Search

Background: Recent findings suggest that individuals with Huntington's disease (HD) have an impaired capacity to execute cognitive and motor tasks simultaneously, or dual task, which gradually worsens as the disease advances. The onset and neuropathological changes mediating impairments in dual tasking in individuals with HD are unclear. The reliability of dual tasking assessments for individuals with HD is also unclear., Objectives: To evaluate differences in dual tasking performance between individuals with HD (presymptomatic and prodromal) and matched controls, to investigate associations between striatal volume and dual tasking performance, and to determine the reliability of dual tasking assessments., Methods: Twenty individuals with HD (10 presymptomatic and 10 prodromal) and 20 healthy controls were recruited for the study. Individuals undertook four single and dual task assessments, comprising motor (postural stability or force steadiness) and cognitive (simple or complex mental arithmetic) components, with single and dual tasks performed three times each. Participants also undertook a magnetic resonance imaging assessment., Results: Compared to healthy controls, individuals with presymptomatic and prodromal HD displayed significant deficits in dual tasking, particularly cognitive task performance when concurrently undertaking motor tasks (P < 0.05). The observed deficits in dual tasking were associated with reduced volume in caudate and putamen structures (P < 0.05),however, not with clinical measures of disease burden. An analysis of the reliability of dual tasking assessments revealed moderate to high test-retest reliability [ICC: 0.61-0.99] for individuals with presymptomatic and prodromal HD and healthy controls., Conclusions: Individuals with presymptomatic and prodromal HD have significant deficits in dual tasking that are associated with striatal degeneration. Findings also indicate that dual tasking assessments are reliable in individuals presymptomatic and prodromal HD and healthy controls., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Huntington's disease (HD) is a progressive autosomal dominant disorder characterised by impairment of movement, cognitive decline and psychiatric impairment. During the premanifest stages of HD (pre-HD), there are notable structural and functional brain changes detectable many decades prior to clinical diagnosis. Although caudate atrophy is one of the earliest and most prominent sites of neuropathology, there is also evidence of cortical atrophy, compromised white and grey matter integrity, cortical hypometabolism, and aberrant task-related functional magnetic resonance imaging (fMRI) activity. Pre-HD individuals typically show increased task-related fMRI activity suggested as a strategy to compensate for early brain anomalies. In this study, we used a quantitative model of compensation, known as the CRUNCH (Compensation-Related Utilization of Neural Circuits Hypothesis), to explicitly characterise compensation in pre-HD. The assumption of the model is that fMRI activity increases as task difficulty increases (compensatory effect). However, when individuals reach the 'CRUNCH' point, where task difficulty exceeds their neural resources, fMRI activity and performance declines. We acquired fMRI data (n = 15 pre-HD; n = 15 controls) during performance of an fMRI visuospatial working memory task with low, intermediate-1, intermediate-2, and high memory loads. Consistent with the CRUNCH prediction, pre-HD individuals showed decreased fMRI activity in left intraparietal sulcus at high memory load, compared to healthy controls who showed increased fMRI activity in left intraparietal sulcus at high memory load. Contrary to the other CRUNCH prediction, the pre-HD group did not show compensatory increase in fMRI activity at lower levels of memory loads in left intraparietal sulcus. Our findings provide partial support for the validity of CRUNCH in pre-HD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Friedreich ataxia is characterized by progressive motor incoordination that is linked to peripheral, spinal, and cerebellar neuropathology. Cerebral abnormalities are also reported in Friedreich ataxia, but their role in disease expression remains unclear., Methods: In this cross-sectional functional magnetic resonance imaging study, 25 individuals with Friedreich ataxia and 33 healthy controls performed simple (self-paced single-finger) and complex (visually cued multifinger) tapping tasks to respectively gauge basic and attentionally demanding motor behavior. For each task, whole brain functional activations were compared between groups and correlated with disease severity and offline measures of motor dexterity., Results: During simple finger tapping, cerebral hyperactivation in individuals with Friedreich ataxia at the lower end of clinical severity and cerebral hypoactivation in those more severely affected was observed in premotor/ventral attention brain regions, including the supplementary motor area and anterior insula. Greater activation in this network correlated with greater offline finger tapping precision. Complex, attentionally demanding finger tapping was also associated with cerebral hyperactivation, but in this case within dorsolateral prefrontal regions of the executive control network and superior parietal regions of the dorsal attention system. Greater offline motor precision was associated with less activation in the dorsal attention network., Discussion: Compensatory activity is evident in the cerebral cortex in individuals with Friedreich ataxia. Early compensation followed by later decline in premotor/ventral attention systems demonstrates capacity-limited neural reserve, while the additional engagement of higher order brain networks is indicative of compensatory task strategies. Network-level changes in cerebral brain function thus potentially serve to mitigate the impact of motor impairments in Friedreich ataxia. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Objective: This study investigated whether dual tasks make disproportionately high demands in Huntington's disease (HD) compared with controls, and also tested the Multiple Resources Theory., Method: Thirteen HD participants and 13 controls completed 2 dual task sets that varied in difficulty and complexity: Set 1 paired simple choice reaction time (RT) with digit forward, and Set 2 paired complex choice RT with digit backward., Results: We found that HD participants were overall slower; however, although they maintained similar levels of accuracy in the simple choice RT tasks with controls, their accuracy decreased in the complex choice RT tasks. In addition, we found that HD participants were more susceptible to speed-accuracy trade-offs. Despite that, they did not show greater dual task costs than controls., Conclusions: Overall, our findings do not support the Multiple Resources Theory, but they do provide some support for the Unitary Resource Theory and the attentional impairment hypothesis., ((c) 2015 APA, all rights reserved).)

Objective: To determine the extent and nature of driving self-regulation in drivers with Parkinson disease (PD) and factors associated with self-regulatory practices., Background: Although people with PD have consistently been shown to have driving impairments, few studies have examined self-regulatory driving practices and their relationship to driving performance., Methods: We used a self-report driving questionnaire to examine driving self-regulation in 37 drivers with PD and 37 healthy age-matched controls. We also analyzed factors associated with self-regulatory practices, primarily demographic, disease-related, psychological, and simulated driving performance variables., Results: The drivers with PD reported significantly higher rates of self-perceived decline in their driving ability (P=0.008) and driving significantly shorter distances per week (P=0.004) than controls. Unfamiliar situations (P=0.009), in-car distractions (P<0.001), low visibility conditions (P=0.004), and long journeys (P=0.003) were particularly challenging for the drivers with PD, and their pattern of driving avoidance mirrored these difficulties. The use of self-regulatory strategies among drivers with PD was associated with female sex (rho=0.42, P=0.009) and perceived decline in driving ability (rho=-0.55, P<0.001), but not with age or objective measures of disease severity, cognition, or simulated driving performance., Conclusions: Drivers with PD reported driving less overall and restricting their driving to avoid particularly difficult circumstances. Further research is warranted on effective use of self-regulation strategies to improve driving performance in people with PD.

Huntington's disease (HD) is associated with impairments in dual-task performance. Despite that, only a few studies have investigated dual-tasking in HD. We examined dual-task performance in 15 participants in the early stages of HD and 15 healthy controls. Participants performed direct circle tracing (able to view arm) and indirect circle tracing (arm obscured) either on their own (single tasks) or paired with serial subtraction by twos or threes (dual tasks). Overall, our results suggested that HD participants were significantly slower and less accurate than controls. Both groups were slower and less accurate when performing indirect circle tracing compared with direct circle tracing. HD participants experienced greater dual-task interference in terms of accuracy when performing direct circle tracing compared with indirect circle tracing. Despite that, controls were more inclined to speed-accuracy trade-offs compared with HD participants. Importantly, unlike controls, HD participants were not disproportionately faster when performing direct circle tracing as a single task compared with the dual-task conditions. Our results suggest that simple tasks place greater attentional demands on HD participants compared with controls. These findings support that impaired automaticity may be responsible for some of the attentional deficits manifested in HD.

Objective: We sought to quantify subtle changes in motor control in multiple sclerosis (MS) using a Fitts law reciprocal aiming task presented on a computer touchscreen., Background: Upper-limb motor control is impaired in MS. However, many commonly used motor assessments do not detect subtle changes in motor function or differentiate between aspects of movement such as planning and online control. Fitts law states that movement time varies as a function of task difficulty, with smaller targets and greater distances making the task more difficult., Methods: We gave a Fitts aiming task to 22 patients with MS and 22 matched controls. We manipulated movement difficulty by changing the targets' size and distance apart., Results: The patients spent a significantly longer time than the controls stationary in each target before starting the next movement, and had a lower peak velocity, suggesting deficits in movement planning. The patients also spent longer in the deceleration phase of each movement, indicating deficits in the online control of movement., Conclusions: The computerized Fitts task allows quick, easy, and sensitive measurement of subtle aspects of movement. This task should be useful in clinical and research settings for assessing MS motor symptoms, disease progression, and treatment efficacy.

Objectives: To examine longitudinal changes in movement sequencing in prodromal Huntington's disease (HD) participants (795 prodromal HD; 225 controls) from the PREDICT-HD study., Methods: Prodromal HD participants were tested over seven annual visits and were stratified into three groups (low, medium, high) based on their CAG-Age Product (CAP) score, which indicates likely increasing proximity to diagnosis. A cued movement sequence task assessed the impact of advance cueing on response initiation and execution via three levels of advance information., Results: Compared to controls, all CAP groups showed longer initiation and movement times across all conditions at baseline, demonstrating a disease gradient for the majority of outcomes. Across all conditions, the high CAP group had the highest mean for baseline testing, but also demonstrated an increase in movement time across the study. For initiation time, the high CAP group showed the highest mean baseline time across all conditions, but also faster decreasing rates of change over time., Conclusions: With progress to diagnosis, participants may increasingly use compensatory strategies, as evidenced by faster initiation. However, this occurred in conjunction with slowed execution times, suggesting a decline in effectively accessing control processes required to translate movement into effective execution.

Objective and Background: The interplay between motor and cognitive functions during performance of concurrent tasks is not fully understood but is known to vary depending on task characteristics and across clinical populations. Our controlled study examined how a concurrent digit span task affected a motor stability and motor overflow task in patients with multiple sclerosis (MS)., Method: We asked 22 patients with MS and 22 matched controls to exert force on a transducer using 1 index finger at a time. We measured their motor stability (accuracy of voluntary force production) and motor overflow (involuntary force produced by the opposite, inactive finger). During half of the trials, the participants concurrently performed a digit span task., Results: Overall, the patients with MS had more motor overflow and less motor stability than the controls; these measures correlated with the patients' disease severity. Adding the concurrent task affected motor stability; this relationship varied with the required level of exerted force. Motor overflow was lower during trials with the concurrent task. The concurrent task affected patients and controls similarly for both motor stability and overflow., Conclusions: This study demonstrates preserved motor function in a concurrent-task paradigm in patients with MS, and sheds further light on the relationship between attention and motor function in both the patients and controls. This research may help to inform rehabilitation for everyday life situations in which patients routinely perform cognitive and motor tasks simultaneously.

Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We sought to examine motor planning ability in 13 individuals with FRDA and 13 age- and sex-matched control participants using two experimental paradigms that examined the ability to incorporate different levels of advance information to plan sequential movements. Individuals with FRDA demonstrated a differential pattern of motor response to advance information and were significantly disadvantaged by conditions requiring initiation of movement without a direct visual cue. There was also a significant negative correlation with age of disease onset and differing levels of advance information, suggesting an impact of FRDA on the development of motor cognition, independent of the effect of disease duration. We suggest that deficits are 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.

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., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Motor overflow refers to involuntary movement or muscle activity coinciding with voluntary movement. We examined whether 16 young adults (18-30 years) and 16 older adults (50-80 years) could voluntarily inhibit overflow. Participants performed a finger pressing task, exerting 50% of their maximal force. Overflow was concurrently recorded in the non-task hand. In the first condition, participants were not made aware of their motor overflow. Then participants, though informed of it, were asked to ignore their overflow. Finally, participants were requested to inhibit overflow with, and then without visual feedback, or vice versa. Overflow was exacerbated when older adults were unaware of it, and was reduced once they were informed. For young adults there was no significant difference between these conditions. Both Age Groups could significantly reduce overflow when so requested, independent of visual feedback. Thus motor overflow can be modulated by higher order cognitive control with directed attention., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

The cerebellar and spinocerebellar dysfunction seen in Friedreich ataxia (FRDA) has known effects on motor function. Recently, it was suggested that people with FRDA may also have impairment in motor planning, either because of cortical pathology or because of cerebello-cortical projections. Fifteen adults with FRDA and 15 matched controls completed a task requiring reciprocating movements between two buttons on a tapping board. Occasionally there was one of three "oddball" stimuli requiring reprogramming of movement. These were change in (1) direction, (2) extent or (3) direction and extent. We hypothesized that people with FRDA would have prolonged movement times due to their movement disorder, and that changes in preparation time would be affected in a way similar to controls, unless there was impairment in motor planning in FRDA. Movement execution and, to a lesser degree, movement preparation were impaired in individuals with FRDA. We argue this points to disturbed cortical function. There was a significant negative correlation between age of onset and all three reprogramming conditions, suggesting an impact of FRDA on developing motor planning. Future studies will be required to establish whether this dysfunction is due to cerebellar impairment interrupting cerebro-ponto-cerebello-thalamo-cerebral loops, primary cortical pathology or a combination of the two.

This study investigated the influence of attentional and motor demands on motor overflow in 17 healthy young (18-35 years) and 17 older adults (60-80 years). Participants performed a finger pressing task by exerting either 33% or 66% of their maximal force output using their dominant or nondominant hand. Overflow was concurrently recorded in the passive hand. Attention was manipulated via a tactile stimulus presented to one or both hands for certain trials. Results showed that older adults exhibited greater overflow than young adults and that the effect of target force was exacerbated in older adults. Further, only older adult overflow was increased when tactile stimulation was directed to one or both hands. Increased overflow in older adults may result from bilateral cortical activation that is influenced by increased task demands. To perform comparatively to younger adults, older adults may compensate for age-related brain changes by recruiting an increased cortical network.

Cognitive deficits in Huntington's disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate-frontal-motor-parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits.

Motor disturbances in major depressive disorder (MDD) are increasingly recognized and may differentiate melancholic, from non-melancholic depression. Motor impairments in melancholic depression have been likened to Parkinson's disease and proposed to have a frontostriatal basis. This study investigated self-pacing and reprogramming skills, thought to rely on frontostriatal functioning, in groups of healthy individuals (n=15), non-melancholic depression patients (n=10) and melancholic depression patients (n=9) using ocular motor tasks. Self-paced saccades were requested to be performed at a rhythm of 1 Hz between two continuously illuminated targets, before and after external cueing. Saccade reprogramming, for direction and amplitude, was explored using a saccadic "oddball" task. Results indicated no group differences for accuracy, intersaccadic intervals (during the self-paced task), latency or peak velocity. However, the melancholic group showed greater intrasubject variability of latencies than the control group, lower peak saccade velocities compared to the non-melancholic group, and reduced accuracy of the primary saccade when compared to the control and the non-melancholic groups. These findings provide further support for distinct motor impairments associated with melancholia that may reflect frontostriatal abnormalities.

A predictive central-cueing paradigm was used to compare visuospatial deficits in patients with Parkinson's (PD) and Huntington's diseases (HD), employing directionally valid and invalid visual cues over a range of stimulus onset asynchronies (SOA) to elicit a saccadic response. Compared to age-matched control groups, both PD and HD patients responded erroneously to cue stimuli more frequently, increasing significantly over longer SOAs. Both valid and invalid cues resulted in elevated latencies compared to un-cued visually guided saccades, the associated 'cost' of invalid cueing significantly greater than that for valid cueing, over all SOAs. Unlike control subjects, PD and HD patients demonstrated temporal variation with cue presentation. For PD patients, latencies following directionally invalid cues were significantly longer for intermediate SOAs, suggesting difficulty overcoming a build-up of inhibitory activity over time. No validity effect was found at 1000 ms. For HD patients, latencies for validly cued saccades with 150 ms SOAs were shorter than latencies for no-cue trials, representing a 'benefit' of valid cueing. For 500 ms SOAs latencies were comparably elevated following directionally valid and invalid cues, and for 1000 ms SOAs neither cue condition resulted in increased latencies. These findings reflect the consequence of disruption to the balance of activity over the basal ganglia facilitatory and inhibitory pathways. Imbalance in PD resulted in difficulty sustaining goal-directed behaviour, and in HD, difficulty gating inappropriate behaviour.

This study sought to evaluate impaired response tendencies and modulation of automatic processes in Parkinson's disease (PD), utilising a saccadic Simon task with stimulus-response (S-R) compatibility determined on the basis of cue shape. The appearance of either a circle or a square in one of two boxes presented peripherally required the generation of a leftward or rightward horizontal saccade, respectively. These goal-directed responses were considered behaviourally relevant to an examination of visuospatial performance. Although response times are typically faster when stimulus and response are spatially compatible than when they are not, sequence-dependent modulation of this effect results in large differences between S-R compatible and S-R incompatible trials when stimulus and response are spatially compatible in the preceding trial, and reduced or absent differences when stimulus and response are spatially incompatible in the preceding trial. Unlike control subjects, PD patients demonstrated significantly shorter saccadic latencies overall, compared to a baseline condition involving endogenously-driven saccades. Patients also responded erroneously to cue stimuli with greater frequency. Analyses of both saccadic latency and errors to cue demonstrated a Simon effect (relatively faster response for S-R compatible trials), irrespective of the preceding trial. This suggests impaired modulation of the Simon effect in PD, consistent with predictions of inhibitory dysfunction, or impaired episodic memory. These results demonstrate the pivotal role of the basal ganglia in the regulation of context-dependent neural activity.

Objectives and Background: Obsessive-compulsive disorder (OCD) is characterized by recurrent obsessions and/or compulsions that affect daily functioning. This study aimed to ascertain whether OCD patients have problems in orienting attention, via the use of a vibrotactile choice reaction time task., Methods: Participants were required to depress a button in response to a vibration delivered to the index finger of either the right or left hand. Prior to the stimulus, one of three precues was administered: valid (precue delivered to the same hand as stimulus), invalid (precue delivered to opposite hand to stimulus), or neutral (precue delivered simultaneously to both hands)., Results: Obsessive-compulsive disorder participants were overall slower and less accurate than controls. Contrary to our predictions, OCD participants did not show increased costs or benefits. However, unlike controls, patients did not show the normal pattern of faster reaction times on neutral compared with invalid precues, which may reflect a problem in inhibiting irrelevant information., Conclusions: Both patients and controls may benefit from the provision of directed attention in tactile tasks when difficulty levels are maximal. OCD patients may have problems with inhibitory control.