Inverted U-shape-like functional connectivity alterations in cognitive resting-state networks depending on exercise intensity: An fMRI study.

Acute physical activity influences cognitive performance. However, the relationship between exercise intensity, neural network activity, and cognitive performance remains poorly understood. This study examined the effects of different exercise intensities on resting-state functional connectivity (rsFC) and cognitive performance. Twenty male athletes (27.3 ± 3.6 years) underwent cycling exercises of different intensities (high, low, rest/control) on different days in randomized order. Before and after, subjects performed resting-state functional magnetic resonance imaging and a behavioral Attention Network Test (ANT). Independent component analysis and Linear mixed effects models examined rsFC changes within ten resting-state networks. No significant changes were identified in ANT performance. Resting-state analyses revealed a significant interaction in the Left Frontoparietal Network, driven by a non-significant rsFC increase after low-intensity and a significant rsFC decrease after high-intensity exercise, suggestive of an inverted U-shape relationship between exercise intensity and rsFC. Similar but trend-level rsFC interactions were observed in the Dorsal Attention Network (DAN) and the Cerebellar Basal Ganglia Network. Explorative correlation analysis revealed a significant positive association between rsFC increases in the right superior parietal lobule (part of DAN) and better ANT orienting in the low-intensity condition. Results indicate exercise intensity-dependent subacute rsFC changes in cognition-related networks, but their cognitive-behavioral relevance needs further investigation.

Coherent Structural and Functional Network Changes after Thalamic Lesions in Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus is a novel incisionless ablative treatment for essential tremor (ET). OBJECTIVE: The aim was to study the structural and functional network changes induced by unilateral sonication of the ventral intermediate nucleus in ET. METHODS: Fifteen essential tremor patients (66.2 ± 15.4 years) underwent probabilistic tractography and functional magnetic resonance imaging (MRI) during unilateral postural tremor-eliciting tasks using 3-T MRI before, 1 month (N = 15), and 6 months (N = 10) post unilateral sonication. RESULTS: Tractography identified tract-specific alterations within the dentato-thalamo-cortical tract (DTCT) affected by the unilateral lesion after sonication. Relative to the treated hand, task-evoked activation was significantly reduced in contralateral primary sensorimotor cortex and ipsilateral cerebellar lobules IV/V and VI, and vermis. Dynamic causal modeling revealed a significant decrease in excitatory drive from the cerebellum to the contralateral sensorimotor cortex. CONCLUSIONS: Thalamic lesions induced by sonication induce specific functional network changes within the DTCT, notably reducing excitatory input to ipsilateral sensorimotor cortex in ET. ©[2022] International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Differential modulation of resting-state functional connectivity between amygdala and precuneus after acute physical exertion of varying intensity: indications for a role in affective regulation.

Introduction: Physical activity influences psychological well-being. This study aimed to determine the impact of exercise intensity on psychological well-being and alterations in emotion-related brain functional connectivity (FC). Methods: Twenty young, healthy, trained athletes performed a low- and high-intensity interval exercise (LIIE and HIIE) as well as a control condition in a within-subject crossover design. Before and after each condition, Positive And Negative Affect Scale (PANAS) was assessed as well as resting-state functional MRI (rs-fMRI). Voxel-wise FC was examined for bilateral amygdala seed region to whole-brain and emotion-related anatomical regions (e.g., insula, temporal pole, precuneus). Data analyses were performed using linear mixed-effect models with fixed factors condition and time. Results: The PANAS Positive Affect scale showed a significant increase after LIIE and HIIE and a significant reduction in Negative Affect after the control condition. In rs-fMRI, no significant condition-by-time interactions were observed between the amygdala and whole brain. Amygdala-precuneus FC analysis showed an interaction effect, suggesting reduced post-exercise anticorrelation after the control condition, but stable, or even slightly enhanced anticorrelation for the exercise conditions, especially HIIE. Discussion: In conclusion, both LIIE and HIIE had positive effects on mood and concomitant effects on amygdala-precuneus FC, particularly after HIIE. Although no significant correlations were found between amygdala-precuneus FC and PANAS, results should be discussed in the context of affective disorders in whom abnormal amygdala-precuneus FC has been observed.

Fractional amplitude of low-frequency fluctuations associated with µ-opioid and dopamine receptor distributions in the central nervous system after high-intensity exercise bouts.

Introduction: Dopaminergic, opiod and endocannabinoid neurotransmission are thought to play an important role in the neurobiology of acute exercise and, in particular, in mediating positive affective responses and reward processes. Recent evidence indicates that changes in fractional amplitude of low-frequency fluctuations (zfALFF) in resting-state functional MRI (rs-fMRI) may reflect changes in specific neurotransmitter systems as tested by means of spatial correlation analyses. Methods: Here, we investigated this relationship at different exercise intensities in twenty young healthy trained athletes performing low-intensity (LIIE), high-intensity (HIIE) interval exercises, and a control condition on three separate days. Positive And Negative Affect Schedule (PANAS) scores and rs-fMRI were acquired before and after each of the three experimental conditions. Respective zfALFF changes were analyzed using repeated measures ANOVAs. We examined the spatial correspondence of changes in zfALFF before and after training with the available neurotransmitter maps across all voxels and additionally, hypothesis-driven, for neurotransmitter maps implicated in the neurobiology of exercise (dopaminergic, opiodic and endocannabinoid) in specific brain networks associated with "reward" and "emotion." Results: Elevated PANAS Positive Affect was observed after LIIE and HIIE but not after the control condition. HIIE compared to the control condition resulted in differential zfALFF decreases in precuneus, temporo-occipital, midcingulate and frontal regions, thalamus, and cerebellum, whereas differential zfALFF increases were identified in hypothalamus, pituitary, and periaqueductal gray. The spatial alteration patterns in zfALFF during HIIE were positively associated with dopaminergic and µ-opioidergic receptor distributions within the 'reward' network. Discussion: These findings provide new insight into the neurobiology of exercise supporting the importance of reward-related neurotransmission at least during high-intensity physical activity.

Hippocampal subfield plasticity is associated with improved spatial memory.

Physical exercise studies are generally underrepresented in young adulthood. Seventeen subjects were randomized into an intervention group (24.2 ± 3.9 years; 3 trainings/week) and 10 subjects into a passive control group (23.7 ± 4.2 years), over a duration of 6 months. Every two months, performance diagnostics, computerized spatial memory tests, and 3 Tesla magnetic resonance imaging were conducted. Here we find that the intervention group, compared to controls, showed increased cardiorespiratory fitness, spatial memory performance and subregional hippocampal volumes over time. Time-by-condition interactions occurred in right cornu ammonis 4 body and (trend only) dentate gyrus, left hippocampal tail and left subiculum. Increases in spatial memory performance correlated with hippocampal body volume changes and, subregionally, with left subicular volume changes. In conclusion, findings support earlier reports of exercise-induced subregional hippocampal volume changes. Such exercise-related plasticity may not only be of interest for young adults with clinical disorders of hippocampal function, but also for sedentary normal cohorts.

Whole-brain network transitions within the framework of ignition and transfer entropy following VIM-MRgFUS in essential tremor patients.

Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS. Eighteen ET patients (mean age 71.44 years) underwent repeated 3T resting-state functional magnetic resonance imaging combined with Clinical Rating Scale for Tremor (CRST) assessments one day before (T0) and one month (T1) and six months (T2) post-MRgFUS, respectively. We observed increased whole brain ignition-driven mean integration (IDMI) at T1 (p < 0.05), along with trend increases at T2. Further, constraining to motor network nodes, we identified significant increases in information-broadcasting (bilateral supplementary motor area (SMA) and left cerebellar lobule III) and information-receiving (right precentral gyrus) at T1. Remarkably, increased information-broadcasting in bilateral SMA was correlated with relative improvement of the CRST in the treated hand. In addition, causal TE-based effective connectivity (EC) at T1 showed an increase from right SMA to left cerebellar lobule crus II and from left cerebellar lobule III to right thalamus. In conclusion, results suggest a change in information transmission capacity in ET after MRgFUS and a shift towards a more integrated functional state with increased levels of global and directional information flow.

Physical Activity Alters Functional Connectivity of Orbitofrontal Cortex Subdivisions in Healthy Young Adults: A Longitudinal fMRI Study.

Physical activity (PA) plays an important role in affect processing. Studies describe the orbitofrontal cortex (OFC) as a major hub for emotion processing and the pathophysiology of affective disorders. Subregions of the OFC show diverse functional connectivity (FC) topographies, but the effect of chronic PA on subregional OFC FC still lacks scientific understanding. Therefore, we aimed at investigating the effects of regular PA on the FC topographies of OFC subregions in healthy individuals within a longitudinal randomized controlled exercise study. Participants (age: 18-35 years) were randomly assigned to either an intervention group (IG; N = 18) or a control group (CG; N = 10). Fitness assessments, mood questionnaires, and resting state functional magnetic resonance imaging (rsfMRI) were performed four times over the duration of 6 months. Using a detailed parcellation of the OFC, we created subregional FC topography maps at each time point and applied a linear mixed model to assess the effects of regular PA. The posterior-lateral right OFC showed a group and time interaction, revealing decreased FC with the left dorsolateral prefrontal cortex in the IG, while FC in the CG increased. Group and time interaction in the anterior-lateral right OFC with the right middle frontal gyrus was driven by increased FC in the IG. The posterior-lateral left OFC showed a group and time interaction based on differential change in FC to the left postcentral gyrus and the right occipital gyrus. This study emphasized regionally distinctive FC changes induced by PA within the lateral OFC territory, while providing aspects for further research.

Are We There Yet? The Value of Deep Learning in a Multicenter Setting for Response Prediction of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy.

This retrospective study aims to evaluate the generalizability of a promising state-of-the-art multitask deep learning (DL) model for predicting the response of locally advanced rectal cancer (LARC) to neoadjuvant chemoradiotherapy (nCRT) using a multicenter dataset. To this end, we retrained and validated a Siamese network with two U-Nets joined at multiple layers using pre- and post-therapeutic T2-weighted (T2w), diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps of 83 LARC patients acquired under study conditions at four different medical centers. To assess the predictive performance of the model, the trained network was then applied to an external clinical routine dataset of 46 LARC patients imaged without study conditions. The training and test datasets differed significantly in terms of their composition, e.g., T-/N-staging, the time interval between initial staging/nCRT/re-staging and surgery, as well as with respect to acquisition parameters, such as resolution, echo/repetition time, flip angle and field strength. We found that even after dedicated data pre-processing, the predictive performance dropped significantly in this multicenter setting compared to a previously published single- or two-center setting. Testing the network on the external clinical routine dataset yielded an area under the receiver operating characteristic curve of 0.54 (95% confidence interval [CI]: 0.41, 0.65), when using only pre- and post-therapeutic T2w images as input, and 0.60 (95% CI: 0.48, 0.71), when using the combination of pre- and post-therapeutic T2w, DW images, and ADC maps as input. Our study highlights the importance of data quality and harmonization in clinical trials using machine learning. Only in a joint, cross-center effort, involving a multidisciplinary team can we generate large enough curated and annotated datasets and develop the necessary pre-processing pipelines for data harmonization to successfully apply DL models clinically.

Effects of a 6-Month Aerobic Exercise Intervention on Mood and Amygdala Functional Plasticity in Young Untrained Subjects.

Acute exercise has beneficial effects on mood and is known to induce modulations in functional connectivity (FC) within the emotional network. However, the long-term effects of exercise on affective brain circuits remain largely unknown. Here, we investigated the effects of 6 months of regular exercise on mood, amygdala structure, and functional connectivity. This study comprised N = 18 healthy sedentary subjects assigned to an intervention group (IG; 23.9 ± 3.9 years; 3 trainings/week) and N = 10 subjects assigned to a passive control group (CG; 23.7 ± 4.2 years). At baseline and every two months, performance diagnostics, mood questionnaires, and structural and resting-state-fMRI were conducted. Amygdala-nuclei segmentation and amygdala-to-whole-brain FC analysis were performed. Linear mixed effects models and correlation analyses were conducted between FC, relVO2max, and mood scores. Data showed increases in relVO2max exclusively in the IG. Stronger anticorrelation in amygdala-precuneus FC was found, along with a stronger positive correlation in the amygdala-temporal pole FC in the IG after 4 and 6 months, while mood and amygdala volume did not reveal significant interactions. The relVO2max/amygdala-temporal pole FC correlated positively, and the amygdala-precuneus/amygdala-temporal pole FC correlated negatively. Findings suggest that exercise induced long-term modulations of the amygdala FC with the precuneus and temporal pole, shedding light on potential mechanisms by which exercise has positive influences on mood-related networks, typically altered in affective disorders.

Regional cortical perfusion increases induced by a 6-month endurance training in young sedentary adults.

Physical inactivity is documented as a health risk factor for chronic diseases, accelerated aging, and cognitive impairment. Physical exercise, on the other hand, plays an important role in healthy aging by promoting positive muscular, cardiovascular, and central nervous system adaptions. Prior studies on the effects of exercise training on cerebral perfusion have focused largely on elderly cohorts or patient cohorts, while perfusion effects of exercise training in young sedentary adults have not yet been fully assessed. Therefore, the present study examined the physiological consequence of a 6-month endurance exercise training on brain perfusion in 28 young sedentary adults randomly assigned to an intervention group (IG; regular physical exercise) or a control group (CG; without physical exercise). The IG performed an extensive running interval training three times per week over 6 months. Performance diagnostics and MRI were performed every 2 months, and training intensity was adapted individually. Brain perfusion measurements with pseudo-continuous arterial spin labeling were analyzed using the standard Oxford ASL pipeline. A significant interaction effect between group and time was found for right superior temporal gyrus (STG) perfusion, driven by an increase in the IG and a decrease in the CG. Furthermore, a significant time effect was observed in the right middle occipital region in the IG only. Perfusion increases in the right STG, in the ventral striatum, and in primary motor areas were significantly associated with increases in maximum oxygen uptake (VO2max). Overall, this study identified region-specific increases in local perfusion in a cohort of young adults that partly correlated with individual performance increases, hence, suggesting exercise dose dependency. Respective adaptations in brain perfusion are discussed in the context of physical exercise-induced vascular plasticity.

Cortical representation of experimental periodontal pain: a functional magnetic resonance imaging study.

The aim of this study was to investigate central pain representations during loading of the periodontium induced by orthodontic and occlusal stress. Nineteen healthy male volunteers (25.7 ± 2.8 years) were tested on two consecutive days: after phenotyping (questionnaires) and determination of warmth (WPT) and heat (HPT) pain thresholds, functional magnetic resonance imaging was performed as event-related paradigm including 36 tooth clenchings of 3 s duration, alternating with rest periods varying between 20-30 s. The task was performed in absence (T1) and 24 h after placement of an elastic separator between the second bicuspid and the first molar on the right side of the lower jaw (T2). No significant changes in WPT and HPT were observed but pain ratings were significantly elevated at T2. Significantly elevated activation at T2, as compared to T1, was found in bilateral sensorimotor cortex, bilateral secondary sensory cortex, supplementary motor area, right rolandic operculum, and bilateral insula. Our data show for the first time in humans that periodontal stimulation, as tested by tooth clenching in the presence of an elastic separator, goes along with specific expressions of pain at behavioral and neuronal network levels. Findings supplement the existing neuroimaging literature on odontogenic pain.

Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status.

BACKGROUND: Amyloid-ß accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework. OBJECTIVE: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus. METHODS: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAß+) and amyloidnegative SCD (SCDß-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB). RESULTS: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAß+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAß+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAß+) and precuneus SUVRFBB (both groups). CONCLUSION: While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAß+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-ß load, highlighting incipient pathology in stage 2 of the AD continuum.

Body Image Relates to Exercise-Induced Antinociception and Mood Changes in Young Adults: A Randomized Longitudinal Exercise Intervention.

Background: An important motivation for adolescents and young adults to engage in aerobic exercise (AE) is to improve fitness, body composition and physical appearance. These parameters have an impact on bodily perception as conceptualized by the 'body image' (BI) construct. AE is known to have positive effects on pain perception, mood, and body image (BI). However, no study has hitherto investigated their interrelationship within one study. Methods: Participants were randomly assigned to an intervention group (IG, n = 16, 6 months of AE) or a passive control group (CG, n = 10). Frankfurt Body-Concept Scales (FKKS), Positive and Negative Affect Scale (PANAS), State and Trait Anxiety Inventory, warmth and heat pain thresholds (WPT, HPT), pain tolerance, and graded exercise test data from baseline (T0) and the end of the intervention (T6) were analyzed using a paired t-test (p < 0.05). Results: A significant increase in the BI dimension 'physical efficacy' was identified from T0 to T6, which correlated positively with PANAS Positive Affect Scale and HPT. Conclusion: Data in young adults undergoing AE indicate that changes in the BI sub-category 'physical efficacy' are closely linked with changes in positive affect and antinociception. These novel findings suggest that BI plays a role in antinociception and positive affect.