Investigation of physical activity, sleep, and mental health recovery in treatment resistant depression (TRD) patients receiving repetitive transcranial magnetic stimulation (rTMS) treatment

Background : Repetitive transcranial magnetic stimulation (rTMS) is effective in treating depression; however, the effect on physical activity, sleep and recovery is unclear. This study investigated rTMS effect on physical activity and sleep through providing patients with a Fitbit and software apps; and reports the impact of rTMS on depression, anxiety and mental health recovery. Methods : Study design was a pre and post data collection without a control, with twenty-four participants with treatment-resistant depression (TRD). Measures used were Fitbit activity and sleep data, and patient-rated Recovering Quality of Life (ReQoL-20), Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder (GAD-7). Results : Response and remission rates were, respectively: 34.8% and 39% for PHQ-9; 34.8% and 47.8% for GAD-7. ReQoL-20 response and reliable improvement were 29.4% and 53%. PHQ-9, GAD-7 and ReQol-20 scores significantly improved, with large effect sizes. Analysis of Fitbit activity and sleep data yielded non-significant results. The Fitbit data machine learning model classified two levels of depression to 82% accuracy. Limitations : rTMS treatment was open-label and adjunct to existing antidepressant medication. No control group. Female patients were overrepresented. Conclusions : Improvements on the ReQoL-20 and aspects of sleep and activity indicate the positive impact of rTMS on the individual’s real world functioning and quality of life. A wearable activity tracker can provide feedback to patients and clinicians on sleep, physical activity and depression levels. Further research could be undertaken through a sufficiently powered RCT comparing rTMS versus rTMS with use of a Fitbit, its software applications, and sleep and physical activity advice

How are nature-based interventions defined in mild cognitive impairment and dementia studies? A conceptual systematic review and novel taxonomy

Objectives To systematically review research testing nature-based interventions for people living with mild cognitive impairment or dementia, and to report how authors have defined their interventions by presenting a taxonomy of the nature-based interventions. Methods A conceptual systematic review of research published between 2008 and 2024 investigating nature-based interventions for people living with mild cognitive impairment or dementia was conducted. Three reviewers contributed independently. Exclusion criteria: not specifying if participants had mild cognitive impairment or dementia, only recruiting caregivers, no primary data, study protocols, abstracts, reviews, not peer-reviewed journal articles and any other grey literature. Intervention descriptions within the papers were thematically analysed. Results Fifty-two articles reporting fifty-one studies were included. The most common interventions were nature virtual reality (VR technology) and gardening. From the definition data, we produced a taxonomy with overarching domains of: (a) Other terms used; (b) Characteristics; (c) Activities. Subdomains included: development or approach, modes of action, location, physical features, and activities. Some interventions could be grouped. Structure and standardisation of the interventions varied, with a lack of clear reporting. Conclusion This taxonomy provides conceptualisations of nature-based interventions that can be used by future researchers to guide the development, evaluation and reporting of robust interventions in this area

The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate

Abnormal reward processing is a hallmark of neurodegenerative diseases, most strikingly in frontotemporal dementia. However, the phenotypic repertoire and neuroanatomical substrates of abnormal reward behaviour in these diseases remain incompletely characterized and poorly understood. Here we addressed these issues in a large, intensively phenotyped patient cohort representing all major syndromes of sporadic frontotemporal dementia and Alzheimer's disease. We studied 27 patients with behavioural variant frontotemporal dementia, 58 with primary progressive aphasia (22 semantic variant, 24 non-fluent/agrammatic variant and 12 logopenic) and 34 with typical amnestic Alzheimer's disease, in relation to 42 healthy older individuals. Changes in behavioural responsiveness were assessed for canonical primary rewards (appetite, sweet tooth, sexual activity) and non-primary rewards (music, religion, art, colours), using a semi-structured survey completed by patients' primary caregivers. Changes in more general socio-emotional behaviours were also recorded. We applied multiple correspondence analysis and k-means clustering to map relationships between hedonic domains and extract core factors defining aberrant hedonic phenotypes. Neuroanatomical associations were assessed using voxel-based morphometry of brain MRI images across the combined patient cohort. Altered (increased and/or decreased) reward responsiveness was exhibited by most patients in the behavioural and semantic variants of frontotemporal dementia and around two-thirds of patients in other dementia groups, significantly (P < 0.05) more frequently than in healthy controls. While food-directed changes were most prevalent across the patient cohort, behavioural changes directed toward non-primary rewards occurred significantly more frequently (P < 0.05) in the behavioural and semantic variants of frontotemporal dementia than in other patient groups. Hedonic behavioural changes across the patient cohort were underpinned by two principal factors: a 'gating' factor determining the emergence of altered reward behaviour and a 'modulatory' factor determining how that behaviour is directed. These factors were expressed jointly in a set of four core, trans-diagnostic and multimodal hedonic phenotypes: 'reward-seeking', 'reward-restricted', 'eating-predominant' and 'control-like'-variably represented across the cohort and associated with more pervasive socio-emotional behavioural abnormalities. The principal gating factor was associated (P < 0.05 after correction for multiple voxel-wise comparisons over the whole brain) with a common profile of grey matter atrophy in anterior cingulate, bilateral temporal poles, right middle frontal and fusiform gyri: the cortical circuitry that mediates behavioural salience and semantic and affective appraisal of sensory stimuli. Our findings define a multi-domain phenotypic architecture for aberrant reward behaviours in major dementias, with novel implications for the neurobiological understanding and clinical management of these diseases

Aerosol-cloud relationships in continental shallow cumulus

Aerosol-cloud relationships are derived from 14 warm continental cumuli cases sampled during the 2006 Gulf of Mexico Atmospheric Composition and Climate Study (GoMACCS) by the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) Twin Otter aircraft. Cloud droplet number concentration is clearly proportional to the subcloud accumulation mode aerosol number concentration. An inverse correlation between cloud top effective radius and subcloud aerosol number concentration is observed when cloud depth variations are accounted for. There are no discernable aerosol effects on cloud droplet spectral dispersion; the averaged spectral relative dispersion is 0.30 ± 0.04. Aerosol-cloud relationships are also identified from comparison of two isolated cloud cases that occurred under different degrees of anthropogenic influence. Cloud liquid water content, cloud droplet number concentration, and cloud top effective radius exhibit subadiabaticity resulting from entrainment mixing processes. The degree of LWC subadiabaticity is found to increase with cloud depth. Impacts of subadiabaticity on cloud optical properties are assessed. It is estimated that owing to entrainment mixing, cloud LWP, effective radius, and cloud albedo are decreased by 50–85%, 5–35%, and 2–26%, respectively, relative to adiabatic values of a plane-parallel cloud. The impact of subadiabaticity on cloud albedo is largest for shallow clouds. Results suggest that the effect of entrainment mixing must be accounted for when evaluating the aerosol indirect effect

Frontal theta dynamics during response conflict in long-term mindfulness meditators

Mindfulness meditators often show greater efficiency in resolving response conflicts than non-meditators. However, the neural mechanisms underlying the improved behavioral efficiency are unclear. Here, we investigated frontal theta dynamics—a neural mechanism involved in cognitive control processes—in long-term mindfulness meditators. The dynamics of EEG theta oscillations (4–8 Hz) recorded over the medial frontal cortex (MFC) were examined in terms of their power (MFC theta power) and their functional connectivity with other brain areas (the MFC-centered theta network). Using a flanker-type paradigm, EEG data were obtained from 22 long-term mindfulness meditators and compared to those from 23 matched controls without meditation experience. Meditators showed more efficient cognitive control after conflicts, evidenced by fewer error responses irrespective of response timing. Furthermore, meditators exhibited enhanced conflict modulations of the MFC-centered theta network shortly before the response, in particular for the functional connection between the MFC and the motor cortex. In contrast, MFC theta power was comparable between groups. These results suggest that the higher behavioral efficiency after conflicts in mindfulness meditators could be a function of increased engagement to control the motor system in association with the MFC-centered theta network

Alteration of EGFR Spatiotemporal Dynamics Suppresses Signal Transduction

The epidermal growth factor receptor (EGFR), which regulates cell growth and survival, is integral to colon tumorigenesis. Lipid rafts play a role in regulating EGFR signaling, and docosahexaenoic acid (DHA) is known to perturb membrane domain organization through changes in lipid rafts. Therefore, we investigated the mechanistic link between EGFR function and DHA. Membrane incorporation of DHA into immortalized colonocytes altered the lateral organization of EGFR. DHA additionally increased EGFR phosphorylation but paradoxically suppressed downstream signaling. Assessment of the EGFR-Ras-ERK1/2 signaling cascade identified Ras GTP binding as the locus of the DHA-induced disruption of signal transduction. DHA also antagonized EGFR signaling capacity by increasing receptor internalization and degradation. DHA suppressed cell proliferation in an EGFR-dependent manner, but cell proliferation could be partially rescued by expression of constitutively active Ras. Feeding chronically-inflamed, carcinogen-injected C57BL/6 mice a fish oil containing diet enriched in DHA recapitulated the effects on the EGFR signaling axis observed in cell culture and additionally suppressed tumor formation. We conclude that DHA-induced alteration in both the lateral and subcellular localization of EGFR culminates in the suppression of EGFR downstream signal transduction, which has implications for the molecular basis of colon cancer prevention by DHA