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Biomedical subjects

J L Bradshaw

Publications and source records attributed to J L Bradshaw.

At least 19 recordsLinked to original sources

Functional connectivity of the prefrontal cortex in Huntington's disease.

BACKGROUND: Huntington's disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. AIM: To assess the functional connectivity between prefrontal brain regions in patients with Huntington's disease, compared with normal controls, using functional magnetic resonance imaging. PATIENTS AND METHODS: 20 patients with Huntington's disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington's disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. RESULTS: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington's disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington's disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington's disease between the left anterior cingulate and prefrontal regions. CONCLUSIONS: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington's disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington's disease. It is speculated whether significantly greater levels of activation in patients with Huntington's disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.

Adult↗

Negative symptoms: A review of schizophrenia, melancholic depression and Parkinson's disease.

Negative symptoms generally refer to a reduction in normal functioning. In schizophrenia they encompass apathy, anhedonia, flat affect, avolition, social withdrawal and, on some accounts, psychomotor retardation. Negative symptoms have been identified in other psychiatric disorders, including melancholic depression, and also in neurological disorders, such Parkinson's disease. Achieving a better understanding of negative symptoms constitutes a priority in mental health. Primarily, negative symptoms represent an unrelenting, intractable and disabling feature for patients, often amounting to a severe burden on families, carers and the patients themselves. Identifying and understanding subgroups within disorders may also contribute to the clinical care and scientific understanding of the pathophysiology of these disorders. The purpose of this paper is to review the current literature on negative symptoms in schizophrenia and explore the idea that negative symptoms may play an important role not only in other psychiatric disorders such as melancholic depression, but also in neurological disorders, such as Parkinson's disease. In each disorder negative symptoms manifest with similar motor and cognitive impairments and are associated with comparable neuropathological and biochemical findings, possibly reflecting analogous impairments in the functioning of frontostriatal-limbic circuits.

Animals↗

The semantic Simon effect in Tourette's syndrome and obsessive-compulsive disorder.

Core symptoms of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD) may be attributed to an impairment in inhibitory control. Neuropsychological studies have addressed inhibition in both disorders, but findings have been inconsistent. The aim of this study was to examine cognitive inhibition, using a semantic Simon effect paradigm, in patients with TS and OCD. Furthermore, to address comorbidity a group of TS+OCD patients was also examined. Results indicated that patients with TS and OCD were affected by the inhibitory components of the task. TS groups performed similarly to controls on simple and choice RT tasks, but were particularly compromised as increasingly complex inhibitory demands were imposed. OCD patients were slower and committed more errors than controls, especially in the more cognitively demanding conditions, and were particularly disadvantaged by incongruent stimulus-response compatibilities. Findings implicate possible fronto-striatal dysfunction, are consistent with previously reported inhibitory deficits in TS and OCD, and support the theory that comorbid TS+OCD is more closely linked to pure TS than OCD.

Cognition Disorders↗

Neuropsychological function and driving ability in people with Parkinson's disease.

In this study the association between cognitive symptoms of PD and driving performance was investigated by examining the correlation between neuropsychological test performance and driving simulator behavior. Eighteen participants with PD and 18 healthy participants in a matched comparison group completed a range of neuropsychological measures. These data were correlated with driving simulator performance results from an earlier study. Significant correlations were found between several measures of neuropsychological test performance and driving behavior in participants with PD. In contrast, few significant correlations were obtained in the comparison group. Results suggest that executive difficulties in people with PD such as working memory, planning and set shifting are associated with reduced tactical level driving performance such as speed adaptation and complex curve navigation. Impaired information processing, visual attention and visual perception in people with PD appears associated with reduced operational level driving performance, such as reacting to road obstacles and maintaining constant lane position. Few correlations were found between measures of physical mobility and psychomotor speed with driving measures. Overall, this study highlights the important role of cognitive function in driving performance within the PD population. Comprehensive assessment of cognitive function should be included when assessing driving competency in people with PD.

Aged↗

A systematic, large-scale study of synaesthesia: implications for the role of early experience in lexical-colour associations.

For individuals with synaesthesia, stimuli in one sensory modality elicit anomalous experiences in another modality. For example, the sound of a particular piano note may be 'seen' as a unique colour, or the taste of a familiar food may be 'felt' as a distinct bodily sensation. We report a study of 192 adult synaesthetes, in which we administered a structured questionnaire to determine the relative frequency and characteristics of different types of synaesthetic experience. Our data suggest the prevalence of synaesthesia in the adult population is approximately 1 in 1150 females and 1 in 7150 males. The incidence of left-handedness in our sample was within the normal range, contrary to previous claims. We did, however, find that synaesthetes are more likely to be involved in artistic pursuits, consistent with anecdotal reports. We also examined responses from a subset of 150 synaesthetes for whom letters, digits and words induce colour experiences ('lexical-colour' synaesthesia). There was a striking consistency in the colours induced by certain letters and digits in these individuals. For example, 'R' elicited red for 36% of the sample, 'Y' elicited yellow for 45%, and 'D' elicited brown for 47%. Similar trends were apparent for a group of non-synaesthetic controls who were asked to associate colours with letters and digits. Based on these findings, we suggest that the development of lexical-colour synaesthesia in many cases incorporates early learning experiences common to all individuals. Moreover, many of our synaesthetes experienced colours only for days of the week, letters or digits, suggesting that inducers that are part of a conventional sequence (e.g. Monday, Tuesday, Wednesday...; A, B, C...; 1, 2, 3...) may be particularly important in the development of synaesthetic inducer-colour pairs. We speculate that the learning of such sequences during an early critical period determines the particular pattern of lexical-colour links, and that this pattern then generalises to other words.

Adolescent↗

Local-global processing in obsessive-compulsive disorder and comorbid Tourette's syndrome.

Neuropsychological and neuroimaging studies implicate attentional difficulties in obsessive-compulsive disorder (OCD), but results are inconsistent due possibly to sample heterogeneity and lack of control of comorbid disorders, such as Tourette's syndrome (TS). Nevertheless, it has been suggested that OCD symptomatology may be a result of over-focused attention at a local level. Therefore, this study aimed to examine the ability of OCD patients (pure and comorbid OCD + TS) to process local and global stimuli. Using a local-global paradigm, participants were required to respond to the directed level (local or global) of various stimuli. Results indicate that pure OCD participants were impaired on the global task, whereas comorbid OCD + TS participants had difficulty processing local information. Results are consistent with previously reported lateralisation anomalies and suggest that OCD negatively affects the ability to process hierarchically presented stimuli.

Adult↗

Fronto-parietal activation in attention-deficit hyperactivity disorder, combined type: functional magnetic resonance imaging study.

A functional magnetic resonance imaging mental rotation paradigm was used to investigate the patterns of activation of fronto-parietal brain areas in male adolescents with attention-deficit hyperactivity disorder, combined type (ADHD-CT) compared with age-, gender-, handedness- and performance IQ-matched healthy controls. The ADHD-CT group had (a) decreased activation of the 'action-attentional' system (including Brodmann's areas (BA) 46, 39, 40) and the superior parietal (BA 7) and middle frontal (BA10) areas and (b) increased activation of the posterior midline attentional system. These different neuroactivation patterns indicate widespread frontal, striatal and parietal dysfunction in adolescents with ADHD-CT.

Adolescent↗

Response selection deficits in melancholic but not nonmelancholic unipolar major depression.

One consistent functional imaging finding from patients with major depression has been abnormality of the anterior cingulate cortex (ACC). Hypoperfusion has been most commonly reported, but some studies suggest relative hyperperfusion is associated with response to somatic treatments. Despite these indications of the possible importance of the ACC in depression there have been relatively few cognitive studies ACC function in patients with major depression. The present study employed a series of reaction time (RT) tasks involving selection with melancholic and nonmelancholic depressed patients, as well as age-matched controls. Fifteen patients with unipolar major depression (7 melancholic, 8 nonmelancholic) and 8 healthy age-matched controls performed a series of response selection tasks (choice RT, spatial Stroop, spatial stimulus-response compatibility (SRC), and a combined Stroop + SRC condition). Reaction time and error data were collected. Melancholic patients were significantly slower than controls on all tasks but were slower than nonmelancholic patients only on the Stroop and Stroop + SRC conditions. Nonmelancholic patients did not differ from the control group on any task. The Stroop task seems crucial in differentiating the two depressive groups, they did not differ on the choice RT or SRC tasks. This may reflect differential task demands, the SRC involved symbolic manipulation that might engage the dorsal ACC and dorsolateral prefrontal cortex (DLPFC) to a greater extent than the, primarily inhibitory, Stroop task which may engage the ventral ACC and orbitofrontal cortex (OFC). This might suggest the melancholic group showed a greater ventral ACC-OFC deficit than the nonmelancholic group, while both groups showed similar dorsal ACC-DLPFC deficit.

Adult↗

Motor overflow in Huntington's disease.

We investigated both motor overflow and ability to control voluntary movement in patients with Huntington's disease (HD). We hypothesised that, compared with controls, overflow would be significantly greater in HD participants and that they would exhibit poorer control of voluntary movement. In a finger flexion task, participants had to maintain target forces representing 25, 50, or 75% of the maximum strength capacity for whichever finger was performing the task; overflow was measured in the corresponding finger of the non-responding hand. HD participants exhibited significantly greater motor overflow than controls, and more difficulty controlling the target force with the active hand. In addition, the degree of overflow in HD participants positively correlated with overall UHDRS motor symptom severity. The presence of exacerbated motor overflow in HD, and its correlation with symptom severity, is an important finding worthy of further investigation.

Biomechanical Phenomena↗

Hypometric primary saccades and increased variability in visually-guided saccades in Huntington's disease.

Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of 11 HD patients and 11 matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10 degrees, 20 degrees, 30 degrees, 40 degrees ), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement.

Adult↗

Attentional asymmetries following ECT in patients with major depression.

Neuropsychological abnormalities of lateralization have been reported after right unilateral electroconvulsive therapy (ECT), that may reflect temporary disruption of the treated hemisphere. A visuospatial task sensitive to lateralization of spatial attention was administered in a test-retest design to patients with unipolar major depression and a group of age and gender matched controls. The patient group underwent right unilateral ECT between the two test sessions. The patient and control groups did not differ significantly at the initial baseline testing. After ECT, the patient group showed a significant shift of attentional bias toward the left, while the control group showed no significant shift in the second session relative to the first. The results suggest that approximately 1 h after termination of ictus there is a leftward attentional bias, possibly reflecting a change in right hemisphere cerebral activity.

Adult↗

Abnormal line bisection judgements in children with Tourette's syndrome.

Tourette's syndrome (TS) has been associated with loss of normal basal ganglia asymmetry, as well as loss of normal functional asymmetry, including the leftward bias on traditional visuospatial tasks such as line bisection and turning bias tests. The aim of the present study was to examine the lateralisation of visuospatial attention in TS. We examined the effect of an irrelevant moving-dot background on line bisection judgements. Nine children with a DSM IV diagnosis of TS participated, in addition to 9 healthy controls, individually matched for age, sex and IQ. Horizontal lines of varying length were presented on a computer screen with either a blank background, or a moving, random-dot field. The dots moved either leftward or rightward across the screen at 40 or 80 mm/s, and participants were instructed to ignore these distracting stimuli when judging the lines. TS children were found to be abnormally right-biased in line bisection in a similar fashion to unmedicated ADHD children who, in a previous study, showed a similar small, yet significant, right-bias in line bisection. Matched controls showed a small, nonsignificant left bias, consistent with past research. Unlike previous findings with hemineglect patients, the irrelevant moving background had no effect on bisection performance for TS children or healthy controls. The present findings suggest a deficit in visuospatial attention consistent with the emerging picture of a lateralised dysfunction of frontostriatal circuitry in TS.

Adolescent↗

Mental rotation in unipolar major depression.

Mental rotation (MR) performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. MR was employed with a sample of both melancholic (n=8) and non-melancholic (n=9) unipolar depressed patients and healthy controls (n=10) to determine if motor slowing associated with depression might be reflected in slowed motor preparation (as reflected in slope of the MR function) independent of actual motor slowing (overall response time). Both melancholic and non-melancholic patients showed a generalised slowing relative to controls, perhaps reflecting bradykinesia and akinesia. This effect was significantly greater in the melancholic group than in the non-melancholic group. Relative to both the controls and the non-melancholic groups, the melancholic patients showed a progressive slowing with increasing angle of orientation indicating a specific slowing of MR. This deficit suggests a role of slowed motor planning in the psychomotor retardation of patients with melancholic depression.

Adult↗

Unconscious priming eliminates automatic binding of colour and alphanumeric form in synaesthesia.

Synaesthesia is an unusual perceptual phenomenon in which events in one sensory modality induce vivid sensations in another. Individuals may 'taste' shapes, 'hear' colours, or 'feel' sounds. Synaesthesia was first described over a century ago, but little is known about its underlying causes or its effects on cognition. Most reports have been anecdotal or have focused on isolated unusual cases. Here we report an investigation of 15 individuals with colour-graphemic synaesthesia, each of whom experiences idiosyncratic but highly consistent colours for letters and digits. Using a colour-form interference paradigm, we show that induced synaesthetic experiences cannot be consciously suppressed even when detrimental to task performance. In contrast, if letters and digits are presented briefly and masked, so that they are processed but unavailable for overt report, the synaesthesia is eliminated. These results show that synaesthetic experiences can be prevented despite substantial processing of the sensory stimuli that otherwise trigger them. We conclude that automatic binding of colour and alphanumeric form in synaesthesia arises after initial processes of letter and digit recognition are complete.

Adult↗

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.

Aged↗

Bimanual coordination in chronic schizophrenia.

Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia, a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0 degrees ) and out-of-phase movements (hands separated by 180 degrees ) at both speeds with an external cue on or off. All participants performed the in-phase movements well, irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved.

Adult↗

Movement-related potentials in Huntington's disease: movement preparation and execution.

Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD, particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.

Adult↗

Focal dystonia: current theories.

Dystonia is a syndrome characterised by abnormal involuntary sustained muscle contractions that often result in twisted and abnormal positions. Focal dystonia affects only a single body part with symptoms varying from permanent (e.g., torticollis) to task-specific (e.g., musician's cramp). The exact causes of focal dystonia have yet to be determined. Possible causative factors have been identified at all levels along the sensorimotor pathway, including anatomical constraints of the hand (musicians), abnormal co-contractions of the muscles due to reciprocal inhibition in the spinal cord, subcortical and cortical remapping, deficiencies in sensorimotor integration and perceptual deficits. A review of the current literature on these topics is provided with a special focus on musicians with focal dystonia. Also reviewed are current treatments of focal dystonia in musicians. On the basis of the currently available evidence, certain risk factors are identified for the development of task-specific focal dystonia, including number of practice hours, personality, genetic predisposition, performance factors and sensory effects. In addition, it is highlighted that dystonic movements occur predominantly in the context of perceptual-motor tasks involving emotions. When emotional and motor traces have become associated, they are difficult to change; it is suggested that this mechanism plays an important role in the preservation of dystonic symptoms.

Adult↗