Acceptability, Feasibility, and Effectiveness of Immersive Virtual Technologies to Promote Exercise in Older Adults: A Systematic Review and Meta-Analysis.

CONTEXT: This review aimed to synthesize the literature on the acceptability, feasibility, and effectiveness of immersive virtual technologies to promote physical exercise in older people. METHOD: We performed a literature review, based on four databases (PubMed, CINAHL, Embase, and Scopus; last search: 30 January 2023). Eligible studies had to use immersive technology with participants aged 60 years and over. The results regarding acceptability, feasibility, and effectiveness of immersive technology-based interventions in older people were extracted. The standardized mean differences were then computed using a random model effect. RESULTS: In total, 54 relevant studies (1853 participants) were identified through search strategies. Concerning the acceptability, most participants reported a pleasant experience and a desire to use the technology again. The average increase in the pre/post Simulator Sickness Questionnaire score was 0.43 in healthy subjects and 3.23 in subjects with neurological disorders, demonstrating this technology's feasibility. Regarding the effectiveness, our meta-analysis showed a positive effect of the use of virtual reality technology on balance (SMD = 1.05; 95% CI: 0.75-1.36; p < 0.001) and gait outcomes (SMD = 0.7; 95% CI: 0.14-0.80; p < 0.001). However, these results suffered from inconsistency and the number of trials dealing with these outcomes remains low, calling for further studies. CONCLUSIONS: Virtual reality seems to be well accepted by older people and its use with this population is feasible. However, more studies are needed to conclude its effectiveness in promoting exercise in older people.

Adding Haptic Feedback to Virtual Environments With a Cable-Driven Robot Improves Upper Limb Spatio-Temporal Parameters During a Manual Handling Task.

Physical interactions within virtual environments are often limited to visual information within a restricted workspace. A new system exploiting a cable-driven parallel robot to combine visual and haptic information related to environmental physical constraints (e.g. shelving, object weight) was developed. The aim of this study was to evaluate the impact on user movement patterns of adding haptic feedback in a virtual environment with this robot. Twelve healthy participants executed a manual handling task under three conditions: 1) in a virtual environment with haptic feedback; 2) in a virtual environment without haptic feedback; 3) in a real physical environment. Temporal parameters (movement time, peak velocity, movement smoothness, time to maximum flexion, time to peak wrist velocity) and spatial parameters of movement (maximum trunk flexion, range of motion of the trunk, length of the trajectory, index of curvature and maximum clearance from the shelf) were analysed during the reaching, lowering and lifting phases. Our results suggest that adding haptic feedback improves spatial parameters of movement to better respect the environmental constraints. However, the visual information presented in the virtual environment through the head mounted display appears to have an impact on temporal parameters of movement leading to greater movement time. Taken together, our results suggest that a cable-driven robot can be a promising device to provide a more ecological context during complex tasks in virtual reality.

Modulation of electric brain responses evoked by pitch deviants through transcranial direct current stimulation.

Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty detecting pitch deviation that is related to abnormal electrical brain responses. Abnormalities found along the right fronto-temporal pathway between the inferior frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism responsible for amusia. To investigate the causal role of these regions during the detection of pitch deviants, we applied cathodal (inhibitory) transcranial direct current stimulation (tDCS) over right frontal and right temporal regions during separate testing sessions. We recorded participants' electrical brain activity (EEG) before and after tDCS stimulation while they performed a pitch change detection task. Relative to a sham condition, there was a decrease in P3 amplitude after cathodal stimulation over both frontal and temporal regions compared to pre-stimulation baseline. This decrease was associated with small pitch deviations (6.25 cents), but not large pitch deviations (200 cents). Overall, this demonstrates that using tDCS to disrupt regions around the IFG and AC can induce temporary changes in evoked brain activity when processing pitch deviants. These electrophysiological changes are similar to those observed in amusia and provide causal support for the connection between P3 and fronto-temporal brain regions.

A Virtual Reality avatar interaction (VRai) platform to assess residual executive dysfunction in active military personnel with previous mild traumatic brain injury: proof of concept.

PURPOSE: This proof of concept study tested the ability of a dual task walking protocol using a recently developed avatar-based virtual reality (VR) platform to detect differences between military personnel post mild traumatic brain injury (mTBI) and healthy controls. METHODS: The VR platform coordinated motion capture, an interaction and rendering system, and a projection system to present first (participant-controlled) and third person avatars within the context of a specific military patrol scene. A divided attention task was also added. A healthy control group was compared to a group with previous mTBI (both groups comprised of six military personnel) and a repeated measures ANOVA tested for differences between conditions and groups based on recognition errors, walking speed and fluidity and obstacle clearance. RESULTS: The VR platform was well tolerated by both groups. Walking fluidity was degraded for the control group within the more complex navigational dual tasking involving avatars, and appeared greatest in the dual tasking with the interacting avatar. This navigational behaviour was not seen in the mTBI group. CONCLUSIONS: The present findings show proof of concept for using avatars, particularly more interactive avatars, to expose differences in executive functioning when applying context-specific protocols (here for the military). Implications for rehabilitation Virtual reality provides a means to control context-specific factors for assessment and intervention. Adding human interaction and agency through avatars increases the ecologic nature of the virtual environment. Avatars in the present application of the Virtual Reality avatar interaction platform appear to provide a better ability to reveal differences between trained, military personal with and without mTBI.

Activation in the Right Inferior Parietal Lobule Reflects the Representation of Musical Structure beyond Simple Pitch Discrimination.

Pitch discrimination tasks typically engage the superior temporal gyrus and the right inferior frontal gyrus. It is currently unclear whether these regions are equally involved in the processing of incongruous notes in melodies, which requires the representation of musical structure (tonality) in addition to pitch discrimination. To this aim, 14 participants completed two tasks while undergoing functional magnetic resonance imaging, one in which they had to identify a pitch change in a series of non-melodic repeating tones and a second in which they had to identify an incongruous note in a tonal melody. In both tasks, the deviants activated the right superior temporal gyrus. A contrast between deviants in the melodic task and deviants in the non-melodic task (melodic > non-melodic) revealed additional activity in the right inferior parietal lobule. Activation in the inferior parietal lobule likely represents processes related to the maintenance of tonal pitch structure in working memory during pitch discrimination.

Interactive virtual feedback improves gait motor imagery after spinal cord injury: An exploratory study.

PURPOSE: Motor imagery can improve motor function and reduce pain. This is relevant to individuals with spinal cord injury (SCI) in whom motor dysfunction and neuropathic pain are prevalent. However, therapy efficacy could be dependent on motor imagery ability, and a clear understanding of how motor imagery might be facilitated is currently lacking. Thus, the aim of the present study was to assess the immediate effects of interactive virtual feedback on motor imagery performance after SCI. METHODS: Nine individuals with a traumatic SCI participated in the experiment. Motor imagery tasks consisted of forward (i.e. simpler) and backward (i.e. more complex) walking while receiving interactive versus static virtual feedback. Motor imagery performance (vividness, effort and speed), neuropathic pain intensity and feasibility (immersion, distraction, side-effects) were assessed. RESULTS: During interactive feedback trials, motor imagery vividness and speed were significantly higher and effort was significantly lower as compared static feedback trials. No change in neuropathic pain was observed. Adverse effects were minor, and immersion was reported to be good. CONCLUSIONS: This exploratory study showed that interactive virtual walking was feasible and facilitated motor imagery performance. The response to motor imagery interventions after SCI might be improved by using interactive virtual feedback.

Attending to pitch information inhibits processing of pitch information: the curious case of amusia.

In normal listeners, the tonal rules of music guide musical expectancy. In a minority of individuals, known as amusics, the processing of tonality is disordered, which results in severe musical deficits. It has been shown that the tonal rules of music are neurally encoded, but not consciously available in amusics. Previous neurophysiological studies have not explicitly controlled the level of attention in tasks where participants ignored the tonal structure of the stimuli. Here, we test whether access to tonal knowledge can be demonstrated in congenital amusia when attention is controlled. Electric brain responses were recorded while asking participants to detect an individually adjusted near-threshold click in a melody. In half the melodies, a note was inserted that violated the tonal rules of music. In a second task, participants were presented with the same melodies but were required to detect the tonal deviation. Both tasks required sustained attention, thus conscious access to the rules of tonality was manipulated. In the click-detection task, the pitch deviants evoked an early right anterior negativity (ERAN) in both groups. In the pitch-detection task, the pitch deviants evoked an ERAN and P600 in controls but not in amusics. These results indicate that pitch regularities are represented in the cortex of amusics, but are not consciously available. Moreover, performing a pitch-judgment task eliminated the ERAN in amusics, suggesting that attending to pitch information interferes with perception of pitch. We propose that an impaired top-down frontotemporal projection is responsible for this disorder.

Real-time modulation of visual feedback on human full-body movements in a virtual mirror: development and proof-of-concept.

BACKGROUND: Virtual reality (VR) provides interactive multimodal sensory stimuli and biofeedback, and can be a powerful tool for physical and cognitive rehabilitation. However, existing systems have generally not implemented realistic full-body avatars and/or a scaling of visual movement feedback. We developed a "virtual mirror" that displays a realistic full-body avatar that responds to full-body movements in all movement planes in real-time, and that allows for the scaling of visual feedback on movements in real-time. The primary objective of this proof-of-concept study was to assess the ability of healthy subjects to detect scaled feedback on trunk flexion movements. METHODS: The "virtual mirror" was developed by integrating motion capture, virtual reality and projection systems. A protocol was developed to provide both augmented and reduced feedback on trunk flexion movements while sitting and standing. The task required reliance on both visual and proprioceptive feedback. The ability to detect scaled feedback was assessed in healthy subjects (n = 10) using a two-alternative forced choice paradigm. Additionally, immersion in the VR environment and task adherence (flexion angles, velocity, and fluency) were assessed. RESULTS: The ability to detect scaled feedback could be modelled using a sigmoid curve with a high goodness of fit (R2 range 89-98%). The point of subjective equivalence was not significantly different from 0 (i.e. not shifted), indicating an unbiased perception. The just noticeable difference was 0.035 ± 0.007, indicating that subjects were able to discriminate different scaling levels consistently. VR immersion was reported to be good, despite some perceived delays between movements and VR projections. Movement kinematic analysis confirmed task adherence. CONCLUSIONS: The new "virtual mirror" extends existing VR systems for motor and pain rehabilitation by enabling the use of realistic full-body avatars and scaled feedback. Proof-of-concept was demonstrated for the assessment of body perception during active movement in healthy controls. The next step will be to apply this system to assessment of body perception disturbances in patients with chronic pain.

Manual segmentation qualification platform for the EADC-ADNI harmonized protocol for hippocampal segmentation project.

BACKGROUND: The use of hippocampal volumetry as a biomarker for Alzheimer's disease (AD) requires that tracers from different laboratories comply with the same segmentation method. Here we present a platform for training and qualifying new tracers to perform the manual segmentation of the hippocampus on magnetic resonance images (MRI) following the European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) Harmonized Protocol (HarP). Our objective was to demonstrate that the training process embedded in the platform leads to increased compliance and qualification with the HarP. METHOD: Thirteen new tracers' segmentations were compared with benchmark images with respect to: (a) absolute segmentation volume; (b) spatial overlap of contour with the reference using the Jaccard similarity index; and (c) spatial distance of contour with the reference. Point by point visual feedback was provided through three training phases on 10 MRI. Tracers were then tested on 10 different MRIs in the qualification phase. RESULTS: Statistical testing of training over three phases showed a significant increase of Jaccard (i.e. mean Jaccard overlap P < .001) between phases on average for all raters, demonstrating that training positively increased compliance with the HarP. Based on these results we defined qualification thresholds which all tracers were able to meet. CONCLUSIONS: This platform is an adequate infrastructure allowing standardized training and evaluation of tracers' compliance with the HarP. This is a necessary step allowing the use of hippocampal volumetry as a biomarker for AD in clinical and research centers.

Harmonized benchmark labels of the hippocampus on magnetic resonance: the EADC-ADNI project.

BACKGROUND: A globally harmonized protocol (HarP) for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer's Disease Consortium (EADC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Our aim was to produce benchmark labels based on the HarP for manual segmentation. METHODS: Five experts of manual hippocampal segmentation underwent specific training on the HarP and segmented 40 right and left hippocampi from 10 ADNI subjects on both 1.5 T and 3 T scans. An independent expert visually checked segmentations for compliance with the HarP. Descriptive measures of agreement between tracers were intraclass correlation coefficients (ICCs) of crude volumes and similarity coefficients of three-dimensional volumes. RESULTS: Two hundred labels have been provided for the 20 magnetic resonance images. Intra- and interrater ICCs were >0.94, and mean similarity coefficients were 1.5 T, 0.73 (95% confidence interval [CI], 0.71-0.75); 3 T, 0.75 (95% CI, 0.74-0.76). CONCLUSION: Certified benchmark labels have been produced based on the HarP to be used for tracers' training and qualification.

Single time point high-dimensional morphometry in Alzheimer's disease: group statistics on longitudinally acquired data.

Quantitative assessment of medial temporal lobe atrophy has been proposed as a biomarker for Alzheimer's disease (AD) diagnostic and prognostic in mild cognitive impairment (MCI) due to AD. We present the first results of our high-dimensional morphometry technique, tracking tissue composition, and atrophy changes on T1-weighted magnetic resonance imaging at various time points. We selected 187 control subjects, 17 control subjects having progressed to MCI and/or AD, 178 subjects with stable MCI, 165 subjects with MCI having progressed to AD, and 147 AD subjects from the Alzheimer's Disease Neuroimaging Initiative study. Results show statistically significant differences between almost every diagnostic and time point comparison pairs (0-12, 12-24, and 24-36 months), including controls having progressed to either MCI or AD and trajectory dynamics that demonstrate the algorithm's ability at tracking specific pathology-related neurodegeneration.

Operationalizing protocol differences for EADC-ADNI manual hippocampal segmentation.

BACKGROUND: Hippocampal volumetry on magnetic resonance imaging is recognized as an Alzheimer's disease (AD) biomarker, and manual segmentation is the gold standard for measurement. However, a standard procedure is lacking. We operationalize and quantitate landmark differences to help a Delphi panel converge on a set of landmarks. METHODS: One hundred percent of anatomic landmark variability across 12 different protocols for manual segmentation was reduced into four segmentation units (the minimum hippocampus, the alveus/fimbria, the tail, and the subiculum), which were segmented on magnetic resonance images by expert raters to estimate reliability and AD-related atrophy. RESULTS: Intra- and interrater reliability were more than 0.96 and 0.92, respectively, except for the alveus/fimbria, which were 0.86 and 0.77, respectively. Of all AD-related atrophy, the minimum hippocampus contributed to 67%; tail, 24%; alveus/fimbria, 4%; and the subiculum, 5%. CONCLUSIONS: Anatomic landmark variability in available protocols can be reduced to four discrete and measurable segmentation units. Their quantitative assessment will help a Delphi panel to define a set of landmarks for a harmonized protocol.

Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance.

BACKGROUND: This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation. METHODS: The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. RESULTS: Agreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. DISCUSSION: Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol.

High-Dimensional Medial Lobe Morphometry: An Automated MRI Biomarker for the New AD Diagnostic Criteria.

Introduction. Medial temporal lobe atrophy assessment via magnetic resonance imaging (MRI) has been proposed in recent criteria as an in vivo diagnostic biomarker of Alzheimer's disease (AD). However, practical application of these criteria in a clinical setting will require automated MRI analysis techniques. To this end, we wished to validate our automated, high-dimensional morphometry technique to the hypothetical prediction of future clinical status from baseline data in a cohort of subjects in a large, multicentric setting, compared to currently known clinical status for these subjects. Materials and Methods. The study group consisted of 214 controls, 371 mild cognitive impairment (147 having progressed to probable AD and 224 stable), and 181 probable AD from the Alzheimer's Disease Neuroimaging Initiative, with data acquired on 58 different 1.5 T scanners. We measured the sensitivity and specificity of our technique in a hierarchical fashion, first testing the effect of intensity standardization, then between different volumes of interest, and finally its generalizability for a large, multicentric cohort. Results. We obtained 73.2% prediction accuracy with 79.5% sensitivity for the prediction of MCI progression to clinically probable AD. The positive predictive value was 81.6% for MCI progressing on average within 1.5 (0.3 s.d.) year. Conclusion. With high accuracy, the technique's ability to identify discriminant medial temporal lobe atrophy has been demonstrated in a large, multicentric environment. It is suitable as an aid for clinical diagnostic of AD.

Brain activity is related to individual differences in the number of items stored in auditory short-term memory for pitch: evidence from magnetoencephalography.

We used magnetoencephalography (MEG) to examine brain activity related to the maintenance of non-verbal pitch information in auditory short-term memory (ASTM). We focused on brain activity that increased with the number of items effectively held in memory by the participants during the retention interval of an auditory memory task. We used very simple acoustic materials (i.e., pure tones that varied in pitch) that minimized activation from non-ASTM related systems. MEG revealed neural activity in frontal, temporal, and parietal cortices that increased with a greater number of items effectively held in memory by the participants during the maintenance of pitch representations in ASTM. The present results reinforce the functional role of frontal and temporal cortices in the retention of pitch information in ASTM. This is the first MEG study to provide both fine spatial localization and temporal resolution on the neural mechanisms of non-verbal ASTM for pitch in relation to individual differences in the capacity of ASTM. This research contributes to a comprehensive understanding of the mechanisms mediating the representation and maintenance of basic non-verbal auditory features in the human brain.

Establishing magnetic resonance images orientation for the EADC-ADNI manual hippocampal segmentation protocol.

BACKGROUND AND PURPOSE: An effort to define and validate a Harmonized Protocol for standard hippocampal segmentation is being carried out. We wished to estimate the effect of magnetic resonance image (MRI) spatial orientation on manual hippocampal segmentations to define optimal standard orientation of MRIs for hippocampal volumetry. METHODS: Three expert tracers segmented twice the hippocampi of 10 ADNI subjects on MRI slices oriented perpendicular to the anterior-posterior commissure (AC-PC) line and the long hippocampal axes plane, following internationally harmonized landmarks. We computed intra and interrater reliability figures for total volumes and similarity coefficients. RESULTS: Total volume reliability was similar for both orientations. Similarity coefficients were significantly higher for the AC-PC orientation (exact P = 0.002). DISCUSSION: These data show that AC-PC orientation is slightly more reliable for manual segmentations, possibly due to better visualization of the cerebrospinal fluid spaces separating hippocampal head and amygdala. A Delphi panel of experts has used these data to decide on the optimal orientation for a Harmonized Protocol for hippocampal segmentation.

Test-retest reliability of a new medial temporal atrophy morphological metric.

Clinicians and researchers alike are in need of quantitative and robust measurement tools to assess medial temporal lobe atrophy (MTA) due to Alzheimer's disease (AD). We recently proposed a morphological metric, extracted from T1-weighted magnetic resonance images (MRI), to track and estimate MTA in cohorts of controls, AD, and mild cognitive impairment subjects, at high-risk of progression to dementia. In this paper, we investigated its reliability through analysis of within-session scan/repeat images and scan/rescans from large multicenter studies. In total, we used MRI data from 1051 subjects recruited at over 60 centers. We processed the data identically and calculated our metric for each individual, based on the concept of distance in a high-dimensional space of intensity and shape characteristics. Over 759 subjects, the scan/repeat change in the mean was 1.97% (SD: 21.2%). Over three subjects, the scan/rescan change in the mean was 0.89% (SD: 22.1%). At this level, the minimum trial size required to detect this difference is 68 individuals for both samples. Our scan/repeat and scan/rescan results demonstrate that our MTA assessment metric shows high reliability, a necessary component of validity.

Tissue-based MRI intensity standardization: application to multicentric datasets.

Intensity standardization in MRI aims at correcting scanner-dependent intensity variations. Existing simple and robust techniques aim at matching the input image histogram onto a standard, while we think that standardization should aim at matching spatially corresponding tissue intensities. In this study, we present a novel automatic technique, called STI for STandardization of Intensities, which not only shares the simplicity and robustness of histogram-matching techniques, but also incorporates tissue spatial intensity information. STI uses joint intensity histograms to determine intensity correspondence in each tissue between the input and standard images. We compared STI to an existing histogram-matching technique on two multicentric datasets, Pilot E-ADNI and ADNI, by measuring the intensity error with respect to the standard image after performing nonlinear registration. The Pilot E-ADNI dataset consisted in 3 subjects each scanned in 7 different sites. The ADNI dataset consisted in 795 subjects scanned in more than 50 different sites. STI was superior to the histogram-matching technique, showing significantly better intensity matching for the brain white matter with respect to the standard image.

Congenital amusia persists in the developing brain after daily music listening.

Congenital amusia is a neurodevelopmental disorder that affects about 3% of the adult population. Adults experiencing this musical disorder in the absence of macroscopically visible brain injury are described as cases of congenital amusia under the assumption that the musical deficits have been present from birth. Here, we show that this disorder can be expressed in the developing brain. We found that (10-13 year-old) children exhibit a marked deficit in the detection of fine-grained pitch differences in both musical and acoustical context in comparison to their normally developing peers comparable in age and general intelligence. This behavioral deficit could be traced down to their abnormal P300 brain responses to the detection of subtle pitch changes. The altered pattern of electrical activity does not seem to arise from an anomalous functioning of the auditory cortex, because all early components of the brain potentials, the N100, the MMN, and the P200 appear normal. Rather, the brain and behavioral measures point to disrupted information propagation from the auditory cortex to other cortical regions. Furthermore, the behavioral and neural manifestations of the disorder remained unchanged after 4 weeks of daily musical listening. These results show that congenital amusia can be detected in childhood despite regular musical exposure and normal intellectual functioning.

Label fusion strategy selection.

Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques-STAPLE, Voting, and Shape-Based Averaging (SBA)-and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall.