Clinical Potential of Transcranial Focused Ultrasound for Neurorehabilitation in Pediatric Cancer Survivors.

Cancer survivors are at a high risk for treatment-related late effects, particularly neurocognitive impairment in the attention and executive function domains. These can be compounded in pediatric populations still undergoing neural development, which has increased interest in survivorship studies and neurorehabilitation approaches to mitigate these effects. Cognitive training regimens have shown promise as a therapeutic intervention for improving cognitive function. Therapist-guided and computerized training programs with adaptive paradigms have been successfully implemented in pediatric populations, with positive outcomes on attention and working memory. Another interventional approach is neuromodulation to alter plasticity. Transcranial electrical stimulation can modulate cortical surface activity, and cranial nerve stimulation alters autonomic activity in afferent brainstem pathways. However, they are more systemic in nature and have diffuse spatial targeting. Transcranial focused ultrasound (tFUS) modulation overcomes these limitations with high spatial specificity and the ability to target deeper brain regions. In this review, we discuss the efficacy of tFUS for modulating specific brain regions and its potential utility to augment cognitive training programs as a complementary intervention.

Multi-session Analysis of Movement Variability While Reaching in a Virtual Environment.

The acquisition of neurophysiological data during awake, behaving animal experiments typically involves experimental sessions lasting several days to weeks. Therefore, it is important to understand natural fluctuations in behavioral performance over such periods. Here we quantified patterns of movement variability for reaches performed by two monkeys across five daily experimental sessions. The monkeys were trained to move in an immersive virtual reality (VR) environment that was designed to resemble the experimental room. Visual feedback of the limb was provided using VR avatar arms that were controlled through a reflective marker-based motion capture system. Additionally, tactile cues were provided in the form of physical reach targets. Spatial variability was characterized at early (peak acceleration) and late (movement endpoint) kinematic landmarks. We found that the magnitude of variability was generally larger at peak acceleration than at the endpoint but was relatively consistent across days and within animals. The spatial characteristics of variability were also generally highly consistent at peak acceleration both within and between animals but were noticeably less so at the endpoint. The results highlight the benefits of using early kinematic landmarks such as peak acceleration for quantifying movement variability in reaching studies involving animals.

Sensory feedback-dependent coding of arm position in local field potentials of the posterior parietal cortex.

Although multisensory integration is crucial for sensorimotor function, it is unclear how visual and proprioceptive sensory cues are combined in the brain during motor behaviors. Here we characterized the effects of multisensory interactions on local field potential (LFP) activity obtained from the superior parietal lobule (SPL) as non-human primates performed a reaching task with either unimodal (proprioceptive) or bimodal (visual-proprioceptive) sensory feedback. Based on previous analyses of spiking activity, we hypothesized that evoked LFP responses would be tuned to arm location but would be suppressed on bimodal trials, relative to unimodal trials. We also expected to see a substantial number of recording sites with enhanced beta band spectral power for only one set of feedback conditions (e.g. unimodal or bimodal), as was previously observed for spiking activity. We found that evoked activity and beta band power were tuned to arm location at many individual sites, though this tuning often differed between unimodal and bimodal trials. Across the population, both evoked and beta activity were consistent with feedback-dependent tuning to arm location, while beta band activity also showed evidence of response suppression on bimodal trials. The results suggest that multisensory interactions can alter the tuning and gain of arm position-related LFP activity in the SPL.

Virtual Reality Platform for Systematic Investigation of Multisensory Integration and Training of Closed-Loop Prosthetic Control.

Multisensory integration is the process by which information from different sensory modalities is integrated by the nervous system. Understanding this process is important not only from a basic science perspective but also for translational reasons, e.g. for the development of closed-loop neural prosthetic systems. Here we describe a versatile virtual reality platform which can be used to study the neural mechanisms of multisensory integration for the upper limb and could potentially be incorporated into systems for training of robust neural prosthetic control. The platform involves the interaction of multiple computers and programs and allows for selection of different avatar arms and for modification of a selected arm's visual properties. The system was tested with two non-human primates (NHP) that were trained to reach to multiple targets on a tabletop. Reliability of arm visual feedback was altered by applying different levels of blurring to the arm. In addition, tactile feedback was altered by adding or removing physical targets from the environment. We observed differences in movement endpoint distributions that varied between animals and visual feedback conditions, as well as across targets. The results indicate that the system can be used to study multisensory integration in a well-controlled manner.

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal-Dominant Alzheimer's Disease Colombia Trial.

INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.

Functional differences in spatial processing along an anterior-posterior axis: are there implications for the retrosplenial cortex?

The retrosplenial cortex has recently received attention from the neuroscience community for its role in spatial processing and involvement in diseases such as Alzheimer's. Here, we discuss a recent study by Silson et al. (Silson EH, Gilmore AW, Kalinowski SE, Steel A, Kidder A, Martin A, Baker CI. J Neurosci 39: 705-717, 2019.) that reported functionally specific activation within this region during scene perception and (mnemonic) construction. We then propose considerations for future experiments such as adopting standardized methodology and terminology that may improve the interpretation of retrosplenial cortex function within the broader literature.

Multisensory Interactions Influence Neuronal Spike Train Dynamics in the Posterior Parietal Cortex.

Although significant progress has been made in understanding multisensory interactions at the behavioral level, their underlying neural mechanisms remain relatively poorly understood in cortical areas, particularly during the control of action. In recent experiments where animals reached to and actively maintained their arm position at multiple spatial locations while receiving either proprioceptive or visual-proprioceptive position feedback, multisensory interactions were shown to be associated with reduced spiking (i.e. subadditivity) as well as reduced intra-trial and across-trial spiking variability in the superior parietal lobule (SPL). To further explore the nature of such interaction-induced changes in spiking variability we quantified the spike train dynamics of 231 of these neurons. Neurons were classified as Poisson, bursty, refractory, or oscillatory (in the 13-30 Hz "beta-band") based on their spike train power spectra and autocorrelograms. No neurons were classified as Poisson-like in either the proprioceptive or visual-proprioceptive conditions. Instead, oscillatory spiking was most commonly observed with many neurons exhibiting these oscillations under only one set of feedback conditions. The results suggest that the SPL may belong to a putative beta-synchronized network for arm position maintenance and that position estimation may be subserved by different subsets of neurons within this network depending on available sensory information. In addition, the nature of the observed spiking variability suggests that models of multisensory interactions in the SPL should account for both Poisson-like and non-Poisson variability.