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In Huntington's disease (HD), the presence of neurodegeneration in brain regions other than the striatum has been recently gaining attention. The amygdala is one such area, which has been investigated in only eight structural magnetic... more
In Huntington's disease (HD), the presence of neurodegeneration in brain regions other than the striatum has been recently gaining attention. The amygdala is one such area, which has been investigated in only eight structural magnetic resonance imaging studies to date, but with inconsistent findings. This is the largest MRI study to date examining manually traced amygdala volumes in HD participants and the relationship of amygdala volumes to clinical measures of HD. Our study included 35 healthy control participants, and groups of 35 pre-symptomatic, and 36 symptomatic HD participants. When comparing the pre-symptomatic and symptomatic HD groups together against the control group, amygdala volumes were significantly lower in HD than controls and in symptomatic HD than pre-symptomatic HD. When examining relationships between amygdala volumes and clinical measures of HD, significantly smaller amygdala volumes were associated with worse motor and cognitive signs. For pre-symptomati...
Chronic pain is associated with reduced efficiency of cognitive performance, and few studies have investigated methods of remediation. We trialled a computerised cognitive training protocol to determine whether it could attenuate... more
Chronic pain is associated with reduced efficiency of cognitive performance, and few studies have investigated methods of remediation. We trialled a computerised cognitive training protocol to determine whether it could attenuate cognitive difficulties in a chronic pain sample. Thirty-nine adults with chronic pain (mean age = 43.3, 61.5% females) were randomised to an 8-week online course (3 sessions/week from home) of game-like cognitive training exercises, or an active control involving watching documentary videos. Participants received weekly supervision by video call. Primary outcomes were a global neurocognitive composite (tests of attention, speed, and executive function) and self-reported cognition. Secondary outcomes were pain (intensity; interference), mood symptoms (depression; anxiety), and coping with pain (catastrophising; self-efficacy). Thirty participants (15 training and 15 control) completed the trial. Mixed model intention-to-treat analyses revealed significant effects of training on the global neurocognitive composite (net effect size [ES] = 0.43, P = 0.017), driven by improved executive function performance (attention switching and working memory). The control group reported improvement in pain intensity (net ES = 0.65, P = 0.022). Both groups reported subjective improvements in cognition (ES = 0.28, P = 0.033) and catastrophising (ES = 0.55, P = 0.006). Depression, anxiety, self-efficacy, and pain interference showed no change in either group. This study provides preliminary evidence that supervised cognitive training may be a viable method for enhancing cognitive skills in persons with chronic pain, but transfer to functional and clinical outcomes remains to be demonstrated. Active control results suggest that activities perceived as relaxing or enjoyable contribute to improved perception of well-being. Weekly contact was pivotal to successful program completion.
Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain... more
Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene. There is accumulating evidence to suggest that early cognitive and brain imaging signs may be observed in some premutation carriers without motor signs of FXTAS, but few studies have examined the relationships between subcortical brain volumes and cognitive performance in this group. This study examined the relationships between caudate volume and select cognitive measures (executive function and information processing speed) in men at risk of developing FXTAS and controls with normal FMR1 alleles (<45 CGG repeats). The results showed that men with premutation alleles performed worse on measures of executive function and information processing speed, and had significantly reduced caudate volume, compared to controls. Smaller caudate volume in the premutation group was associated with slower processing speed. These findings ...
Intrinsic motivation is essential for academic success and cognitive growth, but limited work has examined the neuroanatomical underpinnings of intrinsic motivation from a network perspective, particularly in early childhood. Using graph... more
Intrinsic motivation is essential for academic success and cognitive growth, but limited work has examined the neuroanatomical underpinnings of intrinsic motivation from a network perspective, particularly in early childhood. Using graph theoretical analysis, this study investigated global and local properties of structural connectivity networks in relation to intrinsic motivation within a vulnerable group of children at early school age. Fifty-three 7 year-old children born extremely preterm (<28 weeks' gestational age)/extremely low birth weight (<1000 g) underwent T1 and diffusion weighted imaging. Structural connectivity networks were generated using 162 cortical and subcortical nodes, and edges were created using constrained spherical deconvolution-based tractography. Global and node-specific network measures were analyzed in association with self-reported aspects of intrinsic motivation for school learning (Mastery, Challenge and Curiosity) using linear regression. R...
Previous research has suggested that heart rate variability (HRV; the variability in the interval between successive heartbeats) can predict the perception of experimentally-induced pain (i.e., pain sensitivity). However, little research... more
Previous research has suggested that heart rate variability (HRV; the variability in the interval between successive heartbeats) can predict the perception of experimentally-induced pain (i.e., pain sensitivity). However, little research has sought to investigate sex-specific associations between HRV and pain sensitivity. This is an important consideration, given that sex differences in resting HRV have been observed, and there has been extensive debate about sex differences in sensitivity to experimentally-induced pain. We examined whether the association between resting HRV and sensitivity to experimentally-induced pain differed in men and women. Fifty-one pain free individuals (26 women, mean age = 21.9 years) participated. Resting electrocardiography (ECG) was collected during a paced breathing task (15 cycles per minute), and measures of HRV were extracted via Fast Fourier Transformation. Thermal heat pain threshold (i.e., the point at which the sensation was first perceived as...
People with Huntington's disease (HD) experience poor social quality of life, relationship breakdown, and social withdrawal, which are mediated to some extent by socially debilitating neuropsychiatric symptoms, such as apathy and... more
People with Huntington's disease (HD) experience poor social quality of life, relationship breakdown, and social withdrawal, which are mediated to some extent by socially debilitating neuropsychiatric symptoms, such as apathy and disinhibition. Social cognitive symptoms, such as impaired emotion recognition, also occur in HD, however, the extent of their association with these socially debilitating neuropsychiatric symptoms is unknown. Our study examined the relationship between emotion recognition and symptom ratings of apathy and disinhibition in HD. Thirty-two people with premanifest or symptomatic-HD completed Part 1 of The Awareness of Social Inference Test (TASIT), which is a facial emotion recognition task. In addition, we obtained severity ratings for apathy and disinhibition on the Frontal Systems Behavior Scale (FrSBe) from a close family member. Our analyses used motor symptom severity as a proxy for disease progression. Emotion recognition performance was significant...
Cerebellar ataxia often results in impairment in ambulation secondary to gait pattern dysfunction and compensatory gait adjustments. Pharmaceutical and therapy-based interventions with potential benefit for gait in ataxia are starting to... more
Cerebellar ataxia often results in impairment in ambulation secondary to gait pattern dysfunction and compensatory gait adjustments. Pharmaceutical and therapy-based interventions with potential benefit for gait in ataxia are starting to emerge, however evaluation of such interventions is hampered by the lack of outcome measures that are responsive, valid and reliable for measurement of gait decline in cerebellar ataxia. This systematic review aimed for the first time to evaluate the psychometric properties of gait and walking outcomes applicable to individuals with cerebellar ataxia. Only studies evaluating straight walking were included. A comprehensive search of three databases (MEDLINE, CINAHL and EMBASE) identified 53 studies meeting inclusion criteria. Forty-nine were rated as 'poor' as assessed by the COnsensus-based Standards for the selection of health Measurement INstruments checklist. The primary objective of most studies was to explore changes in gait related to ...
Navigating obstacles whilst walking might be associated with poorer balance and a higher risk of falling in individuals with symptomatic Huntington's disease (symp-HD). However, this issue has not been investigated within the... more
Navigating obstacles whilst walking might be associated with poorer balance and a higher risk of falling in individuals with symptomatic Huntington's disease (symp-HD). However, this issue has not been investigated within the literature. A unique obstacle navigation experiment was designed to examine adaptive gait patterns in order to identify spatiotemporal gait characteristics that might be associated with poorer balance and a higher risk of falling in symp-HD. Sixteen diagnosed symp-HD participants and 16 age- and sex-matched healthy controls were included. Gait was examined in 3 experimental conditions: baseline walking, walking while navigating around 1 obstacle, and walking while navigating around 2 obstacles. Navigation around obstacle walks was divided into three step phases (approach, navigation, recovery). Group differences in gait variables were analyzed at baseline and during walking for each obstacle condition respectively. Gait variables were also correlated with t...
To determine the effectiveness of a six-week rehabilitation programme followed by a home exercise programme for Friedreich's ataxia. Randomized, delayed-start control single-blind trial. Outpatient rehabilitation centre. Ambulant or... more
To determine the effectiveness of a six-week rehabilitation programme followed by a home exercise programme for Friedreich's ataxia. Randomized, delayed-start control single-blind trial. Outpatient rehabilitation centre. Ambulant or non-ambulant individuals with Friedreich's ataxia. Participants were randomized to a six-week outpatient rehabilitation programme, immediately (intervention group) or after a six-week delayed-start (control group). The rehabilitation was followed by a six-week home exercise programme. The primary outcome was the Functional Independence Measure. Other measures included the Friedreich Ataxia Impact Scale and the Friedreich Ataxia Rating Scale. Outcomes were administered at baseline, 6, 12 and 18 weeks. Of 159 individuals screened, 92 were excluded and 48 declined to participate. A total of 19 participants were enrolled in the study. There was no significant difference in Functional Independence Measure change from baseline to six weeks in the inter...
Many factors can influence the way in which we perceive painful events and noxious stimuli, but less is known about how pain perception is altered by explicit knowledge about the impending sensation. This study aimed to investigate the... more
Many factors can influence the way in which we perceive painful events and noxious stimuli, but less is known about how pain perception is altered by explicit knowledge about the impending sensation. This study aimed to investigate the impact of explicit cueing on anxiety, arousal, and pain experience during the anticipation and delivery of noxious thermal heat stimulations. Fifty-two healthy volunteers were randomised to receive explicit instructions about visual cue-stimulus temperature pairings, or no explicit instructions about the cue-stimulus pairs. A pain anxiety task was used to investigate the effects of explicit cueing on anticipatory anxiety, pain experience and electrophysiological responses. Participants who received explicit instructions about the cue-stimulus pairs (i.e., the relationship between the colour of the cue and the temperature of the associated stimuli) reported significantly higher subjective anxiety prior to the delivery of the thermal heat stimuli (p = ....
People with Huntington's disease (HD) exhibit altered processing of emotional information, especially disgust and other negative emotions. These impairments are likely due to the effects of the disease on underlying brain... more
People with Huntington's disease (HD) exhibit altered processing of emotional information, especially disgust and other negative emotions. These impairments are likely due to the effects of the disease on underlying brain networks. We examined whether oxytocin, when given intranasally, would normalise aberrant brain reactivity to emotional faces in participants with the gene-expansion for HD. In a double-blind placebo-controlled cross-over design, we measured brain activity, using functional magnetic resonance imaging, whilst nine medication-free HD carriers, and ten control participants viewed emotional (disgust, fear, angry, sad, surprise, happy) and neutral faces, following acute intranasal oxytocin (24IU) and placebo. Subjective mood changes were assessed before and after the neuroimaging on each visit. Permutation-based non-parametric statistical testing for the whole brain, showed significant group×drug interactions (p's<0.05, TFCE corrected) in areas of the left frontal pole, superior frontal, and middle frontal gyri cortically, and left putamen and thalamus sub-cortically. Parameter estimates extracted from the middle frontal gyrus and putamen showed that, under placebo, the HD group had lower brain activity to disgust stimuli, compared with controls. After intranasal oxytocin, the pattern of activation to disgust stimuli was normalised in the HD group to similar levels as controls; eight of the nine HD carriers showed increased response in the middle frontal gyrus, and seven of the nine HD carriers showed increased response in the putamen. The observed effects of oxytocin occurred in the absence of changes in subjective mood or state anxiety. These findings provide early evidence for a physiological role of oxytocin in the neuropathology of HD. Our findings are the first reported oxytocin effects in a neurodegenerative disease. Further research should examine the therapeutic benefits of oxytocin in alleviating emotional and social cognition deficits in HD and related disorders.
Heart rate variability (HRV) refers to variation in the interval between successive heart beats. Low HRV is an indicator of potential autonomic nervous system dysfunction. People with chronic pain often display autonomic dysregulation,... more
Heart rate variability (HRV) refers to variation in the interval between successive heart beats. Low HRV is an indicator of potential autonomic nervous system dysfunction. People with chronic pain often display autonomic dysregulation, especially in the parasympathetic nervous system. The hormone oxytocin has been shown to increase HRV in non-clinical samples, but its potential impact on HRV in persons with chronic pain is unknown. This study investigated the impact of intranasal oxytocin on HRV in persons with chronic neck and shoulder pain. Participants included 24 individuals with chronic neck and shoulder pain lasting >12months and 24 age- and sex-matched pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants self-administered intranasal oxytocin (24IU) in one session, and placebo in another, before HRV was recorded at rest and during a mental arithmetic task. Intranasal oxytocin did not influence HRV at rest. However, compared to placebo, intranasal oxytocin elicited small decreases in low-frequency and high-frequency HRV in both groups during the mental arithmetic task. These results suggest that intranasal oxytocin may enhance the salience of the mental arithmetic task, leading to reduced engagement of the parasympathetic nervous system when completing the task. Further investigation and replication of these findings are required to improve our understanding of the effects of intranasal oxytocin on autonomic functioning both at rest and under cognitive stress.
Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of... more
Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404.
Traumatic injury can lead to loss, suffering and feelings of injustice. Previous research has shown that perceived injustice is associated with poorer physical and mental wellbeing in persons with chronic pain. This study aimed to... more
Traumatic injury can lead to loss, suffering and feelings of injustice. Previous research has shown that perceived injustice is associated with poorer physical and mental wellbeing in persons with chronic pain. This study aimed to identify the relative association between injury, compensation and pain-related characteristics and perceived injustice 12-months after traumatic injury. 433 participants were recruited from the Victorian Orthopedic Trauma Outcomes Registry and Victorian State Trauma Registry, and completed questionnaires at 12-14 months after injury as part of an observational cohort study. Using hierarchical linear regression we examined the relationships between baseline demographics (sex, age, education, comorbidities), injury (injury severity, hospital length of stay), compensation (compensation status, fault, lawyer involvement), and health outcomes (SF-12) and perceived injustice. We then examined how much additional variance in perceived injustice was related to wo...
Deficits in the recognition of negative emotions emerge before clinical diagnosis in Huntington's disease (HD). To address emotion recognition deficits, which have been shown in schizophrenia to be improved by computerized training,... more
Deficits in the recognition of negative emotions emerge before clinical diagnosis in Huntington's disease (HD). To address emotion recognition deficits, which have been shown in schizophrenia to be improved by computerized training, we conducted a study of the feasibility and efficacy of computerized training of emotion recognition in HD. We randomly assigned 22 individuals with premanifest or early symptomatic HD to the training or control group. The training group used a self-guided online training program, MicroExpression Training Tool (METT), twice weekly for 4 weeks. All participants completed measures of emotion recognition at baseline and post-training time-points. Participants in the training group also completed training adherence measures. Participants in the training group completed seven of the eight sessions on average. Results showed a significant group by time interaction, indicating that METT training was associated with improved accuracy in emotion recognition. ...
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... more
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. 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. 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...
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with subtle impact on cognition. Inhibitory processes and cognitive flexibility were examined in FRDA by assessing the ability to suppress a predictable verbal... more
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with subtle impact on cognition. Inhibitory processes and cognitive flexibility were examined in FRDA by assessing the ability to suppress a predictable verbal response. We administered the Hayling Sentence Completion Test (HSCT), the Trail Making Test, and the Stroop Test to 43 individuals with FRDA and 42 gender- and age-matched control participants. There were no significant group differences in performance on the Stroop or Trail Making Test whereas significant impairment in cognitive flexibility including the ability to predict and inhibit a pre-potent response as measured in the HSCT was evident in individuals with FRDA. These deficits did not correlate with clinical characteristics of FRDA (age of disease onset, disease duration, number of guanine-adenine-adenine repeats on the shorter or larger FXN allele, or Friedreich Ataxia Rating Scale score), suggesting that such impairment may not be related t...
Recent evidence indicates that adults with a premutation (PM: 55-199 CGG repeats) expansion in the fragile X mental retardation 1 (FMR1) gene show postural control deficits that may reflect disruption to cerebellar motor regions. Less is... more
Recent evidence indicates that adults with a premutation (PM: 55-199 CGG repeats) expansion in the fragile X mental retardation 1 (FMR1) gene show postural control deficits that may reflect disruption to cerebellar motor regions. Less is known about the influence of reduced cerebellar volume and structural changes, and increase in CGG repeat and FMR1 mRNA levels on the attentional demands of step initiation in PM males. We investigated the effects of a concurrent cognitive task on choice stepping reaction time (CSRT) and explored the associations between CSRT performance, cerebellar volume, CGG size, and FMR1 mRNA levels in blood in PM males. We examined 19 PM males (ages 28-75) and 23 matched controls (CGG <44; ages 26-77), who performed a verbal fluency task during CSRT performance and single-task stepping without a secondary cognitive task. Our results provide preliminary evidence that smaller cerebellar volume (β = -2.73, p = 0.002) and increasing CGG repeat length (β = 1.69,...
Friedreich ataxia (FRDA) is traditionally associated with neuropathology in the cerebellar dentate nucleus and spinal cord. Growing evidence also suggests involvement of the cerebral and cerebellar cortices, although reports of structural... more
Friedreich ataxia (FRDA) is traditionally associated with neuropathology in the cerebellar dentate nucleus and spinal cord. Growing evidence also suggests involvement of the cerebral and cerebellar cortices, although reports of structural abnormalities remain mixed. This study assessed the structural integrity of cortical grey matter in FRDA, focussing on regions in which pathology may underlie the motor deficits characteristic of this disorder. T1-weighted anatomical magnetic resonance imaging scans were acquired from 31 individuals with FRDA and 37 healthy controls. Cortical thickness (FreeSurfer) and cortical volume (SPM-VBM) were measured in cerebral motor regions-of-interest (primary motor, dorsal and ventral premotor, and supplementary motor areas) alongside unconstrained exploratory analyses of the cerebral and cerebellar cortices. Correlations were assessed between cortical thickness/volume measures and each of disease severity, length of the causative genetic triplet-repeat expansion, and finger-tapping behavioural measures. Individuals with FRDA had significantly reduced cortical thickness, relative to controls, in the premotor and supplementary motor areas. Reduced cortical thickness and/or volume were also observed in the cuneus and precuneus, posterior aspects of the medial and lateral prefrontal cortices, insula, temporal poles, and cerebellar lobules V, VI, and VII. Measures of clinical severity, genetic abnormality, and motor dysfunction correlated with volume loss in the lateral cerebellar hemispheres. These results suggest that atrophy preferentially affects premotor relative to primary areas of the cortical motor system, and also extends to a range of non-motor brain regions. Furthermore, cortical thickness and cortical volume findings were largely divergent, suggesting that each is sensitive to different aspects of neuropathology in FRDA. Overall, this study supports a disease model involving neural aberrations within the cerebral and cerebellar cortices, beyond those traditionally associated with this disorder.
Lower limb spasticity compromises the independence of people with Friedreich's ataxia (FRDA). This study sought to examine lower limb spasticity in FRDA in order to offer new... more
Lower limb spasticity compromises the independence of people with Friedreich's ataxia (FRDA). This study sought to examine lower limb spasticity in FRDA in order to offer new insight as to the best approach and timing of spasticity management. Gastrocnemius and soleus spasticity and muscle length were measured by the Modified Tardieu Scale (MTS) in 31 participants with typical and late-onset FRDA. Relationships between the MTS and the Friedreich Ataxia Rating Scale (FARS), Functional Independence Measure (FIM), and disease duration were analysed. Differences between ambulant (n=18) and non-ambulant (n=13) participants were also examined. All participants had spasticity in at least one muscle, and 38.9% of ambulant and 69.2% of non-ambulant participants had contracture in one or both of their gastrocnemius muscles. Significant negative correlations were found between both gastrocnemius and soleus angle of catch and the FARS score. The FIM score also demonstrated significant correlations with gastrocnemius muscle length and angle of catch. Gastrocnemius and soleus spasticity and contracture is apparent in people with FRDA. Spasticity is evident early in the disease and in ambulant participants. Management of spasticity and reduced muscle length should be considered in people with FRDA at disease onset to optimise function.
Purpose Traumatic injury is a leading cause of work disability. Receiving compensation post-injury has been consistently found to be associated with poorer return to work. This study investigated whether the relationship between receiving... more
Purpose Traumatic injury is a leading cause of work disability. Receiving compensation post-injury has been consistently found to be associated with poorer return to work. This study investigated whether the relationship between receiving compensation and return to work was associated with elevated symptoms of psychological distress (i.e., anxiety, depression, and posttraumatic stress disorder) and perceived injustice. Methods Injured persons, who were employed at the time of injury (n = 364), were recruited from the Victorian State Trauma Registry, and Victorian Orthopaedic Trauma Outcomes Registry. Participants completed the Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist, Injustice Experience Questionnaire, and appraisals of pain and work status 12-months following traumatic injury. Results Greater financial worry and indicators of actual/perceived injustice (e.g., consulting a lawyer, attributing fault to another, perceived injustice, sustaining co...
Subjective reports of sleep disturbance are a common feature of Huntington's disease (HD); however, there is limited research investigating the relationship between sleep problems with changes in brain and... more
Subjective reports of sleep disturbance are a common feature of Huntington's disease (HD); however, there is limited research investigating the relationship between sleep problems with changes in brain and behaviour. This study aimed to investigate whether subjective reports of sleep problems in HD are associated with brain volume, neurocognitive decline, and neuropsychiatric symptoms. This retrospective pilot study used brain volume, neurocognitive and neuropsychiatric data from premanifest (pre-HD) and symptomatic HD (symp-HD). Subjective sleep problem was measured using the sleep item of the Beck's Depression Inventory-II (BDI-II). Pre-HD individuals reporting sleep problems had significantly poorer neuropsychiatric outcomes compared to those not reporting sleep problems. In the symp-HD group, those with sleep problems had significantly accelerated thalamic degeneration and poorer neuropsychiatric outcomes compared to those without sleep problems. There was no relationship between subjective sleep problems and neurocognitive measures. These findings suggest an association between subjective sleep disturbance, neuropathology, and development of neuropsychiatric symptoms in HD. Further studies using quantitative EEG-based monitoring of sleep in HD and changes in the brain and behaviour will be necessary to establish the causal nature of this relationship.
Neuropsychiatric disturbances are common in Huntington's Disease (HD) and have been observed in gene-positive individuals several years prior to the onset of motor symptoms. The neural mechanism underpinning the development of... more
Neuropsychiatric disturbances are common in Huntington's Disease (HD) and have been observed in gene-positive individuals several years prior to the onset of motor symptoms. The neural mechanism underpinning the development of neuropsychiatric problems in HD remain unclear. To investigate whether neural activity during working memory is associated with neuropsychiatric symptoms in premanifest Huntington's Disease. functional magnetic resonance imaging (fMRI) data from Pre-HD far from onset (pre-HDfar, n = 18), pre-HD close to onset (pre-HDclose, n = 17), and controls (n = 32) were analysed. Correlations were performed between fMRI activity in three regions of interest [bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC)] and neuropsychiatric scores. In the pre-HDclose group, increased symptoms of obsessive compulsion and depression were associated with decreased blood-oxygen-level-dependent (BOLD) fMRI activity in the right DLPFC and ACC duri...
Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder defined by pathology within the cerebellum and spinal tracts. Although FRDA is most readily linked to motor and sensory dysfunctions, reported impairments in working... more
Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder defined by pathology within the cerebellum and spinal tracts. Although FRDA is most readily linked to motor and sensory dysfunctions, reported impairments in working memory and executive functions indicate that abnormalities may also extend to associations regions of the cerebral cortex and/or cerebello-cerebral interactions. To test this hypothesis, 29 individuals with genetically confirmed FRDA and 34 healthy controls performed a verbal n-back working memory task while undergoing functional magnetic resonance imaging. No significant group differences were evident in task performance. However, individuals with FRDA had deficits in brain activations both in the lateral cerebellar hemispheres, principally encompassing lobule VI, and the prefrontal cortex, including regions of the anterior insular and rostrolateral prefrontal cortices. Functional connectivity between these brain regions was also impaired, supporting ...
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Huntington's disease (HD) causes progressive motor dysfunction through characteristic atrophy. Changes to neural structure begin in premanifest stages yet individuals are able to maintain a high degree of function, suggesting... more
Huntington's disease (HD) causes progressive motor dysfunction through characteristic atrophy. Changes to neural structure begin in premanifest stages yet individuals are able to maintain a high degree of function, suggesting involvement of supportive processing during motor performance. Electroencephalography (EEG) enables the investigation of subtle impairments at the neuronal level, and possible compensatory strategies, by examining differential activation patterns. We aimed to use EEG to investigate neural motor processing (via the Readiness Potential; RP), premotor processing and sensorimotor integration (Contingent Negative Variation; CNV) during simple motor performance in HD. We assessed neural activity associated with motor preparation and processing in 20 premanifest (pre-HD), 14 symptomatic HD (symp-HD), and 17 healthy controls. Participants performed sequential tapping within two experimental paradigms (simple tapping; Go/No-Go). RP and CNV potentials were calculated...
Although progress has been made towards understanding the gross cortical and subcortical pathology of Huntington's disease (HD), there remains little understanding of the progressive pathophysiological changes that occur in the brain... more
Although progress has been made towards understanding the gross cortical and subcortical pathology of Huntington's disease (HD), there remains little understanding of the progressive pathophysiological changes that occur in the brain circuits underlying the disease. Transcranial magnetic stimulation (TMS) enables investigation of the functional integrity of cortico-subcortical pathways, yet it has not been widely applied in HD research to date. This study sought to characterise profiles of cortical excitability, including inhibition and facilitation, in groups of premanifest and symptomatic HD participants via the use of TMS. We also investigated the clinical, neurocognitive and psychiatric correlates of cortical excitability to better understand the development of phenotypic heterogeneity. The sample comprised 16 premanifest HD, 12 early symptomatic HD and 17 healthy control participants. Single- and paired-pulse TMS protocols were administered to the left primary motor cortex,...
We examined changes in pain sensitivity in the rubber hand illusion (RHI). Experiment 1 investigated changes in pain tolerance immediately after a... more
We examined changes in pain sensitivity in the rubber hand illusion (RHI). Experiment 1 investigated changes in pain tolerance immediately after a "healthy" and "wounded" RHI when immersing the hand in a cold pressor ice bath. There was 19% increased pain tolerance and increased perception detection threshold after the healthy RHI, but 11% reduction after the wounded RHI. Experiment 2 examined pain experience during the wounded RHI with capsaicin-induced hyperalgesia. Pain intensity and unpleasantness was higher on the illusion arm during the synchronous RHI, compared with asynchronous trials. There was no change in pain experience on the control arm, and both arms had similar pain sensitivity after the experiment. Our results highlight the impact of embodying a substitute limb on pain, with increased tolerance and reduced tactile sensitivity when the fake limb is healthy and apparently pain-free, but increased pain sensitivity when the self-attributed limb appears to be wounded.
Although the experience of vicarious sensations when observing another in pain have been described postamputation, the underlying mechanisms are unknown. We investigated whether vicarious sensations are related to posttraumatic stress... more
Although the experience of vicarious sensations when observing another in pain have been described postamputation, the underlying mechanisms are unknown. We investigated whether vicarious sensations are related to posttraumatic stress disorder (PTSD) symptoms and chronic pain. In Study 1, 236 amputees completed questionnaires about phantom limb phenomena and vicarious sensations to both innocuous and painful sensory experiences of others. There was a 10.2% incidence of vicarious sensations, which was significantly more prevalent in amputees reporting PTSD-like experiences, particularly increased arousal and reexperiencing the event that led to amputation (φ = .16). In Study 2, 63 amputees completed the Empathy for Pain Scale and PTSD Checklist-Civilian Version. Cluster analyses revealed 3 groups: 1 group did not experience vicarious pain or PTSD symptoms, and 2 groups were vicarious pain responders, but only 1 had increased PTSD symptoms. Only the latter group showed increased chron...
To determine the extent and nature of driving self-regulation in drivers with Parkinson disease (PD) and factors associated with self-regulatory practices. Although people with PD have consistently been shown to have driving impairments,... more
To determine the extent and nature of driving self-regulation in drivers with Parkinson disease (PD) and factors associated with self-regulatory practices. 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. 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. 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. 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.
In an acute environment pain has potential protective benefits. However when pain becomes chronic this protective effect is lost and the pain becomes an encumbrance. Previously unheralded substances are being investigated in an attempt to... more
In an acute environment pain has potential protective benefits. However when pain becomes chronic this protective effect is lost and the pain becomes an encumbrance. Previously unheralded substances are being investigated in an attempt to alleviate the burden of living with chronic pain. Oxytocin, a neuropeptide hormone, is one prospective pharmacotherapeutic agent gaining popularity. Oxytocin has the potential to modulate the pain experience due to its ubiquitous involvement in central and peripheral psychological and physiological processes, and thus offers promise as a therapeutic agent. In this review, we discuss previous effective applications of oxytocin in pain-free clinical populations and its potential use in the modulation of pain experience. We also address the slowly growing body of literature investigating the administration of oxytocin in clinical and experimentally induced pain in order to investigate the potential mechanisms of its reported analgesic actions. We conc...
SUMMARY  In Huntington's disease (HD), there is growing evidence of neural compensation during neurodegeneration, and that these processes might be modifiable by environmental factors. Cognitive intervention to improve brain function... more
SUMMARY  In Huntington's disease (HD), there is growing evidence of neural compensation during neurodegeneration, and that these processes might be modifiable by environmental factors. Cognitive intervention to improve brain function has been trialled only to a very limited extent in HD; however, it has shown promise in other neurodegenerative diseases. In this review, we discuss the evidence for the use of cognitive intervention to boost neural compensation in HD, and find it has potential to delay clinical decline, particularly if applied early in the disease process. Randomized controlled trials of cognitive intervention in HD should be implemented as a next step to gauging the efficacy of this approach to improve outcomes for those with the HD gene.
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Through two studies, we introduce and validate the Empathy for Pain Scale (EPS), which characterizes the phenomenology of empathy for pain, including the vicarious experience of pain when seeing others in pain. In study 1, 406 individuals... more
Through two studies, we introduce and validate the Empathy for Pain Scale (EPS), which characterizes the phenomenology of empathy for pain, including the vicarious experience of pain when seeing others in pain. In study 1, 406 individuals completed the EPS and Interpersonal Reactivity Index (IRI). In the EPS, four painful scenarios (witnessing surgery, patient recovering from surgery, assault and accidental injury) were rated for 12 emotional, empathic and sensory responses. In study 2, 59 participants completed the same questionnaires and then watched and rated videos of sporting injuries. In study 1, we identified three factors of the EPS with principal component analysis, which were validated with confirmatory factor analysis: affective distress; vicarious pain; and empathic concern. The EPS demonstrated good psychometric properties, re-test reliability (n = 105) and concurrent validity. In study 2, we validated the EPS against empathic reactions to the pain of others as displaye...
This experiment sought to quantify the extent to which patients with Huntington disease (HD) have difficulties in orienting attention, via a vibrotactile version of a Posner-type cost-benefit paradigm. Participants were required to push a... more
This experiment sought to quantify the extent to which patients with Huntington disease (HD) have difficulties in orienting attention, via a vibrotactile version of a Posner-type cost-benefit paradigm. Participants were required to push a button in response to a vibration delivered to the index finger of either hand. Prior to each stimulus vibration, a precue (valid, neutral, or invalid) was delivered to the finger. Benefits and costs were calculated from valid and invalid precues. Although patients with HD were overall slower than the controls, their performance was no different; both patients and controls demonstrated increased benefits from valid compared with invalid and neutral cues. Of interest was the finding that patients, unlike controls, performed significantly slower with the cue presented to the left compared with the right side. The crossed arm configuration proved to be too difficult for the patients with HD, and thus an analysis on these data was not permitted. Patien...
Through two studies, we introduce and validate the Empathy for Pain Scale (EPS), which characterizes the phenomenology of empathy for pain, including the vicarious experience of pain when seeing others in pain. In study 1, 406 individuals... more
Through two studies, we introduce and validate the Empathy for Pain Scale (EPS), which characterizes the phenomenology of empathy for pain, including the vicarious experience of pain when seeing others in pain. In study 1, 406 individuals completed the EPS and Interpersonal Reactivity Index (IRI). In the EPS, four painful scenarios (witnessing surgery, patient recovering from surgery, assault and accidental injury) were rated for 12 emotional, empathic and sensory responses. In study 2, 59 participants completed the same questionnaires and then watched and rated videos of sporting injuries. In study 1, we identified three factors of the EPS with principal component analysis, which were validated with confirmatory factor analysis: affective distress; vicarious pain; and empathic concern. The EPS demonstrated good psychometric properties, re-test reliability (n = 105) and concurrent validity. In study 2, we validated the EPS against empathic reactions to the pain of others as displayed in video clips depicting sporting injuries and showed that the scale has unique utility to characterize empathic reactions to pain above general trait empathy measures. Both studies showed that the affective distress and empathic concern subscales of the EPS correlated with measures of cognitive and affective empathy from the IRI, whereas the vicarious pain subscale was only correlated with the personal distress IRI subscale. The EPS is a psychometrically sound new scale that characterizes empathy for pain and vicarious pain. The EPS offers valuable insight to the phenomenological profile of the affective, empathic and sensory dimensions of empathy for pain.
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