Neural correlates of bradykinesia in Parkinson's disease: a kinematic and functional MRI study.

Bradykinesia is defined as a "complex" of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson's disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV-V-VI, vermis IV-V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the "bradykinesia complex".

Sensory-motor training with virtual reality as a complementary intervention to manual therapy for persistent non-specific neck pain: a randomized controlled trial.

BACKGROUND: Persistent non-specific neck pain (NP) is a widespread condition described as a complex biopsychosocial disorder, characterized by physical and psychological symptoms. Virtual reality (VR) shows promise in NP treatment, potentially reducing pain, kinesiophobia, and improving range of motion (ROM) and motor control. AIM: The primary aim of the study was to assess the effectiveness of VR sensorimotor training, combined with manual therapy, in reducing the level of disability in persistent non-specific NP individuals. The secondary aim was to determine if this VR-enhanced approach also contributes to improvement in overall function, pain perception and kinesiophobia. DESIGN: Monocentric, single-blind, randomized controlled trial. SETTING: We conducted this trial at San Raffaele Scientific Institute, Department of Rehabilitation and Functional Recovery, Milan, Italy. POPULATION: Forty NP participants were enrolled in the study and randomly allocated into two groups. METHODS: The study involved a 6-week rehabilitation program, comprising 12 sessions of 45 minutes each, twice weekly. Both intervention groups underwent manual therapy as a consistent component of their treatment. The Experimental Group (VRT) was additionally engaged in sensorimotor rehabilitation exercises using Virtual Reality, whereas the Control Group (CT) performed the same exercises without VR. We assessed subjects at baseline (T0) and after six weeks of rehabilitation (T1). The primary outcome was the disability (Neck Disability Index) while the secondary outcomes were: pain perception (Numeric Rating Scale, NP and Disability Scale, Central Sensitization Inventory) function (Cervical Kinematics) and kinesiophobia (Tampa Scale of Kinesiophobia). RESULTS: Both groups demonstrated significant reduction in level of disability, pain perception, and kinesiophobia. Significant advancements in kinematics were observed: VRT group showed enhanced ROM during craniocervical rotation (P=0.039), lateral bending (P=0.001), flexion-extension (P=0.009), and mean velocity across movements (P<0.001), whereas CT group improved in maximal ROM during lateral bending rotation (P=0.001). Between-group analysis, after Bonferroni's correction for multiple comparisons, revealed that VRT group had significantly better outcomes in ROM during rotation (P=0.040), ratio of the primary over the secondary movement while performing rotation (P=0.021), and mean velocity during lateral bending (P=0.031). CONCLUSIONS: Sensorimotor training, combined with manual therapy, could enhance kinematic outcomes for NP patients, supporting the potential of VR in rehabilitation. CLINICAL REHABILITATION IMPACT: This study highlighted that both groups demonstrated significant reduction in level of disability, pain perception, and kinesiophobia after sensorimotor training combined with manual therapy. It is important to underscore that in terms of reducing the level of neck disability, both interventions proved to be equally effective. This parity in efficacy is a critical finding, reaffirming the robustness of our therapeutic approaches for this specific outcome.

On the brain struggles to recognize basic facial emotions with face masks: an fMRI study.

Introduction: The COVID-19 pandemic impacted public health and our lifestyles, leading to new social adaptations such as quarantine, social distancing, and facial masks. Face masks, covering extended facial zones, hamper our ability to extract relevant socio-emotional information from others' faces. In this fMRI study, we investigated how face masks interfere with facial emotion recognition, focusing on brain responses and connectivity patterns as a function of the presence of a face mask. Methods: A total of 25 healthy participants (13F; mean age: 32.64 ± 7.24y; mean education: 18.28 ± 1.31y) were included. Participants underwent task-related fMRI during the presentation of images of faces expressing basic emotions (joy or fear versus neutral expression). Half of the faces were covered by a face mask. Subjects had to recognize the facial emotion (masked or unmasked). FMRI whole-brain and regions-of-interest analyses were performed, as well as psychophysiological interaction analysis (PPI). Results: Subjects recognized better and faster emotions on unmasked faces. FMRI analyses showed that masked faces induced a stronger activation of a right occipito-temporal cluster, including the fusiform gyrus and the occipital face area bilaterally. The same activation pattern was found for the neutral masked > neutral unmasked contrast. PPI analyses of the masked > unmasked contrast showed, in the right occipital face area, a stronger correlation with the left superior frontal gyrus, left precentral gyrus, left superior parietal lobe, and the right supramarginal gyrus. Discussion: Our study showed how our brain differentially struggles to recognize face-masked basic emotions, implementing more neural resources to correctly categorize those incomplete facial expressions.

Increased interhemispheric functional connectivity after right anodal tDCS in chronic non-fluent aphasia: preliminary findings.

Introduction: Anodal transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost and environment-friendly brain neuromodulation technique that increases cortical excitability. In post-stroke aphasia, the role of the right hemisphere in language recovery remains debated. In this preliminary study, we aimed to investigate the efficacy of excitatory tDCS on the right hemisphere in chronic aphasic patients. Methods: We applied anodal tDCS to the right homologous region of Broca's area in four chronic aphasic patients while performing a one-month naming rehabilitation treatment. Longitudinal data on language assessment and naming performance were collected. Resting-state fMRI images were acquired before and after treatment to measure changes in functional connectivity. Results: Results showed enhanced positive functional connectivity of the right Broca homologous with the left middle frontal and middle temporal gyri. Every patient showed improvements in language functions, but no major changes in naming performance. Conclusion: These preliminary findings suggest that tDCS applied over the unaffected hemisphere may result in longitudinal inter-hemispheric functional neuroplastic changes that could specifically improve language recovery and could potentially be included in therapeutic neurorehabilitative plans.

Cervical motion alterations and brain functional connectivity in cervical dystonia.

INTRODUCTION: Evaluating the neural correlates of sensorimotor control deficits in cervical dystonia (CD) is fundamental to plan the best treatment. This study aims to assess kinematic and resting-state functional connectivity (RS-FC) characteristics in CD patients relative to healthy controls. METHODS: Seventeen CD patients and 14 age-/sex-matched healthy controls were recruited. Electromagnetic sensors were used to evaluate dystonic pattern, mean/maximal cervical movement amplitude and joint position error with eyes open and closed, and movement quality during target reaching with the head. RS-fMRI was acquired to compare the FC of brain sensorimotor regions between patients and controls. In patients, correlations between motion analysis and FC data were assessed. RESULTS: CD patients relative to controls showed reduced mean and maximal cervical range of motion (RoM) in rotation both towards and against dystonia pattern and reduced total RoM in rotation both with eyes open and closed. They had less severe dystonia pattern with eyes open vs eyes closed. CD patients showed an altered movement quality and sensorimotor control during target reaching and a higher joint position error. Compared to controls, CD patients showed reduced FC between supplementary motor area (SMA), occipital and cerebellar areas, which correlated with lower cervical RoM in rotation both with eyes open and closed and with worse movement quality during target reaching. CONCLUSIONS: FC alterations between SMA and occipital and cerebellar areas may represent the neural basis of cervical sensorimotor control deficits in CD patients. Electromagnetic sensors and RS-fMRI might be promising tools to monitor CD and assess the efficacy of rehabilitative interventions.

Longitudinal brain functional connectivity changes induced by neurosurgical thalamotomy for tremor in Parkinson's disease: a preliminary study.

The hypothesis that the effectiveness of neurosurgical procedures in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of the stimulation and other brain regions is growing. This study aimed to assess resting-state functional connectivity between thalamic ventral intermediate nucleus (Vim) and the rest of the brain before and after thalamotomy in PD. A 76-year-old right-handed woman with refractory tremor-dominant PD was selected as a candidate for left Vim radiosurgery thalamotomy. Clinical and motion sensor evaluation and brain resting-state functional MRI (rs-fMRI) were carried out before treatment and 3, 6, and 12 months later. Targeted Vim was selected as region of interest and a seed-based rs-fMRI analysis was performed in the patient and ten age- and sex-matched controls at baseline and over time. Furthermore, a correlation analysis between functional connectivity and tremor data was carried out. Both clinical and motion sensor measurements showed a progressive tremor improvement over time on right side after radiosurgery. In the patient, seed-based analysis showed a significantly increased functional connectivity between targeted Vim and ipsilateral visual areas relative to controls before treatment. Over 1 year, a normalization of aberrant pre-therapeutic functional connectivity between Vim and visual areas was obtained. At correlation analysis, the reduction of tremor metrics over time, assessed by clinical evaluation and wearable motion sensors, was related to the reduction of the left Vim-left visual cortex functional connectivity. Our findings support the evidence that fMRI was able to detect targeted Vim connectivity and its changes over time after thalamotomy.

Continuity of care for patients with dementia during COVID-19 pandemic: flexibility and integration between in-person and remote visits.

Introduction: During the pandemic, the Cognitive Disorders Unit of San Raffaele Hospital (Milan, Italy) offered patients the opportunity to undergo neuropsychological evaluations and cognitive training through telemedicine. Method: We conducted an investigation to assess how patients responded to this option and to determine if telemedicine could ensure continuity of care. Results: Between October 2019 and May 2022, a total of 5,768 telemedicine appointments and 8,190 in-person outpatient appointments were conducted, resulting in an increase in the rate of telemedicine activity from 16.81% in January 2020 to 23.21% in May 2022. Peaks in telemedicine activity reached 85.64% in May 2020 and 83.65% in February 2021, both representing a significant portion of the total activity. Interestingly, there was a notable positive correlation between telemedicine activity and the worsening of the Italian pandemic (r = 0.433, p = 0.027). Discussion: During the peaks of contagion, the total number of visits remained stable, highlighting that telemedicine effectively served as a valuable and efficient tool to ensure continuity of care for vulnerable patients. This was evident from the integration of remote visits with in-person appointments.

Mobile application tool for remote rehabilitation after discharge from coronavirus disease-19 rehabilitation unit.

A smartphone application (Medico-Amico) has been developed by the collaboration of San Raffaele Scientific Institute and Khymeia Group S.R.L. with the aim of providing physical exercises and communicating with patients after their hospitalization in a coronavirus disease (COVID)-rehabilitation unit. Thirty patients used the application for remote rehabilitation for 4 weeks. They were prescribed personalized motor exercises to perform three times a week. Clinicians could interact with each patient by an encrypted video call in order to give encouragement, mental support, modify intensity during training sessions, or to prescribe new exercises. Patients were asked to perform motor exercises and also to monitor their vital signs, such as temperature, blood pressure, and oxygen saturation, inserting scores in a specific section of the application. After 4 weeks of remote rehabilitation patients showed improvements in independence during activity of daily living and strength. Also, satisfaction and mobile application usability scores reached patients' appreciation and enjoyment.

Virtual Reality Augmented Feedback Rehabilitation Associated to Action Observation Therapy in Buccofacial Apraxia: Case Report.

BACKGROUND: Buccofacial Apraxia is defined as the inability to perform voluntary movements of the larynx, pharynx, mandible, tongue, lips and cheeks, while automatic or reflexive control of these structures is preserved. Buccofacial Apraxia frequently co-occurs with aphasia and apraxia of speech and it has been reported as almost exclusively resulting from a lesion of the left hemisphere. Recent studies have demonstrated the benefit of treating apraxia using motor training principles such as Augmented Feedback or Action Observation Therapy. In light of this, the study describes the treatment based on immersive Action Observation Therapy and Virtual Reality Augmented Feedback in a case of Buccofacial Apraxia. PARTICIPANT AND METHODS: The participant is a right-handed 58-years-old male. He underwent a neurosurgery intervention of craniotomy and exeresis of infra axial expansive lesion in the frontoparietal convexity compatible with an atypical meningioma. Buccofacial Apraxia was diagnosed by a neurologist and evaluated by the Upper and Lower Face Apraxia Test. Buccofacial Apraxia was quantified also by a specific camera, with an appropriately developed software, able to detect the range of motion of automatic face movements and the range of the same movements on voluntary requests. In order to improve voluntary movements, the participant completed fifteen 1-hour rehabilitation sessions, composed of a 20-minutes immersive Action Observation Therapy followed by a 40-minutes Virtual Reality Augmented Feedback sessions, 5 days a week, for 3 consecutive weeks. RESULTS: After treatment, participant achieved great improvements in quality and range of facial movements, performing most of the facial expressions (eg, kiss, smile, lateral angle of mouth displacement) without unsolicited movement. Furthermore, the Upper and Lower Face Apraxia Test showed an improvement of 118% for the Upper Face movements and of 200% for the Lower Face movements. CONCLUSION: Performing voluntary movement in a Virtual Reality environment with Augmented Feedbacks, in addition to Action Observation Therapy, improved performances of facial gestures and consolidate the activations by the central nervous system based on principles of experience-dependent neural plasticity.

Efficacy of virtual reality to reduce chronic low back pain: Proof-of-concept of a non-pharmacological approach on pain, quality of life, neuropsychological and functional outcome.

OBJECTIVES: Chronic pain, such as low-back pain, can be a highly disabling condition degrading people's quality of life (QoL). Not every patient responds to pharmacological therapies, thus alternative treatments have to be developed. The chronicity of pain can lead to a somatic dysperception, meaning a mismatch between patients' own body perception and its actual physical state. Since clinical evaluation of pain relies on patients' subjective reports, a body image disruption can be associated with an incorrect pain rating inducing incorrect treatment and a possible risk of drug abuse. Our aim was to reduce chronic low-back pain through a multimodal neurorehabilitative strategy using innovative technologies to help patients regain a correct body image. METHODS: Twenty patients with chronic low-back pain were included. Before and after treatment, patients underwent: a neurological exam; a neuro-psychological evaluation testing cognitive functions (memory, attention, executive functions) and personality traits, QoL and mood; pain ratings; sensorimotor functional abilities' testing. Patients underwent a 6 week-neurorehabilitative treatment (total 12 sessions) using virtual reality (VRRS system, Khymeia, Italy). Treatment consisted on teaching patients to execute correct movements with the painful body parts to regain a correct body image, based on the augmented multisensory feedback (auditory, visual) provided by the VRRS. RESULTS: Our data showed significant reductions in all pain rating scale scores (p<0.05); significant improvements of QoL in the domains of physical functioning, physical role functioning, bodily pain, vitality, and social role functioning; improvements in cognitive functions (p<0.05); improvements in functional scales (p<0.05) and mood (p = 0.04). CONCLUSION: This non-pharmacological approach was able to act on the multi-dimensional aspects of pain and improved patients' QoL, pain intensity, mood and patient's functional abilities.