Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Toxin Therapy for Treatment of Focal Spasticity

Functional magnetic resonance imaging (fMRI) has provided evidence of neuroplastic changes following rehabilitation in stroke survivors. Botulinum toxin (BoNT) injection therapy has become a common approach to combating spasticity—a motor disorder characterized by a velocity dependent increase in muscle tone. The neurotoxin acts to inhibit muscle contraction, relieving spasticity symptoms with peak effects occurring between 4 and 6 weeks. With decreases in muscle tone, BoNT injections could free arm movement for rehabilitation, creating the opportunity for enhanced control of the upper limb, which would have underpinnings in altered brain activity. Given evidence of cortical activation changes following other stroke rehabilitative methods, it is expected that BoNT therapy would produce similar types of changes. The aim of this study was to quantify changes in task-related activity throughout the brain in stroke survivors undergoing BoNT therapy. Understanding the changes in cortical activity resulting from BoNT injections could help improve rehabilitation methods and predict functional outcome. Changes in cortical activation in response to BoNT injections have only been documented in a handful of studies. Of these past studies, participant pools tended to include patients with moderate to high functional ability of the affected limb. Although patients receiving BoNT injections often fall within a wide range of severity, BoNT injections have been shown to provide the biggest impact on the highly impaired population. BoNT injections have also been shown to provide greatest effects during the initial injections, and the effects on long-term spasticity treatment are less prevalent in the literature. In this study, we used a voxel-based approach to quantify neuroplastic effects and capture changes in activity throughout the brain, including regions outside the primary sensorimotor cortices. We recruited a majority of participants that presented with severe spasticity, who were scheduled to receive a round of BoNT injections as part of their standard of care. By assessing the brain activation associated with repeated injections, we obtained insight into BoNT on a long-term basis, as it is traditionally prescribed

"Enriching 360-degree technologies through human-computer interaction: psychometric validation of two memory tasks"

This doctoral dissertation explores the domain of neuropsychological assessment, with the objective of gaining a comprehensive understanding of an individual's cognitive functioning and detecting possible impairments. Traditional assessment tools, while possessing inherent value, frequently exhibit a deficiency in ecological validity when evaluating memory, as they predominantly concentrate on short-term, regulated tasks. To overcome this constraint, immersive technologies, specifically virtual reality and 360° videos, have surfaced as promising instruments for augmenting the ecological validity of cognitive assessments. This work examines the potential advantages of immersive technologies, particularly 360° videos, in enhancing memory evaluation. First, a comprehensive overview of contemporary virtual reality tools employed in the assessment of memory, as well as their convergence with conventional assessment measures has been provided. Then, the present study utilizes cluster and network analysis techniques to categorize 360° videos according to their content and applications, thereby offering significant insights into the potential of this nascent medium. The study introduces then a novel platform, Mindscape, that aims to address the existing technological disparity, thereby enhancing the accessibility of clinicians and researchers in developing cognitive tasks within immersive environments. The conclusion of the thesis encompasses the psychometric validation of two memory tasks, which have been specifically developed with Mindscape to assess episodic and spatial memory. The findings demonstrate disparities in cognitive performance between individuals diagnosed with Mild Cognitive Impairment and those without cognitive impairments, underscoring the interrelated nature of cognitive processes and the promising prospects of virtual reality technology in improving the authenticity of real-world experiences. Overall, this dissertation aims to respond to the demand for practical and ecologically valid neuropsychological assessments within the dynamic field of neuropsychology. It achieves this by integrating user-friendly platforms and immersive cognitive tasks into its methodology. By highlighting a shift in the field of neuropsychology towards prioritizing functional and practical assessments over theoretical frameworks, this work indicates a changing perspective within the discipline. This study highlights the potential of comprehensive and purpose-oriented assessment methods in cognitive evaluations, emphasizing the ongoing significance of research in fully comprehending the capabilities of immersive technologies

Sensorimotor experience in virtual environments

The goal of rehabilitation is to reduce impairment and provide functional improvements resulting in quality participation in activities of life, Plasticity and motor learning principles provide inspiration for therapeutic interventions including movement repetition in a virtual reality environment, The objective of this research work was to investigate functional specific measurements (kinematic, behavioral) and neural correlates of motor experience of hand gesture activities in virtual environments stimulating sensory experience (VE) using a hand agent model. The fMRI compatible Virtual Environment Sign Language Instruction (VESLI) System was designed and developed to provide a number of rehabilitation and measurement features, to identify optimal learning conditions for individuals and to track changes in performance over time. Therapies and measurements incorporated into VESLI target and track specific impairments underlying dysfunction. The goal of improved measurement is to develop targeted interventions embedded in higher level tasks and to accurately track specific gains to understand the responses to treatment, and the impact the response may have upon higher level function such as participation in life. To further clarify the biological model of motor experiences and to understand the added value and role of virtual sensory stimulation and feedback which includes seeing one\u27s own hand movement, functional brain mapping was conducted with simultaneous kinematic analysis in healthy controls and in stroke subjects. It is believed that through the understanding of these neural activations, rehabilitation strategies advantaging the principles of plasticity and motor learning will become possible. The present research assessed successful practice conditions promoting gesture learning behavior in the individual. For the first time, functional imaging experiments mapped neural correlates of human interactions with complex virtual reality hands avatars moving synchronously with the subject\u27s own hands, Findings indicate that healthy control subjects learned intransitive gestures in virtual environments using the first and third person avatars, picture and text definitions, and while viewing visual feedback of their own hands, virtual hands avatars, and in the control condition, hidden hands. Moreover, exercise in a virtual environment with a first person avatar of hands recruited insular cortex activation over time, which might indicate that this activation has been associated with a sense of agency. Sensory augmentation in virtual environments modulated activations of important brain regions associated with action observation and action execution. Quality of the visual feedback was modulated and brain areas were identified where the amount of brain activation was positively or negatively correlated with the visual feedback, When subjects moved the right hand and saw unexpected response, the left virtual avatar hand moved, neural activation increased in the motor cortex ipsilateral to the moving hand This visual modulation might provide a helpful rehabilitation therapy for people with paralysis of the limb through visual augmentation of skills. A model was developed to study the effects of sensorimotor experience in virtual environments, and findings of the effect of sensorimotor experience in virtual environments upon brain activity and related behavioral measures. The research model represents a significant contribution to neuroscience research, and translational engineering practice, A model of neural activations correlated with kinematics and behavior can profoundly influence the delivery of rehabilitative services in the coming years by giving clinicians a framework for engaging patients in a sensorimotor environment that can optimally facilitate neural reorganization

Long-Dose Intensive Therapy Is Necessary for Strong, Clinically Significant, Upper Limb Functional Gains and Retained Gains in Severe/Moderate Chronic Stroke

Background. Effective treatment methods are needed for moderate/severely impairment chronic stroke. Objective. The questions were the following: (1) Is there need for long-dose therapy or is there a mid-treatment plateau? (2) Are the observed gains from the prior-studied protocol retained after treatment? Methods. Single-blind, stratified/randomized design, with 3 applied technology treatment groups, combined with motor learning, for long-duration treatment (300 hours of treatment). Measures were Arm Motor Ability Test time and coordination-function (AMAT-T, AMAT-F, respectively), acquired pre-/posttreatment and 3-month follow-up (3moF/U); Fugl-Meyer (FM), acquired similarly with addition of mid-treatment. Findings. There was no group difference in treatment response (P ≥ .16), therefore data were combined for remaining analyses (n = 31; except for FM pre/mid/post, n = 36). Pre-to-Mid-treatment and Mid-to-Posttreatment gains of FM were statistically and clinically significant (P \u3c .0001; 4.7 points and P \u3c .001; 5.1 points, respectively), indicating no plateau at 150 hours and benefit of second half of treatment. From baseline to 3moF/U: (1) FM gains were twice the clinically significant benchmark, (2) AMAT-F gains were greater than clinically significant benchmark, and (3) there was statistically significant improvement in FM (P \u3c .0001); AMAT-F (P \u3c .0001); AMAT-T (P \u3c .0001). These gains indicate retained clinically and statistically significant gains at 3moFU. From posttreatment to 3moF/U, gains on FM were maintained. There were statistically significant gains in AMAT-F (P = .0379) and AMAT-T P = .003

Predicting later categories of upper limb activity from earlier clinical assessments following stroke: An exploratory analysis

BACKGROUND: Accelerometers allow for direct measurement of upper limb (UL) activity. Recently, multi-dimensional categories of UL performance have been formed to provide a more complete measure of UL use in daily life. Prediction of motor outcomes after stroke have tremendous clinical utility and a next step is to explore what factors might predict someone\u27s subsequent UL performance category. PURPOSE: To explore how different machine learning techniques can be used to understand how clinical measures and participant demographics captured early after stroke are associated with the subsequent UL performance categories. METHODS: This study analyzed data from two time points from a previous cohort (n = 54). Data used was participant characteristics and clinical measures from early after stroke and a previously established category of UL performance at a later post stroke time point. Different machine learning techniques (a single decision tree, bagged trees, and random forests) were used to build predictive models with different input variables. Model performance was quantified with the explanatory power (in-sample accuracy), predictive power (out-of-bag estimate of error), and variable importance. RESULTS: A total of seven models were built, including one single decision tree, three bagged trees, and three random forests. Measures of UL impairment and capacity were the most important predictors of the subsequent UL performance category, regardless of the machine learning algorithm used. Other non-motor clinical measures emerged as key predictors, while participant demographics predictors (with the exception of age) were generally less important across the models. Models built with the bagging algorithms outperformed the single decision tree for in-sample accuracy (26-30% better classification) but had only modest cross-validation accuracy (48-55% out of bag classification). CONCLUSIONS: UL clinical measures were the most important predictors of the subsequent UL performance category in this exploratory analysis regardless of the machine learning algorithm used. Interestingly, cognitive and affective measures emerged as important predictors when the number of input variables was expanded. These results reinforce that UL performance, in vivo, is not a simple product of body functions nor the capacity for movement, instead being a complex phenomenon dependent on many physiological and psychological factors. Utilizing machine learning, this exploratory analysis is a productive step toward the prediction of UL performance. Trial registration NA

Long-Dose Intensive Therapy Is Necessary for Strong, Clinically Significant, Upper Limb Functional Gains and Retained Gains in Severe/Moderate Chronic Stroke

Background. Effective treatment methods are needed for moderate/severely impairment chronic stroke. Objective. The questions were the following: (1) Is there need for long-dose therapy or is there a mid-treatment plateau? (2) Are the observed gains from the prior-studied protocol retained after treatment? Methods. Single-blind, stratified/randomized design, with 3 applied technology treatment groups, combined with motor learning, for long-duration treatment (300 hours of treatment). Measures were Arm Motor Ability Test time and coordination-function (AMAT-T, AMAT-F, respectively), acquired pre-/posttreatment and 3-month follow-up (3moF/U); Fugl-Meyer (FM), acquired similarly with addition of mid-treatment. Findings. There was no group difference in treatment response (P ≥ .16), therefore data were combined for remaining analyses (n = 31; except for FM pre/mid/post, n = 36). Pre-to-Mid-treatment and Mid-to-Posttreatment gains of FM were statistically and clinically significant (P \u3c .0001; 4.7 points and P \u3c .001; 5.1 points, respectively), indicating no plateau at 150 hours and benefit of second half of treatment. From baseline to 3moF/U: (1) FM gains were twice the clinically significant benchmark, (2) AMAT-F gains were greater than clinically significant benchmark, and (3) there was statistically significant improvement in FM (P \u3c .0001); AMAT-F (P \u3c .0001); AMAT-T (P \u3c .0001). These gains indicate retained clinically and statistically significant gains at 3moFU. From posttreatment to 3moF/U, gains on FM were maintained. There were statistically significant gains in AMAT-F (P = .0379) and AMAT-T P = .003

A multimodal approach to investigate brain reorganization after spinal cord injury using functional magnetic resonance imaging and functional near-infrared spectroscopy

Traumatic Spinal Cord Injury (SCI) results in structural and functional neurological changes at both the brain and the level of the spinal cord. Anatomical studies indicate decreased grey matter volume in sensorimotor and non-sensorimotor regions of the cortex following SCI; whereas, neurophysiological findings mostly report altered functional activity in the sensorimotor nodes of the cortex, subcortex, and cerebellum. Therefore, it is currently unknown whether tissue atrophy observed in non-motor related areas has any concomitant functional consequences. Furthermore, the neural underpinnings of adaptive neuroplasticity after SCI is not well-defined in the current literature. Hence, this dissertation is a pioneer study investigating the structural and functional changes in the whole brain after SCI, with particular focus on subcortical regions, using a multimodal approach employing magnetic resonance imaging (MRI), resting-state functional MRI (fMRI) and functional near-infrared spectroscopy (fNIRS), that may take best advantage of each of these three tools. MRI scans from 23 healthy controls (HC) and 36 individuals with complete SCI within two years of injury were used to demonstrate that both injury level and duration since injury are important factors contributing to recovery. Specifically, cervical level injury when compared to thoracolumbar level injury exhibits a greater loss of cortical grey matter volume in the orbitofrontal cortex, insula, and anterior cingulate cortex. Next, using the fMRI scans of the same participants during a resting-state scan, the intrinsic functional connectivity of the mediodorsal, pulvinar and ventrolateral nuclei of the thalamus to the regions of salient network and the fronto-parietal network is observed to be dynamic and altered in the SCI group. Lastly, a continuous-wave fNIRS is used to reliably measure brain function in individuals with SCI during both dynamic and static tasks while accounting for cerebrovascular reactivity. Five min of resting-state data and 26 min of motor data including finger tapping, finger tapping imagery and ankle tapping were acquired to identify the spatial activation pattern unique to each of the movement type. A breath-hold paradigm is also used to quantify cerebrovascular reactivity as a means to calibrate task activity from neurovascular constraints. Sixteen HC were scanned at two separate visits to determine the sensitivity and test-retest reliability of fNIRS data from the sensorimotor cortex. Following validation, the same procedure was repeated in 13 individuals with paraplegia resulting from SCI and 13 HC to quantify alterations in the cortical activity of the motor cortex and cerebrovascular reactivity between the two groups. Results indicate that SCI group exhibit altered cerebrovascular reactivity with greater delay in response and greater pre-stimulus undershoot. As hypothesized, the hemodynamic response to ankle movement resulted in only a small change in oxyhemoglobin concentration in the sensorimotor cortex of SCI group when compared to HC. The application of fNIRS to assess cortical reorganization following SCI is unique and expands our understanding of the neurophysiology after SCI. It paves the groundwork for extending the implementation of fNIRS to rehabilitation research and other clinical populations with vascular dysfunction. This dissertation is one of the first studies to comprehensively examine both the structural and functional alterations of the brain in humans with complete SCI and opens promising avenues for SCI research using fNIRS modality

Function and Dysfunction in Distinct Facets of Empathy

Empathy is crucial for successful social interactions and it is impaired in many devastating disorders. Empathy deficits are highly burdensome for affected individuals, caregivers, and significant others, and costly for society as a whole. However, empathy is thought to be a multifaceted construct, including cognitive empathy, affective sharing, and empathic concern components. These constituents may be linked to different behavioural outcomes and neurocognitive substrates, and presentation varies depending on the facets affected. Thus, there is a critical need to determine the behavioural and neurocognitive substrates of different components of empathic responding, and how these are affected in particular disorders. The present work aimed to elucidate the nature of different components of empathy and how they vary as a function of clinical diagnoses and individual differences in subclinical traits, as well as their underlying functional neural mechanisms. Study I used the Multifaceted Empathy Test, a performance-based task tapping cognitive empathy, affective sharing, and empathic concern elicited by realistic emotional images, in patients with behavioural variant frontotemporal dementia (bvFTD). This revealed a global cognitive empathy deficit, deficient affective sharing for negative experiences, and a generalized processing impairment for negative stimuli in bvFTD. In Study II, healthy adults completed the Multifaceted Empathy Test and questionnaire measures of autistic traits, coldhearted psychopathic traits, and trait anxiety. Coldhearted traits were found to disrupt affective sharing and empathic concern, whereas trait anxiety appeared to influence subjective affective experience via generalized arousal. Study III investigated the involvement of action-perception matching, simulation mechanisms in cognitive versus emotional empathy, using fMRI during cognitive empathy, emotional empathy, and simulation network localizer tasks in healthy adults. Increased activation was observed in identified simulation regions during emotional versus cognitive empathy, providing evidence for greater involvement of simulation mechanisms in emotional empathy. Taken together, this work suggests that cognitive empathy, and emotional empathy, including affective sharing and empathic concern, represent aspects of empathy that are distinguishable and differentially linked with certain patient populations, subclinical traits, and neurocognitive mechanisms. These findings are discussed with respect to the nature and conceptualization of empathy and its components, as well as implications for disorders featuring empathy dysfunction

Evidence-informed discharge planning model for stroke rehabilitation

Stroke is a leading cause of long-term disability (Benjamin et al., 2017) and patients with this diagnosis have been found to have higher incidences of inappropriately long hospital lengths of stay (McDonagh, Smith, & Goddard, 2000). Generalist training in occupational therapy curriculum coupled with variable research utilization (Dysart & Tomlin, 2002; McKenna et al., 2005) leads to inconsistent methods of evaluation and decreased communication between providers across settings. Furthermore, there are currently no standardized discharge planning models or guidelines for clinicians to follow when evaluating patients or making recommendations (Ilett, Brock, Graven, & Cotton, 2010). An evidence-informed discharge planning model was created to address these issues. This model utilizes a multidisciplinary approach, with guidelines for selecting and administering evaluations to quantify a patient’s functional status. Assessments are clustered into four domains: activities of daily living, balance and mobility, cognition, and other (i.e. visual inattention, motor control and spasticity). These assessments supplement a basic patient evaluation, and results are used to guide clinical decision making regarding recommendations for the next level of care. Stroke rehabilitation and care cannot be standardized, but the methods used to select measures and make discharge recommendations should have distinct guidelines. By choosing from a core set of measures, clinicians can use a common “language” to describe patient function and measure progress across settings over time. This will ensure patients are discharged to the appropriate level of rehabilitation to optimize their recovery, and it will also help prevent excessively long hospital admissions