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BackgroundRecovery of walking post-stroke is highly variable. Accurately measuring and documenting functional brain activation characteristics during walking can help guide rehabilitation. Previous work in this area has been limited to investigations of frontal brain regions and have not utilized recent technological and analytical advances for more accurate measurements. There were three aims for this study: to characterize the hemodynamic profile during walking post-stroke, to investigate regional changes in brain activation during different phases of walking, and to related brain changes to clinical measures.MethodsFunctional near-infrared spectroscopy (fNIRS) along the pre-frontal, premotor, sensorimotor, and posterior parietal cortices was used on twenty individuals greater than six months post-stroke. Individual fNIRS optodes were digitized and used to estimate channel locations on each participant and short separation channels were used to control for extracerebral hemodynamic changes. Participants walked at their comfortable pace several times along a hallway while brain activation was recorded. Exploratory cluster analysis was conducted to determine if there was a link between brain activation and clinical measures.ResultsSustained activation was observed in the pre-frontal cortex with the ipsilesional hemisphere showing greater activation compared to the contralesional side. Sensorimotor cortex was active during the early, acceleration stage of walking only. Posterior parietal cortex showed changes in activation during the later, steady-state stage of walking. Faster gait speeds also related to increased activation in contralesional sensorimotor and posterior parietal cortices. Exploratory analysis clustered participants into two distinct groups based on their brain activation profiles and generally showed that individuals with greater activation tended to have better physical outcomes.ConclusionsThese findings can guide future research for obtaining adequate power and determining factors that can be used as effect modifiers to reduce inter-subject variability. Overall, this is the first study to report specific oxygenated and deoxygenated hemoglobin changes in frontal to parietal regions during walking in the stroke population. Our results shed light on the importance of measuring brain activation across the cortex and show the importance of pre-frontal, sensorimotor, and posterior parietal cortices in walking after a stroke.

Independent ambulation in the community is often stated as important amongst people post-stroke. Walking within the community can be complex, requiring speed changes during walking, attention or interaction with the environment and other people. After a stroke, the ability to complete these specific walking tasks is often impaired. Currently, determining appropriate gait rehabilitation interventions post-stroke is based on clinical observations such as motor, sensory, cognitive, and balance ability. These methods, however, may not be sensitive or objective enough to detect change or appropriateness for specific interventions. Assessment of individual functional brain activation is a promising method for determining appropriateness of gait rehabilitation interventions and can provide insight on resource allocation, neural efficiency, and neural compensations. This dissertation consists of four independent studies. The first is a review of the current findings of brain activation during walking post-stroke and identified the gaps within the literature. This review then informed the next three studies where functional near-infrared spectroscopy was used to assess real-time brain activation during different types of walking: normal-paced, slow, fast, and dual-task walking. Results from these studies show task- specific activation of brain regions across the frontal and parietal cortices as well as relationships between brain activation and clinical measures of impairment and performance. Notably, consistent increases in ipsilesional prefrontal cortex was observed with each walking task, premotor cortex was involved when walking was not at a normal-pace, and activation in sensorimotor and posterior parietal cortices related to gait speed. Results from these studies contribute basic scientific knowledge towards the neural correlates of walking after a stroke and can be an important reference for future interventions aimed to improve walking recovery.

Lida A Mina,1 Shannon Lim,2 Shakeela W Bahadur,1 Abdul T Firoz3 1Hematology Oncology Department, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 2Pharmacy Department, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 3Science Department, Arizona State University, Tempe, AZ, USACorrespondence: Lida A MinaBanner MD Anderson Cancer Center, Suite 400, 2946 E Banner Gateway Dr, Gilbert, AZ 85234, USATel +1 480 256 3676Fax +1 480 256 4624Email Lida.mina@bannerhealth.comAbstract: Breast cancer is the most common type of cancer affecting women in the United States. Triple-negative breast cancer remains the most aggressive molecular subtype secondary to a lack of therapeutic targets. The search for a target has led us to investigate immunotherapeutic agents. Immunotherapy has recently demonstrated significant breakthroughs in various types of cancers that are refractory to traditional therapies including melanoma and Non-Small Cell Lung Cancer (NSCLC). Breast cancer however remains one of the tumors that was initially least investigated because of being considered to have a low immunogenic potential and a low mutational load. Over the past few years, antiPD1/PDL1 drugs have started to make progress in the triple-negative subtype with more promising outcomes. In this report, we review the treatment of triple-negative breast cancer and specifically shed light on advances in immunotherapy and newly approved drugs in this challenging disease.Keywords: breast cancer, immunotherapy, PD1, PDL1, atezolizumab

Background: Mirror therapy is less commonly used to target the lower extremity after stroke to improve outcomes but is simple to perform. This review and meta-analysis aimed to evaluate the efficacy of lower extremity mirror therapy in improving balance, gait, and motor function for individuals with stroke.Methods: PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, PEDro, and PsychINFO were searched from inception to May 2018 for randomized controlled trials (RCTs) comparing lower extremity mirror therapy to a control intervention for people with stroke. Pooled effects were determined by separate meta-analyses of gait speed, mobility, balance, and motor recovery.Results: Seventeen RCTs involving 633 participants were included. Thirteen studies reported a significant between-group difference favouring mirror therapy in at least one lower extremity outcome. In a meta-analysis of six trials that reported change in gait speed, a large beneficial effect was observed following mirror therapy training (SMD = 1.04 [95% CI = 0.43, 1.66], I2 = 73%, p

The vestibular system is a complex network that plays an important role in balance control. When postural perturbations are exerted on the individual, it appears that the vestibular system plays a role in modulating the amplitude of the responses. The vestibular system is also susceptible to changes in psychosocial and autonomic states. Despite these findings, the inability to precisely record from and directly manipulate the system has hindered the field in completely understanding how the vestibular system is involved in balance. Therefore, the purposes of this thesis were 1) to investigate if there was phase-dependent modulation of the vestibular reflex during the postural responses and 2) to determine if the vestibular reflex was altered with postural threat. Stochastic vestibular stimulation (SVS) was used to electrically probe the vestibular system while participants stood on a rotating platform. The vestibular reflex was analyzed by estimating the vestibulo-muscular (SVS-EMG) relationship using time-dependent SVS-EMG coherence throughout the postural response for the first purpose while, for the second purpose, SVS-EMG coherence, cumulant density, and gain were calculated between non-threatening and threatening conditions. Results from this thesis were unable to determine if there were phase-dependent modulations of the SVS-induced vestibular reflex. However, further testing and pilot data provides a promising method for further investigation. Furthermore, an increase gain in and coupling of the vestibular reflex was observed in the most muscles while a decrease in coupling was observed for the paraspinal muscles in the threatening situation. These results suggest that the central nervous system has the ability to prepare the body for responding to an upcoming postural perturbation by optimizing the vestibular output to the muscles.

Investigations of real-time brain activations during walking have become increasingly important to aid in recovery of walking after a stroke. Individual brain activation patterns can be a valuable biomarker of neuroplasticity during the rehabilitation process and can result in improved personalized medicine for rehabilitation. The purpose of this systematic review is to explore the brain activation characteristics during walking post-stroke by determining: (1) if different components of gait (i.e., initiation/acceleration, steady-state, complex) result in different brain activations, (2) whether brain activations differ from healthy individuals. Six databases were searched resulting in 22 studies. Initiation/acceleration showed bilateral activation in frontal areas; steady-state and complex walking showed broad activations with the majority exploring and finding increases in frontal regions and some studies also showing increases in parietal activation. Asymmetrical activations were often related to performance asymmetry and were more common in studies with slower gait speed. Hyperactivations and asymmetrical activations commonly decreased with walking interventions and as walking performance improved. Hyperactivations often persisted in individuals who had experienced severe strokes. Only a third of the studies included comparisons to a healthy group: individuals post-stroke employed greater brain activation compared to young adults, while comparisons to older adults were less clear and limited. Current literature suggests some indicators of walking recovery however future studies investigating more brain regions and comparisons with healthy age-matched adults are needed to further understand the effect of stroke on walking-related brain activation.