Application of Electroencephalography to the Study of Cognitive and Brain Functions in Schizophrenia

The electroencephalogram (EEG) recorded from the human scalp is widely used to study cognitive and brain functions in schizophrenia. Current research efforts are primarily devoted to the assessment of event-related potentials (ERPs) and event-related oscillations (EROs), extracted from the ongoing EEG, in patients with schizophrenia and in clinically unaffected individuals who, due to their family history and current mental status, are at high risk for developing schizophrenia. In this article, we discuss the potential usefulness of ERPs and EROs as genetic vulnerability markers, as pathophysiological markers, and as markers of possible ongoing progressive cognitive and cortical deterioration in schizophrenia. Our main purpose is to illustrate that these neurophysiological measures can offer valuable quantitative biological markers of basic pathophysiological mechanisms and cognitive dysfunctions in schizophrenia, yet they may not be specific to current psychiatry's diagnosis and classification. These biological markers can provide unique information on the nature and extent of cognitive and brain dysfunction in schizophrenia. Moreover, they can be utilized to gain deeper theoretical insights into illness etiology and pathophysiology and may lead to improvements in early detection and more effective and targeted treatment of schizophrenia. We conclude by addressing several key methodological, conceptual, and interpretative issues involved in this research field and by suggesting future research directions

Atypical modulation of cognitive control by arousal in autism

We examined the effects of viewing high-arousal pictures on regional brain activations elicited by a cognitive control task in participants with high-functioning autism and neurotypical controls. Specifically, using event-related functional magnetic resonance imaging, we assessed the effects of brief presentations of highly arousing pictures (i.e., both very pleasant and very unpleasant) on the processing of stimuli requiring cognitive control. Similar to previous findings, when stimuli with high cognitive control demands were preceded by low-arousal pictures, individuals with autism demonstrated regional brain activations that were comparable to neurotypical control individuals. When the presentation of the cognitive control stimuli was preceded by high-arousal pictures, however, the control group was characterized by relatively greater activation in the right lateral midfrontal cortex in response to cognitive control stimuli. In contrast, preceding high-arousal stimuli did not modulate activity elicited in this region by cognitive control stimuli in the autism group. Differential modulation of right lateral midfrontal activation by high-arousal stimuli in autism is consistent with the “inefficiency model” of brain functioning in autism spectrum disorders, and contributes to a growing body of evidence that autism may be characterized by anomalous sensitivity of cognitive control brain regions to social-emotional context

Social stimuli interfere with cognitive control in autism

Autism spectrum disorders are characterized by cognitive control deficits as well as impairments in social interactions. However, the brain mechanisms mediating the interactive effects of these deficits have not been addressed. We employed event-related functional magnetic resonance imaging (fMRI) to examine the effects of processing directional information from faces on activity within brain regions mediating cognitive control. High-functioning individuals with autism and age-, gender-, and IQ-matched neurotypical individuals attended to the direction of a centrally-presented arrow or gaze stimulus with similar flanker stimuli oriented in the same (“congruent”) or opposite (“incongruent”) direction. The incongruent arrow condition was examined to assess functioning of brain regions mediating cognitive control in a context without social-cognitive demands, whereas the incongruent gaze condition assessed functioning of the same brain regions in a social-cognitive context. Consistent with prior studies, the incongruent arrow condition recruited activity in bilateral midfrontal gyrus, right inferior frontal gyrus, bilateral intraparietal sulcus, and the anterior cingulate relative to the congruent arrow condition in neurotypical participants. Notably, there were not diagnostic group differences in patterns of regional fMRI activation in response to the arrow condition. However, while viewing the incongruent gaze stimuli, although neurotypical participants recruited the same brain regions, participants with autism showed marked hypoactivation in these areas. These findings suggest that processing social-cognitive stimuli interferes with functioning of brain regions recruited during cognitive control tasks in autism. Implications for research into cognitive control deficits in autism are discussed

Graded Visual Attention Modulates Brain Responses Evoked by Task-irrelevant Auditory Pitch Changes

Previous studies suggested that auditory change-specific neural responses are attention-independent and reflect central auditory processing. The automaticity of the brain's response to infrequent changes in pitch within a series of auditory tone pips was examined in parallel functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies. Subjects performed a continuous perceptual-motor visual tracking task at two levels of difficulty while simultaneously hearing a series of task-irrelevant standard tone pips and infrequent pitch-deviant tones. fMRI results revealed that the unattended pitch-deviant tones strongly activated superior temporal and frontal cortical regions. These activations were significantly modulated by the tracking difficulty of the primary task. ERP results revealed that the amplitude of the scalp-negative component evoked by deviant tones (MMN) was attenuated during the more difficult tracking task. Our results demonstrate that the brain's response to task-irrelevant sensory changes is strongly influenced by intermodal attentional demands

Eye Tracking Reveals Impaired Attentional Disengagement Associated with Sensory Response Patterns in Children with Autism

This study used a gap-overlap paradigm to examine the impact of distractor salience and temporal overlap on the ability to disengage and orient attention in 50 children (4–13 years) with ASD, DD and TD, and associations between attention and sensory response patterns. Results revealed impaired disengagement and orienting accuracy in ASD. Disengagement was impaired across all groups during temporal overlap for dynamic stimuli compared to static, but only ASD showed slower disengagement from multimodal relative to unimodal dynamic stimuli. Attentional disengagement had differential associations with distinct sensory response patterns in ASD and DD. Atypical sensory processing and temporal binding appear to be intertwined with development of disengagement in ASD, but longitudinal studies are needed to unravel causal pathways

The Neural Circuitry Mediating Shifts in Behavioral Response and Cognitive Set in Autism

Recent studies have suggested that the social and cognitive impairments in autism are associated with neural processing deficits in specific brain regions. However, these studies have primarily focused on neural systems responsible for face processing and social behaviors. Although repetitive, stereotyped behaviors are a hallmark of autism, little is known about the neural mechanisms underlying these behaviors in the disorder

Emotional priming effects during Stroop task performance

The ability to make decisions within an emotional context requires a balance between two functionally integrated neural systems that primarily support executive control and affective processing. Several studies have demonstrated effects of emotional interference presented during an ongoing cognitive task, but it is unclear how activating the emotional circuitry prior to a cognitive task may enhance or disrupt the executive system. In this study we used fMRI to examine the effects of emotional priming on executive processing during a number Stroop task. Our results indicated that during trials with less executive requirements, there was a greater aversive emotional attenuation effect in a network of regions including the ventrolateral prefrontal cortex (vlPFC), insula and cingulate gyrus. This attenuation effect was counteracted during trials with increased executive demand, suggesting that while pre-activation of the emotional system may lead to an automatic attenuation of activity in multiple regions, requirements for executive function may override the aversive emotional attenuation effect. Furthermore, this override effect was found to be associated with faster reaction times during executive processing. These findings demonstrate that activity in the vlPFC, cingulate and insula is dynamically adjusted in order to optimize performance, and illustrate the importance of the timing of each system’s engagement in determining how competing cognitive and emotional information is processed

Functional magnetic resonance imaging measure of automatic and controlled auditory processing

Activity within fronto-striato-temporal regions during processing of unattended auditory deviant tones and an auditory target detection task was investigated using event-related functional magnetic resonance imaging. Activation within the middle frontal gyrus, inferior frontal gyrus, anterior cingulate gyrus, superior temporal gyrus, thalamus, and basal ganglia were analyzed for differences in activity patterns between the two stimulus conditions. Unattended deviant tones elicited robust activation in the superior temporal gyrus; by contrast, attended tones evoked stronger superior temporal gyrus activation and greater frontal and striatal activation. The results suggest that attention enhances neural activation evoked by auditory pitch deviance in auditory brain regions, possibly through top-down control from the dorsolateral prefrontal cortex involved in goal-directed selection and response generation

Visuospatial executive function in Turner syndrome: functional MRI and neurocognitive findings

Turner syndrome is a genetic disorder that results from an abnormal or missing X chromosome in females and is typically associated with impairments in visuospatial, but not verbal, information processing. These visuospatial processing impairments may be exacerbated with increased task demands, such as those engaged during working memory (WM). While previous studies have examined spatial WM function in Turner syndrome, none have directly compared the neural correlates of spatial and verbal WM processes across the encoding, maintenance and retrieval phases. We employed both neurocognitive assessments and functional MRI (fMRI) to examine the neural circuitry underlying both verbal and visuospatial WM functions in individuals with Turner syndrome and normal controls. We furthermore examined the vulnerability of task-related fMRI activation to distracters presented during WM maintenance. Fifteen healthy female volunteers and eight individuals with Turner syndrome performed a delayed-response WM task during fMRI scanning. Neurocognitive tests revealed impaired performance across both verbal and spatial domains in Turner syndrome, with greater impairment on tasks with WM demands. Frontoparietal regions in controls showed significantly sustained levels of activation during visuospatial WM. This sustained activation was significantly reduced in the group with Turner syndrome. Domain-specific activation of temporal regions, in contrast, did not differ between the two groups. Sensory distraction during the WM maintenance phase did not differentially alter frontoparietal activation between the two groups. The results reveal impaired frontoparietal circuitry recruitment during visuospatial executive processing in Turner syndrome, suggesting a significant role for the X chromosome in the development of these pathways

Mapping social target detection with functional magnetic resonance imaging

The neural correlates of cognitive control and social processing functions, as well as the characteristic patterns of anomalous brain activation patterns in psychiatric conditions associated with impairment in these functions, have been well characterized. However, these domains have primarily been examined in isolation. The present study used event-related functional magnetic resonance imaging to map brain areas recruited during a target-detection task designed to evaluate responses to both non-social (i.e. shape) and social (i.e. face) target stimuli. Both shape and face targets activated a similar brain network, including the postcentral gyrus, the anterior and posterior cingulate gyri and the right midfrontal gyrus, whereas face targets additionally activated the thalamus, fusiform and temporooccipital cortex, lingual gyrus and paracingulate gyrus. Comparison of activations to social and non-social target events revealed that a small portion of the dorsal anterior cingulate gyrus (Brodmann's area 32) and the supracalcarine cortex were preferentially activated to face targets. These findings indicate that non-social and social stimuli embedded within a cognitive control task activate overlapping and distinct brain regions. Clinical cognitive neuroscience research of disorders characterized by cognitive dysfunction and impaired social processing would benefit from the use of tasks that evaluate the combined effects of deficits in these two domains