Susan L. Rossell

Reduced connectivity of the auditory cortex in patients with auditory hallucinations: a resting state functional magnetic resonance imaging study

BACKGROUND Previous research has reported auditory processing deficits that are specific to schizophrenia patients with a history of auditory hallucinations (AH). One explanation for these findings is that there are abnormalities in the interhemispheric connectivity of auditory cortex pathways in AH patients; as yet this explanation has not been experimentally investigated. We assessed the interhemispheric connectivity of both primary (A1) and secondary (A2) auditory cortices in n=13 AH patients, n=13 schizophrenia patients without auditory hallucinations (non-AH) and n=16 healthy controls using functional connectivity measures from functional magnetic resonance imaging (fMRI) data. METHOD Functional connectivity was estimated from resting state fMRI data using regions of interest defined for each participant based on functional activation maps in response to passive listening to words. Additionally, stimulus-induced responses were regressed out of the stimulus data and the functional connectivity was estimated for the same regions to investigate the reliability of the estimates. RESULTS AH patients had significantly reduced interhemispheric connectivity in both A1 and A2 when compared with non-AH patients and healthy controls. The latter two groups did not show any differences in functional connectivity. Further, this pattern of findings was similar across the two datasets, indicating the reliability of our estimates. CONCLUSIONS These data have identified a trait deficit specific to AH patients. Since this deficit was characterized within both A1 and A2 it is expected to result in the disruption of multiple auditory functions, for example, the integration of basic auditory information between hemispheres (via A1) and higher-order language processing abilities (via A2).

Greater superior than inferior parietal lobule activation with increasing rotation angle during mental rotation: An fMRI study

Mental rotation is a task known to activate the parietal cortical regions. The present study aimed to investigate whether there is differential activation of regions within the parietal lobe and to reveal functional subspecialisation of this region by examining the effects of increasing angle of rotation. Functional magnetic resonance imaging was performed in nine healthy female subjects whilst undertaking a parametric mental rotation task. The task comprised 6 alphanumeric characters presented in their normal or mirror-reversed orientation. Behaviourally, subjects showed increased reaction times with increased angle of rotation, with differential effects between the alphanumeric characters; numbers having greater reaction times than letters. BOLD signal increase was observed bilaterally in the middle occipital gyrus and medial frontal gyrus, in the right superior and inferior parietal lobules and in the left superior temporal gyrus. Parametric increases in activation with increasing angle of rotation were observed bilaterally in the superior and inferior parietal lobules and in the right medial frontal gyrus, with greater parametric effects in the superior parietal lobules compared to the inferior parietal lobules. Our findings suggest subspecialisation of the posterior parietal lobules during mental rotation, with differential responses in the superior and inferior regions.

Configural face processing in schizophrenia

Evidence suggests schizophrenia patients may have problems integrating visual features into perceptual wholes using configural information. This deficit may impact on higher order socio-cognitive abilities such as facial emotion perception. Twenty-six schizophrenia patients and 26 age and gender matched healthy control participants completed a Fractured Faces Task which disrupted configural face information yet maintained featural information. While participants were matched for performance when viewing whole, unaltered faces; schizophrenia patients were significantly less affected than control participants when the configural information was disrupted. The results indicate altered configural processing and potential over-reliance on featural processing in schizophrenia. The implications of such impaired processing strategies are discussed.

An empirical evaluation of the MATRICS Consensus Cognitive Battery in bipolar disorder

There is a large body of evidence to indicate that neurocognitive impairments in bipolar disorder (BD) may represent viable endophenotypes; however, a standard consensus‐based battery of cognitive tests used to measure them is yet to appear. There is potential for a neurocognitive battery which was developed for use in the related disorder, schizophrenia – the MATRICS Consensus Cognitive Battery (MCCB) – to provide a consistent measurement tool with a standard to which the cognitive capacity of BD can be compared to other disorders. However, its suitability for capturing neurocognitive impairment in BD cohorts is not well established. Moreover, neurocognitive tests recently recommended by the International Society for Bipolar Disorders (ISBD) for inclusion in a consensus neurocognitive battery for BD have not been evaluated in the context of the MCCB. An evaluation of (i) the clinical efficacy of the MCCB and (ii) the tests recommended by the ISBD in a BD cohort were the aims of the current study.

The neurobiology of anorexia nervosa: A systematic review

Objective: Recent advances in neuroimaging techniques have enabled a better understanding of the neurobiological underpinnings of anorexia nervosa (AN). The aim of this paper was to summarise our current understanding of the neurobiology of AN. Methods: The literature was searched using the electronic databases PubMed and Google Scholar, and by additional hand searches through reference lists and specialist eating disorders journals. Relevant studies were included if they were written in English, only used human participants, had a specific AN group, used clinical populations of AN, group comparisons were reported for AN compared to healthy controls and not merely AN compared to other eating disorders or other psychiatric groups, and were not case studies. Results: The systematic review summarises a number of structural and functional brain differences which are reported in individuals with AN, including differences in neurotransmitter function, regional cerebral blood flow, glucose metabolism, volumetrics and the blood oxygen level dependent response. Conclusion: Several structural and functional differences have been reported in AN, some of which reverse and others which persist following weight restoration. These findings have important implications for our understanding of the neurobiological underpinnings of AN, and further research in this field may provide new direction for the development of more effective treatments.

Gender differences in prepulse inhibition (PPI) in bipolar disorder: men have reduced PPI, women have increased PPI

Prepulse inhibition (PPI) is a measure of sensorimotor gating or information processing. Few studies have examined PPI in bipolar disorder (BD); two studies reported a PPI disruption and two reported no change. There are gender differences in PPI and within the clinical profile of BD, which may explain some of these discrepancies. Thus, the effect of gender on PPI in BD was the focus of the current study. Euthymic BD patients (14 male/15 female) were compared to age- and IQ-matched healthy control participants (16 male/16 female). Assessment of PPI included 21 pulse-alone trials (115 dB) and a total of 42 prepulse-pulse trials (seven of each prepulse: 74, 78, 86 dB) at two stimulus onset asynchrony levels (SOA: 60, 120 ms). There was a group x SOA and a group x gender interaction, reflecting that men with BD showed reduced PPI compared to control males at the 60-ms SOA (3% in BD vs. 26% in controls), but not the 120-ms SOA. In contrast, women with BD had significantly increased PPI compared to female controls at the 120-ms SOA (49% in BD vs. 29% in controls), but not the 60-ms SOA. Compared to control participants BD patients showed changes in PPI, which are gender-dependent; male BD participants had reduced PPI, whereas female BD participants had increased PPI. This gender difference highlights the need to consider men and women with BD as two distinct groups, at least in PPI studies.

Executive function in body dysmorphic disorder

BACKGROUND Body dysmorphic disorder (BDD) is a poorly understood disorder that involves a preoccupation with imagined or minor bodily defects. Only a few studies of neuropsychological function have been conducted. Two previous studies have indicated executive dysfunction in BDD. The current study sought to further define these executive deficits. METHOD Fourteen DSM-IV BDD patients and 14 age- and sex-matched control participants took part. Because of the high incidence of co-morbidity in BDD, patients with co-morbid Axis I disorders were not excluded. Control participants had no history of psychiatric illness. All participants completed the following executive function (EF) tests: Spatial Span (SS), Spatial Working Memory (SWM) and the Stockings of Cambridge (SOC) task. They also completed the Pattern Recognition (PR) test, a test of visual memory (VM). RESULTS BDD participants made significantly more between-search errors on the SWM task, an effect that increased with task difficulty. Between-search errors are an example of poor maintenance and manipulation of information. SOC results indicated slower subsequent thinking times (i.e. the time taken to plan) in BDD participants. There were no group differences in SS or PR scores. The severity of BDD, depressive or anxiety symptoms was not correlated with performance on any of the cognitive tasks. CONCLUSIONS The results of this study indicate that BDD patients have EF deficits in on-line manipulation, planning and organization of information. By contrast, spatial memory capacity, motor speed and visual memory were intact. Considered with evidence from lesion and neuroimaging studies, these results suggest frontal lobe dysfunction in BDD.

Improving performance on the WCST: variations on the original procedure

There have been several studies on WCST training in schizophrenia. However, it is still unclear what aspects of the test schizophrenic patients find most difficult: are they failing because of impaired attention, memory or planning, to name a few possibilities? To address this, seven different versions of the WCST were developed, including a range of alternative stimuli and training techniques. The subjects were 24 schizophrenics and 24 elderly controls, divided into eight groups of three pairs (one group merely repeating the standard version), matched on their poor performance of the WCST (< 3 categories). Results on retesting with the standard WCST after carrying out a modified version, suggest levels of test performance are not fixed, and that modifications which promote planning, pacing and error detection are the most successful in improving WCST score, especially in schizophrenics. Additionally, performance was improved in controls, but not schizophrenic patients by increasing the verbal information contained in the task. The results indicate that WCST deficits in elderly controls are due to limited capacity, whereas in patient with schizophrenia, the problem may be due to the impaired monitoring of responses.

The muscarinic system, cognition and schizophrenia

An increasing body of evidence has implicated the central muscarinic system as contributing to a number of symptoms of schizophrenia and serving as a potential target for pharmaceutical interventions. A theoretical review is presented that focuses on the central muscarinic systems contribution to the cognitive symptoms of schizophrenia. The aim is to bridge the void between pertinent neuropsychological and neurobiological research to provide an explanatory account of the role that the central muscarinic system plays in the symptoms of schizophrenia. First, there will be a brief overview of the relevant neuropsychological schizophrenia literature, followed by a concise introduction to the central muscarinic system. Subsequently, we will draw from animal, neuropsychological and pharmacological literature, and discuss the findings in relation to cognition, schizophrenia and the muscarinic system. Whilst unifying the multiple domains of research into a concise review will act as a useful line of enquiry into the central muscarinic systems contribution to the symptoms of schizophrenia, it will be made apparent that more research is needed in this field.

Testosterone improves verbal learning and memory in postmenopausal women: Results from a pilot study

OBJECTIVE To explore the effects of testosterone on cognitive performance in healthy postmenopausal women. STUDY DESIGN Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47-60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison. MAIN OUTCOME MEASURES Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks. RESULTS There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group (p<0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p<0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p<0.02). CONCLUSION Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study.