Motor Imagery Performance through Embodied Digital Twins in a Virtual Reality-Enabled Brain-Computer Interface Environment.

This study introduces an innovative framework for neurological rehabilitation by integrating brain-computer interfaces (BCI) and virtual reality (VR) technologies with the customization of three-dimensional (3D) avatars. Traditional approaches to rehabilitation often fail to fully engage patients, primarily due to their inability to provide a deeply immersive and interactive experience. This research endeavors to fill this gap by utilizing motor imagery (MI) techniques, where participants visualize physical movements without actual execution. This method capitalizes on the brain's neural mechanisms, activating areas involved in movement execution when imagining movements, thereby facilitating the recovery process. The integration of VR's immersive capabilities with the precision of electroencephalography (EEG) to capture and interpret brain activity associated with imagined movements forms the core of this system. Digital Twins in the form of personalized 3D avatars are employed to significantly enhance the sense of immersion within the virtual environment. This heightened sense of embodiment is crucial for effective rehabilitation, aiming to bolster the connection between the patient and their virtual counterpart. By doing so, the system not only aims to improve motor imagery performance but also seeks to provide a more engaging and efficacious rehabilitation experience. Through the real-time application of BCI, the system allows for the direct translation of imagined movements into virtual actions performed by the 3D avatar, offering immediate feedback to the user. This feedback loop is essential for reinforcing the neural pathways involved in motor control and recovery. The ultimate goal of the developed system is to significantly enhance the effectiveness of motor imagery exercises by making them more interactive and responsive to the user's cognitive processes, thereby paving a new path in the field of neurological rehabilitation.

Predictors of pulmonary dysfunction vis-à-vis the hypertension status of mine workers in Gujarat, western India: A cross-sectional study on the need to further investigate the role of anti-hypertensive drugs.

BACKGROUND: Mine workers face various health risks from occupational hazards, notably dust-related pulmonary dysfunction. This dysfunction is also attributed to diverse risk factors and health conditions. Despite the variety of underlying mechanisms, conflicting evidence persists regarding hypertension as a potential risk factor for such dysfunction. OBJECTIVE: To determine the predictors of pulmonary dysfunction vis-à-vis the hypertension status of mine workers. METHODS: We conducted a cross-sectional study among 444 mine workers from ten open-cast mines in Gujarat state (western part of India) from November 2020 to February 2022. We collected data on demographics, occupation, addiction, and comorbidities, including measurements like anthropometry, blood pressure, blood sugar, haemoglobin, and lipid levels. Hypertension was confirmed based on self-reported history and/or onsite blood pressure measurement, while pulmonary functions were assessed using a spirometer (expressed as forced expiratory volume in the first second FEV1 and forced vital capacity FVC). Multiple linear regression analysis was performed to determine the significant predictor of FEV1 or FVC vis-à-vis the hypertension status after adjusting for confounding variables. In addition, we assessed the effect of anti-hypertensive medications on pulmonary dysfunction. RESULTS: A total of 41% (95% CI: 36-45%) of mine workers were suffering from hypertension. On multiple linear regression, only being a male and work experience duration were the significant predictors of FEV1 [0.900 (0.475-1.092), p=<0.001; -0.029 (-0.034 - -0.021, p=<0.001] and FVC [1.088 (0.771-1.404), p=<0.001; -0.031 (-0.038 - -0.024, p = 0.001] respectively. While unadjusted analysis indicated hypertension led to FEV1 and FVC reduction, this effect lost significance after adjusting for confounders. Nevertheless, subgroup analysis revealed those on antihypertensive medications had reductions in FEV1 and FVC by -0.263 (95% CI: -0.449 - -0.078, p = 0.006) L and -0.271 (95% CI: -0.476 - -0.067, p = 0.009) L respectively. CONCLUSION: In our study among mine workers, alterations in lung function (FEV1 and FVC) on spirometry were predicted by gender and duration of work experience, while hypertension did not serve as a predictor. It is noteworthy that antihypertensive drugs were found to reduce lung functions on spirometry, highlighting the need for further research.

Feasibility and usability of a virtual-reality-based sensorimotor activation apparatus for carpal tunnel syndrome patients.

PURPOSE: This study aimed to assess the usability of a virtual reality-assisted sensorimotor activation (VRSMA) apparatus for individual digit rehabilitation. The study had two main objectives: Firstly, to collect preliminary data on the expectations and preferences of patients with carpal tunnel syndrome (CTS) regarding virtual reality (VR) and an apparatus-assisted therapy for their affected digits. Secondly, to evaluate the usability of the VRSMA apparatus that was developed. METHODS: The VRSMA system consists of an apparatus that provides sensory and motor stimulation via a vibratory motor and pressure sensor attached to a button, and a virtual reality-based visual cue provided by texts overlaid on top of a 3D model of a hand. The study involved 10 CTS patients who completed five blocks of VRSMA with their affected hand, with each block corresponding to the five digits. The patients were asked to complete a user expectations questionnaire before experiencing the VRSMA, and a user evaluation questionnaire after completing the VRSMA. Expectations for VRSMA were obtained from the questionnaire results using a House of Quality (HoQ) analysis. RESULTS: In the survey for expectations, participants rated certain attributes as important for a rehabilitation device for CTS, with mean ratings above 4 for attributes such as ease of use, ease of understanding, motivation, and improvement of hand function based on clinical evidence. The level of immersion and an interesting rehabilitation regime received lower ratings, with mean ratings above 3.5. The survey evaluating VRSMA showed that the current prototype was overall satisfactory with a mean rating of 3.9 out of 5. Based on the HoQ matrix, the highest priority for development of the VRSMA was to enhance device comfort and usage time. This was followed by the need to perform more clinical studies to provide evidence of the efficacy of the VRSMA. Other technical characteristics, such as VRSMA content and device reliability, had lower priority scores. CONCLUSION: The current study presents a potential for an individual digit sensorimotor rehabilitation device that is well-liked by CTS patients.

The effect of combining action observation in virtual reality with kinesthetic motor imagery on cortical activity.

Introduction: In the past, various techniques have been used to improve motor imagery (MI), such as immersive virtual-reality (VR) and kinesthetic rehearsal. While electroencephalography (EEG) has been used to study the differences in brain activity between VR-based action observation and kinesthetic motor imagery (KMI), there has been no investigation into their combined effect. Prior research has demonstrated that VR-based action observation can enhance MI by providing both visual information and embodiment, which is the perception of oneself as part of the observed entity. Additionally, KMI has been found to produce similar brain activity to physically performing a task. Therefore, we hypothesized that utilizing VR to offer an immersive visual scenario for action observation while participants performed kinesthetic motor imagery would significantly improve cortical activity related to MI. Methods: In this study, 15 participants (9 male, 6 female) performed kinesthetic motor imagery of three hand tasks (drinking, wrist flexion-extension, and grabbing) both with and without VR-based action observation. Results: Our results indicate that combining VR-based action observation with KMI enhances brain rhythmic patterns and provides better task differentiation compared to KMI without action observation. Discussion: These findings suggest that using VR-based action observation alongside kinesthetic motor imagery can improve motor imagery performance.

Evaluation of EEG Oscillatory Patterns and Classification of Compound Limb Tactile Imagery.

Objective: The purpose of this study was to investigate the cortical activity and digit classification performance during tactile imagery (TI) of a vibratory stimulus at the index, middle, and thumb digits within the left hand in healthy individuals. Furthermore, the cortical activities and classification performance of the compound TI were compared with similar compound motor imagery (MI) with the same digits as TI in the same subjects. Methods: Twelve healthy right-handed adults with no history of upper limb injury, musculoskeletal condition, or neurological disorder participated in the study. The study evaluated the event-related desynchronization (ERD) response and brain-computer interface (BCI) classification performance on discriminating between the digits in the left-hand during the imagery of vibrotactile stimuli to either the index, middle, or thumb finger pads for TI and while performing a motor activity with the same digits for MI. A supervised machine learning technique was applied to discriminate between the digits within the same given limb for both imagery conditions. Results: Both TI and MI exhibited similar patterns of ERD in the alpha and beta bands at the index, middle, and thumb digits within the left hand. While TI had significantly lower ERD for all three digits in both bands, the classification performance of TI-based BCI (77.74 ± 6.98%) was found to be similar to the MI-based BCI (78.36 ± 5.38%). Conclusions: The results of this study suggest that compound tactile imagery can be a viable alternative to MI for BCI classification. The study contributes to the growing body of evidence supporting the use of TI in BCI applications, and future research can build on this work to explore the potential of TI-based BCI for motor rehabilitation and the control of external devices.

The Effect of Tactile Imagery Training on Reaction Time in Healthy Participants.

BACKGROUND: Reaction time is an important measure of sensorimotor performance and coordination and has been shown to improve with training. Various training methods have been employed in the past to improve reaction time. Tactile imagery (TI) is a method of mentally simulating a tactile sensation and has been used in brain-computer interface applications. However, it is yet unknown whether TI can have a learning effect and improve reaction time. OBJECTIVE: The purpose of this study was to investigate the effect of TI on reaction time in healthy participants. METHODS: We examined the reaction time to vibratory stimuli before and after a TI training session in an experimental group and compared the change in reaction time post-training with pre-training in the experimental group as well as the reaction time in a control group. A follow-up evaluation of reaction time was also conducted. RESULTS: The results showed that TI training significantly improved reaction time after TI compared with before TI by approximately 25% (pre-TI right-hand mean ± SD: 456.62 ± 124.26 ms, pre-TI left-hand mean ± SD: 448.82 ± 124.50 ms, post-TI right-hand mean ± SD: 340.32 ± 65.59 ms, post-TI left-hand mean ± SD: 335.52 ± 59.01 ms). Furthermore, post-training reaction time showed significant reduction compared with the control group and the improved reaction time had a lasting effect even after four weeks post-training. CONCLUSION: These findings indicate that TI training may serve as an alternate imagery strategy for improving reaction time without the need for physical practice.

The Effects of Subthreshold Vibratory Noise on Cortical Activity During Motor Imagery.

Previous studies have demonstrated that both visual and proprioceptive feedback play vital roles in mental practice of movements. Tactile sensation has been shown to improve with peripheral sensory stimulation via imperceptible vibratory noise by stimulating the sensorimotor cortex. With both proprioception and tactile sensation sharing the same population of posterior parietal neurons encoding within high-level spatial representations, the effect of imperceptible vibratory noise on motor imagery-based brain-computer interface is unknown. The objective of this study was to investigate the effects of this sensory stimulation via imperceptible vibratory noise applied to the index fingertip in improving motor imagery-based brain-computer interface performance. Fifteen healthy adults (nine males and six females) were studied. Each subject performed three motor imagery tasks, namely drinking, grabbing, and flexion-extension of the wrist, with and without sensory stimulation while being presented a rich immersive visual scenario through a virtual reality headset. Results showed that vibratory noise increased event-related desynchronization during motor imagery compared with no vibration. Furthermore, the task classification percentage was higher with vibration when the tasks were discriminated using a machine learning algorithm. In conclusion, subthreshold random frequency vibration affected motor imagery-related event-related desynchronization and improved task classification performance.

Three-Dimensional Carpal Arch Morphology Using Robot-Assisted Ultrasonography.

OBJECTIVE: The morphology of the carpal arch implicates the available space for the median nerve within the carpal tunnel. The purposes of this study were to 1) reconstruct the three-dimensional (3D) carpal arch by robot-assisted ultrasonography with a linear array transducer using cadaveric hands, and 2) investigate the 3D morphological properties of the carpal arch. METHODS: An ultrasound probe with two-dimensional (2D) linear array was integrated on a robotic arm and maneuvered over the cadaveric carpal tunnels to scan the entire transverse carpal ligament and its osseous attachments to carpal bones. The acquired series of 2D ultrasound images together with robot positioning were utilized to reconstruct the 3D carpal arch for morphometric analyses. RESULTS: Total carpal arch volume was 1099.4 ± 163.2 mm3 with the distal, middle, and proximal regions contributing 18.2 ± 1.5%, 32.7 ± 1.2%, and 49.1 ± 2.3%, respectively. The ligament surface area was 420.1 ± 63.9 mm2. The carpal arch width, height, curvature, length, area, and palmar bowing index progressively increased from the distal to proximal locations within the tunnel (p < 0.01). CONCLUSION: The incorporation of the robot technology with the ultrasound system advanced the applications of traditional 2D ultrasound imaging for a 3D carpal arch reconstruction, allowing for comprehensive morphological assessment of the carpal arch. SIGNIFICANCE: The developed workflow can be used for the reconstruction and analysis of other anatomical features in vivo.

Median nerve and carpal arch morphology changes in women with type 2 diabetes: a case-control study.

BACKGROUND: The aim of this study is to investigate the changes in median nerve and transverse carpal ligament (TCL)-formed carpal arch morphology as possible risk factors for median nerve entrapment in women with type 2 diabetes. METHODS: The distal carpal tunnel was imaged using ultrasound in 30 female subjects (15 with type 2 diabetes, 15 controls). The morphological parameters of the median nerve and carpal arch were derived from the ultrasound images. One-way analysis of variance (ANOVA) was used for statistical analysis. RESULTS: Diabetic women had an enlarged median nerve area (p < 0.05), salong with a maller carpal arch size, as indicated by a reduced palmar bowing index of the TCL (p < 0.05), and arch area (p < 0.05) than controls. The distance from the median nerve centroid to the volar boundary of the TCL was reduced in diabetic women (p < 0.05) compared to the controls. CONCLUSIONS: Women with type 2 diabetes have reduced available space for the median nerve within the carpal arch due to the enlarged nerve and reduced arch size, making the median nerve more susceptible to entrapment within the tunnel. The current study shows that presence of diabetes increases the risk of median nerve entrapment in women and requires early detection of symptoms to avoid carpal tunnel syndrome.

Ligament and Bone Arch Partition of the Carpal Tunnel by Three-Dimensional Ultrasonography.

The carpal tunnel is geometrically irregular due to the complex composition of many carpal bones intercalated by numerous intercarpal ligaments. The purpose of the study was to investigate the relative contributions of the ligament and bone arches to carpal tunnel space at the proximal, middle, and distal tunnel regions. A catheter ultrasound probe acquired fan-like images inside cadaveric carpal tunnels for three-dimensional reconstruction of the tunnel. The total tunnel volume was 5367.6 ± 940.1 mm3 with contributions of 12.0%, 6.9%, and 4.1% by proximal, middle, and distal ligament arches, respectively, and 27.0%, 25.3%, and 24.7% by proximal, middle, and distal bone arches, respectively. The bone arch occupied more tunnel space than the ligament arch at all regions (p < 0.05). The ligament arch was largest at the proximal region of the tunnel and significantly decreased toward the distal region (p < 0.05). However, the bone arch significantly decreased only from the proximal to middle region (p < 0.05) but not from the middle to distal region (p = 0.311). Consequently, it was observed that the ligament arch was the key contributor to the unequal carpal tunnel space across regions. Partitional and regional tunnel morphometric information may provide a better understanding of tunnel abnormality associated with various wrist pathological conditions. The developed framework of ultrasonography and data processing can be applied to other areas of interest in the musculoskeletal system.

Morphological and positional changes of the carpal arch and median nerve associated with wrist deviations.

BACKGROUND: Carpal tunnel and median nerve dynamically change with wrist motion. The purpose of this study was to investigate the morphological changes and positional migration of the carpal arch and median nerve, as well as nerve-arch positional relationship associated with wrist deviation in healthy volunteers. METHODS: Twenty asymptomatic male volunteers performed wrist motion from neutral to deviated positions combining flexion-extension and radioulnar deviation. Ultrasound images of the carpal arch and median nerve at the distal carpal tunnel were collected during wrist motion. Morphological and positional parameters of the carpal arch and median nerve were derived from the ultrasound images. FINDINGS: Carpal arch height, area, and palmar bowing of the transverse carpal ligament (TCL) increased with flexion related wrist motion and decreased with extension related motion (P < 0.05). Arch width increased with radial flexion and decreased with extension and ulnar extension (P < 0.05). Median nerve circularity increased with flexion and radial flexion but decreased with extension, ulnar extension, and ulnar deviation (P < 0.05). Nerve centroid displaced ulnarly with radial deviation, radial flexion, and radial extension and displaced radially with ulnar deviation, ulnar flexion, and ulnar extension (P < 0.05). Nerve centroid displaced in the dorsal direction with flexion and radial flexion, but in the palmar direction with extension (P < 0.05). Nerve-TCL distance increased with flexion related motion and decreased with extension relation motion (P < 0.05). INTERPRETATION: The current study advances our understanding the effect of wrist motion on the carpal tunnel and its contents, which has implications for pathomorphological and pathokinematic changes associated with wrist disorders.

Sex-related differences in carpal arch morphology.

The purpose of this study was to investigate the sex-based differences in the carpal arch morphology. Carpal arch morphology was quantified using palmar bowing and area of the arch formed by the transverse carpal ligament. The carpal arch was imaged at the distal and proximal tunnel levels using ultrasonography in 20 healthy young adults (10 women and 10 men). It was found that females had a smaller carpal arch height compared to men at both distal and proximal levels (p<0.05) and smaller carpal arch width only at the proximal level (p<0.05) but not distally. Palmar bowing index, the carpal arch height to width ratio, was significantly smaller in females at the distal level (p<0.05) but not at the proximal level. Carpal arch cross-sectional area normalized to the wrist cross-sectional area was found to be significantly smaller in females at both tunnel levels compared to men (p<0.05). This study demonstrates that females have a smaller carpal arch compared to men with a reduced palmar bowing distally and a smaller arch area at both tunnel levels. The findings help explain the higher incidence of carpal tunnel syndrome in women as a smaller carpal arch makes the median nerve more vulnerable to compression neuropathy.

A neoepitope derived from a novel human germline APC gene mutation in familial adenomatous polyposis shows selective immunogenicity.

Familial adenomatous polyposis (FAP) is an inherited condition arising from genetic defects in the Adenomatous polyposis coli (APC) gene. Carriers with mutations in the APC gene develop polyps in the colon and rectum which if not managed, transition into colon cancer. In this study, we identified a novel germline mutation in the APC gene in members of an FAP-affected (Familial adenomatous polyposis) family. This unique heterozygous variant (c.735_736insT; p.Ser246PhefsTer6) was identified in ten out of twenty six family members, ranging in age from 6 to 60 years. Polyps were detected in six of the ten individuals (35-60 years) carrying this mutation. The remaining four members (6-23 years) remain polyp free. A significant fraction of FAP affected individuals eventually develop colon cancer and therapeutic interventions to prevent cancer progression remain elusive. To address this issue, we sought to determine if peptides derived from the novel APC mutation could induce a cytotoxic T cell response, thereby qualifying them as vaccine candidates. Peptides harboring the variant amino acids were first interrogated in silico for their immunogenicity using a proprietary neoepitope prioritization pipeline, OncoPeptVAC. A single 9-mer peptide was predicted to be immunogenic. Remarkably, CD8+ T cells isolated from either an FAP+/ APCmut individual, or from a FAP-/ APCmut individual, failed to respond to the peptide, whereas those from either an unaffected family member (FAP-/ APCwt) or from healthy unrelated donors, showed a robust response, suggesting that CD8+ T cells from individuals carrying this germline APC mutation have been tolerized to the mutation. Furthermore, experimental testing of six additional reported APC gene mutation-derived peptides revealed one of the six to be immunogenic. While not all APC mutant peptides are inmmunogenic, a few qualify as vaccine candidates offering novel treatment opportunities to patients with somatic APC gene mutations to delay/treat colorectal cancer.

A cancer vaccine approach for personalized treatment of Lynch Syndrome.

Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70-80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families. Since defects in DNA mismatch repair genes generate frame-shift mutations giving rise to highly immunogenic neoepitopes, we postulated that vaccination with these mutant peptide antigens could offer promising treatment options to LS patients. To this end we performed whole-exome and RNA seq analysis on the blood and tumour samples from an LS-CRC patient, and used our proprietary neoepitope prioritization pipeline OncoPeptVAC to select peptides, and confirm their immunogenicity in an ex vivo CD8+ T cell activation assay. Three neoepitopes derived from the tumour of this patient elicited a potent CD8+ T cell response. Furthermore, analysis of the tumour-associated immune infiltrate revealed CD8+ T cells expressing low levels of activation markers, suggesting mechanisms of immune suppression at play in this relapsed tumour. Taken together, our study paves the way towards development of a cancer vaccine to treat or delay the onset/relapse of LS-CRC.