Increased Cognitive Control During Execution of Finger Tap Movement in People with Parkinson's Disease.

BACKGROUND: Previous studies employed demanding and complex hand tasks to study the brain activation in people with Parkinson's Disease (PD). There is inconsistent finding about the cerebellar activity during movement execution of this patient population. OBJECTIVES: This study aimed to examine the brain activation patterns of PD individuals in the on-state and healthy control subjects in a simple finger tapping task. METHODS: Twenty-seven patients with PD and 22 age-matched healthy subjects were recruited for the study. Subjects were instructed to perform simple finger tapping tasks under self- and cue-initiated conditions in separate runs while their brain activations were captured using fMRI. RESULTS: Healthy subjects had higher brain activity in contralateral precentral gyrus during the self-initiated task, and higher brain activity in the ipsilateral middle occipital gyrus during the cue-initiated task. PD patients had higher brain activity in the cerebellum Crus I (bilateral) and lobules VI (ipsilateral) during the self-initiated task and higher brain activity in the contralateral middle frontal gyrus during the cue-initiated task. When compared with healthy controls, PD patients had lower brain activity in the contralateral inferior parietal lobule during the self-initiated task, and lower brain activity in the ipsilateral cerebellum lobule VIII, lobule VIIB and vermis VIII, and thalamus during the cue-initiated task. Conjunction analysis indicated that both groups had activation in bilateral cerebellum and SMA and ipsilateral precentral gyrus and postcentral gyrus during both self- and cue-initiated movement. Individuals with PD exhibited higher brain activity in the executive zone (cerebellum Crus I and II) during self-initiated movement, and lower brain activity in the sensorimotor zone (i.e. lobule VIIb and VIII of the cerebellum) during cue-initiated movement. DISCUSSIONS: The findings suggest that individuals with PD may use more executive control when performing simple movements.

Effects of integrated supported employment plus cognitive remediation training for people with schizophrenia and schizoaffective disorders.

OBJECTIVES: The present study aims to investigate the synergistic effects of cognitive remediation training (CRT) on Integrated Supported Employment (ISE). ISE blends individual placement support service with work-related social skills training for Chinese people suffering from schizophrenia or schizoaffective disorder. METHOD: Ninety participants with schizophrenia or schizoaffective disorders were recruited from two psychiatric outpatient services in Hong Kong. They were randomly assigned into the ISE+CRT (n=45) and ISE (n=45) conditions. Blinded assessments on vocational, clinical, psychological, and neurocognitive outcomes were conducted by independent assessors. The two groups were followed up at 7 and 11months. RESULTS: Both groups yielded similar improvements across several outcome domains assessed immediately after the interventions and at 7 and 11month follow-ups, but no significant group differences were found. Significant positive trends over time in vocational, clinical and cognitive outcomes consistently favored the ISE+CRT condition. CONCLUSION: While both the ISE+CRT and ISE groups demonstrated improvement in vocational, clinical, psychological, and neurocognitive outcomes, there was no evidence to show that cognitive remediation facilitated further improvement in these domains beyond gains associated with ISE alone. Further investigation is needed to fully exploit the synergistic potential of ISE combined with CRT, and to better understand which individuals experience a maximal benefit from the specific rehabilitation program components.

Importance of punishment frequency in the Iowa gambling task: an fMRI study.

It has been widely found that in the Iowa Gambling Task (IGT; Bechara et al. Cognition, 50(1), 7-15 1994) normal subjects would gradually learn to prefer obtaining rewards for long-term benefits than seeking immediate rewards to maximize the overall profit. The current study aimed to gain an understanding of how punishment frequency in the IGT would be processed and its association with subjects' reward preferences. In this study, we employed the clinical version of the IGT, in which response options are not only different in the long-term outcome, but also associated with different punishment frequencies. Event-related functional Magnetic Resonance Imaging (fMRI) was used to capture the subjects' brain activity when performing the IGT. A total of 24 male subjects (mean age = 21.7 years, SD = 1.8 years), who were university students, participated in the experiment. It is found that subjects learned to select more from the decks that were advantageous in the long-term, but they were more sensitive to the effect of long-term outcome under the condition of high punishment frequency. The corresponding brain activation showed that the Anterior Cingulate Cortex (ACC) had significantly higher activation during the disadvantageous choices than the advantageous choices. Such activity difference between the two conditions of long-term outcome was more prominent with high punishment frequency than low punishment frequency; and this brain activity difference was significantly correlated with the behavioral performance under the condition of high punishment frequency. The results suggested that only in the context with high punishment frequency, there would be increased neural activity in ACC when subjects intended to select from the disadvantageous choices so that these choices would be inhibited and advantageous choices would be selected.

MRI predicts remission at 1 year in first-episode schizophrenia in females with larger striato-thalamic volumes.

BACKGROUND/AIMS: The Remission in Schizophrenia Working Group has defined remission as 'a low-mild symptom intensity level, maintained for a minimum of 6 months, where such symptoms do not affect an individual's behaviour' [Andreasen et al.: Am J Psychiatry 2005;162:441-449]. Since brain morphology relates to symptomatology, treatment and illness progression, MRI may assist in predicting remission. METHODS: Thirty-nine patients newly diagnosed with DSM-IV schizophrenia underwent MRI brain scan prior to antipsychotic exposure. The Global Assessment of Functioning (GAF) score was entered into a voxel-based analysis to evaluate its relationship with cerebral grey matter volume from the baseline MRI. We entered age, total intracranial volume and intake GAF score as co-variates. Males and females were analysed separately because gender is a potent determinant of outcome. RESULTS: Males had lower GAF scores than females, both at intake and at 1 year. Males comprised only 40% (12 out of 39) of the early remission group. For females only, early remission was strongly and positively correlated with bilateral lentiform and striatal volumes. For males, there was no such relationship. CONCLUSION: Larger striato-thalamic volume correlated with early remission in females only. These baseline MRI findings were unlikely to be confounded by antipsychotic treatment and chronicity. These brain morphological markers show gender dimorphism and may assist in the prediction of early remission in newly diagnosed schizophrenia.

Voxel-based analysis of postnatal white matter microstructure in mice exposed to immune challenge in early or late pregnancy.

Maternal infection during prenatal life is a risk factor for neurodevelopmental disorders, including schizophrenia and autism, in the offspring. We and others have reported white mater microstructure abnormalities in prefrontal-striato-temporal networks in these disorders. In addition we have shown that early rather than late maternal immune challenge in the mouse model precipitates ventricular volume change and impairs sensorimotor gating similar to that found in schizophrenia. However, it is not known whether the timing of maternal infection has a differential impact upon white matter microstructural indices. Therefore this study directly tested the effect of early or late gestation maternal immune activation on post-natal white matter microstructure in the mouse. The viral mimic PolyI:C was administered on day 9 or day 17 of gestation. In-vivo diffusion tensor imaging (DTI) was carried out when the offspring reached adulthood. We describe a novel application of voxel-based analysis to evaluate fractional anisotrophy (FA). In addition we conducted a preliminary immunohistochemical exploration of the oligodendrocyte marker, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), to determine whether differences in myelination might contribute to any changes in FA observed. Our results provide experimental evidence that prenatal exposure to inflammation elicits widespread differences in FA throughout fronto-striatal-limbic circuits compared to control saline exposure. Moreover, FA changes were more extensive in the group exposed earliest in gestation.

A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia.

BACKGROUND: Anti-psychotic treatment appears to be associated with striatal volume increase, but how early this change occurs is still unknown. METHODS: A single prospective cohort of 20 anti-psychotic-naïve patients, newly diagnosed with schizophrenia, underwent magnetic resonance imaging brain scan at baseline. This was repeated following up to 8 weeks of anti-psychotic treatment. Ten patients had repeat scan within only 3 weeks. The choice of anti-psychotic medication was naturalistic, i.e., clinician-led. Well-matched healthy individuals were also scanned to control for non-specific changes over a 3-week period. RESULTS: After 3 weeks of anti-psychotic treatment, significant grey matter volume increase in the right caudate, superior and inferior frontal gyrus, precentral gyrus, and left inferior parietal lobule was noted. However, after 8 weeks of anti-psychotic treatment, volume increase in the right thalamus and bilateral cerebellum was observed. Significant grey matter reduction was detected in the left medial frontal gyrus at both 3- and 8-week intervals. CONCLUSIONS: Early increase in striatal volume change occurs as early as 3 weeks after anti-psychotic treatment, whilst thalamic volume increase is apparent later, by 8 weeks of treatment. We speculate that drug-mediated neuroplasticity may provide a biomarker for clinical recovery.

Age-related grey matter volume correlates of response inhibition and shifting in attention-deficit hyperactivity disorder.

BACKGROUND: Children with attention-deficit hyperactivity disorder (ADHD) have difficulties with executive function and impulse control which may improve with age. AIMS: To map the brain correlates of executive function in ADHD and determine age-related changes in reaction times and brain volumes. METHOD: Attention-deficit hyperactivity disorder and control groups were compared on the change task measures of response inhibition (stop signal reaction time, SSRT) and shifting (change response reaction time, CRRT). Voxel-wise magnetic resonance imaging (MRI) correlations of reaction times and grey matter volume were determined, along with bivariate correlations of reaction times, brain volumes and age. RESULTS: Individuals in the ADHD group had longer SSRTs and CRRTs. Anterior cingulate, striatal and medial temporal volumes highly correlated with SSRT. Striatal and cerebellar volumes strongly correlated with CRRT. Older children had faster reaction times and larger regional brain volumes. In controls, orbitofrontal, medial temporal and cerebellar volumes correlated with CRRT but not SSRT. Neither reaction times nor regional brain volumes were strongly age-dependent. CONCLUSIONS: Our evidence supports delayed brain maturation in ADHD and implies that some features of ADHD improve with age.

Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome.

BACKGROUND: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger's syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance imaging (MRI) studies of autism are in disagreement. One possible reason is that the diagnosis of autism takes precedence over Asperger's syndrome and a distinction in language acquisition is rarely made. We therefore planned to examine a whole brain hypothesis that the patterns of grey matter differences in Asperger's syndrome and HFA can be distinguished. METHODS: We used voxel-based computational morphometry to map grey matter volume differences in 33 children with either Asperger's syndrome or high-functioning autism compared to 55 typical developing control children balanced for age, IQ, gender, maternal language and ethnicity. RESULTS: Children with HFA had significantly smaller grey matter volumes in subcortical, posterior cingulate and precuneus regions than the Asperger's group. Compared to controls, children with HFA had smaller grey matter volumes in predominantly fronto-pallidal regions, while children with Asperger's had less grey matter in mainly bilateral caudate and left thalamus. In addition we found a significant negative correlation between the size of a grey matter cluster around BA44 language area and the age of acquisition of phrase speech in the children with HFA. When the groups were combined we confirmed a mixed picture of smaller grey matter volumes in frontal, basal ganglia, temporal and parietal regions. CONCLUSIONS: Our study suggests that the underlying neurobiology in HFA and Asperger's syndrome is at least partly discrete. Future studies should therefore consider the history of language acquisition as a valuable tool to refine investigation of aetiological factors and management options in pervasive developmental disorders.

Evidence of normal hearing laterality in familial schizophrenic patients and their relatives.

Dichotic listening (DL) has been used as a tool to investigate possible left cerebral dysfunction in schizophrenia. However, the wide range of DL tests (e.g., words, emotions, sentences) as well as patient groups ("heterogeneity") has introduced several confounders. Assessing relatives of patients with schizophrenia may overcome some of these problems, and may be more useful in determining if loss of functional cerebral laterality in schizophrenia is a state or a trait phenomenon. The fused consonant-vowel DL test was administered to 114 subjects: 20 individuals with familial schizophrenia, 42 of their healthy relatives, and 52 healthy volunteers. We did this to investigate whether the normal language processing asymmetry-a right ear advantage (REA)-is present, and whether it could serve as a marker for genetic liability. General performance accuracy level was lower in schizophrenia patients and their relatives but the expected REA was present in all groups. Adjusting for age, accuracy, and obligate status made no difference. In conclusion, familial schizophrenic patients and their relatives have normal REA and hearing laterality on the fused DL test.

Stress and psychological distress among SARS survivors 1 year after the outbreak.

OBJECTIVE: Our study examined the stress level and psychological distress of severe acute respiratory syndrome (SARS) survivors 1 year after the outbreak. METHOD: During the SARS outbreak in 2003, we used the 10-item Perceived Stress Scale (PSS-10) to assess SARS survivors treated in 2 major hospitals (non-health care workers, n = 49; health care workers, n = 30). We invited SARS survivors from the same hospitals (non-health care workers, n = 63; health care workers, n = 33) to complete the PSS-10 again in 2004. At that time, they were also asked to complete the General Health Questionnaire (GHQ-12) and measures of depression, anxiety, and posttraumatic symptoms. PSS-10 scores were also obtained from matched community control subjects during the outbreak (n = 145) and again in 2004 (n = 112). RESULTS: SARS survivors had higher stress levels during the outbreak, compared with control subjects (PSS-10 scores = 19.8 and 17.9, respectively; P < 0.01), and this persisted 1 year later (PSS-10 scores = 19.9 and 17.3, respectively; P < 0.01) without signs of decrease. In 2004, SARS survivors also showed worrying levels of depression, anxiety, and posttraumatic symptoms. An alarming proportion (64%) scored above the GHQ-12 cut-off that suggests psychiatric morbidity. During the outbreak, health care worker SARS survivors had stress levels similar to those of non-health care workers, but health care workers showed significantly higher stress levels in 2004 (PSS-10 score = 22.8, compared with PSS-10 score = 18.4; P < 0.05) and had higher depression, anxiety, posttraumatic symptoms, and GHQ-12 scores. CONCLUSIONS: One year after the outbreak, SARS survivors still had elevated stress levels and worrying levels of psychological distress. The situation of health care worker SARS survivors is particularly worrying. The long-term psychological implications of infectious diseases should not be ignored. Mental health services could play an important role in rehabilitation.

Immediate and sustained psychological impact of an emerging infectious disease outbreak on health care workers.

OBJECTIVE: To assess the immediate and sustained psychological health of health care workers who were at high risk of exposure during the severe acute respiratory syndrome (SARS) outbreak. METHODS: At the peak of the 2003 SARS outbreak, we assessed health care workers in 2 acute care Hong Kong general hospitals with the Perceived Stress Scale (PSS-10). One year later, we reassessed these health care workers with the PSS-10, the 21-Item Depression and Anxiety Scale (DASS-21), and the Impact of Events Scale-Revised (IES-R). We recruited high-risk health care workers who practised respiratory medicine and compared them with nonrespiratory medicine workers, who formed the low-risk health care worker control group. RESULTS: In 2003, high-risk health care workers had elevated stress levels (PSS-10 score = 17.0) that were not significantly different from levels in low-risk health care worker control subjects (PSS-10 score = 15.9). More high-risk health care workers reported fatigue, poor sleep, worry about health, and fear of social contact, despite their confidence in infection-control measures. By 2004, however, stress levels in the high-risk group were not only higher (PSS-10 score = 18.6) but also significantly higher than scores among low-risk health care worker control subjects (PSS-10 score = 14.8, P < 0.05). In 2004, the perceived stress levels in the high-risk group were associated with higher depression, anxiety, and posttraumatic stress scores (P < 0.001). Posttraumatic stress scores were a partial mediator of the relation between the high risk of exposure to SARS and higher perceived stress. CONCLUSIONS: Health care workers who were at high risk of contracting SARS appear not only to have chronic stress but also higher levels of depression and anxiety. Front-line staff could benefit from stress management as part of preparation for future outbreaks.

Mapping brain structure in attention deficit-hyperactivity disorder: a voxel-based MRI study of regional grey and white matter volume.

The neuroanatomical basis of attention deficit-hyperactivity disorder (ADHD) is postulated to involve brain circuitry responsible for attention and executive function. Relatively new automated methods of MRI analysis allow rapid examination of each volume element (voxel) of whole brain, therefore we planned a comprehensive quantitative examination of brain anatomy in children with ADHD using voxel-based methods. We aimed to quantify whole brain, global tissue class and regional grey and white matter volume differences in 28 male children with ADHD and 31 closely matched controls. Since ADHD is often complicated by comorbid oppositional defiant disorder (ODD) and conduct disorder (CD), we also conducted post-hoc analyses of subgroups of children with ADHD with and without these comorbidities. Significant regional deficits in ADHD were observed within a predominantly right-sided frontal-pallidal-parietal grey matter network and bilateral white matter tracts. Post-hoc comparisons suggested that comorbid ODD or CD did not greatly alter the extent of regional pathology in ADHD. The exceptions being cerebellar and striatal volume deficits which were significantly greater in children with ADHD plus comorbidities, but not those with ADHD alone, compared to controls. Overall, restricted structural brain abnormalities caused by ADHD were localized to brain systems known to be necessary for attention and executive function.

Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia.

We report the first voxel-based morphometric (VBM) study to examine cerebral grey and white matter and cerebrospinal fluid (CSF) using computational morphometry in never-medicated, first-episode psychosis (FEP). Region-of-interest (ROI) analysis was also performed blind to group membership. 26 never-medicated individuals with FEP (23 with DSM-IV schizophrenia) and 38 healthy controls had MRI brain scans. Groups were balanced for age, sex, handedness, ethnicity, paternal socio-economic status, and height. Healthy controls were recruited from the local community by advertisement. Grey matter, white matter, and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in L and R caudate nuclei, cingulate gyri, parahippocampal gyri, superior temporal gyri, cerebellum and R thalamus, prefrontal cortex. They also had significantly less white matter volume in the R anterior limb of the internal capsule fronto-occipital fasciculus and L and R fornices, and significantly greater CSF volume especially in the R lateral ventricle. Excluding the 3 subjects with brief psychotic disorder did not alter our results. Our data suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in never-medicated, schizophrenia. ROI analysis comparing the schizophrenia group (n=23) with the healthy controls (n=38) confirmed caudate volumes were significantly smaller bilaterally by 11%, and lateral ventricular volume was significantly larger on the right by 26% in the patients. Caudate nuclei and lateral ventricular volume measurements were uncorrelated (Pearson correlation coefficient 0.30, p=0.10), ruling out the possibility of segmentation artefact. Ratio of lateral ventricle to caudate volume was bilaterally significantly increased (p<0.005, 2-tailed), which could represent an early biomarker in first-episode, never-medicated schizophrenia.

Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism.

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Stress and psychological impact on SARS patients during the outbreak.

OBJECTIVE: To examine stress and psychological impact in severe acute respiratory syndrome (SARS) patients during the 2003 outbreak. SARS is a novel, highly infectious pneumonia, and its psychological impact is still unclear. METHOD: At the peak of the outbreak, SARS patients (n = 79) and healthy control subjects (n = 145) completed the Perceived Stress Scale (PSS) and documented a range of psychological responses. Groups were balanced for age, sex, education, and living circumstances. RESULTS: Stress was significantly higher in SARS patients than in healthy control subjects. Stress correlated significantly with negative psychological effects. Of SARS patients, 39% (n = 30) were infected health care workers; these individuals reported significantly more fatigue and worries about health than did other patients. Of patients, 25% (n = 20) requested psychological follow-up. CONCLUSIONS: General stress and negative psychological effects are increased in SARS patients, particularly among infected health care workers. This may increase the risk of mood and stress-related disorders. Functional impairment is apparent in the postrecovery phase.

Psychological effects of the SARS outbreak in Hong Kong on high-risk health care workers.

OBJECTIVE: To quantify stress and the psychological impact of severe acute respiratory syndrome (SARS) on high-risk health care workers (HCWs). METHOD: We evaluated 271 HCWs from SARS units and 342 healthy control subjects, using the Perceived Stress Scale (PSS) to assess stress levels and a structured list of putative psychological effects of SARS to assess its psychological effects. Healthy control subjects were balanced for age, sex, education, parenthood, living circumstances, and lack of health care experience. RESULTS: Stress levels were raised in both groups (PSS = 18) but were not relatively increased in the HCWs. HCWs reported significantly more positive (94%, n = 256) and more negative psychological effects (89%, n = 241) from SARS than did control subjects. HCWs declared confidence in infection-control measures. CONCLUSIONS: In HCWs, adaptive responses to stress and the positive effects of infection control training may be protective in future outbreaks. Elevated stress in the population may be an important indicator of future psychiatric morbidity.

Psychological responses to the SARS outbreak in healthcare students in Hong Kong.

This paper reports a cross-sectional questionnaire study that investigated perceived stress and psychological responses to the SARS outbreak in healthcare students at the height of the outbreak in Hong Kong in 2003. Non-healthcare university students served as controls. All the groups reported high levels of perceived stress. Despite being similarly confident in infection control procedures, nursing students were significantly more stressed than medical students, possibly reflecting a perceived higher risk of infection due to more prolonged contact with patients. Non-healthcare students also had high stress levels due to the perceived risks of dying from SARS, reflecting a fear of the unknown. Suitable psychological and occupational support services should be made available in case of future outbreaks.

A comparison between schizophrenia patients and healthy controls on the expression of attentional blink in a rapid serial visual presentation (RSVP) paradigm.

The expression of attentional blink (AB) in 24 schizophrenia inpatients was compared to 22 healthy subjects in a dual-target rapid serial visual presentation (RSVP) paradigm in which a sequence of discrete stimuli was presented in rapid succession. Correct identification of the first target led to poorer detection of the second one when they were interspersed by distractors. This second-target deficit constitutes the AB effect, which is most pronounced between 200 and 500 ms after the offset of the first target stimulus and steadily decays as the number of intervening distractors increases. Despite relatively poor performance in terms of target identification within RSVP streams, schizophrenia patients expressed an AB effect that was as clear as that seen in healthy subjects. Moreover, there was evidence for an enhanced AB effect in schizophrenia patients. This outcome contrasts with the robust finding that schizophrenia patients are attenuated in the expression of prepulse inhibition, another paradigm believed to assess attentional control. The present results add to the extensive literature on the nature and specification of attentional dysfunction implicated in schizophrenia.