Publications by authors named "Govinda R Poudel"

31 Publications

Cortical morphometry and neural dysfunction in Huntington's disease: a review.

Eur J Neurol 2020 Nov 19. Epub 2020 Nov 19.

School of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia.

Numerous neuroimaging techniques have been used to identify biomarkers of disease progression in Huntington's disease (HD). To date, the earliest and most sensitive of these is caudate volume; however, it is becoming increasingly evident that numerous changes to cortical structures, and their interconnected networks, occur throughout the course of the disease. The mechanisms by which atrophy spreads from the caudate to these cortical regions remains unknown. In this review, the neuroimaging literature specific to T1-weighted and diffusion-weighted magnetic resonance imaging is summarized and new strategies for the investigation of cortical morphometry and the network spread of degeneration in HD are proposed. This new avenue of research may enable further characterization of disease pathology and could add to a suite of biomarker/s of disease progression for patient stratification that will help guide future clinical trials.
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http://dx.doi.org/10.1111/ene.14648DOI Listing
November 2020

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

Neural Correlates of Attention Lapses During Continuous Tasks.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3196-3199

Attention lapses (ALs) are common phenomenon, which can affect our performance and productivity by slowing or suspending responsiveness. Occurrence of ALs during continuous monitoring tasks, such as driving or operating machinery, can lead to injuries and fatalities. However, we have limited understanding of what happens in the brain when ALs intrude during such continuous tasks. Here, we analyzed fMRI data from a study, in which participants performed a continuous visuomotor tracking task during fMRI scanning. A total of 68 ALs were identified from 20 individuals, using visual rating of tracking performance and video-based eye-closure. ALs were found to be associated with increased BOLD fMRI activity partially in the executive control network, and sensorimotor network. Surprisingly, we found no evidence of deactivations.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176297DOI Listing
July 2020

Exploring the brain-body composition relationship in Huntington's disease.

J Musculoskelet Neuronal Interact 2020 09;20(3):332-338

School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.

Objective: Changes in body composition are a common feature of Huntington's disease (HD) and are associated with disease progression. However, whether these changes in body composition are associated with degeneration of the striatum is unknown. This study aimed to explore the associations between body composition metrics and striatal brain volume in individuals with premanifest HD and healthy controls.

Methods: Twenty-one individuals with premanifest HD and 22 healthy controls participated in this cross-sectional study. Body composition metrics were measured via dual-energy X-ray absorptiometry. Structural magnetic resonance imaging of subcortical structures of the brain was performed to evaluate striatal volume.

Results: There were no significant differences in body composition metrics between the premanifest HD and healthy controls group. Striatal volume was significantly reduced in individuals with premanifest HD compared to healthy controls. A significant association between bone mineral density (BMD) and right putamen volume was also observed in individuals with premanifest HD.

Conclusion: These findings show striatal degeneration is evident during the premanifest stages of HD and associated with BMD. Additional longitudinal studies are nevertheless needed to confirm these findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493441PMC
September 2020

Network diffusion modeling predicts neurodegeneration in traumatic brain injury.

Ann Clin Transl Neurol 2020 03 27;7(3):270-279. Epub 2020 Feb 27.

Cognitive Neuroscience Unit, School of Psychology, Deakin University, Burwood, VIC, Australia.

Objective: Traumatic brain injury (TBI) is a heterogeneous disease with multiple neurological deficits that evolve over time. It is also associated with an increased incidence of neurodegenerative diseases. Accordingly, clinicians need better tools to predict a patient's long-term prognosis.

Methods: Diffusion-weighted and anatomical MRI data were collected from 17 adolescents (mean age = 15y8mo) with moderate-to-severe TBI and 19 healthy controls. Using a network diffusion model (NDM), we examined the effect of progressive deafferentation and gray matter thinning in young TBI patients. Moreover, using a novel automated inference method, we identified several injury epicenters in order to determine the neural degenerative patterns in each TBI patient.

Results: We were able to identify the subject-specific patterns of degeneration in each patient. In particular, the hippocampus, temporal cortices, and striatum were frequently found to be the epicenters of degeneration across the TBI patients. Orthogonal transformation of the predicted degeneration, using principal component analysis, identified distinct spatial components in the temporal-hippocampal network and the cortico-striatal network, confirming the vulnerability of these networks to injury. The NDM model, best predictive of the degeneration, was significantly correlated with time since injury, indicating that NDM can potentially capture the pathological progression in the chronic phase of TBI.

Interpretation: These findings suggest that network spread may help explain patterns of distant gray matter thinning, which would be consistent with Wallerian degeneration of the white matter connections (i.e., "diaschisis") from diffuse axonal injuries and multifocal contusive injuries, and the neurodegenerative patterns of abnormal protein aggregation and transmission, which are hallmarks of brain changes in TBI. NDM approaches could provide highly subject-specific biomarkers relevant for disease monitoring and personalized therapies in TBI.
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http://dx.doi.org/10.1002/acn3.50984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086000PMC
March 2020

Robust Markers and Sample Sizes for Multicenter Trials of Huntington Disease.

Ann Neurol 2020 05 14;87(5):751-762. Epub 2020 Mar 14.

Center for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom.

Objective: The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective imaging HD dataset to identify a set of imaging markers robust to multicenter variation and to derive upper estimates on sample sizes for clinical trials in HD.

Methods: We used 1 postprocessing pipeline to retrospectively analyze T1-weighted magnetic resonance imaging (MRI) scans from 624 participants at 3 time points, from the PREDICT-HD, TRACK-HD, and IMAGE-HD studies. We used mixed effects models to adjust regional brain volumes for covariates, calculate effect sizes, and simulate possible treatment effects in disease-affected anatomical regions. We used our model to estimate the statistical power of possible treatment effects for anatomical regions and clinical markers.

Results: We identified a set of common anatomical regions that have similarly large standardized effect sizes (>0.5) between healthy control and premanifest HD (PreHD) groups. These included subcortical, white matter, and cortical regions and nonventricular cerebrospinal fluid (CSF). We also observed a consistent spatial distribution of effect size by region across the whole brain. We found that multicenter studies were necessary to capture treatment effect variance; for a 20% treatment effect, power of >80% was achieved for the caudate (n = 661), pallidum (n = 687), and nonventricular CSF (n = 939), and, crucially, these imaging markers provided greater power than standard clinical markers.

Interpretation: Our findings provide the first cross-study validation of structural imaging markers in HD, supporting the use of these measurements as endpoints for both observational studies and clinical trials. ANN NEUROL 2020;87:751-762.
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http://dx.doi.org/10.1002/ana.25709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187160PMC
May 2020

Network spread determines severity of degeneration and disconnection in Huntington's disease.

Hum Brain Mapp 2019 10 12;40(14):4192-4201. Epub 2019 Jun 12.

School of Psychological Sciences & Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, Victoria, Australia.

Trans-neuronal propagation of mutant huntingtin protein contributes to the organised spread of cortico-striatal degeneration and disconnection in Huntington's disease (HD). We investigated whether the network diffusion model, which models transneuronal spread as diffusion of pathological proteins via the brain connectome, can determine the severity of neural degeneration and disconnection in HD. We used structural magnetic resonance imaging (MRI) and high-angular resolution diffusion weighted imaging (DWI) data from symptomatic Huntington's disease (HD) (N = 26) and age-matched healthy controls (N = 26) to measure neural degeneration and disconnection in HD. The network diffusion model was used to test whether disease spread, via the human brain connectome, is a viable mechanism to explain the distribution of pathology across the brain. We found that an eigenmode identified in the healthy human brain connectome Laplacian matrix, accurately predicts the cortico-striatal spatial pattern of degeneration in HD. Furthermore, the spread of neural degeneration from sub-cortical brain regions, including the accumbens and thalamus, generates a spatial pattern which represents the typical neurodegenerative characteristics in HD. The white matter connections connecting the nodes with the highest amount of disease factors, when diffusion based disease spread is initiated from the striatum, were found to be most vulnerable to disconnection in HD. These findings suggest that trans-neuronal diffusion of mutant huntingtin protein across the human brain connectome may explain the pattern of gray matter degeneration and white matter disconnection that are hallmarks of HD.
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http://dx.doi.org/10.1002/hbm.24695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865500PMC
October 2019

Imaging Individual Differences in the Response of the Human Suprachiasmatic Area to Light.

Front Neurol 2018 29;9:1022. Epub 2018 Nov 29.

Monash Institute of Cognitive and Clinical Neurosciences and School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.

Circadian disruption is associated with poor health outcomes, including sleep and mood disorders. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus acts as the master biological clock in mammals, regulating circadian rhythms throughout the body. The clock is synchronized to the day/night cycle via retinal light exposure. The BOLD-fMRI response of the human suprachiasmatic area to light has been shown to be greater in the night than in the day, consistent with the known sensitivity of the clock to light at night. Whether the BOLD-fMRI response of the human suprachiasmatic area to light is related to a functional outcome has not been demonstrated. In a pilot study ( = 10), we investigated suprachiasmatic area activation in response to light in a 30 s block-paradigm of lights on (100 lux) and lights off (< 1 lux) using the BOLD-fMRI response, compared to each participant's melatonin suppression response to moderate indoor light (100 lux). We found a significant correlation between activation in the suprachiasmatic area in response to light in the scanner and melatonin suppression, with increased melatonin suppression being associated with increased suprachiasmatic area activation in response to the same light level. These preliminary findings are a first step toward using imaging techniques to measure individual differences in circadian light sensitivity, a measure that may have clinical relevance in understanding vulnerability in disorders that are influenced by circadian disruption.
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http://dx.doi.org/10.3389/fneur.2018.01022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281828PMC
November 2018

Temporal evolution of neural activity and connectivity during microsleeps when rested and following sleep restriction.

Neuroimage 2018 07 16;174:263-273. Epub 2018 Mar 16.

New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medical Physics and Bioengineering, Christchurch Hospital, Christchurch, New Zealand; Department of Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand; Department of Psychology, University of Canterbury, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand.

Even when it is critical to stay awake, such as when driving, sleep deprivation weakens one's ability to do so by substantially increasing the propensity for microsleeps. Microsleeps are complete lapses of consciousness but, paradoxically, are associated with transient increases in cortical activity. But do microsleeps provide a benefit in terms of attenuating the need for sleep? And is the neural response to microsleeps altered by the degree of homeostatic drive to sleep? In this study, we continuously monitored eye-video, visuomotor responsiveness, and brain activity via fMRI in 20 healthy subjects during a 20-min visuomotor tracking task following a normally-rested night and a sleep-restricted (4-h) night. As expected, sleep restriction led to an increased number of microsleeps and an increased variability in tracking error. Microsleeps exhibited transient increases in regional activity in the fronto-parietal and parahippocampal area. Network analyses revealed divergent transient changes in the right fronto-parietal, dorsal-attention, default-mode, and thalamo-cortical functional networks. In all subjects, tracking error immediately following microsleeps was improved compared to before the microsleeps. Importantly, post-microsleep recovery in tracking response speed was associated with hyperactivation in the thalamo-cortical network. The temporal evolution of functional connectivity within the frontal and posterior nodes of the default-mode network and between the right fronto-parietal and default-mode networks was associated with temporal changes in visuomotor responsiveness. These findings demonstrate distinct brain-network-level changes in brain activity during microsleeps and suggest that neural activity in the thalamo-cortical network may facilitate the transient recovery from microsleeps. The temporal pattern of evolution in brain activity and performance is indicative of dynamic changes in vigilance during the struggle to stay awake following sleep loss.
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http://dx.doi.org/10.1016/j.neuroimage.2018.03.031DOI Listing
July 2018

Neural correlates of decision-making during a Bayesian choice task.

Neuroreport 2017 Mar;28(4):193-199

aSchool of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia bDepartment of Economics and the CERPA (Center for Economic Research and Policy Analysis), Appalachian State University, Boone, North Carolina cESI (Economic Science Institute), Chapman University, Orange dDepartment of Psychiatry, University of California San Diego, La Jolla, California, USA eIZA (Institute for the Study of Labor), Bonn, Germany.

Many critical decisions require evaluation of accumulated previous information and/or newly acquired evidence. Although neural correlates of belief updating have been investigated, how these neural processes guide decisions involving Bayesian choice is less clear. Here, we used functional MRI to investigate neural activity during a Bayesian choice task involving two sources of information: base rate odds ('odds') and sample evidence ('evidence'). Thirty-seven healthy control individuals performed the Bayesian choice task in which they had to make probability judgements. Average functional MRI activity during the trials where choice was consistent with use of Odds, use of Evidence, and use of Both was compared. Decision-making consistent with odds, evidence and both each strongly activated the bilateral executive network encompassing the bilateral frontal, cingulate, posterior parietal and occipital cortices. The Evidence consistent, compared with Odds consistent, decisions showed greater activity in the bilateral middle and inferior frontal and right lateral occipital cortices. Decisions consistent with the use of Both strategies were associated with increased activity in the bilateral middle frontal and superior frontal cortices. These findings support the conclusion that both overlapping and distinct brain regions within the frontoparietal network underlie the incorporation of different types of information into a Bayesian decision.
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http://dx.doi.org/10.1097/WNR.0000000000000730DOI Listing
March 2017

Subjective sleep problems in Huntington's disease: A pilot investigation of the relationship to brain structure, neurocognitive, and neuropsychiatric function.

J Neurol Sci 2016 May 12;364:148-53. Epub 2016 Mar 12.

School of Psychological Sciences/Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Victoria, Australia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jns.2016.03.021DOI Listing
May 2016

Microsleeps are Associated with Stage-2 Sleep Spindles from Hippocampal-Temporal Network.

Int J Neural Syst 2016 Jun 16;26(4):1650015. Epub 2016 Feb 16.

1 New Zealand Brain Research Institute, Christchurch, New Zealand.

Behavioral microsleeps are associated with complete disruption of responsiveness for [Formula: see text][Formula: see text]s to 15[Formula: see text]s. They can result in injury or death, especially in transport and military sectors. In this study, EEGs were obtained from five nonsleep-deprived healthy male subjects performing a 1[Formula: see text]h 2D tracking task. Microsleeps were detected in all subjects. Microsleep-related activities in the EEG were detected, characterized, separated from eye closure-related activity, and, via source-space-independent component analysis and power analysis, the associated sources were localized in the brain. Microsleeps were often, but not always, found to be associated with strong alpha-band spindles originating bilaterally from the anterior temporal gyri and hippocampi. Similarly, theta-related activity was identified as originating bilaterally from the frontal-orbital cortex. The alpha spindles were similar to sleep spindles in terms of frequency, duration, and amplitude-profile, indicating that microsleeps are equivalent to brief instances of Stage-2 sleep.
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http://dx.doi.org/10.1142/S0129065716500155DOI Listing
June 2016

Functional Brain Correlates of Neuropsychiatric Symptoms in Presymptomatic Huntington's Disease: The IMAGE-HD Study.

J Huntingtons Dis 2015 ;4(4):325-32

Monash Institute of Cognitive and Clinical Neurosciences/School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.

Background: 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.

Objective: To investigate whether neural activity during working memory is associated with neuropsychiatric symptoms in premanifest Huntington's Disease.

Methods: 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.

Results: 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 during 1-BACK and 2-BACK working memory conditions. In the pre-HDfar group increased symptoms of depression was associated with decreased right DLPFC BOLD fMRI activity during 2-BACK working memory only.

Conclusions: The findings suggest that association between neuropsychiatric function and fMRI activity is more readily detectable at higher working memory loads, and becomes more pronounced in those closer to onset.
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http://dx.doi.org/10.3233/JHD-150154DOI Listing
October 2016

Fronto-cerebellar dysfunction and dysconnectivity underlying cognition in friedreich ataxia: The IMAGE-FRDA study.

Hum Brain Mapp 2016 Jan 27;37(1):338-50. Epub 2015 Oct 27.

School of Psychological Sciences, Monash University, Melbourne, Australia.

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 a putative link between primary cerebellar dysfunction and subsequent cerebral abnormalities. Disease severity and genetic markers of disease liability were correlated specifically with cerebellar dysfunction, while correlations between behavioural performance and both cerebral activations and cerebello-cerebral connectivity were observed in controls, but not in the FRDA cohort. Taken together, these findings support a diaschisis model of brain dysfunction, whereby primary disease effects in the cerebellum result in functional changes in downstream fronto-cerebellar networks. These fronto-cerebellar disturbances provide a putative biological basis for the nonmotor symptoms observed in FRDA, and reflect the consequence of localized cerebellar pathology to distributed brain function underlying higher-order cognition.
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http://dx.doi.org/10.1002/hbm.23034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867314PMC
January 2016

Time-varying effective connectivity of the cortical neuroelectric activity associated with behavioural microsleeps.

Neuroimage 2016 Jan 10;124(Pt A):421-432. Epub 2015 Sep 10.

New Zealand Brain Research Institute, Christchurch, New Zealand; Electrical and Computer Engineering, University of Canterbury, Christchurch, New Zealand; Medicine, University of Otago, Christchurch, New Zealand; Psychology, University of Canterbury, Christchurch, New Zealand.

An episode of complete failure to respond during an attentive task accompanied by behavioural signs of sleep is called a behavioural microsleep. We proposed a combination of high-resolution EEG and an advanced method for time-varying effective connectivity estimation for reconstructing the temporal evolution of the causal relations between cortical regions when microsleeps occur during a continuous visuomotor task. We found connectivity patterns involving left-right frontal, left-right parietal, and left-frontal/right-parietal connections commencing in the interval [-500; -250] ms prior to the onset of microsleeps and disappearing at the end of the microsleeps. Our results from global graph indices derived from effective connectivity analysis have revealed EEG-based biomarkers of all stages of microsleeps (preceding, onset, pre-recovery, recovery). In particular, this raises the possibility of being able to predict microsleeps in real-world tasks and initiate a 'wake-up' intervention to avert the microsleeps and, hence, prevent injurious and even multi-fatality accidents.
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http://dx.doi.org/10.1016/j.neuroimage.2015.08.059DOI Listing
January 2016

Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study.

Neurobiol Dis 2015 Feb 12;74:406-12. Epub 2014 Dec 12.

School of Psychological Sciences, Monash University, Clayton, Victoria, Australia. Electronic address:

Objective: To quantify 18-month changes in white matter microstructure in premanifest (pre-HD) and symptomatic Huntington's disease (symp-HD). To investigate baseline clinical, cognitive and motor symptoms that are predictive of white matter microstructural change over 18months.

Method: Diffusion tensor imaging (DTI) data were analyzed for 28 pre-HD, 25 symp-HD, and 27 controls scanned at baseline and after 18months. Unbiased tract-based spatial statistics (TBSS) methods were used to identify longitudinal changes in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) of white matter. Stepwise linear regression models were used to identify baseline clinical, cognitive, and motor measures that are predictive of longitudinal diffusion changes.

Results: Symp-HD compared to controls showed 18-month reductions in FA in the corpus callosum and cingulum white matter. Symp-HD compared to pre-HD showed increased RD in the corpus callosum and striatal projection pathways. FA in the body, genu, and splenium of the corpus callosum was significantly associated with a baseline clinical motor measure (Unified Huntington's Disease Rating Scale: total motor scores: UHDRS-TMS) across both HD groups. This measure was also the only independent predictor of longitudinal decline in FA in all parts of the corpus callosum across both HD groups.

Conclusions: We provide direct evidence of longitudinal decline in white matter microstructure in symp-HD. Although pre-HD did not show longitudinal change, clinical symptoms and motor function predicted white matter microstructural changes for all gene positive subjects. These findings suggest that loss of axonal integrity is an early hallmark of neurodegenerative changes which are clinically relevant.
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http://dx.doi.org/10.1016/j.nbd.2014.12.009DOI Listing
February 2015

White matter connectivity reflects clinical and cognitive status in Huntington's disease.

Neurobiol Dis 2014 May 28;65:180-7. Epub 2014 Jan 28.

School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Monash Biomedical Imaging (MBI), Monash University, Melbourne, VIC, Australia; Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia; VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia.

Objective: To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease.

Method: Diffusion tensor imaging (DTI) data were acquired from 35 pre-HD, 36 symp-HD, and 35 controls. Structural connectivity was mapped between 40 brain regions of interest using tractography. Between-group differences in structural connectivity were identified using network based statistics. Radial diffusivity (RD) and fractional anisotropy (FA) were compared in the white matter tracts from aberrant networks. RD values in aberrant tracts were correlated with clinical severity, and cognitive and motor performance.

Results: A network connecting putamen with prefrontal and motor cortex demonstrated significantly reduced tractography streamlines in pre-HD. Symp-HD individuals showed reduced streamlines in a network connecting prefrontal, motor, and parietal cortices with both caudate and putamen. The symp-HD group, compared to controls and pre-HD, showed both increased RD and decreased FA in the fronto-parietal and caudate-paracentral tracts and increased RD in the putamen-prefrontal and putamen-motor tracts. The pre-HDclose, compared to controls, showed increased RD in the putamen-prefrontal and fronto-parietal tracts. In the pre-HD group, significant negative correlations were observed between SDMT and Stroop performance and RD in the bilateral putamen-prefrontal tract. In the symp-HD group, RD in the fronto-parietal tract was significantly positively correlated with UHDRS motor scores and significantly negatively correlated with performance on SDMT and Stroop tasks.

Conclusions: We have provided evidence of aberrant connectivity and microstructural integrity in white matter networks in HD. Microstructural changes in the cortico-striatal fibers were associated with cognitive and motor performance in pre-HD, suggesting that changes in axonal integrity provide an early marker for clinically relevant impairment in HD.
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http://dx.doi.org/10.1016/j.nbd.2014.01.013DOI Listing
May 2014

Functional changes during working memory in Huntington's disease: 30-month longitudinal data from the IMAGE-HD study.

Brain Struct Funct 2015 Jan 16;220(1):501-12. Epub 2013 Nov 16.

School of Psychology and Psychiatry, Monash University, Clayton, VIC, 3800, Australia.

We characterized 30-month longitudinal change in functional activation and connectivity during working memory in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease (HD). In a case-control longitudinal study (baseline, 18 months, and 30 months), we compared change in fMRI activity over time during working memory in 22 pre-HD, 11 symp-HD, and 20 control participants. Outcome measures were BOLD (blood-oxygen-level-dependent) activity during 1-BACK and 2-BACK working memory and functional connectivity between dorsolateral prefrontal cortex (DLPFC) and caudate. Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK in the left DLPFC and medial frontal cortex, and further increased activation during 2-BACK in the bilateral caudate, putamen, and temporal cortex. Longitudinal change in symp-HD was not significantly different from controls. Longitudinal changes in pre-HD were associated with disease burden and years to onset. The pre-HD group showed longitudinal decreased functional connectivity between left DLPFC and caudate during both 1-BACK and 2-BACK performance. We provide an evidence for longitudinal changes in BOLD activity during working memory prior to clinical manifestations of HD. The ability to increase activation in the prefrontal cortex over time may represent an early compensatory response during the premanifest stage, which may reflect an early marker for clinically relevant functional changes in HD.
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http://dx.doi.org/10.1007/s00429-013-0670-zDOI Listing
January 2015

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study.

J Psychiatry Neurosci 2014 Mar;39(2):87-96

The School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, VIC, Australia.

Background: Functional neural impairments have been documented in people with symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre-HD). This study aimed to characterize synchrony in resting state cerebral networks in both pre-HD and symp-HD populations and to determine its association with disease burden and neurocognitive functions.

Methods: We acquired functional magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control participants. The fMRI data were analyzed using multisubject independent component analysis and dual regression. We compared networks of interest among the groups using a nonparametric permutation method and correcting for multiple comparisons.

Results: Our study included 25 people in the pre-HD, 23 in the symp-HD and 18 in the healthy control groups. Compared with the control group, the pre-HD group showed decreased synchrony in the sensorimotor and dorsal attention networks; decreased level of synchrony in the sensorimotor network was associated with poorer motor performance. Compared with the control group, the symp-HD group showed widespread reduction in synchrony in the dorsal attention network, which was associated with poorer cognitive performance. The posterior putamen and superior parietal cortex were functionally disconnected from the frontal executive network in the symp-HD compared with control and pre-HD groups. Furthermore, the left frontoparietal network showed areas of increased synchrony in the symp-HD compared with the pre-HD group.

Limitations: We could not directly correct for influence of autonomic changes (e.g., heart rate) and respiration on resting state synchronization.

Conclusion: Our findings suggest that aberrant synchrony in the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD individuals. The altered synchrony in dorsal attention, frontoparietal and corticostriatal networks may contribute to the development of clinical symptoms in people with Huntington disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937285PMC
http://dx.doi.org/10.1503/jpn.120226DOI Listing
March 2014

Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 month longitudinal data from the IMAGE-HD study.

PLoS One 2013 16;8(9):e74131. Epub 2013 Sep 16.

School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia.

IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI) study in premanifest and early symptomatic Huntington's disease (pre-HD and symp-HD, respectively). In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume) and microstructural (diffusivity) longitudinal change in HD. We used a 3T MRI scanner to acquire T1 and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter) and in caudate and putamen (volume and diffusivity change). Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years), close to diagnosis (<15 years) and after diagnosis. Of the two diffusion metrics (mean diffusivity, MD; fractional anisotropy, FA), only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074131PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774648PMC
May 2014

Efficient and regular patterns of nighttime sleep are related to increased vulnerability to microsleeps following a single night of sleep restriction.

Chronobiol Int 2013 Nov 3;30(9):1187-96. Epub 2013 Sep 3.

New Zealand Brain Research Institute , Christchurch , New Zealand .

Sleep-deprived people, or those performing extended monotonous tasks, can exhibit brief episodes in which they suspend performance and appear to fall asleep momentarily-behavioral microsleeps ("microsleeps"). In this study, microsleeps were identified using eye video and tracking response during a 20-min continuous tracking task undertaken by 16 healthy volunteers (mean age 24.9 yrs; 8 females, 8 males) in the early afternoon following a normally rested night and a night of restricted sleep (time-in-bed restricted to 4 h). Sessions were 1 wk apart and counterbalanced. Wrist actigraphy, self-reported sleepiness, and sleep quality were also recorded. We hypothesized that high microsleep rates when normally rested or after a night of sleep restriction would be related to poor sleep quality, sleep disturbance, circadian type, irregular sleep patterns, low daily sleep duration, or poor sleep efficiency. We also hypothesized that prior performance on a 10-min psychomotor vigilance task (PVT) (mean reaction time or number of PVT lapses) would be related to the number of microsleeps during the tracking task and that PVT performance could, therefore, be used as a fitness-for-duty indicator. The number of microsleeps during the tracking task increased following sleep restriction (mean 11.4 versus 27.9; p = 0.03). There were no correlations between the number of microsleeps in the normally rested session and any of the actigraphically measured or self-reported sleep measures. However, the number of microsleeps following sleep restriction was correlated with sleep efficiency (r = 0.73, p = 0.001), sleep onset latency (r = -0.57, p = 0.02), and sleep onset time-of-day standard deviation (r = -0.54, p = 0.03) over 11 normally rested nights. There was no correlation between PVT performance and the subsequent number of microsleeps during the tracking task in either session. Attributes usually associated with beneficial nighttime sleep patterns-going to sleep at a similar time each night, falling asleep quickly, and infrequent arousals-were related to greater vulnerability to microsleeps following sleep restriction. There were intercorrelations between all the sleep measures associated with microsleep rate following sleep restriction, indicating that the measures form a pattern of behaviors and are not independently related to microsleep rate. Perhaps some people maintain a regular sleep pattern because they experience sleepiness the following day when their pattern is disrupted. Conversely, people with more variation in their sleep pattern may do so because this does not substantially increase sleepiness the following day. We conclude that people with consistent sleep patterns and efficient sleep may be more prone to microsleeps than other people when their usual regular pattern is disrupted by sleep restriction.
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http://dx.doi.org/10.3109/07420528.2013.810222DOI Listing
November 2013

Functional and connectivity changes during working memory in Huntington's disease: 18 month longitudinal data from the IMAGE-HD study.

Brain Cogn 2013 Oct 9;83(1):80-91. Epub 2013 Aug 9.

School of Psychology and Psychiatry, Monash University, Clayton, VIC 3800, Australia.

Background: This study aimed to characterize, for the first time, 18 month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington's disease (pre-HD) and symptomatic HD (symp-HD).

Methods: Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18 months follow-up.

Results: Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18months only in the pre-HD group.

Conclusions: Longitudinal reductions in connectivity over 18 months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.
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http://dx.doi.org/10.1016/j.bandc.2013.07.004DOI Listing
October 2013

Distinct neural correlates of time-on-task and transient errors during a visuomotor tracking task after sleep restriction.

Neuroimage 2013 Aug 1;77:105-13. Epub 2013 Apr 1.

New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medical Physics and Bioengineering, Christchurch Hospital, Christchurch, New Zealand.

Sleep loss leads to both time-on-task slowing of responsiveness and increased frequency of transient response errors. The consequences of such errors during real-world visuomotor tasks, such as driving, are serious and life threatening. To investigate the neuronal underpinning of time-on-task and transient errors during a visuomotor tracking task following sleep restriction, we performed fMRI on 20 healthy individuals when well-rested and when sleep-restricted while they performed a 2-D pursuit-tracking task. Sleep restriction to 4-h time-in-bed was associated with significant time-on-task decline in tracking performance and an increased number of transient tracking errors. Sleep restriction was associated with time-on-task decreases in BOLD activity in task-related areas, including the lateral occipital cortex, intraparietal cortex, and primary motor cortex. In contrast, thalamic, anterior cingulate, and medial frontal cortex areas showed overall increases irrespective of time-on-task after sleep-restriction. Furthermore, transient errors after sleep-restriction were associated with distinct transient BOLD activations in areas not involved in tracking task per se, in the right superior parietal cortex, bilateral temporal cortex, and thalamus. These results highlight the distinct cerebral underpinnings of sustained and transient modulations in alertness during increased homeostatic drive to sleep. Ability to detect neuronal changes associated with both sustained and transient changes in performance in a single task allowed us to disentangle neuronal mechanisms underlying two important aspects of sustained task performance following sleep loss.
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http://dx.doi.org/10.1016/j.neuroimage.2013.03.054DOI Listing
August 2013

Losing the struggle to stay awake: divergent thalamic and cortical activity during microsleeps.

Hum Brain Mapp 2014 Jan 24;35(1):257-69. Epub 2012 Sep 24.

New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand; Department of Medical Physics and Bioengineering, Christchurch Hospital, Christchurch, New Zealand.

Maintaining alertness is critical for safe and successful performance of most human activities. Consequently, microsleeps during continuous visuomotor tasks, such as driving, can be very serious, not only disrupting performance but sometimes leading to injury or death due to accidents. We have investigated the neural activity underlying behavioral microsleeps--brief (0.5-15 s) episodes of complete failure to respond accompanied by slow eye-closures--and EEG theta activity during drowsiness in a continuous task. Twenty healthy normally-rested participants performed a 50-min continuous tracking task while fMRI, EEG, eye-video, and responses were simultaneously recorded. Visual rating of performance and eye-video revealed that 70% of the participants had frequent microsleeps. fMRI analysis revealed a transient decrease in thalamic, posterior cingulate, and occipital cortex activity and an increase in frontal, posterior parietal, and parahippocampal activity during microsleeps. The transient activity was modulated by the duration of the microsleep. In subjects with frequent microsleeps, power in the post-central EEG theta was positively correlated with the BOLD signal in the thalamus, basal forebrain, and visual, posterior parietal, and prefrontal cortices. These results provide evidence for distinct neural changes associated with microsleeps and with EEG theta activity during drowsiness in a continuous task. They also suggest that the occurrence of microsleeps during an active task is not a global deactivation process but involves localized activation of fronto-parietal cortex, which, despite a transient loss of arousal, may constitute a mechanism by which these regions try to restore responsiveness.
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http://dx.doi.org/10.1002/hbm.22178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869765PMC
January 2014

Cerebral perfusion differences between drowsy and nondrowsy individuals after acute sleep restriction.

Sleep 2012 Aug 1;35(8):1085-96. Epub 2012 Aug 1.

New Zealand Brain Research Institute; Medicine, University of Otago, Christchurch, New Zealand.

Objectives: To investigate changes in resting cerebral blood flow (CBF) after acute sleep restriction. To investigate the extent to which changes in CBF after sleep restriction are related to drowsiness as manifested in eye-video.

Design: Participants were scanned for 5 min using arterial spin labeling (ASL) perfusion imaging after both sleep-restricted and rested nights. Participants were rated for visual signs of drowsiness in the eye-video recorded during the scan.

Setting: Lying supine in a 3-Tesla magnetic resonance imaging scanner.

Participants: Twenty healthy adults (age 20-37 yr) with no history of neurologic, psychiatric, or sleep disorder, and with usual time in bed of 7.0-8.5 h.

Interventions: In the night before the sleep-restricted session, participants were restricted to 4 h time in bed.

Results: There was an overall reduction in CBF in the right-lateralized fronto-parietal attentional network after acute sleep restriction, although this was largely driven by participants who showed strong signs of drowsiness in the eye-video after sleep restriction. Change in CBF correlated with change in drowsiness in the basal forebrain-cingulate regions. In particular, there was a pronounced increase in CBF in the basal forebrain and anterior and posterior cingulate cortex of participants who remained alert after sleep restriction.

Conclusions: The pattern of cerebral activity after acute sleep restriction is highly dependent on level of drowsiness. Nondrowsy individuals are able to increase activity in the arousal-promoting brain regions and maintain activity in attentional regions. In contrast, drowsy individuals are unable to maintain arousal and show decreased activity in both arousal-promoting and attentional regions.
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http://dx.doi.org/10.5665/sleep.1994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397813PMC
August 2012

Lapses of responsiveness: Characteristics, detection, and underlying mechanisms.

Annu Int Conf IEEE Eng Med Biol Soc 2010 ;2010:1788-91

Department of Medical Physics and Bioengineering, Christchurch Hospital, New Zealand.

Lapses in responsiveness ('lapses'), particularly microsleeps and attention lapses, are complete disruptions in performance from approximately 0.5-15 s. They are of particular importance in the transport sector in which there is a need to maintain sustained attention for extended periods and in which lapses can lead to multiple-fatality accidents.
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http://dx.doi.org/10.1109/IEMBS.2010.5626385DOI Listing
April 2011

The relationship between behavioural microsleeps, visuomotor performance and EEG theta.

Annu Int Conf IEEE Eng Med Biol Soc 2010 ;2010:4452-5

Department of Medical Physics and Bioengineering, Christchurch Hospital, New Zealand.

Visuomotor performance and responsiveness deteriorates with time-on-task due to drowsiness and increased propensity to sleep. Frequent episodes of behavioural microsleep (BM) are also common during extended and monotonous tasks. In this study, simultaneous recording of EEG, eye-video, and continuous visuomotor response is used to investigate visuomotor performance and EEG activity during tonic drowsiness and phasic BMs. The data were collected from 20 healthy volunteers while they performed a continuous 2-D pursuit tracking task for 50 min. We identified episodes of BMs by expert visual rating of eye-video and visuomotor response using a set of pre-defined criteria. Visuomotor performance and EEG activity were correlated with and without BM events. A moderate correlation was observed between visuomotor error and theta activity in EEG at a posterior channel (Pz) before the removal of BMs. However, when BMs were removed from the data, the correlation dropped in most subjects. Furthermore, most of the large fluctuations in performance observed during the visuomotor task disappeared after the removal of BMs. This suggests that episodic behaviours such as BMs contribute substantially to fluctuations in performance and to EEG theta activity during an extended task, and that they should be taken into account when studying tonic drowsiness.
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http://dx.doi.org/10.1109/IEMBS.2010.5625956DOI Listing
March 2011

Behavioural microsleeps in normally-rested people.

Annu Int Conf IEEE Eng Med Biol Soc 2010 ;2010:4448-51

Department of Medical Physics and Bioengineering, Christchurch Hospital, 8011, New Zealand.

Sleep-deprived people, or those performing extended monotonous tasks, frequently have brief episodes when performance is suspended and they appear to fall asleep momentarily - behavioural microsleeps (BMs). As BM rates are highly variable between normally-rested people, this study aimed to determine whether there is a relationship between propensity for BMs and measures of sleep. Subjects undertook a continuous 50-min 2-D tracking task and BMs were identified with high temporal accuracy based on simultaneous analysis of visuomotor response, tracking speed, tracking error, vertical electrooculogram, and eye-video. BM rates and durations were correlated with measures of sleep (i.e., wrist actigraphy, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, and Horne-Ostberg Morning-Eveningness Questionnaire). BMs occurred frequently during the task but rates were highly variable between participants (mean 79.1/h ± 66.2, range 0-226/h). There were correlations between ESS score and BM rate and duration. However, BMs were not related to other sleep measures. Thus, there is a very large variability in BM propensity in normally-rested subjects which cannot be explained by variation in sleep duration, quality, or efficiency. Propensity to fall asleep in situations in which sustained performance is required may be a trait characteristic in normally-rested people.
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http://dx.doi.org/10.1109/IEMBS.2010.5625953DOI Listing
March 2011

Measurement of BOLD changes due to cued eye-closure and stopping during a continuous visuomotor task via model-based and model-free approaches.

IEEE Trans Neural Syst Rehabil Eng 2010 Oct 3;18(5):479-88. Epub 2010 Jun 3.

Department of Medical Physics and Bioengineering, Christchurch Hospital, 8011 Christchurch, New Zealand.

As a precursor for investigation of changes in neural activity underlying lapses of responsiveness, we set up a system to simultaneously record functional magnetic resonance imaging (fMRI), eye-video, EOG, and continuous visuomotor response inside an MRI scanner. The BOLD fMRI signal was acquired during a novel 2-D tracking task in which participants (10 males, 10 females) were cued to either briefly stop tracking and close their eyes (Stop +Close) or to briefly stop tracking (Stop) only. The onset and duration of eye-closure and stopping were identified post hoc from eye-video, EOG, and visuomotor response. fMRI data were analyzed using a general linear model (GLM) and tensorial independent component analysis (TICA). The GLM-based analysis identified predominantly increased blood oxygenation level dependent (BOLD) activity during eye-closure and stopping in multisensory areas, sensory-motor integration areas, and default-mode regions. Stopping during tracking elicited increased activity in visual processing areas, sensory-motor integration areas, and premotor areas. TICA separated the spatio-temporal pattern of activity into multiple task-related networks including the 1) occipito-medial frontal eye-movement network, 2) sensory areas, 3) left-lateralized visuomotor network, and 4) fronto-parietal visuomotor network, which were modulated differently by Stop +Close and Stop. The results demonstrate the merits of using simultaneous fMRI, behavioral, and physiological recordings to investigate the mechanisms underlying complex human behaviors in the human brain. Furthermore, knowledge of widespread modulations in brain activity due to voluntary eye-closure or stopping during a continuous visuomotor task is important for studies of the brain mechanisms underlying involuntary behaviors, such as microsleeps and attention lapses, which are often accompanied by brief eye-closure and/or response failures.
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http://dx.doi.org/10.1109/TNSRE.2010.2050782DOI Listing
October 2010

fMRI correlates of behavioural microsleeps during a continuous visuomotor task.

Annu Int Conf IEEE Eng Med Biol Soc 2009 ;2009:2919-22

Department of Medicine, University of Otago, Christchurch, New Zealand.

Behavioural microsleeps (BMs) are brief episodes of absent responsiveness accompanied by slow-eye-closure. They frequently occur as a consequence of sleep-deprivation, an extended monotonous task, and are modulated by the circadian rhythm and sleep homeostatic pressure. In this paper, a multimodal method to investigate the neural correlates of BMs using simultaneous recording of fMRI, eye-video, VEOG, and continuous visuomotor response is presented. The data were collected from 20 healthy volunteers while they performed a continuous visuomotor tracking task inside an MRI scanner for 50 min. The BMs were identified post-hoc by expert visual rating of eye-video and visuomotor response using a set of pre-defined criteria. fMRI analysis of BMs revealed changes in haemodynamic activity in several cortical and sub-cortical regions associated with visuomotor control and arousal.
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http://dx.doi.org/10.1109/IEMBS.2009.5334486DOI Listing
March 2010