropsychological aspects of decision-making in OCD. Previous investigations of OCD patients demonstrated deficits in the Iowa Gambling Task (IGT), a decision-making task with implicit rules. Results were interpreted as reflecting orbitofrontal cortex dysfunctions observed in OCD. The aim of the present study is to investigate OCD patients' performance on the Game of Dice Task (GDT), a decision-making task with explicit and stable rules. For this purpose, 23 patients with OCD and 22 healthy comparison subjects were examined with the GDT and the IGT as well as with tests of executive functioning. While patients performed worse than comparison subjects on the IGT, they were unimpaired on the GDT and executive functioning tasks. Results further emphasize dysfunctions of the orbitofrontal cortex, but indicate intact functioning of the dorsolateral prefrontal cortex in patients with OCD.     

Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia

Frontal lobe dysfunction in individuals with schizophrenia has frequently been detected using both neuroimaging and neuropsychological testing. Results from previous studies vary in the findings of regional specificity vs. generalized frontal cortical dysfunction. We sought to examine potential regional differences in frontal cortical functioning among patients with schizophrenia vs. a comparison group using two different neurocognitive tasks: the Gambling Task (GT) and the Wisconsin Card Sorting Test (WCST). In general, the GT is thought to reflect function of the ventromedial prefrontal cortex (VMPFC), while the WCST reflects function of the dorsolateral prefrontal cortex (DLPFC). Twenty individuals with schizophrenia or schizoaffective disorder and 15 nonpsychiatrically ill comparison subjects underwent an assessment battery consisting of the GT, WCST, and positive and negative symptom ratings. Patients with schizophrenia performed worse on the GT with respect to total monetary gain (p=0.05) and total monetary loss (p<0.05). They also preferred disadvantaged vs. advantaged cards (p<0.04). Surprisingly, WCST performance was poor in both groups and was not significantly different between groups. These findings are at some variance with those in the previously reported literature, but nonetheless support the idea that prefrontal cortical areas mediating different cognitive tasks may be distinguished by specific neurocognitive assessments.     

Preserved orbitofrontal function in first-episode schizophrenia: further evidence from the object alternation paradigm

Neuropsychological literature indicates that performance on Object Alternation Task (OAT) can be linked to the orbitofrontal cortex (OFC). Patients with chronic schizophrenia perform poorly on behavioral and neuropsychological tasks related to OFC functions. In a previous study using the Iowa Gambling Task, we found unimpaired performance in a sample of individuals with first-episode schizophrenia (FES) spectrum disorders. In this study, we aimed to extend our study of OFC functions by using the OAT paradigm, to determine whether there are abnormalities in the early phases of schizophrenia. We examined the performance of 70 patients with FES and 21 healthy controls on a computerized version of OAT. There were no significant differences between patients and control subjects with respect to the OAT. This finding suggests that the OFC function, as measured by decision-making tasks, is preserved in the early phases of schizophrenia.     

Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis

OBJECTIVE: Context processing is a cognitive construct associated with activity in the middle frontal gyrus. Schizophrenia-related deficits in context processing tasks have been associated with prefrontal cortical dysfunction. This study evaluated whether prefrontal cortical dysfunction related to context processing occurred in first-episode, never-medicated schizophrenia patients, whether this dysfunction also occurred in patients with nonschizophrenia psychosis, and whether this dysfunction was related to psychotic symptom expression. METHOD: A modified version of the AX continuous performance task was conducted during event-related functional magnetic resonance imaging in 18 never-medicated, first-episode schizophrenia patients, 12 never-medicated patients with first-episode nonschizophrenia psychosis, and 28 comparison participants without psychiatric disorder. RESULTS: In-scanner measures of errors and interference reaction time showed that the schizophrenia patients had a specific deficit in context processing. Trials with greater context processing demands corresponded to activity in the middle frontal gyrus (Brodmann's area 9) in the comparison subjects and in the patients with nonschizophrenia psychosis, but not in the schizophrenia patients. Individual differences in prefrontal cortical dysfunction were associated with context processing measures and disorganization symptoms. The schizophrenia patients also showed increased activity in the anterior (Brodmann's area 10) and inferior prefrontal cortices (Brodmann's area 45/46) when they were maintaining context over a delay. CONCLUSIONS: Prefrontal dysfunctions related to context processing were found only in schizophrenia patients early in the course of the illness, and these dysfunctions were related to disorganization symptoms. Instead of using context processing during a continuous performance task, schizophrenia patients may use an inefficient encoding and retrieval strategy.     

The neural substrates of impaired prosodic detection in schizophrenia and its sensorial antecedents

OBJECTIVE: Individuals with schizophrenia show severe deficits in their ability to decode emotions based upon vocal inflection (affective prosody). This study examined neural substrates of prosodic dysfunction in schizophrenia with voxelwise analysis of diffusion tensor magnetic resonance imaging (MRI). METHOD: Affective prosodic performance was assessed in 19 patients with schizophrenia and 19 comparison subjects with the Voice Emotion Identification Task (VOICEID), along with measures of basic pitch perception and executive processing (Wisconsin Card Sorting Test). Diffusion tensor MRI fractional anisotropy valves were used for voxelwise correlation analyses. In a follow-up experiment, performance on a nonaffective prosodic perception task was assessed in an additional cohort of 24 patients and 17 comparison subjects. RESULTS: Patients showed significant deficits in VOICEID and Distorted Tunes Task performance. Impaired VOICEID performance correlated significantly with lower fractional anisotropy values within primary and secondary auditory pathways, orbitofrontal cortex, corpus callosum, and peri-amygdala white matter. Impaired Distorted Tunes Task performance also correlated with lower fractional anisotropy in auditory and amygdalar pathways but not prefrontal cortex. Wisconsin Card Sorting Test performance in schizophrenia correlated primarily with prefrontal fractional anisotropy. In the follow-up study, significant deficits were observed as well in nonaffective prosodic performance, along with significant intercorrelations among sensory, affective prosodic, and nonaffective measures. CONCLUSIONS: Schizophrenia is associated with both structural and functional disturbances at the level of primary auditory cortex. Such deficits contribute significantly to patients' inability to decode both emotional and semantic aspects of speech, highlighting the importance of sensorial abnormalities in social communicatory dysfunction in schizophrenia.     

A neuropsychological investigation of prefrontal cortex involvement in acute mania

OBJECTIVE: Mania has received little attention from a contemporary neuropsychological perspective despite its clear resemblance to the disinhibition syndrome sometimes seen after frontal brain injury, particularly injury to the inferior aspect of the prefrontal cortex. The purpose of this investigation was to describe the neuropsychological profile of severe acute mania by using a range of tasks selected primarily for the detection of localized neural disruption within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated Neuropsychological Test Battery (Tower of London, spatial working memory, intradimensional-extradimensional attentional shift, and rapid visual information processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a verbal fluency task, and the California Verbal Learning Test. RESULTS: Discriminant function analysis identified deficits in sustained attention (on the rapid visual information processing task) and verbal learning (on the California Verbal Learning Test) as the best indicators of manic performance, rather than deficits on any of the tests of executive functioning. The model correctly classified 91% of subjects overall and 87% of manic subjects. Manic patients did not resemble patients with ventromedial prefrontal cortex damage in their performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized by core deficits in verbal memory and sustained attention against a background of milder impairments in functions that are traditional measures of prefrontal cortex integrity (attentional set shifting, planning, working memory). The data do not implicate ventral prefrontal cortex disruption as a locus of pathology in acute mania. Verbal memory and sustained attention deficits may relate differentially to the state and trait characteristics of bipolar disorder.     

Executive function and in-patient violence in forensic patients with schizophrenia

BACKGROUND: The literature on the association between neuropsychological deficits and in-patient violence in schizophrenia is limited and the findings inconsistent. AIMS: To examine the role of executive function deficits in inpatient violence using measures of dorsolateral (DLPFC) and ventrolateral prefrontal cortical (VLPFC) function. METHODS: Thirty-three violent and forty-nine non-violent male forensic in-patients with schizophrenia were assessed using neuropsychological tasks probing DLPFC and VLPFC function and on measures of symptoms and psychopathy. RESULTS: There were no significant group differences in neuropsychological task performance. Higher rates of violence were significantly associated with lower current IQ scores and higher excitement symptom scores. The 'violent' group had significantly higher interpersonal and antisocial domain psychopathy scores. In a logistic regression analysis, IQ and the interpersonal domain of psychopathy were significant discriminators of violent v. non-violent status. CONCLUSIONS: Personality factors rather than symptoms and neuropsychological function may be important in understanding in-patient violence in forensic patients with schizophrenia.     

Frontopolar cortical inefficiency may underpin reward and working memory dysfunction in bipolar disorder

Abstract

Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems.     

Cerebral network deficits in post-acute catatonic schizophrenic patients measured by fMRI

Twelve patients with catatonic schizophrenia and 12 matched healthy controls were examined with functional MRI while performing a motor task. The aim of our study was to identify the intracerebral pathophysiological correlates of motor symptoms in catatonic patients.The motor task included three conditions: a self-initiated (SI), an externally triggered (ET) and a rest condition. Statistical analysis was performed with SPM5.During the self-initiated movements patients showed significantly less activation than healthy controls in the supplementary motor area (SMA), the prefrontal and parietal cortex.Our results suggest a dysfunction of the “medial motor system” in catatonic patients. Self-initiated and externally triggered movements are mediated by different motor loops. The “medial loop” includes the SMA, thalamus and basal ganglia, and is necessary for self-initiated movements. The “lateral loop” includes parts of the cerebellum, lateral premotor cortex, thalamus and parietal association areas. It is involved in the execution of externally triggered movements.Our findings are in agreement with earlier behavioral data, which show deficits in self-initiated movements in catatonic patients but no impairment of externally triggered movements.     

Emotion recognition in Chinese people with schizophrenia

This study examined whether people with paranoid or nonparanoid schizophrenia would show emotion-recognition deficits, both facial and prosodic. Furthermore, this study examined the neuropsychological predictors of emotion-recognition ability in people with schizophrenia. Participants comprised 86 people, of whom: 43 were people diagnosed with schizophrenia and 43 were controls. The 43 clinical participants were placed in either the paranoid group (n=19) or the nonparanoid group (n=24). Each participant was administered the Facial Emotion Recognition task and the Prosodic Recognition task, together with other neuropsychological measures of attention and visual perception. People suffering from nonparanoid schizophrenia were found to have deficits in both facial and prosodic emotion recognition, after correction for the differences in the intelligence and depression scores between the two groups. Furthermore, spatial perception was observed to be the best predictor of facial emotion identification in individuals with nonparanoid schizophrenia, whereas attentional processing control predicted both prosodic emotion identification and discrimination in nonparanoid schizophrenia patients. Our findings suggest that patients with schizophrenia in remission may still suffer from impairment of certain aspects of emotion recognition.     

Dissociation of emotional decision-making from cognitive decision-making in chronic schizophrenia

Recent studies have examined the decision-making ability of schizophrenic patients using the Iowa Gambling Task (IGT). These studies, however, were restricted to the assessment of emotional decision-making. Decision-making depends on cognitive functions as well as on emotion. The purpose of this study was to examine the performance of schizophrenic patients on the IGT and the Game of Dice Task (GDT), a decision-making task with explicit rules for gains and losses. In addition, it was intended to test whether poor performance on IGT is attributable to impairments in reversal learning within the schizophrenia group using the Simple Reversal Learning Task (SRLT), which is sensitive to measure the deficit of reversal learning following ventromedial prefrontal cortex damage. A group of 23 stable schizophrenic patients and 28 control subjects performed computerized versions of the IGT, GDT, SRLT and Wisconsin Card Sorting Test (WCST). While schizophrenic patients performed poorly on the IGT relative to normal controls, there was no significant difference between the two groups on GDT performance. The performance of the schizophrenia group on the SRLT was poorer than that of controls, but was not related to IGT performance. These data suggest that schizophrenic patients have impaired emotional decision-making but intact cognitive decision-making, suggesting that these two processes of decision-making are different. Furthermore, the impairments in reversal learning did not contribute to poor performance on the IGT in schizophrenia. Therefore, schizophrenic patients have difficulty in making decisions under ambiguous and uncertain situations whereas they make choices easily in clear and unequivocal ones. The emotional decision-making deficits in schizophrenia might be attributable more to another mechanism such as a somatic marker hypothesis than to an impairment in reversal learning.     

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.     

An evaluation of structural and functional prefrontal deficits in schizophrenia: MRI and neuropsychological measures.

Magnetic resonance imaging was used to assess prefrontal brain structure in 17 schizophrenic, 18 psychiatric control, and 19 normal control subjects of comparable age, social background, and educational status, while three neuropsychological measures were used to assess prefrontal functioning. Schizophrenic patients had significantly smaller prefrontal areas than both psychiatric control and normal control subjects in all three planes. When posterior brain area and temporal lobe were entered into statistical analysis as covariates, they did not explain the prefrontal deficits. Schizophrenic patients made more perseveration errors on the Wisconsin Card Sorting Task and had fewer correct responses on the Spatial Delayed Response Task than normal control subjects. Schizophrenic patients performed more poorly than psychiatric control subjects on the Block Design Test. No group differences were found on three other nonfrontal tasks. These data lend some support to the role of prefrontal deficits in the development of schizophrenia.     

Delayed transition from ambiguous to risky decision making in alcohol dependence during Iowa Gambling Task

It has been demonstrated that alcohol-dependent patients exhibit decision-making deficits, particularly, hypersensitivity to reward and executive dysfunction. Yet, how the impaired motivational process and executive dysfunction in the patients affect decisions under ambiguity and risk with different degrees of uncertainty is little known. To investigate the neuropsychological origin of the impaired decision making under uncertainty in alcohol dependence, we administered the Iowa Gambling Task (IGT), Game of Dice Task (GDT) and Wisconsin Card Sorting Test (WCST) to 23 alcohol-dependent patients and 21 healthy subjects, and calculated the correlations between the task performances. We found that the patients showed poor performance in all three tasks compared with the healthy subjects. Moreover, correlations between performances on the GDT and the later trials of the IGT were delayed in alcohol-dependent patients when compared with healthy subjects. There is also a significant correlation between performances of earlier trials of the IGT and the WCST in the patients. These findings suggest that executive dysfunction in alcohol-dependent patients hampers appropriate estimation of probability distributions of possible alternatives, leading to a delayed transition from ambiguous to risky conditions in the Iowa Gambling Task.