Attentional Mechanisms in Autism, ADHD, and Autism-ADHD Using a Local-Global Paradigm.

OBJECTIVE: Cognitive flexibility or attentional set-shifting capacity has long been considered a core area of executive dysfunction for individuals with autism. Whether these difficulties are due to higher-level attentional difficulties associated with comorbid ADHD remains unclear. METHOD: The current study compared the performance of 48 participants with autism, ADHD, autism-ADHD, and a comparison group ( N = 12 per group) on a set-shifting task, which included a local-global paradigm. RESULTS: Results of this study revealed that participants with attentional difficulties (autism + ADHD and ADHD alone) exhibited a significant shifting cost (difference between maintaining and shifting attention). CONCLUSION: Attentional difficulties associated with ADHD may be associated with an enhanced attentional shifting cost. Implications of these results were discussed in relation to screening for ADHD symptoms in studies of individuals with autism which seek to determine the neuropsychological profile of this condition.

Symbolic sequence learning is associated with cognitive-affective profiles in female FMR1 premutation carriers.

This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)-carriers. A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and intelligence quotient-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers.

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.

The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression.

Gait adaptation during obstacle crossing reveals impairments in the visual control of locomotion in Williams syndrome.

Recent evidence indicates that individuals with Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, show abnormalities of parietal and cerebellar regions of the brain that may be involved in the visual control of locomotion. Here we examined whether parietal and cerebellar abnormalities contribute to deficits in spatiotemporal characteristics and foot placement variability during obstacle crossing in adults with WS, when compared with an IQ-matched group of adults with Down syndrome (DS) and typically developing adult controls. We used the GAITRite walkway to examine the spatiotemporal characteristics and foot placement variability relative to a small ground-based obstacle in the travel path. We found that adults with WS showed late adjustments to spatiotemporal gait characteristics alongside an exaggerated and more spatially constrained visual guidance of foot positioning in the final steps prior to stepping over the obstacle. In contrast, the adults with DS showed longer step duration and more variable step length and step duration during the crossing and recovery steps after the obstacle, suggestive of cerebellar dysfunction. Although the controls were able to reduce the variability of foot placement across the obstacle crossing trials, both the WS and DS groups did not become more consistent with practice. These findings indicate a less flexible and overly constrained visuomotor system in WS, which is consistent with more widespread and diffuse abnormalities in parietal and cerebellar regions.

The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity?

Friedreich ataxia (FRDA) is the most common of the inherited ataxias. We have suggested that people with FRDA may have impairment in cognitive and/or psychomotor capacity either due to disturbance of projections of the cerebellum to the cortex, direct cortical pathology or perhaps both. To further explore this possibility, we used a movement task incorporating Fitts' Law, a robust description of the relationship between movement time and accuracy in goal-directed aiming movements. By manipulating task difficulty, according to target size and distance, we were able to quantify processes related to motor planning in 10 individuals with FRDA and 10 matched control participants. Compared to control participants, people with FRDA were significantly disadvantaged in terms of movement time to targets with an increasing index of difficulty. Successful completion of this task requires both preplanning of movement and online error detection and correction. The cerebellum and its connections to the frontal cortex via cerebro-ponto-cerebello-thalamo-cerebral loops are fundamental to both processes. These results lend further support to our contention that in FRDA these loops are impaired, reflecting a failure to access prefrontal/anterior regions necessary for effective management of preplanning of movement and online error correction.

Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task.

Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We recently demonstrated that people with FRDA have impairment in motor planning - most likely because of pathology affecting the cerebral cortex and/or cerebello-cortical projections. We used the Simon interference task to examine how effective 13 individuals with FRDA were at inhibiting inappropriate automatic responses associated with stimulus-response incompatibility in comparison with control participants. Participants had to respond to arrow targets according to two features which were either congruent or incongruent. We found that individuals with FRDA were differentially affected in reaction time to incongruent, compared with congruent stimuli, when compared with control participants. There was a significant negative correlation between age of onset and the incongruency effect, suggesting an impact of FRDA on the developmental unfolding of motor cognition, independent of the effect of disease duration. Future neuroimaging studies will be required to establish whether this dysfunction is due to cerebellar impairment disrupting cerebro-ponto-cerebello-thalamo-cerebral loops (and thus cortical function), direct primary cortical pathology, or a possible combination of the two.

Right-sided spatial difficulties in ADHD demonstrated in continuous movement control.

Children with Attention Deficit Hyperactivity Disorder (ADHD) often show spatial attentional deficits, exhibiting a subtle rightwards bias, possibly due to dysfunction within the right hemisphere fronto-parietal network. Approximately 50% of children with ADHD also show signs of movement dysfunction. The nature of this movement dysfunction and possible interactions with spatial attention difficulties has not been clearly described. This study compared 31 children with and 31 children without ADHD on a movement kinematic task that tested hand-drawing movement precision. Participants used an electronic pen on a digitizing tablet. The pen tip position was sampled as X and Y coordinates at 200Hz. The task was to join targets of either 10 or 20mm diameter that were separated by a distance of 62.5 or 125 mm. Constant error in the X and Y planes, peak absolute velocity and acceleration, movement time, the number of pauses and pause time were analysed. Apart from a significantly increased rate of acceleration across all conditions, the children with ADHD demonstrated no temporal difficulties with the task; rather they showed subtle spatial difficulties, possibly suggestive of cerebellar involvement. The children with ADHD showed difficulties in accuracy of movement towards the right. They were less accurate in the X plane when moving towards the right-sided targets over the long distance. Greater variability in target accuracy was shown when moving towards the small target on the right side. The children with ADHD made significantly more pauses on the left target, when preparing the right movement, than the control group. These results suggest that the subtle spatial bias towards the right that has been demonstrated in ADHD in spatial attention also extends into the continuous movement domain.

Right parietal dysfunction in children with attention deficit hyperactivity disorder, combined type: a functional MRI study.

Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, striatal and parietal activation with a mental rotation task shown in adolescents with ADHD-CT is also evident in children with ADHD-CT. A cross-sectional study of 12 pre-pubertal, right-handed, 8-12-year-old boys with ADHD-CT and 12 pre-pubertal, right-handed, performance IQ-matched, 8-12-year-old healthy boys, recruited from local primary schools, was completed. Participants underwent functional magnetic resonance imaging while performing a mental rotation task that requires spatial working memory. The two groups did not differ in their accuracy or response times for the mental rotation task. The ADHD-CT group showed significantly less activation in right parieto-occipital areas (cuneus and precuneus, BA 19), the right inferior parietal lobe (BA 40) and the right caudate nucleus. Our findings with a child cohort confirm previous reports of right striatal-parietal dysfunction in adolescents with ADHD-CT. This dysfunction suggests a widespread maturational deficit that may be developmental stage independent.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.