Papers by Nellie Georgiou-Karistianis
NeuroImage. Clinical, 2018
In Huntington's disease (HD), the presence of neurodegeneration in brain regions other than t... 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...
PAIN
Chronic pain is associated with reduced efficiency of cognitive performance, and few studies have... 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.
Brain imaging and behavior, Jan 25, 2018
Fragile X-associated tremor ataxia syndrome is an inherited neurodegenerative disorder caused by ... 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 ...
Brain imaging and behavior, Jan 30, 2018
Intrinsic motivation is essential for academic success and cognitive growth, but limited work has... 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...
International journal of psychophysiology : official journal of the International Organization of Psychophysiology, Jan 2, 2018
Previous research has suggested that heart rate variability (HRV; the variability in the interval... 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...
Journal of the International Neuropsychological Society : JINS, Jan 28, 2017
People with Huntington's disease (HD) experience poor social quality of life, relationship br... 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...
Gait & posture, Mar 4, 2018
Cerebellar ataxia often results in impairment in ambulation secondary to gait pattern dysfunction... 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 ...
Neurorehabilitation and neural repair, 2017
Navigating obstacles whilst walking might be associated with poorer balance and a higher risk of ... 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...
Clinical rehabilitation, 2017
To determine the effectiveness of a six-week rehabilitation programme followed by a home exercise... 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...
PloS one, 2017
Many factors can influence the way in which we perceive painful events and noxious stimuli, but l... 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 = ....
Neurorehabilitation and Neural Repair
Genetic degenerative ataxia encompasses a heterogeneous group of autosomal recessive, autosomal d... more Genetic degenerative ataxia encompasses a heterogeneous group of autosomal recessive, autosomal dominant, X-linked, and mitochondrial ataxias. 1 The dominant ataxias are classified into more than 40 subtypes of spinocerebellar ataxia (SCA), 1 while Friedreich ataxia (FRDA), ataxia-telangiectasia (AT), and ataxia with oculomotor apraxia types 1 and 2 are the most common of the recessive ataxias. 1,2 In some ataxias, the neuropathology is purely cerebellar; however, extrapyramidal, spinocerebellar tract, dorsal column, or peripheral nerve pathology is present in many. Disease onset, clinical presentation, and progression are variable between, and even within disease categories. Nevertheless, a universal feature is significant loss of function and mobility secondary to ataxia. 2 Although a number of trials are underway, proven pharmacological therapies for these disorders is rare. 3 Primary treatment is generally based on symptom management and maintenance of function, 4 of which rehabilitation and physical therapy is a crucial component. However, despite the known benefits in other neurological degenerative diseases, 5,6 inaccessibility to quality care, therapists' lack of understanding of rehabilitation potential, and minimal scientific evidence limit the utilization of physical therapy for individuals with degenerative ataxia. 7 In 2013, a review of prospective trials examining high-intensity coordination 712469N NRXXX10.
PAIN Reports
Introduction: Chronic pain is common after traumatic injury and frequently co-occurs with posttra... more Introduction: Chronic pain is common after traumatic injury and frequently co-occurs with posttraumatic stress disorder (PTSD) and PTSD symptoms (PTSS). Objectives: This study sought to understand the association between probable PTSD, PTSS, and pain. Methods: Four hundred thirty-three participants were recruited from the Victorian Orthopaedic Trauma Outcomes Registry and Victorian State Trauma Registry and completed outcome measures. Participants were predominantly male (n 5 324, 74.8%) and aged 17-75 years at the time of their injury (M 5 44.83 years, SD 5 14.16). Participants completed the Posttraumatic Stress Disorder Checklist, Brief Pain Inventory, Pain Catastrophizing Scale, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia, EQ-5D-3L and Roland-Morris Disability Questionnaire 12 months after hospitalization for traumatic injury. Data were linked with injury and hospital admission data from the trauma registries. Results: Those who reported having current problems with pain were 3 times more likely to have probable PTSD than those without pain. Canonical correlation showed that pain outcomes (pain severity, interference, catastrophizing, kinesiophobia, self-efficacy, and disability) were associated with all PTSSs, but especially symptoms of cognition and affect, hyperarousal, and avoidance. Posttraumatic stress disorder symptoms, on the contrary, were predominantly associated with high catastrophizing and low selfefficacy. When controlling for demographics, pain and injury severity, depression, and self-efficacy explained the greatest proportion of the total relationship between PTSS and pain-related disability. Conclusion: Persons with both PTSS and chronic pain after injury may need tailored interventions to overcome fear-related beliefs and to increase their perception that they can engage in everyday activities, despite their pain.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
People with Huntington&#39;s disease (HD) exhibit altered processing of emotional information... more People with Huntington&#39;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&#39;s&lt;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.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Heart rate variability (HRV) refers to variation in the interval between successive heart beats. ... 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 &amp;amp;amp;amp;gt;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.
Psychoneuroendocrinology
Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is li... 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 &amp;amp;amp;amp;gt;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&amp;amp;amp;amp;#39;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.
PloS one, 2017
Traumatic injury can lead to loss, suffering and feelings of injustice. Previous research has sho... 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...
Journal of the International Neuropsychological Society : JINS, Apr 1, 2017
Deficits in the recognition of negative emotions emerge before clinical diagnosis in Huntington&#... 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. ...
Movement disorders : official journal of the Movement Disorder Society, 2017
Friedreich ataxia is characterized by progressive motor incoordination that is linked to peripher... 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...
Cerebellum (London, England), Aug 22, 2017
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with subtle impact ... 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...
Neurobiology of aging, Feb 1, 2017
Recent evidence indicates that adults with a premutation (PM: 55-199 CGG repeats) expansion in th... 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,...
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Papers by Nellie Georgiou-Karistianis