Browsing by Author "Hu, Bin"

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    Differentiating cognitive or motor dimensions associated with the perception of fall-related self-efficacy in Parkinson's disease
    (Nature Publishing Group, 2018-01) Chomiak, Taylor; Watts, Alexander; Burt, Jacqueline; Camicioli, Richard M.; Tan, Sun Nee; McKeown, Martin; Hu, Bin
    In Parkinson's disease (PD), concurrent declines in cognitive and motor domain function can severely limit an individual's ability to conduct daily tasks. Current diagnostic methods, however, lack precision in differentiating domain-specific contributions of cognitive or motor impairments based on a patients' clinical manifestation. Fear of falling (FOF) is a common clinical manifestation among the elderly, in which both cognitive and motor impairments can lead to significant barriers to a patients' physical and social activities. The present study evaluated whether a set of analytical and machine-learning approaches could be used to help delineate boundary conditions and separate cognitive and motor contributions to a patient's own perception of self-efficacy and FOF. Cognitive and motor clinical scores, in conjunction with FOF, were collected from 57 Parkinson's patients during a multi-centre rehabilitation intervention trial. Statistical methodology was used to extract a subset of uncorrelated cognitive and motor components associated with cognitive and motor predictors, which were then used to independently identify and visualize cognitive and motor dimensions associated with FOF. We found that a central cognitive process, extracted from tests of executive, attentional, and visuoperceptive function, was a unique and significant independent cognitive predictor of FOF in PD. In addition, we provide evidence that the approaches described here may be used to computationally discern specific types of FOF based on separable cognitive or motor models. Our results are consistent with a contemporary model that the deterioration of a central cognitive mechanism that modulates self-efficacy also plays a critical role in FOF in PD.
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    Intrinsic Optical Imaging of Cortex During Deep Brain Stimulation: Parameters, Spatiotemporal Dynamics and Neurovascular Coupling
    (2018-04-23) Noor, Muhammad Sohail; Kiss, Zelma H. T.; Murari, Kartikeya; Frayne, Richard; Hu, Bin
    Deep brain stimulation (DBS) is clinically used to treat various movement disorders and has a potential to ameliorate other conditions such as depression, epilepsy etc. However, the mechanism through which DBS alleviates symptoms is not clear which prevents its efficient application and expansion to new conditions. Modulation of motor cortex due to DBS is thought to be imperative in this therapy. Recent electrophysiology and imaging studies investigating the effects of DBS on motor cortex have reported contradictory results. One reason of this disagreement is that functional imaging techniques (functional magnetic resonance imaging and positron imaging tomography) commonly used to study DBS are neither suited for mechanistic understanding nor for chronic measurements. In this thesis, I tested a similar functional imaging technique, called intrinsic optical imaging (IOI), which can be used to better probe the functioning of DBS in animals models because it allows simultaneous imaging and electrophysiology, neurochemical manipulations, and long-term recording over months. I established that IOI can measure DBS-induced cortical perfusion consistently and using this technique I studied how various parameters of DBS, which are critical to its therapeutic effect, modulate motor cortex perfusion in rodents. The temporal and spatial dynamics of perfusion were dependent on the parameters of DBS. 'Maximum change in reflectance' and its spatial spread (two measures of hemodynamic response) increased linearly with increases in current amplitude or pulse width and had a non-linear relationship with frequency. Using simultaneous imaging and electrophysiology, I studied the relationship between DBS-induced neural and vascular response — neurovascular coupling, understanding which is necessary to interpret the data acquired with functional imaging techniques used in patients. Neurovascular coupling relationship was developed between 'maximum change in reflectance' (MCR, a measure of vascular response) and 'integrated evoked potential (IEP)' or 'multiunit broadband power' (two measures of neural response). The relationship between MCR and IEP was maintained to a stimulation frequency of 60 Hz: both increased with the frequency of stimulation. However, above 60 Hz MCR saturated while IEP increased linearly to the maximum frequency tested of 100 Hz. The relationship between MCR and multi-unit power remained coupled for the whole range of stimulation frequency applied. These relationships will help researchers in the interpretation of functional imaging studies during DBS. The technique established here and my results will further our understanding of DBS, help to improve this therapy and provide an opportunity to expand it to treat new neurologic and psychiatric conditions.
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    Membrane Dynamics of Inferior Colliculus Neurons in the Young Rat
    (2008) Tennent, Adrien F.; Hu, Bin
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    Mild behavioral impairment is related to frailty in non-dementia older adults: a cross-sectional study
    (2020-11-27) Fan, Shaoyi; Liang, Ximin; Yun, Tianchan; Pei, Zhong; Hu, Bin; Ismail, Zahinoor; Yang, Zhimin; Xu, Fuping
    Abstract Background Frailty and cognitive decline are highly prevalent among older adults. However, the relationship between frailty and mild behavioral impairment (MBI), a dementia risk syndrome characterized by later-life emergence of persistent neuropsychiatric symptoms, has yet to be elucidated. We aimed to evaluate the associations between MBI and frailty in older adults without dementia. Methods In this cross-sectional study, a consecutive series of 137 older adults without dementia in the Anti-Aging Study, recruited from primary care clinics, were enrolled. Frailty was estimated using the Fried phenotype. MBI was evaluated by the Mild Behavioral Impairment Checklist (MBI-C) at a cut-off point of > 8. Cognition was assessed with the Chinese versions of the Montreal Cognitive Assessment (MoCA-BC) and Mini-mental State Examination (MMSE). Multivariable logistic regression was performed to estimate the relationship between MBI and objective cognition with frailty status. Results At baseline, 30.7% of the older adults had frailty and 18.2% had MBI (MBI+ status). Multivariable logistic regression analysis demonstrated that compared to those without MBI (MBI- status), MBI+ was more likely to have frailty (odds ratio [OR] = 7.44, 95% CI = 1.49–37.21, p = 0.02). Frailty and MBI were both significantly associated with both MMSE and MoCA-BC score (p < 0.05). Conclusions Both frailty and MBI status were associated with higher odds of cognitive impairment. MBI was significantly associated with an increased risk of having frailty in the absence of dementia. This association merits further study to identify potential strategies for the early detection, prevention and therapeutic intervention of frailty.
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    Neurotrophic Theory of Accelerated Temporal Cortex Maturation in the Valproic Acid Rat Model of Autism
    (2014-09-30) Hung, Johanna; Hu, Bin
    Neuronal networks in the human ventro-anterior temporal lobe play a critical role in mediating object perception, long term semantic memory and social communication. A unique feature of this region is its delayed acquisition of peak cortical thickness, which is not reached until the second decade of life. In the majority of individuals with Autism Spectrum Disorders (henceforth referred to as autism) there is premature overgrowth of the temporal lobe during childhood. In this thesis, I studied the maturation trajectory of neurons from a homologous region in the albino rat, the posterior temporal association cortex (TeA), and how it is altered with exposure to the autism-linked teratogen valproic acid (VPA). My overarching hypothesis was that the slow maturation of TeA neurons during the first three weeks of postnatal development is a result of low local production and/or secretion of brain derived neurotrophic factor (BDNF), and that VPA can accelerate maturation of TeA neurons during this period by prematurely increasing BDNF signalling. Chapter 1 is a general introduction that describes the importance of the temporal association cortex in cognitive development and autism research (Section 1.1), the phenomenon of slow maturation of heteromodal association cortices in humans (Section 1.2), the anatomy, function and development of the rat cortex (Section 1.3 and 1.4), and the rodent VPA model of autism (Section 1.5). The aim of the introduction is to clearly define the context, significance, and rationale for the thesis hypothesis and aims, which are summarized in Section 1.6. Materials and methods used in this thesis are presented in Chapter 2. Chapters 3-7 are the results of experimental work. These chapters are ordered to provide a general characterization of neuroanatomy of the TeA in normal and VPA treated animals in intact brains, before moving into increasingly mechanistic investigations using primary neuronal cultures. In Chapter 3, I compare the cortical thickness trajectory of the TeA with that of other cortical regions. In Chapter 4, I show that VPA increases the cortical thickness and density of Golgi-Cox stained processes in the TeA and that this may have behavioural consequences. In Chapter 5, I report that TeA neurons grow slowly in vitro as they do in vivo. Maturation of TeA neurons lagged behind that of primary sensorimotor areas and the hippocampus as measured by single-cell morphometry, dendrite density, and electrophysiology. These data suggest that endogenous properties are essential for regulating neuronal maturation rate. In Chapter 6, I describe my investigations of the effect of VPA on TeA maturation using the cell culture paradigm. VPA increased dendrite density in TeA and entorhinal cortex cultures but not those prepared from frontal association cortex, parietal association cortex, hippocampus, or primary sensorimotor cortices of the temporal, parietal and occipital lobes. VPA exposure also increased the percentage of spiking neurons in TeA cultures. These results suggest that TeA and EC cultures are intrinsically different from the other cortical areas examined. In Chapter 7, I investigated the mechanism by which TeA neurite outgrowth was selectively enhanced after VPA treatment. I found that the TeA normally has a significantly lower level of brain-derived neurotrophic factor (BDNF) immunostaining than many other brain regions during the early postnatal period. VPA exposure increased the intensity of BDNF staining in cultured TeA neurons, and its effect on dendrite growth was blocked by the specific tropomyosin-receptor kinase B (trkB) inhibitor ANA-12. Direct application of BDNF to TeA cultures reproduced the effect of VPA on neuronal morphology. Based on the results presented in this thesis and existing literature, I propose a hypothesis about the mechanism of slow TeA maturation and the developmental pathology of autism, presented in Chapter 8 along with a discussion of the mechanism by which VPA increases BDNF expression.
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    Thalamocortical forward modulation in the auditory cortex
    (2017-12-18) Xiong, Colin; Yan, Jun; Eggermont, Jos; Stell, Bill; Hu, Bin
    Auditory masking is a psychoacoustic phenomenon with strong physiological correlates in the central auditory system such as in the primary auditory cortex. The caveat of conventional two-tone paradigms in testing the neurophysiology of forward masking (i.e., forward suppression) is that tones are processed at every auditory center, meaning the recorded activities do not represent the pure characteristics of the recorded site. Thus, there is a great need for a specialized protocol to tease out and uncover the pure suppression characteristics at each site, particularly the thalamocortical system - the primary sensory input to the auditory cortex. This study implemented an in vivo thalamocortical model in C57 mice along with common electrophysiological techniques to examine the pure role of the thalamocortical system in cortical forward modulation; focal electrical stimulation (ES) of the ventral division of the medial geniculate body (MGBv, ESMGBv) substituted for one or both tones of the conventional two-tone stimulus paradigm. With this ameliorative approach, I demonstrated that ESMGBv facilitated succeeding ESMGBv while suppressing succeeding tones. This suggests that the default state of the thalamocortical system is facilitation while maintaining the capability of forward suppression through heterosynaptic thalamocortical inputs. Forward suppression of tones by ESMGBv was comparatively weaker than forward suppression of ESMGBv by tone stimulus. The period of complete suppression in the cortex for all stimuli was approximately 100 ms. Furthermore, the thalamocortical forward suppression spectral areas were found to be mirrored images of the receptive fields of recorded cortical neurons. Together, these data suggest that thalamocortical forward facilitation and suppression in the recorded cortical neurons can be accomplished without the involvement of complex cortical circuitry. This idea is further supported by the finding that cortical GABAA inhibition was not required for the thalamocortical forward suppression. Additionally, it was shown that two-tone stimulus resulted in complete MGBv suppression for approximately 75 ms. This means that the thalamus provides the cortex with a 75 ms “silent window” during which cortical mechanisms, such as GABAA inhibition, are not necessary for forward suppression. Following careful investigation of literature, a novel "single-cell” model appears to account for thalamocortical forward modulation.  
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    Walking with Music Is a Safe and Viable Tool for Gait Training inParkinson's Disease: The Effect of a 13-Week Feasibility Study onSingle and Dual Task Walking
    (2010-07-13) de Bruin, Natalie; Doan, Jon B.; Turnbull, George; Suchowersky, Oksana; Bonfield, Stephan; Hu, Bin; Brown, Lesley A.
    This study explored the viability and efficacy of integrating cadence-matched, salient music into a walking intervention for patients with Parkinson's disease (PD). Twenty-two people with PD were randomised to a control (CTRL, n=11) or experimental (MUSIC, n=11) group. MUSIC subjects walked with an individualised music playlist three times a week for the intervention period. Playlists were designed to meet subject's musical preferences. In addition, the tempo of the music closely matched (±10–15 bpm) the subject's preferred cadence. CTRL subjects continued with their regular activities during the intervention. The effects of training accompanied by “walking songs” were evaluated using objective measures of gait score. The MUSIC group improved gait velocity, stride time, cadence, and motor symptom severity following the intervention. This is the first study to demonstrate that music listening can be safely implemented amongst PD patients during home exercise.
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    What We Have Learned about Autism Spectrum Disorder from Valproic Acid
    (2013-12-08) Chomiak, Taylor; Turner, Nathanael; Hu, Bin
    Two recent epidemiological investigations in children exposed to valproic acid (VPA) treatment in utero have reported a significant risk associated with neurodevelopmental disorders and autism spectrum disorder (ASD) in particular. Parallel to this work, there is a growing body of animal research literature using VPA as an animal model of ASD. In this focused review we first summarize the epidemiological evidence linking VPA to ASD and then comment on two important neurobiological findings linking VPA to ASD clinicopathology, namely, accelerated or early brain overgrowth and hyperexcitable networks. Improving our understanding of how the drug VPA can alter early development of neurological systems will ultimately improve our understanding of ASD.