Grey matter volume predicts improvement in geriatric depression in response to Tai Chi compared to Health Education.

OBJECTIVES: Geriatric depression (GD) is associated with cognitive impairment and brain atrophy. Tai-Chi-Chih (TCC) is a promising adjunct treatment to antidepressants. We previously found beneficial effects of TCC on resting state connectivity in GD. We now tested the effect of TCC on gray matter volume (GMV) change and the association between baseline GMV and clinical outcome. PARTICIPANTS: Forty-nine participants with GD (>=60 y) underwent antidepressant treatment (38 women). INTERVENTION: Participants completed 3 months of TCC (N = 26) or health and wellness education control (HEW; N = 23). MEASUREMENTS: Depression and anxiety symptoms and MRI scans were acquired at baseline and 3-month follow-up. General linear models (GLMs) tested group-by-time interactions on clinical scores. Freesurfer 6.0 was used to process T1-weighted images and to perform voxel-wise whole-brain GLMs of group on symmetrized percent GMV change, and on the baseline GMV and symptom change association, controlling for baseline symptom severity. Age and sex served as covariates in all models. RESULTS: There were no group differences in baseline demographics or clinical scores, symptom change from baseline to follow-up, or treatment-related GMV change. However, whole-brain analysis revealed that lower baseline GMV in several clusters in the TCC, but not the HEW group, was associated with larger improvements in anxiety. This was similar for right precuneus GMV and depressive symptoms. CONCLUSIONS: While we observed no effect on GMV due to the interventions, baseline regional GMV predicted symptom improvements with TCC but not HEW. Longer trials are needed to investigate the long-term effects of TCC on clinical symptoms and neuroplasticity.

Impact of Yoga Versus Memory Enhancement Training on Hippocampal Connectivity in Older Women at Risk for Alzheimer's Disease.

BACKGROUND: Yoga may be an ideal early intervention for those with modifiable risk factors for Alzheimer's disease (AD) development. OBJECTIVE: To examine the effects of Kundalini yoga (KY) training versus memory enhancement training (MET) on the resting-state connectivity of hippocampal subregions in women with subjective memory decline and cardiovascular risk factors for AD. METHODS: Participants comprised women with subjective memory decline and cardiovascular risk factors who participated in a parent randomized controlled trial (NCT03503669) of 12-weeks of KY versus MET and completed pre- and post-intervention resting-state magnetic resonance imaging scans (yoga: n = 11, age = 61.45±6.58 years; MET: n = 11, age = 64.55±6.41 years). Group differences in parcellated (Cole-anticevic atlas) hippocampal connectivity changes (post- minus pre-intervention) were evaluated by partial least squares analysis, controlling for age. Correlations between hippocampal connectivity and perceived stress and frequency of forgetting (assessed by questionnaires) were also evaluated. RESULTS: A left anterior hippocampal subregion assigned to the default mode network (DMN) in the Cole-anticevic atlas showed greater increases in connectivity with largely ventral visual stream regions with KY than with MET (p < 0.001), which showed associations with lower stress (p < 0.05). Several posterior hippocampal subregions assigned to sensory-based networks in the Cole-anticevic atlas showed greater increases in connectivity with regions largely in the DMN and frontoparietal network with MET than with KY (p < 0.001), which showed associations with lower frequency of forgetting (p < 0.05). CONCLUSION: KY training may better target stress-related hippocampal connectivity, whereas MET may better target hippocampal sensory-integration supporting better memory reliability, in women with subjective memory decline and cardiovascular risk factors.

Impact of Tai Chi as an adjunct treatment on brain connectivity in geriatric depression.

BACKGROUND: As an adjunct to antidepressant treatment, Tai Chi Chih (TCC) is superior to health education and wellness (HEW) training in improving the general health of patients with geriatric depression (GD). This study investigated the brain connectivity changes associated with TCC and HEW in combination with antidepressant treatment in patients with GD. METHODS: Forty patients with GD under stable antidepressant treatment underwent TCC training (n = 21) or HEW training (n = 19) for 12 weeks, and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. Within-group and between-group differences in parcel-to-parcel connectivity changes with intervention were evaluated by general linear modeling. Relationships between significant connectivity changes and symptom/resilience improvement were evaluated by partial least squares correlation analysis. RESULTS: Significantly greater increases in connectivity with TCC than with HEW (FDR-corrected p < .05) were observed for 167 pairwise connections, most frequently involving the default mode network (DMN). In both groups, increased connectivity involving largely DMN regions was significantly and positively correlated with improvement in symptoms/resilience. LIMITATIONS: The sample size was relatively small, mainly due to neuroimaging contraindications (e.g., implants). Additionally, the standard antidepressant treatment varied greatly among patients, adding heterogeneity. CONCLUSIONS: Non-pharmacological adjuncts, such as TCC, may enhance DMN connectivity changes associated with improved depressive symptoms and psychological resilience in the treatment of GD.

Yoga Prevents Gray Matter Atrophy in Women at Risk for Alzheimer's Disease: A Randomized Controlled Trial.

BACKGROUND: Female sex, subjective cognitive decline (SCD), and cardiovascular risk factors (CVRFs) are known risk factors for developing Alzheimer's disease (AD). We previously demonstrated that yoga improved depression, resilience, memory and executive functions, increased hippocampal choline concentrations, and modulated brain connectivity in older adults with mild cognitive impairment. OBJECTIVE: In this study (NCT03503669), we investigated brain gray matter volume (GMV) changes in older women with SCD and CVRFs following three months of yoga compared to memory enhancement training (MET). METHODS: Eleven women (mean age = 61.45, SD = 6.58) with CVRF and SCD completed twelve weeks of Kundalini Yoga and Kirtan Kriya (KY + KK) while eleven women (mean age = 64.55, SD = 6.41) underwent MET. Anxiety, resilience, stress, and depression were assessed at baseline and 12 weeks, as were T1-weighted MRI scans (Siemens 3T Prisma scanner). We used Freesurfer 6.0 and tested group differences in GMV change, applying Monte-Carlo simulations with alpha = 0.05. Region-of-interest analysis was performed for hippocampus and amygdala. RESULTS: Compared to KY + KK, MET showed reductions in GMV in left prefrontal, pre- and post-central, supramarginal, superior temporal and pericalcarine cortices, right paracentral, postcentral, superior and inferior parietal cortices, the banks of the superior temporal sulcus, and the pars opercularis. Right hippocampal volume increased after yoga but did not survive corrections. CONCLUSION: Yoga training may offer neuroprotective effects compared to MET in preventing neurodegenerative changes and cognitive decline, even over short time intervals. Future analyses will address changes in functional connectivity in both groups.

Machine Learning Prediction of Treatment Outcome in Late-Life Depression.

Background: Recent evidence suggests that integration of multi-modal data improves performance in machine learning prediction of depression treatment outcomes. Here, we compared the predictive performance of three machine learning classifiers using differing combinations of sociodemographic characteristics, baseline clinical self-reports, cognitive tests, and structural magnetic resonance imaging (MRI) features to predict treatment outcomes in late-life depression (LLD). Methods: Data were combined from two clinical trials conducted with depressed adults aged 60 and older, including response to escitalopram (N = 32, NCT01902004) and Tai Chi (N = 35, NCT02460666). Remission was defined as a score of 6 or less on the 24-item Hamilton Rating Scale for Depression (HAMD) at the end of 24 weeks of treatment. Features subsets were constructed from baseline sociodemographic and clinical features, gray matter volumes (GMVs), or both. Three classification algorithms were compared: (1) Support Vector Machine-Radial Bias Function (SVMRBF), (2) Random Forest (RF), and (3) Logistic Regression (LR). A repeated 5-fold cross-validation approach with a wrapper-based feature selection method was used for model fitting. Model performance metrics included Area under the ROC Curve (AUC) and Matthews correlation coefficient (MCC). Cross-validated performance significance was tested by permutation analysis. Classifiers were compared by Cochran's Q and post-hoc pairwise comparisons using McNemar's Chi-Square test with Bonferroni correction. Results: For the RF and SVMRBF algorithms, the combined feature set outperformed the clinical and GMV feature sets with a final cross-validated AUC of 0.83 ± 0.11 and 0.80 ± 0.11, respectively. Both classifiers passed permutation analysis. The LR algorithm performed best using GMV features alone (AUC 0.79 ± 0.14) but failed to pass permutation analysis using any feature set. Performance of the three classifiers differed significantly for all three features sets. Important predictive features of treatment response included anterior and posterior cingulate volumes, depression characteristics, and self-reported health-related quality scores. Conclusion: This preliminary exploration into the use of ML and multi-modal data to identify predictors of general treatment response in LLD indicates that integration of clinical and structural MRI features significantly increases predictive capability. Identified features are among those previously implicated in geriatric depression, encouraging future work in this arena.

Variations in myo-inositol in fronto-limbic regions and clinical response to electroconvulsive therapy in major depression.

Though electroconvulsive therapy (ECT) is an established treatment for severe depression, the neurobiological factors accounting for the clinical effects of ECT are largely unknown. Myo-inositol, a neurometabolite linked with glial activity, is reported as reduced in fronto-limbic regions in patients with depression. Whether changes in myo-inositol relate to the antidepressant effects of ECT is unknown. Using magnetic resonance spectroscopy ((1)H-MRS), we measured dorsomedial anterior cingulate cortex (dmACC) and left and right hippocampal myo-inositol in 50 ECT patients (mean age: 43.78, 14 SD) and 33 controls (mean age: 39.33, 12 SD) to determine cross sectional effects of diagnosis and longitudinal effects of ECT. Patients were scanned prior to treatment, after the second ECT and at completion of the ECT index series. Controls were scanned twice at intervals corresponding to patients' baseline and end of treatment scans. Myo-inositol increased over the course of ECT in the dmACC (p = 0.042). A significant hemisphere by clinical response effect was observed for the hippocampus (p = 0.003) where decreased myo-inositol related to symptom improvement in the left hippocampus. Cross-sectional differences between patients and controls at baseline were not detected. Changes in myo-inositol observed in the dmACC in association with ECT and in the hippocampus in association with ECT-related clinical response suggest the mechanisms of ECT could include gliogenesis or a reversal of gliosis that differentially affect dorsal and ventral limbic regions. Change in dmACC myo-inositol diverged from control values with ECT suggesting compensation, while hippocampal change suggested normalization.

Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study.

BACKGROUND: No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. OBJECTIVES: This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). METHODS: Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active "gold-standard" control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. RESULTS: Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. CONCLUSION: Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies.

Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings.

BACKGROUND: Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. METHODS: Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. RESULTS: Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. CONCLUSIONS: Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.

Meditation effects within the hippocampal complex revealed by voxel-based morphometry and cytoarchitectonic probabilistic mapping.

Scientific studies addressing anatomical variations in meditators' brains have emerged rapidly over the last few years, where significant links are most frequently reported with respect to gray matter (GM). To advance prior work, this study examined GM characteristics in a large sample of 100 subjects (50 meditators, 50 controls), where meditators have been practicing close to 20 years, on average. A standard, whole-brain voxel-based morphometry approach was applied and revealed significant meditation effects in the vicinity of the hippocampus, showing more GM in meditators than in controls as well as positive correlations with the number of years practiced. However, the hippocampal complex is regionally segregated by architecture, connectivity, and functional relevance. Thus, to establish differential effects within the hippocampal formation (cornu ammonis, fascia dentata, entorhinal cortex, subiculum) as well as the hippocampal-amygdaloid transition area, we utilized refined cytoarchitectonic probabilistic maps of (peri-) hippocampal subsections. Significant meditation effects were observed within the subiculum specifically. Since the subiculum is known to play a key role in stress regulation and meditation is an established form of stress reduction, these GM findings may reflect neuronal preservation in long-term meditators-perhaps due to an attenuated release of stress hormones and decreased neurotoxicity.

Global and regional alterations of hippocampal anatomy in long-term meditation practitioners.

Studies linking meditation and brain structure are still relatively sparse, but the hippocampus is consistently implicated as one of the structures altered in meditation practitioners. To explore hippocampal features in the framework of meditation, we analyzed high-resolution structural magnetic resonance imaging data from 30 long-term meditators and 30 controls, closely matched for sex, age, and handedness. Hippocampal formations were manually traced following established protocols. In addition to calculating left and right hippocampal volumes (global measures), regional variations in surface morphology were determined by measuring radial distances from the hippocampal core to spatially matched surface points (local measures). Left and right hippocampal volumes were larger in meditators than in controls, significantly so for the left hippocampus. The presence and direction of this global effect was confirmed locally by mapping the exact spatial locations of the group differences. Altogether, radial distances were larger in meditators compared to controls, with up to 15% difference. These local effects were observed in several hippocampal regions in the left and right hemisphere though achieved significance primarily in the left hippocampal head. Larger hippocampal dimensions in long-term meditators may constitute part of the underlying neurological substrate for cognitive skills, mental capacities, and/or personal traits associated with the practice of meditation. Alternatively, given that meditation positively affects autonomic regulation and immune activity, altered hippocampal dimensions may be one result of meditation-induced stress reduction. However, given the cross-sectional design, the lack of individual stress measures, and the limited resolution of brain data, the exact underlying neuronal mechanisms remain to be established.