Gavin Cooper

Auditory lateralization in schizophrenia--mismatch negativity and behavioral evidence of a selective impairment in encoding interaural time cues.

OBJECTIVE Behavioural evidence suggests that individuals with schizophrenia may exhibit impairment in the encoding of cues to sound location. There are three primary cues used by the auditory system to locate the position of a sound in space: interaural differences in the arrival-time (ITD), phase (IPD), and the loudness (ILD) of the sound at the two ears. The goal in this study was to obtain an electrophysiological index of preattentive detection of change in sound lateralization created by these cues. METHODS The amplitude of mismatch negativity (MMN) was measured in 18 individuals with schizophrenia and 19 healthy comparison subjects to changes in sound lateralization produced by interaural temporal cues (ITD and IPD) and interaural loudness cues (ILD). Performance was also investigated on a target detection task, where targets were defined by ITD, IPD, or ILD cues. RESULTS Individuals with schizophrenia had reduced MMN amplitudes and decreased hit rates when deviants were created by interaural temporal cues, but not when loudness cues were used. CONCLUSIONS Results from both the MMN and behavioural task revealed a selective impairment in the use of temporal cues to sound lateralization in individuals with schizophrenia. SIGNIFICANCE This finding supports previous research that suggests impairment in the encoding of the temporal information in schizophrenia.

Divergent Patterns of Social Cognition Performance in Autism and 22q11.2 Deletion Syndrome (22q11DS)

Individuals with developmental disorders frequently report a range of social cognition deficits including difficulties identifying facial displays of emotion. This study examined the specificity of face emotion processing deficits in adolescents with either autism or 22q11DS compared to typically developing (TD) controls. Two tasks (face emotion recognition and weather scene recognition) were used to explore group differences in visual scanpath strategy and concurrent recognition accuracy. For faces, the autism and 22q11DS groups demonstrated lower emotion recognition accuracy and fewer fixations compared to the TD group. Individuals with autism demonstrated fewer fixations to some weather scene stimuli compared to 22q11DS and TD groups, yet achieved a level of recognition accuracy comparable to the TD group. These findings provide evidence for a divergent pattern of social cognition dysfunction in autism and 22q11DS.

Autonomic hyper-vigilance in post-infective fatigue syndrome

This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation. Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.

Pre-pulse inhibition and antisaccade performance indicate impaired attention modulation of cognitive inhibition in 22q11.2 deletion syndrome (22q11DS)

Background22q11.2 deletion syndrome (22q11DS) is associated with a number of physical anomalies and neuropsychological deficits including impairments in executive and sensorimotor function. It is estimated that 25% of children with 22q11DS will develop schizophrenia and other psychotic disorders later in life. Evidence of genetic transmission of information processing deficits in schizophrenia suggests performance in 22q11DS individuals will enhance understanding of the neurobiological and genetic substrates associated with information processing. In this report, we examine information processing in 22q11DS using measures of startle eyeblink modification and antisaccade inhibition to explore similarities with schizophrenia and associations with neurocognitive performance.MethodsStartle modification (passive and active tasks; 120- and 480-ms pre-pulse intervals) and antisaccade inhibition were measured in 25 individuals with genetically confirmed 22q11DS and 30 healthy control subjects.ResultsIndividuals with 22q11DS exhibited increased antisaccade error as well as some evidence (trend-level effect) of impaired sensorimotor gating during the active condition, suggesting a dysfunction in controlled attentional processing, rather than a pre-attentive dysfunction using this paradigm.ConclusionsThe findings from the present study show similarities with previous studies in clinical populations associated with 22q11DS such as schizophrenia that may indicate shared dysfunction of inhibition pathways in these groups.

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition

BackgroundPeople with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills.MethodsA cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery.ResultsThe 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group.ConclusionsThe findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.

Electrophysiological, cognitive and clinical profiles of at-risk mental state: the longitudinal Minds in Transition (MinT) study

The onset of schizophrenia is typically preceded by a prodromal period lasting several years during which sub-threshold symptoms may be identified retrospectively. Clinical interviews are currently used to identify individuals who have an ultra-high risk (UHR) of developing a psychotic illness with a view to provision of interventions that prevent, delay or reduce severity of future mental health issues. The utility of bio-markers as an adjunct in the identification of UHR individuals is not yet established. Several event-related potential measures, especially mismatch-negativity (MMN), have been identified as potential biomarkers for schizophrenia. In this 12-month longitudinal study, demographic, clinical and neuropsychological data were acquired from 102 anti-psychotic naive UHR and 61 healthy controls, of whom 80 UHR and 58 controls provided valid EEG data during a passive auditory task at baseline. Despite widespread differences between UHR and controls on demographic, clinical and neuropsychological measures, MMN and P3a did not differ between these groups. Of 67 UHR at the 12-month follow-up, 7 (10%) had transitioned to a psychotic illness. The statistical power to detect differences between those who did or did not transition was limited by the lower than expected transition rate. ERPs did not predict transition, with trends in the opposite direction to that predicted. In exploratory analysis, the strongest predictors of transition were measures of verbal memory and subjective emotional disturbance.

Deficits in temporal cue dependent processing of auditory information in schizophrenia

To improve human-computer interaction, computers need to recognize and respond properly to their users’ emotional state. As a first step to such systems, we investigated how emotional experiences are expressed in various statistical parameters of facial EMG signals. 22 Subjects were presented with 8 emotional film fragments while a TMS Portilab system was used to measure the activity of frontalis above the left eye (EMG1), right corrugator supercilii (EMG2), and left zygomaticus major (EMG3). Additionally, subjects rated the intensity of both their positive and negative feelings for each film. Based on average positive and negative ratings, films were classified into 4 emotion categories (with 2 films each): Mixed, Neutral, Positive, and Negative. From each EMG signal, 6 statistical parameters were derived: mean, absolute deviation, standard deviation, variance, skewness and kurtosis. For each of the resulting 18 parameters, a REMANOVA was conducted, with the 4 emotions and 2 films as within-subject factors. The effect of emotion was significant for EMG2 skewness (F(3,18)53.500, p=.037), EMG3 mean (F(3,18)59.711, p<.001), EMG3 absolute deviation (F(3,18)58.369, p<.001), EMG3 standard deviation (F(3,18)55.837, p=.006) and EMG3 variance (F(3,18)54.064, p=.023). Thus, only few of the EMG parameters reached significance, possibly because mimicking a potential human-computer situation we did not correct our data for baseline values and averaged over a period as long as 120s. Nevertheless, the EMG3 signal remains promising in its differentiation among emotion categories.

Neurocognitive recovery after hospital-treated deliberate self-poisoning with central nervous system depressant drugs: a longitudinal cohort study

AbstractHospital-treated deliberate self-poisoning (DSP) by central nervous system depressant drugs (CNS-D) has been associated with impairments in cognitive and psychomotor functions at the time of discharge. We aimed to replicate this finding and to compare recovery in the first month after discharge for CNS-D and CNS nondepressant drug ingestions. We also examined a series of multivariate explanatory models of recovery of neurocognitive outcomes over time. The CNS-D group was impaired at discharge compared with the CNS-nondepressant group in cognitive flexibility, cognitive efficiency, and working memory. There were no significant differences at discharge in visual attention, processing speed, visuomotor speed, or inhibition speed. Both groups improved in the latter measures over 1 month of follow-up. However, the CNS-D groups recovery was significantly slower for key neurocognitive domains underlying driving in complex traffic situations, namely, cognitive flexibility, cognitive efficiency, and working memory. Patients discharged after DSP with CNS-D drugs have impairments of some critical cognitive functions that may require up to 1 month to recover. Although more pre- than post-DSP variables were retained as explanatory models of neurocognitive performance overall, recovery over time could not be explained by any one of the measured covariates. Tests of cognitive flexibility could be used in clinical settings as a proxy measure for recovery of driving ability. Regulatory authorities should also consider the implications of these results for the period of nondriving advised after ingestion of CNS-D in overdose. Future research, with adequate sample size, should examine contributions of other variables to the pattern of recovery over time.

MMN evidence of a pervasive temporal processing deficit in schizophrenia

This study aims to identify correlates of vocational functioning in a first episode psychosis (FEP) sample 7.5 years after presentation at a specialized early psychosis treatment service. The study involved a prospective, naturalistic follow-up of FEP patients commencing treatment with the Early Psychosis Prevention & Intervention Centre (EPPIC) in Melbourne, Australia, between 1995 and 1997. At treatment entry the Royal Park Multidiagnostic Instrument for Psychosis was used to assess duration of untreated psychosis (DUP), age at onset of psychotic disorder, and premorbid work/social functioning. At 7.5-year follow-up measures included the Brief Psychiatric Rating Scale (Thinking Disturbance subscale), Scale for the Assessment of Negative Symptoms (Alogia subscale), WHO Life Chart Schedule (to assess course of illness, treatment history, and duration of receipt of a disability support pension (DSP)), and the Structured Clinical Interview for DSM-IV (to derive Axis I diagnoses). Analyses involved 180 participants. Univariate and multivariate logistic regression analyses were used to estimate the effects of demographic, clinical and treatment variables on two outcomes: current employment; and durable employment (employment for more than 6 months in the past 2 years). The sample was primarily male (72%), with a mean age at follow-up of 29 years (sd=3.4). 45% reported current participation in competitive employment at 7.5 year follow-up (28% full-time, 17% part-time), and 53% reported recent durable employment. Multivariate analyses showed that, after controlling for other variables (including positive and negative thought disorder, premorbid functioning, and recent psychiatric treatment), current employment was negatively associated with continuous or episodic illness course characterized by worsening trajectory or incomplete remissions, disrupted education, and receiving a DSP for longer than 2 years. Lifetime diagnosis of schizophrenia, receipt of a DSP (regardless of duration) and disrupted education were negatively associated with durable employment. Educational attainment appears to be an important predictor of vocational outcome in the Australian labor market, although its relationship with premorbid functioning requires further investigation. The inverse relationship between DSP and employment, after controlling for symptom levels and course of illness, supports evidence from US studies that such payments may act as a disincentive to employment.The purpose of this study is to examine the long-term clinical and functional outcome of first-episode psychosis (FEP). The study was a naturalistic, prospective follow-up of a large epidemiologically representative sample of 765 FEP patients, mean 7.4-years after initial presentation to a specialist early psychosis service (EPPIC) in Melbourne, Australia. Standardised assessments were used at the followup to assess participants’ demographic characteristics, axis I diagnosis, psychopathology and level of work and social functioning. Follow-up interviews were conducted on 511 participants; 133 refused; 39 were deceased and 82 were un-contactable. No participant bias due to study attrition was found. Some 230 (45.0%) of the interviewed group, met DSM-IV criteria of a current psychotic disorder; 281 (55.0%) individuals received a lifetime diagnosis of psychotic disorder. Numbers of individuals diagnosed with schizophrenia, schizoaffective disorder, affective psychosis and other psychosis, were 306 (59.6%), 48 (9.4%), 110 (21.5%) and 47 (9.2%), respectively. Comparisons between the diagnostic groups found the schizophrenia group to have significantly higher BPRS (total, psychotic subscale) and SANS (total) mean scores and significantly lower GAF, SOFAS and QLS mean scores than the other diagnostic groups at follow-up. The prevalence of current psychotic disorder was significantly higher in the schizophrenia group (60.1%) as compared to the other diagnostic groups (χ2=78.4, df=3, p<0.001). Considering the course of the psychotic disorder over the most recent two years, the majority (49.1%) reported that they have never been actively psychotic, 31.6% reported a continuous course, 17.1% reported an episodic course and 2.2% individuals neither episodic nor continuous course of illness. In contrast to previous medium and longer term follow-up studies of first episode schizophrenia where 19-37% were reported to be occupationally engaged,(and 10-15% of those with established schizophrenia in Australia) the proportion of individuals observed in this study with some level of employment in the last two years was substantially higher (schizophrenia, 52%; affective psychosis, 74.5%; schizoaffective, 60.4%; and other psychotic group, 72.3%). Findings from the EPPIC long term follow-up study emphasis that a specialised early intervention service program might result in better functional outcomes in contrast to previous assumptions, especially for those with schizophrenia.