Rehabilitation of Communicative Abilities in Patients with a History of TBI: Behavioral Improvements and Cerebral Changes in Resting-State Activity

A targeted training program for the rehabilitation of communicative abilities—Cognitive Pragmatic Treatment (CPT)—has been developed and previously tested on a sample of patients with traumatic brain injury (TBI), whose performance was found to have improved. Since cortical plasticity has been recognized as the main mechanism of functional recovery, we investigated whether and how behavioral improvements following the training program are accompanied by brain modifications. Eight TBI patients took part in the training program and were behaviorally assessed pre- and post-treatment; six of these patients were also evaluated with pre- and post-treatment resting state (rs) functional magnetic resonance imaging (fMRI). At the end of the rehabilitation program patients showed improvement in overall communicative performance, in both comprehension and production tasks. A follow-up retest revealed the stability of these results 3 months after completing the training program. At the brain level, we found significant increases in the amplitude of low frequency fluctuation (ALFF) index in the bilateral precentral gyrus, in the right middle and superior temporal gyri, in the right cingulate gyrus, and in the left inferior parietal lobule. We discuss these differences of brain activity in terms of their possible contribution to promoting recovery

An Active Exoskeleton Called P.I.G.R.O. Designed for Unloaded Robotic Neurorehabilitation Training

The development of innovative robotic devices allows the design of exoskeletons for robotic neurorehabilitation training. This paper presents the active exoskeleton called pneumatic interactive gait rehabilitation orthosis (P.I.G.R.O.), developed by the authors. The main innovative characteristic of this prototype is its design for fully unloaded robotic neurorehabilitation training, specific for brain-injured patients. It has six degrees of freedom (DOF) in the sagittal plane, an active ankle joint (removable if it is required); a wide range of anthropometric regulations, both for men and for women; a useful human machine interface (HMI); and an innovative harness system for the patient for the unloaded training. It is realized using light and strong materials, and it is electropneumatically controlled. In particular the authors also studied and defined some innovative input control curves useful for the unloaded training. In this paper, the main characteristics and innovations of P.I.G.R.O. are presented

PRELIMINARY STRUCTURAL ANALYSIS OF AN ACTIVE EXOSKELETON FOR ROBOTIC NEURO-REHABILITATION

In this paper the exoskeleton P.I.G.R.O. (Pneumatic Interactive Gait Rehabilitation Orthosis), developed in the Department of Mechanical and Aerospace Engineering (DIMEAS) Politecnico di Torino with the important co-operation with doctors, is presented. It was preliminary designed for a completely unloaded walking gait cycle in order to treat the first steps of the neurorehabilitation trainings. An initial FEM evaluation of P.I.G.R.O. structure is here presented. It underlines a lot of important aspects and techniques to analyse the structural characteristics of P.I.G.R.O. legs rigid parts using a commercial software but analysing both the actions of the pneumatic actuators and of the patients muscles and/or movements. The results obtained are good and allow to verify the P.I.G.R.O. legs structure and to establish a procedure to study its characteristics also with the presence of the patien

Bra.Di.P.O. and P.I.G.R.O.: Innovative Devices for Motor Learning Programs

Two mechatronics prototypes, useful for robotic neurotreatments and new clinical trainings, are here presented. P.I.G.R.O. (pneumatic interactive gait rehabilitation orthosis) is an active exoskeleton with an electropneumatic control. It imposes movements on lower limbs in order to produce in the patient’s brain proper motor cortex activation. Bra.Di.P.O. (brain discovery pneumatic orthosis) is an MR-compatible device, designed to improve fMRI (functional magnetic resonance imaging) analysis. The two devices are presented together because both are involved in the study of new robotic treatments of patients affected by ictus or brain stroke or in some motor learning experimental investigations carried out on healthy subjects

Chemotherapy effects on brain glucose metabolism at rest

Background: A growing number of studies reports that chemotherapy may impair brain functions inducing cognitive changes which can persist in a subset of cancer survivors. Aims: To investigate the neural basis of the chemotherapy-induced neurobehavioral changes by means of metabolic imaging and voxel-based statistical parametric mapping analyses. Methods: We studied the resting brain [18]FDG-PET/CT images of 43 adult cancer patients with solid (n=12, 28%) or hematologic malignancies (n=31, 72%); 12 patients were studied prior to chemotherapy (No chemotherapy) while treated patients were divided into two matched subgroups: Early High (6 chemotherapy cycles, n=10), and Late Low (>9 months after chemotherapy, <6 chemotherapy cycles, n=21). Findings: Compared to No chemotherapy, the Early High subgroup showed a significant bilateral (p<0.05) lower regional cerebral metabolic rate of glucose metabolism in both the prefrontal cortices and white matter, cerebellum, posterior medial cortices and limbic regions. A similar pattern emerged in the Early High versus Low Late comparison, while no significant result was obtained in the Low Late versus No chemotherapy comparison. The number of cycles and the post-chemotherapy time were negatively and positively correlated, respectively, with a set of these same brain regions. Interpretation: The present study shows that chemotherapy induces significant transient changes in the glucose metabolism of multiple cerebral cortical and white matter regions with a prevailing involvement of the prefrontal cortex. The severity of these changes are significantly related with the number of chemotherapy cycles and a subset of brain regions seems to present longer lasting, but more subtle, metabolic changes

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons