Tanja Maria Michel

The glymphatic system supports brain homeostasis by clearing interstitial solutes via perivascular pathways. Alterations in glymphatic function have been linked to neurodevelopmental and neurodegenerative disorders, but its role in autism spectrum disorder (ASD) remains unclear. We analyzed diffusion tensor imaging (DTI) magnetic resonance imaging data from five cohorts in the Autism Brain Imaging Data Exchange (ABIDE) project. Glymphatic function was estimated using the DTI analysis along the perivascular space (ALPS) index. ASD diagnoses were confirmed according to DSM-IV-TR or DSM-5 criteria, and neurotypical (NT) participants had no history of neurological, psychiatric, or developmental disorders. The final sample comprised 250 participants (128 ASD, mean age = 18.57 ± 13.81; 122 NT, mean age = 21.32 ± 14.37). Two-way analysis of variance (ANOVA) revealed a significant main effect of diagnosis, F(1, 246) = 10.44, p = 0.0014, with lower ALPS-indices in ASD. A diagnosis-by-age interaction was also observed, F(1, 246) = 4.71, p = 0.031. Post hoc tests demonstrated that autistic adults (≥ 18 years) had significantly lower ALPS-indices than NT adults ( p = 0.0004), whereas no group differences were demonstrated between younger ASD and NT (< 18 years). In ASD adults, the ALPS-index correlated negatively with depressive symptoms ( r = − 0.489, p = 0.013), but not with IQ or autistic traits. These findings suggest that glymphatic dysfunction in ASD may follow a developmental trajectory, with alterations becoming most evident in adulthood, potentially contributing to an increased risk of developing neurodegenerative disorder in autistic individuals.

Purpose: Dopaminergic signalling and glucose metabolism have been implicated in autism spectrum disorder (ASD), yet in vivo evidence in the human brain remains largely unexplored. This study examined subcortical dopamine D ₂ receptor availability and glucose metabolism in ASD to assess their clinical relevance. Methods: In this dual-tracer PET/MR case–control study, 30 autistic and 30 neurotypical adults (age-, sex-, body mass index-, and IQ-matched) underwent [ ¹¹ C]raclopride PET to assess dopamine D ₂ receptor availability, [ ¹ ⁸F]FDG PET to measure glucose metabolism and resting-state fMRI to evaluate functional connectivity. Results: Autistic individuals demonstrated increased D ₂ receptor availability in the thalamus, with additional increases in the nucleus accumbens and putamen among autistic males compared to neurotypical males. Glucose metabolism was elevated in the thalamus and globus pallidus in ASD relative to NT, and this pattern persisted within both autistic males and autistic females in sex‑stratified comparisons. Globus pallidus and thalamic glucose metabolism correlated positively with social and communication difficulties. Resting-state fMRI analyses revealed diagnosis- and sex-dependent correlations between thalamic D ₂ receptor availability and functional connectivity. Conclusions: This study provides in vivo evidence of elevated subcortical D ₂ R availability and glucose metabolism in autistic adults, a pattern observed across sexes. We also show that D ₂ R availability is tightly linked to glucose metabolism and that D ₂ R-functional connectivity coupling is altered in ASD, both relative to neurotypical adults and between autistic males and females. These findings highlight dopaminergic mechanisms as potential biomarkers and therapeutic targets in ASD.

The global prevalence of Autism Spectrum Condition (ASC) is increasing, yet effective supportive interventions remain largely unidentified, highlighting the urgent need to clarify the underlying neuropathophysiology. Neuroimaging offers a pathway toward this understanding; however, most studies rely on indirect measures of neurophysiology, whereas direct approaches such as [¹⁸F]Fluorodeoxyglucose positron emission tomography (FDG-PET) remain underutilized and lack systematic synthesis in the literature. This review and meta-analysis evaluated FDG-PET research in ASC. A systematic search identified 2,725 records, of which 21 studies compared FDG-PET findings between autistic and neurotypical individuals. Nine met the inclusion criteria for the review, and eight were included in the meta-analysis. The review revealed inconsistent findings, reporting both increased and decreased glucose metabolism in ASC, likely reflecting methodological heterogeneity. The meta-analysis found no statistically significant differences, but indicated a weak non-significant trend toward elevated glucose metabolism in the striatum in autistic compared to neurotypicals individuals (standardized mean difference [SMD] = 0.416; 95% CI − 0.200 to 1.032; p = 0.186). Despite 40 years of FDG-PET research in ASC, the number of studies remains limited, and several exhibit methodological shortcomings. Evidence from FDG-PET studies in other psychiatric and neurological disorders underscores the technique’s potential value in ASC research. The findings of this study further emphasize the urgent need for rigorously designed investigations to clarify the relationship between cerebral glucose metabolism and autism, with the ultimate goal of advancing our understanding of the autistic brain.

Background: Alcohol use disorder (AUD) is associated with cognitive impairments that are known to affect the outcomes of conventional treatment. Digital cognitive training programs have been examined as a possible way of addressing these overlooked challenges. Existing findings regarding the efficacy of such training programs are divergent, and further studies are warranted to examine more engaging cognitive training programs using the latest technology. Smartphone-based training built upon the principles of serious gaming would not only increase the accessibility of the program, but it could also increase the motivation of the patients, potentially maximizing adherence to the training program. Objective: The aim of the present feasibility and efficacy study was to examine the feasibility and acceptability of the Brain+ Alco-Recover app (Brain+ A/S) with gamified elements among patients with AUD when delivered as an add-on to treatment-as-usual (TAU) and with minimal guidance from health care practitioners. In addition, the effects on cognitive and alcohol-related outcomes were examined. Methods: A total of 72 outpatients were randomized into either group A, experimental + TAU (n=36), or group B, sham + TAU (n=36), and they had to complete a 1-month training program in addition to primary treatment. Self-reported experience at the 6-month follow-up as well as actual game usage was used to determine the feasibility of the training program. Cognitive performance and alcohol consumption were assessed as well. Results: The patients in both groups reported a high level of acceptability, and up to 83% of the patients in the experimental group met the minimum requirements for the usage of the app. The experimental group also demonstrated significant improvements in working memory (P<.001). Although no significant differences were found between the 2 groups regarding clinical outcomes, a greater reduction in alcohol consumption was evident at the 6-month follow-up in the experimental group. Conclusions: The acceptability and adherence to the minimum training requirements deems the gamified Brain+ app as a feasible tool for cognitive training when delivered as an add-on to TAU. Furthermore, the potential improvements in cognitive functions should be further replicated in a larger-scale trial to assess whether these could be used to improve the treatment of AUD in the future. International Registered Report Identifier (IRRID): RR2-10.3389/fpsyt.2021.727001

Despite growing awareness, diagnosing Autism Spectrum Condition (ASC) in adulthood remains challenging due to a limited range of diagnostic tools beyond psychological assessments. Although recent neuroimaging advancements have identified social brain regions (SBR) associated with sociability, research on these areas in ASC, particularly within the largely understudied adult ASC population, remains scarce. Explore functional and volumetric differences in the SBR between autistic and neurotypical individuals. We conducted a volumetric and functional assessment of SBRs using open-source MRI data from the Autism Brain Imaging Data Exchange (ABIDE). The sample included 44 adult ASC (37 male, mean age 25.86 ± 6.58) and 64 adult neurotypical individuals (51 male, mean age 25.36 ± 4.05). Autistic adult individuals demonstrated lower left nucleus accumbens volume. The amplitude of low frequency fluctuations was enhanced in the orbitofrontal cortex and temporoparietal junction, and decreased in the caudate, hippocampus, thalamus, and ventral tegmental area in the autistic group. Additionally, a widespread increase in functional connectivity within the SBR was demonstrated in the ASC group. Structural and functional measures allowed classification of autistic and neurotypical individuals with 76% accuracy using a support vector machine model. The results demonstrate significant SBR differences between adult autistic and neurotypical individuals, highlighting the SBR as potentially essential in ASC etiology, we demonstrate its ability to classify autistic and neurotypical individuals. However, further exploration of the SBR using advanced imaging techniques is required.

Purpose: The purpose of this study was to advance our understanding of the neurobiology of healthy aging, which is crucial for improving quality of life and preventing age-related diseases. Despite its importance, a comprehensive investigation of this process has yet to be fully characterized. Methods: We used a hybrid PET/MRI scanner to assess neurophysiological parameters in 80 healthy individuals aged 20–78. Cerebral amyloid-beta (Aβ) deposition and glucose metabolism were assessed using PET scans, while participants underwent simultaneous MRI scans. Results: We found a positive correlation between Aβ-deposition and aging, and a negative correlation between glucose metabolism and aging. The insula showed the strongest negative correlation between glucose metabolism and age (Spearman’s r = -0.683, 95% CI [-0.79, -0.54], p < 0.0001), while the posterior cingulate cortex had the strongest positive correlation between Aβ-deposition and age (Spearman’s r = 0.479, 95% CI [0.28, 0.64], p < 0.0001). These results suggest a spatially dependent link between Aβ-deposition and metabolism in healthy older adults, indicating a compensatory mechanism in early Alzheimer’s. Additionally, Aβ-deposition was linked to changes in interregional neural communication. Conclusions: Our study confirms previous findings on aging and offers new insights, particularly on the role of Aβ-deposition in healthy aging. We observed a linear increase in Aβ-deposition, alongside decreases in white matter integrity, cerebral blood flow, and glucose metabolism. Additionally, we identified a complex regional relationship between Aβ-deposition, glucose metabolism, and neural communication, possibly reflecting compensatory mechanisms.

Despite many years of research into the complex neurobiology of Parkinson’s disease, the precise aetiology cannot be pinpointed down to one causative agent but rather a multitude of mechanisms. Current treatment options can alleviate symptomsbut only slightly slow down the progression and not cure the disease and its underlying causes. Factors that play a role in causing the debilitating neurodegenerative psycho-motoric symptoms include genetic alterations, oxidative stress, neuroinflammation, general inflammation, neurotoxins, iron toxicity, environmental influences, and mitochondrial dysfunction. Recent findings suggest that the characteristic abnormal protein aggregation of alpha-synuclein and destruction of substantia nigra neurons might be due to mitochondrial dysfunction related to disturbances in lipid and glucose metabolism along with insulin resistance. The latter mechanism of action might be mediated by insulin receptor substrate docking to proteins that are involved in neuronal survival and signaling related to cell destruction. The increased risk of developing Type 2 Diabetes Mellitus endorses a connection between metabolic dysfunction and neurodegeneration. Here, we explore and highlight the potential role of glycolipid cellular insults in the pathophysiology of the disorder, opening up new promising avenues for the treatment of PD. Thus, antidiabetic drugs may be employed as neuromodulators to hinder the progression of the disorder.

BACKGROUND Alcohol use disorder (AUD) is associated with cognitive impairments that are known to affect the outcomes of conventional treatment. Digital cognitive training programs have been examined as a possible way of addressing these overlooked challenges. Existing findings regarding the efficacy of such training programs are divergent, and further studies are warranted to examine more engaging cognitive training programs using the latest technology. Smartphone-based training built upon the principles of serious gaming would not only increase the accessibility of the program, but it could also increase the motivation of the patients, potentially maximizing adherence to the training program. OBJECTIVE The aim of the present feasibility and efficacy study was to examine the feasibility and acceptability of the Brain+ Alco-Recover app (Brain+ A/S) with gamified elements among patients with AUD when delivered as an add-on to treatment-as-usual (TAU) and with minimal guidance from health care practitioners. In addition, the effects on cognitive and alcohol-related outcomes were examined. METHODS A total of 72 outpatients were randomized into either group A, experimental + TAU (n=36), or group B, sham + TAU (n=36), and they had to complete a 1-month training program in addition to primary treatment. Self-reported experience at the 6-month follow-up as well as actual game usage was used to determine the feasibility of the training program. Cognitive performance and alcohol consumption were assessed as well. RESULTS The patients in both groups reported a high level of acceptability, and up to 83% of the patients in the experimental group met the minimum requirements for the usage of the app. The experimental group also demonstrated significant improvements in working memory (P<.001). Although no significant differences were found between the 2 groups regarding clinical outcomes, a greater reduction in alcohol consumption was evident at the 6-month follow-up in the experimental group. CONCLUSIONS The acceptability and adherence to the minimum training requirements deems the gamified Brain+ app as a feasible tool for cognitive training when delivered as an add-on to TAU. Furthermore, the potential improvements in cognitive functions should be further replicated in a larger-scale trial to assess whether these could be used to improve the treatment of AUD in the future. CLINICALTRIAL INTERNATIONAL REGISTERED REPORT RR2-10.3389/fpsyt.2021.727001