Marcelo Cetkovich

Executive functions in pathologic gamblers selected in an ecologic setting.

BackgroundRecent studies have reported deficits in measures of decision making in pathologic gamblers (PGs) suggesting an involvement of the prefrontal cortex in the pathophysiology of this disorder. As only 7% to 12% of PGs are thought to seek treatment, most of the studies have relied on few specifically selected groups of PGs recruited from psychiatric units who were undergoing or seeking treatment and therefore their results are poorly representative of the general PG population. MethodsThe present study compared decision making and executive functions among 11 PGs who were selected from an ecologic setting and 11 healthy controls. ResultsThe PG group selected fewer advantageous cards on a decision-making task, the Iowa Gambling Task, and made more commission errors on the Go-No Go task, a test of inhibitory control, compared with controls. ConclusionsThe impairments in decision making are similar to those previously reported in individuals with prefrontal lesions and treatment-seeking PGs. PGs also presented impairment in tasks of inhibitory control suggesting an involvement of the prefrontal cortex in the pathophysiology of pathologic gambling (PG). The deficits in decision making and inhibition of irrelevant information observed in this study may have distinct but additive effects upon the development of PG behavior.

Cortical deficits of emotional face processing in adults with ADHD: Its relation to social cognition and executive function

Although it has been shown that adults with attention-deficit hyperactivity disorder (ADHD) have impaired social cognition, no previous study has reported the brain correlates of face valence processing. This study looked for behavioral, neuropsychological, and electrophysiological markers of emotion processing for faces (N170) in adult ADHD compared to controls matched by age, gender, educational level, and handedness. We designed an event-related potential (ERP) study based on a dual valence task (DVT), in which faces and words were presented to test the effects of stimulus type (faces, words, or face-word stimuli) and valence (positive versus negative). Individual signatures of cognitive functioning in participants with ADHD and controls were assessed with a comprehensive neuropsychological evaluation, including executive functioning (EF) and theory of mind (ToM). Compared to controls, the adult ADHD group showed deficits in N170 emotion modulation for facial stimuli. These N170 impairments were observed in the absence of any deficit in facial structural processing, suggesting a specific ADHD impairment in early facial emotion modulation. The cortical current density mapping of N170 yielded a main neural source of N170 at posterior section of fusiform gyrus (maximum at left hemisphere for words and right hemisphere for faces and simultaneous stimuli). Neural generators of N170 (fusiform gyrus) were reduced in ADHD. In those patients, N170 emotion processing was associated with performance on an emotional inference ToM task, and N170 from simultaneous stimuli was associated with EF, especially working memory. This is the first report to reveal an adult ADHD-specific impairment in the cortical modulation of emotion for faces and an association between N170 cortical measures and ToM and EF.

The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD)

Background Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD. Methodology/Principal Findings We used the Iowa gambling task (IGT), a task of rational decision-making under risk (RDMUR) and a rapid-decision gambling task (RDGT) which elicits behavioral measures as well as event-related potentials (ERPs: fERN and P3) in connection to the motivational impact of events. We did not observe between-group differences for decision-making under risk or ambiguity (RDMUR and IGT); however, there were significant differences for the ERP-assessed RDGT. Compared to controls, the ADHD group showed a pattern of impaired learning by feedback (fERN) and insensitivity to reward magnitude (P3). This ERP pattern (fERN and P3) was associated with impulsivity, hyperactivity, executive function and working memory. Compared to controls, the BD group showed fERN- and P3-enhanced responses to reward magnitude regardless of valence. This ERP pattern (fERN and P3) was associated with mood and inhibitory control. Consistent with the ERP findings, an analysis of source location revealed reduced responses of the cingulate cortex to the valence and magnitude of rewards in patients with ADHD and BD. Conclusions/Significance Our data suggest that neurophysiological (ERPs) paradigms such as the RDGT are well suited to assess subclinical decision-making processes in patients with ADHD and BD as well as for linking the cingulate cortex with action monitoring systems.

Neuropsychological functioning in adult bipolar disorder and ADHD patients: A comparative study

Bipolar disorder (BD) and adult attention deficit hyperactivity disorder (ADHD) usually manifest with shared clinical symptoms, proving quite challenging to thoroughly differentiate one from another. Previous research has characterized these two disorders independently, but no study compared both pathologies from a neuropsychological perspective. The aim of this study was to compare the neuropsychological profile of adult ADHD and BD with each other and against a control group, in order to understand the way in which comprehensive cognitive assessment can contribute to their discrimination as distinct clinical entities as well as their differential diagnosis. All groups were successfully matched for age, sex, years of education, and premorbid IQ. Participants were assessed with an extensive neuropsychological battery evaluating multiple domains. Compared to controls, BD patients had a poorer performance on immediate verbal memory tasks. Both clinical groups exhibited significantly lower scores than controls on the recognition phase of verbal and non-verbal memory tasks, as well as on a task of executive functioning with high working memory demand. Noticeably, however, ADHD had significantly better performance than BD on the recognition phase of both the Rey list memory task and the Rey Figure. The better performance of ADHD patients over BD may reflect the crucial role of the executive component on their memory deficits and gives empirical support to further differentiate the neuropsychological profile of BD and adult ADHD patients in clinical practice.

From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants

It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP.

Context-sensitive social cognition is impaired in schizophrenic patients and their healthy relatives

Social cognition performance has been extensively studied within the schizophrenic population since Frith (1992) proposed amodel relatingmentalizing deficits and symptoms of the disorder. Moreover, recent research has suggested that social cognition is also impaired in unaffected relatives. Their deficits seem to be more pronounced when highly sophisticated tests are used (Janssen et al., 2003). Fifteen clinically-stable medicated schizophrenic patients from multiplex families, fourteen healthy first-degree relatives, and eighteen controls were examined. Groups were similar in age, education, and sex distribution. Initial selection criteria for all patients were: (1) diagnosis of paranoid schizophrenia according to DSM-IV-TR criteria (APA, 2000) and confirmed with Schedules of Clinical Assessment in Neuropsychiatry (SCAN) applied to both the patients and their relatives; and (2) the presence of one or more relativeswith the diagnosis of schizophrenia (no greater than third-degree relative), evidenced by the Family Interview for Genetic Studies (FIGS). Healthy relatives had to be first-degree relatives. SCANwas applied to relatives in order to rule out any psychiatric conditions in this group. All participants were between 20 and 55 years old. Participants completed written informed consent and were paid for their participation in the study. Participants completed the Ravens Coloured Progressive Matrices, Trail Making Test, Reading theMind in the Eyes, and Faux Pas Test. Additionally, Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia were applied to patients to characterize symptomatology and mood. Detailed information about participants, results and discussion is presented as Supplementary data. Main results (Table 1) were:

The roles of interoceptive sensitivity and metacognitive interoception in panic

BackgroundInteroception refers to the ability to sense body signals. Two interoceptive dimensions have been recently proposed: (a) interoceptive sensitivity (IS) –objective accuracy in detecting internal bodily sensations (e.g., heartbeat, breathing)–; and (b) metacognitive interoception (MI) –explicit beliefs and worries about one’s own interoceptive sensitivity and internal sensations. Current models of panic assume a possible influence of interoception on the development of panic attacks. Hypervigilance to body symptoms is one of the most characteristic manifestations of panic disorders. Some explanations propose that patients have abnormal IS, whereas other accounts suggest that misinterpretations or catastrophic beliefs play a pivotal role in the development of their psychopathology. Our goal was to evaluate these theoretical proposals by examining whether patients differed from controls in IS, MI, or both. Twenty-one anxiety disorders patients with panic attacks and 13 healthy controls completed a behavioral measure of IS motor heartbeat detection (HBD) and two questionnaires measuring MI.FindingsPatients did not differ from controls in IS. However, significant differences were found in MI measures. Patients presented increased worries in their beliefs about somatic sensations compared to controls. These results reflect a discrepancy between direct body sensing (IS) and reflexive thoughts about body states (MI).ConclusionOur findings support the idea that hypervigilance to body symptoms is not necessarily a bottom-up dispositional tendency (where patients are hypersensitive about bodily signals), but rather a metacognitive process related to threatening beliefs about body/somatic sensations.

The overlap of symptomatic dimensions between frontotemporal dementia and several psychiatric disorders that appear in late adulthood

Abstract Several factors make diagnosis of a possible behavioural variant of frontotemporal dementia (bvFTD) particularly challenging, especially the overlap of certain symptomatic dimensions such as apathy, disinhibition, depression, anhedonia, stereotyped behaviour, and psychosis between bvFTD and several psychiatric disorders that appear in late adulthood. We discuss the most frequent psychiatric conditions that can simulate early bvFTD symptoms, including late onset bipolar disorder, late onset schizophrenia-like psychosis, late onset depression, and attention deficit hyperactivity disorder in middle and older age.

Neural Processing of Emotional Facial and Semantic Expressions in Euthymic Bipolar Disorder (BD) and Its Association with Theory of Mind (ToM)

Background Adults with bipolar disorder (BD) have cognitive impairments that affect face processing and social cognition. However, it remains unknown whether these deficits in euthymic BD have impaired brain markers of emotional processing. Methodology/Principal Findings We recruited twenty six participants, 13 controls subjects with an equal number of euthymic BD participants. We used an event-related potential (ERP) assessment of a dual valence task (DVT), in which faces (angry and happy), words (pleasant and unpleasant), and face-word simultaneous combinations are presented to test the effects of the stimulus type (face vs word) and valence (positive vs. negative). All participants received clinical, neuropsychological and social cognition evaluations. ERP analysis revealed that both groups showed N170 modulation of stimulus type effects (face > word). BD patients exhibited reduced and enhanced N170 to facial and semantic valence, respectively. The neural source estimation of N170 was a posterior section of the fusiform gyrus (FG), including the face fusiform area (FFA). Neural generators of N170 for faces (FG and FFA) were reduced in BD. In these patients, N170 modulation was associated with social cognition (theory of mind). Conclusions/Significance This is the first report of euthymic BD exhibiting abnormal N170 emotional discrimination associated with theory of mind impairments.

Functional Connectivity and Temporal Variability of Brain Connections in Adults with Attention Deficit/Hyperactivity Disorder and Bipolar Disorder

Objectives: To assess brain functional connectivity and variability in adults with attention deficit/hyperactivity disorder (ADHD) or euthymic bipolar disorder (BD) relative to a control (CT) group. Methods: Electroencephalography (EEG) was measured in 35 participants (BD = 11; ADHD = 9; CT = 15) during an eyes-closed 10-min rest period, and connectivity and graph theory metrics were computed. A coefficient of variation (CV) computed also the connectivitys temporal variability of EEG. Multivariate associations between functional connectivity and clinical and neuropsychological profiles were evaluated. Results: An enhancement of functional connectivity was observed in the ADHD (fronto-occipital connections) and BD (diffuse connections) groups. However, compared with CTs, intrinsic variability (CV) was enhanced in the ADHD group and reduced in the BD group. Graph theory metrics confirmed the existence of several abnormal network features in both affected groups. Significant associations of connectivity with symptoms were also observed. In the ADHD group, temporal variability of functional connections was associated with executive function and memory deficits. Depression, hyperactivity and impulsivity levels in the ADHD group were associated with abnormal intrinsic connectivity. In the BD group, levels of anxiety and depression were related to abnormal frontotemporal connectivity. Conclusions: In the ADHD group, we found that intrinsic variability was associated with deficits in cognitive performance and that connectivity abnormalities were related to ADHD symptomatology. The BD group exhibited less intrinsic variability and more diffuse long-range brain connections, and those abnormalities were related to interindividual differences in depression and anxiety. These preliminary results are relevant for neurocognitive models of abnormal brain connectivity in both disorders.