Exploring morphological similarity and randomness in Alzheimer's disease using adjacent grey matter voxel-based structural analysis.

BACKGROUND: Alzheimer's disease is characterized by large-scale structural changes in a specific pattern. Recent studies developed morphological similarity networks constructed by brain regions similar in structural features to represent brain structural organization. However, few studies have used local morphological properties to explore inter-regional structural similarity in Alzheimer's disease. METHODS: Here, we sourced T1-weighted MRI images of 342 cognitively normal participants and 276 individuals with Alzheimer's disease from the Alzheimer's Disease Neuroimaging Initiative database. The relationships of grey matter intensity between adjacent voxels were defined and converted to the structural pattern indices. We conducted the information-based similarity method to evaluate the structural similarity of structural pattern organization between brain regions. Besides, we examined the structural randomness on brain regions. Finally, the relationship between the structural randomness and cognitive performance of individuals with Alzheimer's disease was assessed by stepwise regression. RESULTS: Compared to cognitively normal participants, individuals with Alzheimer's disease showed significant structural pattern changes in the bilateral posterior cingulate gyrus, hippocampus, and olfactory cortex. Additionally, individuals with Alzheimer's disease showed that the bilateral insula had decreased inter-regional structural similarity with frontal regions, while the bilateral hippocampus had increased inter-regional structural similarity with temporal and subcortical regions. For the structural randomness, we found significant decreases in the temporal and subcortical areas and significant increases in the occipital and frontal regions. The regression analysis showed that the structural randomness of five brain regions was correlated with the Mini-Mental State Examination scores of individuals with Alzheimer's disease. CONCLUSIONS: Our study suggested that individuals with Alzheimer's disease alter micro-structural patterns and morphological similarity with the insula and hippocampus. Structural randomness of individuals with Alzheimer's disease changed in temporal, frontal, and occipital brain regions. Morphological similarity and randomness provide valuable insight into brain structural organization in Alzheimer's disease.

Investigating brain aging trajectory deviations in different brain regions of individuals with schizophrenia using multimodal magnetic resonance imaging and brain-age prediction: a multicenter study.

Although many studies on brain-age prediction in patients with schizophrenia have been reported recently, none has predicted brain age based on different neuroimaging modalities and different brain regions in these patients. Here, we constructed brain-age prediction models with multimodal MRI and examined the deviations of aging trajectories in different brain regions of participants with schizophrenia recruited from multiple centers. The data of 230 healthy controls (HCs) were used for model training. Next, we investigated the differences in brain age gaps between participants with schizophrenia and HCs from two independent cohorts. A Gaussian process regression algorithm with fivefold cross-validation was used to train 90, 90, and 48 models for gray matter (GM), functional connectivity (FC), and fractional anisotropy (FA) maps in the training dataset, respectively. The brain age gaps in different brain regions for all participants were calculated, and the differences in brain age gaps between the two groups were examined. Our results showed that most GM regions in participants with schizophrenia in both cohorts exhibited accelerated aging, particularly in the frontal lobe, temporal lobe, and insula. The parts of the white matter tracts, including the cerebrum and cerebellum, indicated deviations in aging trajectories in participants with schizophrenia. However, no accelerated brain aging was noted in the FC maps. The accelerated aging in 22 GM regions and 10 white matter tracts in schizophrenia potentially exacerbates with disease progression. In individuals with schizophrenia, different brain regions demonstrate dynamic deviations of brain aging trajectories. Our findings provided more insights into schizophrenia neuropathology.

Predicting aging trajectories of decline in brain volume, cortical thickness and fractional anisotropy in schizophrenia.

Brain-age prediction is a novel approach to assessing deviated brain aging trajectories in different diseases. However, most studies have used an average brain age gap (BAG) of individuals with schizophrenia of different illness durations for comparison with healthy participants. Therefore, this study investigated whether declined brain structures as reflected by BAGs may be present in schizophrenia in terms of brain volume, cortical thickness, and fractional anisotropy across different illness durations. We used brain volume, cortical thickness, and fractional anisotropy as features to train three models from the training dataset. Three models were applied to predict brain ages in the hold-out test and schizophrenia datasets and calculate BAGs. We divided the schizophrenia dataset into multiple groups based on the illness duration using a sliding time window approach for ANCOVA analysis. The brain volume and cortical thickness models revealed that, in comparison with healthy controls, individuals with schizophrenia had larger BAGs across different illness durations, whereas the BAG in terms of fractional anisotropy did not differ from that of healthy controls after disease onset. Moreover, the BAG at the initial stage of schizophrenia was the largest in the cortical thickness model. In contrast, the BAG from approximately two decades after disease onset was the largest in the brain volume model. Our findings suggest that schizophrenia differentially affects the decline of different brain structures during the disease course. Moreover, different trends of decline in thickness and volume-based measures suggest a differential decline in dimensions of brain structure throughout the course of schizophrenia.

Functional MRI and ApoE4 genotype for predicting cognitive decline in amyloid-positive individuals.

Background: In light of advancements in machine learning techniques, many studies have implemented machine learning approaches combined with data measures to predict and classify Alzheimer's disease. Studies that predicted cognitive status with longitudinal follow-up of amyloid-positive individuals remain scarce, however. Objective: We developed models based on voxel-wise functional connectivity (FC) density mapping and the presence of the ApoE4 genotype to predict whether amyloid-positive individuals would experience cognitive decline after 1 year. Methods: We divided 122 participants into cognitive decline and stable cognition groups based on the participants' change rates in Mini-Mental State Examination scores. In addition, we included 68 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) database as an external validation data set. Subsequently, we developed two classification models: the first model included 99 voxels, and the second model included 99 voxels and the ApoE4 genotype as features to train the models by Wide Neural Network algorithm with fivefold cross-validation and to predict the classes in the hold-out test and ADNI data sets. Results: The results revealed that both models demonstrated high accuracy in classifying the two groups in the hold-out test data set. The model for FC demonstrated good performance, with a mean F 1-score of 0.86. The model for FC combined with the ApoE4 genotype achieved superior performance, with a mean F 1-score of 0.90. In the ADNI data set, the two models demonstrated stable performances, with mean F 1-scores of 0.77 in the first and second models. Conclusion: Our findings suggest that the proposed models exhibited promising accuracy for predicting cognitive status after 1 year in amyloid-positive individuals. Notably, the combination of FC and the ApoE4 genotype increased prediction accuracy. These findings can assist clinicians in predicting changes in cognitive status in individuals with a high risk of Alzheimer's disease and can assist future studies in developing precise treatment and prevention strategies.

Effectiveness of Digital Cognitive Behavioral Therapy for Insomnia in Young People: Preliminary Findings from Systematic Review and Meta-Analysis.

Various forms of cognitive behavioral therapy for insomnia (CBT-i) have been developed to improve its scalability and accessibility for insomnia management in young people, but the efficacy of digitally-delivered cognitive behavioral therapy for insomnia (dCBT-i) remains uncertain. This study systematically reviewed and evaluated the effectiveness of dCBT-i among young individuals with insomnia. We conducted comprehensive searches using four electronic databases (PubMed, Cochrane Library, PsycINFO, and Embase; until October 2021) and examined eligible records. The search strategy comprised the following three main concepts: (1) participants were adolescents or active college students; (2) dCBT-I was employed; (3) standardized tools were used for outcome measurement. Four randomized controlled trials qualified for meta-analysis. A significant improvement in self-reported sleep quality with a medium-to-large effect size after treatment (Hedges's g = -0.58~-0.80) was noted. However, a limited effect was detected regarding objective sleep quality improvement (total sleep time and sleep efficiency measured using actigraphy). These preliminary findings from the meta-analysis suggest that dCBT-i is a moderately effective treatment in managing insomnia in younger age groups, and CBT-i delivered through the web or a mobile application is an acceptable approach for promoting sleep health in young people.

Modulation of Functional Connectivity in Response to Mirror Visual Feedback in Stroke Survivors: An MEG Study.

BACKGROUND: Several brain regions are activated in response to mirror visual feedback (MVF). However, less is known about how these brain areas and their connectivity are modulated in stroke patients. This study aimed to explore the effects of MVF on brain functional connectivity in stroke patients. MATERIALS AND METHODS: We enrolled 15 stroke patients who executed Bilateral-No mirror, Bilateral-Mirror, and Unilateral-Mirror conditions. The coherence values among five brain regions of interest in four different frequency bands were calculated from magnetoencephalographic signals. We examined the differences in functional connectivity of each two brain areas between the Bilateral-No mirror and Bilateral-Mirror conditions and between the Bilateral-Mirror and Unilateral-Mirror conditions. RESULTS: The functional connectivity analyses revealed significantly stronger connectivity between the posterior cingulate cortex and primary motor cortex in the beta band (adjusted p = 0.04) and possibly stronger connectivity between the precuneus and primary visual cortex in the theta band (adjusted p = 0.08) in the Bilateral-Mirror condition than those in the Bilateral-No mirror condition. However, the comparisons between the Bilateral-Mirror and Unilateral-Mirror conditions revealed no significant differences in cortical coherence in all frequency bands. CONCLUSIONS: Providing MVF to stroke patients may modulate the lesioned primary motor cortex through visuospatial and attentional cortical networks.

Cortical neural activity evoked by bilateral and unilateral mirror therapy after stroke.

OBJECTIVE: This study aimed to investigate the differential effects of bilateral and unilateral mirror therapy (MT) on motor cortical activations in stroke patients by magnetoencephalography (MEG). METHODS: Sixteen stroke patients and 16 right-handed healthy volunteers were recruited. All participants were required to perform 4 conditions: resting, no mirror with bilateral hand movements (Bilateral-No mirror), mirror with bilateral hand movements (Bilateral-Mirror) and mirror with unilateral hand movements (Unilateral-Mirror). Beta oscillatory activities in the primary motor cortex (M1) were collected during each condition using MEG. The percentage change of beta oscillatory activity was calculated for each condition to correct the baseline differences. RESULTS: In the stroke group, the percentage change of M1 beta oscillatory activity significantly decreased more in the Bilateral-Mirror condition than in the Bilateral-No mirror and Unilateral-Mirror conditions. In the healthy group, no significant differences in the percentage change of beta oscillatory activity were found among the 3 conditions. Further, a significant difference in the percentage change of beta oscillatory activity only in the Bilateral-Mirror condition was found between the 2 groups. CONCLUSIONS: This study provides new information on the differential cortical activations modulated by bilateral and unilateral MT. SIGNIFICANCE: Bilateral MT led to greater M1 neural activities than unilateral MT and bilateral movements without a mirror in stroke patients.

Treatment Effects of Upper Limb Action Observation Therapy and Mirror Therapy on Rehabilitation Outcomes after Subacute Stroke: A Pilot Study.

BACKGROUND: Action observation therapy and mirror therapy, two promising rehabilitation strategies, are aimed at enhancing the motor learning and functional improvement of stroke patients through different patterns of visual feedback and observation. OBJECTIVE: This study investigated and compared the treatment effects of the action observation therapy, mirror therapy, and active control intervention on motor and functional outcomes of stroke patients. METHODS: Twenty-one patients with subacute stroke were recruited in this study. All patients were randomly assigned to the action observation therapy, mirror therapy, or active control intervention for 3 weeks. Outcome measures were conducted at baseline, immediately after treatment, and at 3-month follow-up. The primary outcome was the Fugl-Meyer Assessment, and secondary outcomes included the Box and Block Test, Functional Independence Measure, and Stroke Impact Scale. Descriptive analyses and the number of patients whose change score achieved minimal clinically important difference were reported. RESULTS: Both the action observation therapy and active control intervention showed similar improvements on the Fugl-Meyer Assessment, Box and Block Test, and Stroke Impact Scale. Moreover, the action observation therapy had a greater improvement on the Functional Independence Measure than the other 2 groups did. However, the mirror therapy group gained the least improvements on the outcomes. CONCLUSION: The preliminary results found that the patients in the action observation therapy and active control intervention groups had comparable benefits, suggesting that the 2 treatments might be used as an alternative to each other. A further large-scale study with at least 20 patients in each group to validate the study findings is needed. This trial is registered with NCT02871700.

Modulation of Motor Cortical Activities by Action Observation and Execution in Patients with Stroke: An MEG Study.

Action observation therapy has recently attracted increasing attention; however, the mechanisms through which action observation and execution (AOE) modulate neural activity in stroke patients remain unclear. This study was aimed at investigating the effects of action observation and two types of AOE on motor cortical activations after stroke using magnetoencephalography. Twenty patients with stroke and 20 healthy controls were recruited for the collection of data on the beta oscillatory activity in the primary motor cortex (M1). All participants performed the conditions of resting, observation only, and video observation combined with execution (video AOE). Stroke patients performed one additional condition of affected hand observation combined with execution (affected hand AOE). The relative change index of beta oscillations was calculated, and nonparametric tests were used to examine the differences in conditions. In stroke patients, the relative change index of M1 beta oscillatory activity under the video AOE condition was significantly lower than that under the observation only and affected hand AOE conditions. Moreover, M1 cortical activity did not significantly differ under the observation only and affected hand AOE conditions. For healthy controls, the relative change index under the video AOE condition was significantly lower than that under the observation only condition. In addition, no significant differences in relative change indices were found under the observation only and video AOE conditions between the 2 groups. This study provides new insight into the neural mechanisms underlying AOE, which supports the use of observing videos of normal movements during action observation therapy in stroke rehabilitation.

Action observation therapy for improving arm function, walking ability, and daily activity performance after stroke: a systematic review and meta-analysis.

OBJECTIVE: This study was to investigate the effectiveness of action observation therapy on arm and hand motor function, walking ability, gait performance, and activities of daily living in stroke patients. DESIGN: Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Searches were completed in January 2019 from electronic databases, including PubMed, Scopus, the Cochrane Library, and OTseeker. REVIEW METHODS: Two independent reviewers performed data extraction and evaluated the study quality by the PEDro scale. The pooled effect sizes on different aspects of outcome measures were calculated. Subgroup analyses were performed to examine the impact of stroke phases on treatment efficacy. RESULTS: Included were 17 articles with 600 patients. Compared with control treatments, the action observation therapy had a moderate effect size on arm and hand motor outcomes (Hedge's g = 0.564; P < 0.001), a moderate to large effect size on walking outcomes (Hedge's g = 0.779; P < 0.001), a large effect size on gait velocity (Hedge's g = 0.990; P < 0.001), and a moderate to large effect size on activities of daily function (Hedge's g = 0. 728; P = 0.004). Based on subgroup analyses, the action observation therapy showed moderate to large effect sizes in the studies of patients with acute/subacute stroke or those with chronic stroke (Hedge's g = 0.661 and 0.783). CONCLUSION: This review suggests that action observation therapy is an effective approach for stroke patients to improve arm and hand motor function, walking ability, gait velocity, and daily activity performance.