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 connectivity's 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.

The face and its emotion: right N170 deficits in structural processing and early emotional discrimination in schizophrenic patients and relatives.

Previous studies have reported facial emotion recognition impairments in schizophrenic patients, as well as abnormalities in the N170 component of the event-related potential. Current research on schizophrenia highlights the importance of complexly-inherited brain-based deficits. In order to examine the N170 markers of face structural and emotional processing, DSM-IV diagnosed schizophrenia probands (n=13), unaffected first-degree relatives from multiplex families (n=13), and control subjects (n=13) matched by age, gender and educational level, performed a categorization task which involved words and faces with positive and negative valence. The N170 component, while present in relatives and control subjects, was reduced in patients, not only for faces, but also for face-word differences, suggesting a deficit in structural processing of stimuli. Control subjects showed N170 modulation according to the valence of facial stimuli. However, this discrimination effect was found to be reduced both in patients and relatives. This is the first report showing N170 valence deficits in relatives. Our results suggest a generalized deficit affecting the structural encoding of faces in patients, as well as the emotion discrimination both in patients and relatives. Finally, these findings lend support to the notion that cortical markers of facial discrimination can be validly considered as vulnerability markers.

Facial and semantic emotional interference: a pilot study on the behavioral and cortical responses to the Dual Valence Association Task.

BACKGROUND: Integration of compatible or incompatible emotional valence and semantic information is an essential aspect of complex social interactions. A modified version of the Implicit Association Test (IAT) called Dual Valence Association Task (DVAT) was designed in order to measure conflict resolution processing from compatibility/incompatibly of semantic and facial valence. The DVAT involves two emotional valence evaluative tasks which elicits two forms of emotional compatible/incompatible associations (facial and semantic). METHODS: Behavioural measures and Event Related Potentials were recorded while participants performed the DVAT. RESULTS: Behavioural data showed a robust effect that distinguished compatible/incompatible tasks. The effects of valence and contextual association (between facial and semantic stimuli) showed early discrimination in N170 of faces. The LPP component was modulated by the compatibility of the DVAT. CONCLUSIONS: Results suggest that DVAT is a robust paradigm for studying the emotional interference effect in the processing of simultaneous information from semantic and facial stimuli.

High contextual sensitivity of metaphorical expressions and gesture blending: A video event-related potential design.

Human communication in a natural context implies the dynamic coordination of contextual clues, paralinguistic information and literal as well as figurative language use. In the present study we constructed a paradigm with four types of video clips: literal and metaphorical expressions accompanied by congruent and incongruent gesture actions. Participants were instructed to classify the gesture accompanying the expression as congruent or incongruent by pressing two different keys while electrophysiological activity was being recorded. We compared behavioral measures and event related potential (ERP) differences triggered by the gesture stroke onset. Accuracy data showed that incongruent metaphorical expressions were more difficult to classify. Reaction times were modulated by incongruent gestures, by metaphorical expressions and by a gesture-expression interaction. No behavioral differences were found between the literal and metaphorical expressions when the gesture was congruent. N400-like and LPC-like (late positive complex) components from metaphorical expressions produced greater negativity. The N400-like modulation of metaphorical expressions showed a greater difference between congruent and incongruent categories over the left anterior region, compared with the literal expressions. More importantly, the literal congruent as well as the metaphorical congruent categories did not show any difference. Accuracy, reaction times and ERPs provide convergent support for a greater contextual sensitivity of the metaphorical expressions.

Semantic Memory and Lexical Availability in Parkinson's Disease: A Statistical Learning Study.

Parkinson's disease (PD) is a neurodegenerative disorder that causes a progressive impairment in motor and cognitive functions. Although semantic fluency deficits have been described in PD, more specific semantic memory (SM) and lexical availability (LA) domains have not been previously addressed. Here, we aimed to characterize the cognitive performance of PD patients in a set of SM and LA measures and determine the smallest set of neuropsychological (lexical, semantic, or executive) variables that most accurately classify groups. Thirty early-stage non-demented PD patients (age 35-75, 10 females) and thirty healthy controls (age 36-76, 12 females) were assessed via general cognitive, SM [three subtests of the CaGi battery including living (i.e., elephant) and non-living things (i.e., fork)], and LA (eliciting words from 10 semantic categories related to everyday life) measures. Results showed that PD patients performed lower than controls in two SM global scores (picture naming and naming in response to an oral description). This impairment was particularly pronounced in the non-living things subscale. Also, the number of words in the LA measure was inferior in PD patients than controls, in both larger and smaller semantic fields, showing a more inadequate recall strategy. Notably, the classification algorithms indicated that the SM task had high classification accuracy. In particular, the denomination of non-living things had a classification accuracy of ∼80%. These results suggest that frontostriatal deterioration in PD leads to search strategy deficits in SF and the potential disruption in semantic categorization. These findings are consistent with the embodied view of cognition.

P300 and neuropsychological assessment in mild cognitive impairment and Alzheimer dementia.

Only a small proportion of individuals with Mild Cognitive Impairment (MCI) will convert to dementia. Methods currently available to identify risk for conversion do not combine enough sensitivity and specificity, which is even more problematic in low-educated populations. Current guidelines suggest the use of combined markers for dementia to enhance the prediction accuracy of assessment methods. The present study adhered to this proposal and investigated the sensitivity and specificity of the electrophysiological component P300 and standard neuropsychological tests to assess patients with Alzheimer's disease (AD) and MCI recruited from a low-income country. The neuropsychological battery comprised tests of memory, attention, language, praxis, and executive functions. The P300 was recorded using a classical visual odd-ball paradigm. Three variables were found to achieve sensitivity and specificity values above 80% (Immediate and Delayed recall of word list - CERAD - and the latency of P300) for both MCI and AD. When they entered the model together (i.e., combined approach) the sensitivity for MCI increased to 96% and the specificity remained high (80%). Our preliminary findings suggest that the combined use of sensitive neuropsychological tasks and the analysis of the P300 may offer a very useful method for the preclinical assessment of AD, particularly in populations with low socioeconomic and educational levels. Our results provide a platform and justification to employ more resources to convert P300 and related parameters into a biological marker for AD.

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.

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.

The cortical processing of facial emotional expression is associated with social cognition skills and executive functioning: a preliminary study.

Several lines of experimental evidence support an association between facial processing and social cognition, but no direct link between cortical markers of facial processing and complex cognitive processes has been reported until now. In the current study, we tested the hypothesis that cortical electrophysiological markers for the processing of facial emotion are associated with individual differences in executive and social cognition skills. We tested for correlations between the amplitude of event-related potentials (N170) in a dual valence task and participants' scores on three neuropsychological assessments (general neuropsychology, executive functioning, and social cognition). N170 was modulated by the stimulus type (face versus word) and the valence of faces (positive versus negative). The neural source of N170 was estimated to be the fusiform gyrus. Robust correlations were found between neuropsychological markers and measures of facial processing. Social cognition skills (as measured by three tests: the Reading the Mind in the Eyes test, the Faux Pas test, and the Iowa Gambling Task) correlated with cortical measures of emotional discrimination. Executive functioning ability also correlated with the cortical discrimination of complex emotional stimuli. Our findings suggest that the cortical processing of facial emotional expression is associated with social cognition skills.

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.