Natasha Matthews

Imitation, Simulation, and Schizophrenia

The social significance of imitation is that it provides internal tools for understanding the actions of others by simulating or forming internal representations of these actions. Imitation plays a central role in human social behavior by mediating diverse forms of social learning. However, imitation and simulation ability in schizophrenia has not been adequately addressed. The major aim of the present study was to investigate imitation ability in schizophrenia patients and healthy individuals by examining simple motor imitation that involved the replication of meaningless manual and oral gestures, and the imitation of emotional facial expressions, which has implications for mentalizing. A secondary aim of the present study was to investigate the relationships among imitation ability, social functioning, and working memory. Subjects were asked to mimic hand gestures, mouth movements, and facial expressions of others, online. Clinical symptoms, social competence, and working memory were also assessed. Patients with schizophrenia were significantly impaired on all imitation tasks. Imitation errors were significantly correlated with reduced social competence and increased negative symptoms. However, imitation ability was only weakly associated with working memory. To summarize, the present study examined the ability of patients with schizophrenia to imitate the behaviors demonstrated by others. The results indicate a fundamental impairment in imitation ability in schizophrenia and implicate a possible difficulty in simulation. Further research to determine the neural and developmental origins of this difficulty could be extremely helpful in elucidating the role of simulation in schizophrenia and to establish the complex relationships among mental representation, imitation, and social cognition.

Olfactory identification and preference in bipolar disorder and schizophrenia

Olfactory identification deficit appears to be an enduring feature of schizophrenia, but it is unclear whether it is specific to schizophrenia or present in psychotic disorders in general. The aim of the present study was to compare olfactory identification and olfactory preference in schizophrenia and bipolar disorder. Individuals with schizophrenia or bipolar disorder and demographically matched healthy participants were given the University of Pennsylvania Smell Identification Test (UPSIT) to assess olfactory identification ability. To examine olfactory hedonic judgment, participants were also asked to indicate their preference for each UPSIT item on a 5-point rating scale, immediately after odor identification. Clinical symptoms and social competence were also assessed. Both schizophrenic and bipolar groups showed olfactory identification deficits compared with the healthy controls, but schizophrenic patients were more impaired than bipolar patients on the UPSIT accuracy. Interestingly, both bipolar and schizophrenic patients rated odors to be more pleasant than did healthy controls, but all groups preferred odors that they could correctly identify to unidentified smells. Restricted range of preference ratings was associated with the severity of negative symptoms in schizophrenia, and with mania in bipolar disorder. Social competence was associated with better olfactory identification performance. These findings suggest that olfactory identification and preference are compromised in bipolar disorder as well as in schizophrenia, but the precise nature of these abnormalities needs to be further elucidated.

Gesture Imitation in Schizophrenia

Recent evidence suggests that individuals with schizophrenia (SZ) are impaired in their ability to imitate gestures and movements generated by others. This impairment in imitation may be linked to difficulties in generating and maintaining internal representations in working memory (WM). We used a novel quantitative technique to investigate the relationship between WM and imitation ability. SZ outpatients and demographically matched healthy control (HC) participants imitated hand gestures. In Experiment 1, participants imitated single gestures. In Experiment 2, they imitated sequences of 2 gestures, either while viewing the gesture online or after a short delay that forced the use of WM. In Experiment 1, imitation errors were increased in SZ compared with HC. Experiment 2 revealed a significant interaction between imitation ability and WM. SZ produced more errors and required more time to imitate when that imitation depended upon WM compared with HC. Moreover, impaired imitation from WM was significantly correlated with the severity of negative symptoms but not with positive symptoms. In sum, gesture imitation was impaired in schizophrenia, especially when the production of an imitation depended upon WM and when an imitation entailed multiple actions. Such a deficit may have downstream consequences for new skill learning.

DNA Variation in the SNAP25 Gene Confers Risk to ADHD and Is Associated with Reduced Expression in Prefrontal Cortex

Background The Coloboma mouse carries a ∼2 cM deletion encompassing the SNAP25 gene and has a hyperactive phenotype similar to that of ADHD. Such mice are 3 fold more active compared to their control littermates. Genetic association studies support a role for allelic variants of the human SNAP25 gene in predisposing to ADHD. Methods/Principal Findings We performed association analysis across the SNAP25 gene in 1,107 individuals (339 ADHD trios). To assess the functional relevance of the SNAP25-ADHD associated allele, we performed quantitative PCR on post-mortem tissue derived from the inferior frontal gyrus of 89 unaffected adults. Significant associations with the A allele of SNP rs362990 (χ2 = 10, p-corrected = 0.019, OR = 1.5) and three marker haplotypes (rs6108461, rs362990 and rs362998) were observed. Furthermore, a significant additive decrease in the expression of the SNAP25 transcript as a function of the risk allele was also observed. This effect was detected at the haplotype level, where increasing copies of the ADHD-associated haplotype reduced the expression of the transcript. Conclusions Our data show that DNA variation at SNAP25 confers risk to ADHD and reduces the expression of the transcript in a region of the brain that is critical for the regulation of attention and inhibition.

Visuospatial imagery and working memory in schizophrenia

Introduction The ability to form mental images that reconstruct former perceptual experiences is closely related to working memory (WM) ability. However, whereas WM deficits are established as a core feature of schizophrenia, an independent body of work suggests that mental imagery ability is enhanced in the disorder. Across two experiments we investigated mental imagery in schizophrenia and its relationship with WM. Methods In Experiment 1, individuals with schizophrenia (SZ: n=15) and matched controls (CO: n=14) completed a mental imagery generation and inspection task and a spatial delayed-response WM task. In Experiment 2, SZ (n=16) and CO (n=16) completed a novel version of the mental imagery task modified to increase WM maintenance demand. Results In Experiment 1, SZ demonstrated enhanced mental imagery performance, as evidenced by faster response times relative to CO, with preserved accuracy. However, enhanced mental imagery in SZ was accompanied by impaired WM as assessed by the delayed-response task. In Experiment 2, when WM maintenance load was increased, SZ no longer showed superior imagery performance. Conclusions We found evidence for enhanced imagery manipulation in SZ despite their WM maintenance deficit. However, this imagery enhancement was abolished when WM maintenance demands were increased. This profile of enhanced imagery manipulation but impaired maintenance could be used to implement novel remediation strategies in the disorder.

The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD

BackgroundThis study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD.MethodsOne hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory). Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT]) were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test.ResultsSignificant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks.ConclusionsThe working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match–to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task.

An event-related FMRI study of phonological verbal working memory in schizophrenia.

Background While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI. Methodology/Findings Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenance-related cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups. Conclusion These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts.

Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.

Transferability of training benefits differs across neural events: Evidence from erps

Humans can show striking capacity limitations in sensorimotor processing. Fortunately, these limitations can be attenuated with training. However, less fortunately, training benefits often remain limited to trained tasks. Recent behavioral observations suggest that the extent to which training transfers may depend on the specific stage of information processing that is being executed. Training benefits for a task that taps the consolidation of sensory information (sensory encoding) transfer to new stimulus–response mappings, whereas benefits for selecting an appropriate action (decision-making/response selection) remain specific to the trained mappings. Therefore, training may have dissociable influences on the neural events underlying subsequent sensorimotor processing stages. Here, we used EEG to investigate this possibility. In a pretraining baseline session, participants completed two four-alternative-choice response time tasks, presented both as a single task and as part of a dual task (with another task). The training group completed a further 3,000 training trials on one of the four-alternative-choice tasks. Hence, one task became trained, whereas the other remained untrained. At test, a negative-going component that is sensitive to sensory-encoding demands (N2) showed increased amplitudes and reduced latencies for trained and untrained mappings relative to a no-train control group. In contrast, the onset of the stimulus-locked lateralized readiness potential, a component that reflects the activation of motor plans, was reduced only for tasks that employed trained stimulus–response mappings, relative to untrained stimulus–response mappings and controls. Collectively, these results show that training benefits are dissociable for the brain events that reflect distinct sensorimotor processing stages.

Impaired processing of binaural temporal cues to auditory scene analysis in schizophrenia

It is well established that individuals with schizophrenia demonstrate alterations in auditory perception beginning at the very earliest stages of information processing. However, it is not clear how these impairments in basic information processing translate into high-order cognitive deficits. Auditory scene analysis allows listeners to group auditory information into meaningful objects, and as such provides an important link between low-level auditory processing and higher cognitive abilities. In the present study we investigated whether low-level impairments in the processing of binaural temporal information impact upon auditory scene analysis ability. Binaural temporal processing ability was investigated in 19 individuals with schizophrenia and 19 matched controls. Individuals with schizophrenia showed impaired binaural temporal processing ability on an inter-aural time difference (ITD) discrimination task. In addition, patients demonstrated impairment in two measures of auditory scene analysis. Specifically, patients had reduced ability to use binaural temporal cues to extract signal from noise in a masking level difference paradigm, and to separate the location of a source sound in the presence of an echo in the precedence effect paradigm. These findings demonstrate that individuals with schizophrenia have impairments in the accuracy with which simple binaural temporal information is encoded in the auditory system, and furthermore, this impairment has functional consequences in terms of the use of these cues to extract information in complex auditory environments.