Mismatch negativity in recent-onset and chronic schizophrenia : a current source density analysis

Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia.

Potentiation of the early visual response to learned danger signals in adults and adolescents

The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents.

Facial emotion modulates the neural mechanisms responsible for short interval time perception

Emotionally arousing events can distort our sense of time. We used mixed block/event-related fMRI design to establish the neural basis for this effect. Nineteen participants were asked to judge whether angry, happy and neutral facial expressions that varied in duration (from 400 to 1,600 ms) were closer in duration to either a short or long duration they learnt previously. Time was overestimated for both angry and happy expressions compared to neutral expressions. For faces presented for 700 ms, facial emotion modulated activity in regions of the timing network Wiener et al. (NeuroImage 49(2):1728–1740, 2010) namely the right supplementary motor area (SMA) and the junction of the right inferior frontal gyrus and anterior insula (IFG/AI). Reaction times were slowest when faces were displayed for 700 ms indicating increased decision making difficulty. Taken together with existing electrophysiological evidence Ng et al. (Neuroscience, doi: 10.3389/fnint.2011.00077, 2011), the effects are consistent with the idea that facial emotion moderates temporal decision making and that the right SMA and right IFG/AI are key neural structures responsible for this effect.

Stop-signal task difficulty and the right inferior frontal gyrus

The stop-signal paradigm is increasingly being used as a probe of response inhibition in basic and clinical neuroimaging research. The critical feature of this task is that a cued response is countermanded by a secondary ‘stop-signal’ stimulus offset from the first by a ‘stop-signal delay’. Here we explored the role of task difficulty in the stop-signal task with the hypothesis that what is critical for successful inhibition is the time available for stopping, that we define as the difference between stop-signal onset and the expected response time (approximated by reaction time from previous trial). We also used functional magnetic resonance imaging (fMRI) to examine how the time available for stopping affects activity in the putative right inferior frontal gyrus and presupplementary motor area (right IFG-preSMA) network that is known to support stopping. While undergoing fMRI scanning, participants performed a stop-signal variant where the time available for stopping was kept approximately constant across participants, which enabled us to compare how the time available for stopping affected stop-signal task difficulty both within and between subjects. Importantly, all behavioural and neuroimaging data were consistent with previous findings. We found that the time available for stopping distinguished successful from unsuccessful inhibition trials, was independent of stop-signal delay, and affected successful inhibition depending upon individual SSRT. We also found that right IFG and adjacent anterior insula were more strongly activated during more difficult stopping. These findings may have critical implications for stop-signal studies that compare different patient or other groups using fixed stop-signal delays.

Brain networks subserving the evaluation of static and dynamic facial expressions

Because moving depictions of face emotion have greater ecological validity than their static counterparts, it has been suggested that still photographs may not engage ‘authentic’ mechanisms used to recognize facial expressions in everyday life. To date, however, no neuroimaging studies have adequately addressed the question of whether the processing of static and dynamic expressions rely upon different brain substrates. To address this, we performed an functional magnetic resonance imaging (fMRI) experiment wherein participants made emotional expression discrimination and Sex discrimination judgements to static and moving face images. Compared to Sex discrimination, Emotion discrimination was associated with widespread increased activation in regions of occipito-temporal, parietal and frontal cortex. These regions were activated both by moving and by static emotional stimuli, indicating a general role in the interpretation of emotion. However, portions of the inferior frontal gyri and supplementary/pre-supplementary motor area showed task by motion interaction. These regions were most active during emotion judgements to static faces. Our results demonstrate a common neural substrate for recognizing static and moving facial expressions, but suggest a role for the inferior frontal gyrus in supporting simulation processes that are invoked more strongly to disambiguate static emotional cues.

Electrophysiological responses to violations of expectation from eye gaze and arrow cues

Isolating processes within the brain that are specific to human behavior is a key goal for social neuroscience. The current research was an attempt to test whether recent findings of enhanced negative ERPs in response to unexpected human gaze are unique to eye gaze stimuli by comparing the effects of gaze cues with the effects of an arrow cue. ERPs were recorded while participants (N¼30) observed a virtual actor or an arrow that gazed (or pointed) either toward (object congruent) or away from (object incongruent) a flashing checkerboard. An enhanced negative ERP (N300) in response to object incongruent compared to object congruent trials was recorded for both eye gaze and arrow stimuli. The findings are interpreted as reflecting a domain general mechanism for detecting unexpected events.

Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Facial emotion and identity processing development in 5- to 15-year-old children

Most developmental studies of emotional face processing to date have focused on infants and very young children. Additionally, studies that examine emotional face processing in older children do not distinguish development in emotion and identity face processing from more generic age-related cognitive improvement. In this study, we developed a paradigm that measures processing of facial expression in comparison to facial identity and complex visual stimuli. The three matching tasks were developed (i.e., facial emotion matching, facial identity matching, and butterfly wing matching) to include stimuli of similar level of discriminability and to be equated for task difficulty in earlier samples of young adults. Ninety-two children aged 5–15 years and a new group of 24 young adults completed these three matching tasks. Young children were highly adept at the butterfly wing task relative to their performance on both face-related tasks. More importantly, in older children, development of facial emotion discrimination ability lagged behind that of facial identity discrimination.

Design after design to bridge between people living with cognitive or sensory impairments, their friends and proxies

A carer or teacher often plays the role of proxy or spokesperson for a person living with an intellectual disability or form of cognitive or sensory impairment. Our research undertook co-design with people living with cognitive and sensory impairments and their proxies in order to explore new ways of facilitating communication. We developed simple functioning interactive prototypes to support people with a diverse range of competencies to communicate and explore their use. Deployment of the prototypes enabled use, appropriation and design after design by our two participant groups; adults living with cognitive or sensory impairments and children identified with language delays and autism spectrum disorder. The prototypes supported concrete expression of likes, dislikes, capabilities, emotional wants and needs and forms of expression that hitherto had not been fostered, further informing design. Carers and designers were surprised at the ways in which the technology was used and how it fostered new forms of social interaction and expression. We elaborate on how design after design can be an effective approach for engaging people living with intellectual disabilities, giving them greater capacity for expression and power in design and offering the potential to expand and deepen their social relationships.

An organization of visual and auditory fear conditioning in the lateral amygdala

Pavlovian fear conditioning is an evolutionary conserved and extensively studied form of associative learning and memory. In mammals, the lateral amygdala (LA) is an essential locus for Pavlovian fear learning and memory. Despite significant progress unraveling the cellular mechanisms responsible for fear conditioning, very little is known about the anatomical organization of neurons encoding fear conditioning in the LA. One key question is how fear conditioning to different sensory stimuli is organized in LA neuronal ensembles. Here we show that Pavlovian fear conditioning, formed through either the auditory or visual sensory modality, activates a similar density of LA neurons expressing a learning-induced phosphorylated extracellular signal-regulated kinase (p-ERK1/2). While the size of the neuron population specific to either memory was similar, the anatomical distribution differed. Several discrete sites in the LA contained a small but significant number of p-ERK1/2-expressing neurons specific to either sensory modality. The sites were anatomically localized to different levels of the longitudinal plane and were independent of both memory strength and the relative size of the activated neuronal population, suggesting some portion of the memory trace for auditory and visually cued fear conditioning is allocated differently in the LA. Presenting the visual stimulus by itself did not activate the same p-ERK1/2 neuron density or pattern, confirming the novelty of light alone cannot account for the specific pattern of activated neurons after visual fear conditioning. Together, these findings reveal an anatomical distribution of visual and auditory fear conditioning at the level of neuronal ensembles in the LA.

Steady state visually evoked potential correlates of static and dynamic emotional face processing

While the neural regions associated with facial identity recognition are considered to be well defined, the neural correlates of non-moving and moving images of facial emotion processing are less clear. This study examined the brain electrical activity changes in 26 participants (14 males M = 21.64, SD = 3.99; 12 females M = 24.42, SD = 4.36), during a passive face viewing task, a scrambled face task and separate emotion and gender face discrimination tasks. The steady state visual evoked potential (SSVEP) was recorded from 64-electrode sites. Consistent with previous research, face related activity was evidenced at scalp regions over the parieto-temporal region approximately 170 ms after stimulus presentation. Results also identified different SSVEP spatio-temporal changes associated with the processing of static and dynamic facial emotions with respect to gender, with static stimuli predominately associated with an increase in inhibitory processing within the frontal region. Dynamic facial emotions were associated with changes in SSVEP response within the temporal region, which are proposed to index inhibitory processing. It is suggested that static images represent non-canonical stimuli which are processed via different mechanisms to their more ecologically valid dynamic counterparts.

Facial identity and facial expression matching in 5 - 12-year-old children and adults

Facial identity and facial expression matching tasks were completed by 5–12-year-old children and adults using stimuli extracted from the same set of normalized faces. Configural and feature processing were examined using speed and accuracy of responding and facial feature selection, respectively. Facial identity matching was slower than face expression matching for all age groups. Large age effects were found on both speed and accuracy of responding and feature use in both identity and expression matching tasks. Eye region preference was found on the facial identity task and mouth region preference on the facial expression task. Use of mouth region information for facial expression matching increased with age, whereas use of eye region information for facial identity matching peaked early. The feature use information suggests that the specific use of primary facial features to arrive at identity and emotion matching judgments matures across middle childhood.

Mirror neuron activation is associated with facial emotion processing

Theoretical accounts suggest that mirror neurons play a crucial role in social cognition. The current study used transcranial-magnetic stimulation (TMS) to investigate the association between mirror neuron activation and facialemotion processing, a fundamental aspect of social cognition, among healthy adults (n = 20). Facial emotion processing of static (but not dynamic) images correlated significantly with an enhanced motor response, proposed to reflect mirror neuron activation. These correlations did not appear to reflect general facial processing or pattern recognition, and provide support to current theoretical accounts linking the mirror neuron system to aspects of social cognition. We discuss the mechanism by which mirror neurons might facilitate facial emotion recognition.

Reduced motor facilitation during action observation in schizophrenia : a mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.

Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMGrecorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.