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Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of taus phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus.

BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli and is related to cognition in cerebrovascular and neurodegenerative conditions. However, few studies have examined CVR in the medial temporal lobe, known to be affected early in Alzheimer disease and to influence memory function. We aimed to examine whether medial temporal CVR is associated with memory function in older adults with and without mild cognitive impairment (MCI). METHODS: In this observational study, independently living older adults free of dementia or stroke were recruited from the community and underwent brain MRI, neuropsychological assessment, and blood draw in an academic research setting. pCASL MRI quantified medial temporal lobe cerebral perfusion during CVR response to hypercapnia. Hypercapnia was induced by visually guided breathing exercises (15 seconds breath holds) during capnographic monitoring. MCI diagnosis and memory performance were assessed through comprehensive neuropsychological assessment. Aβ42/40 and pTau181 levels were quantified in blood plasma. Logistic and hierarchical linear regression examined medial temporal CVR in relation to MCI diagnosis and memory function. RESULTS: In a sample of 144 older adults (mean age = 69.6 years; SD = 7.4%; 34.7% male; mean education = 16.6 years, SD = 2.3), CVR to hypercapnia in the medial temporal lobe was attenuated in individuals with MCI after adjusting for age, sex, education, apolipoprotein ε4 carrier status, Aβ42/40 and pTau181 levels, and vascular risk factors (OR = 0.87, 95% CI [0.77-0.97], p = 0.013). Cerebrovascular reactivity to hypercapnia was associated with verbal memory performance for stories (B = 0.33, 95% CI [0.09-0.57], p = 0.009), a word list (B = 0.10, 95% CI [0.001-0.20], p = 0.048), and visual memory (B = 0.33, 95% CI [0.09-0.57], p = 0.008). DISCUSSION: Deficits in medial temporal CVR are observed in older adults with MCI and are related to worse memory function. Findings suggest that medial temporal cerebrovascular dysfunction is related to cognition and memory before the onset of dementia, independent of changes in Alzheimer pathophysiologic markers. Limitations of the study include the cross-sectional design. Future longitudinal studies are warranted to examine whether early cerebrovascular changes can predict progressive memory decline.

ObjectiveIdentifying persons with HIV (PWH) at increased risk for Alzheimer's disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.DesignWe examined 92 PWH from the CHARTER Program, ages 45-68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).ResultsAt baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.ConclusionsEpisodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Associating different aspects of experience with discrete events is critical for human memory. A potential mechanism for linking memory components is phase precession, during which neurons fire progressively earlier in time relative to theta oscillations. However, no direct link between phase precession and memory has been established. Here we recorded single-neuron activity and local field potentials in the human medial temporal lobe while participants (n = 22) encoded and retrieved memories of movie clips. Bouts of theta and phase precession occurred following cognitive boundaries during movie watching and following stimulus onsets during memory retrieval. Phase precession was dynamic, with different neurons exhibiting precession in different task periods. Phase precession strength provided information about memory encoding and retrieval success that was complementary with firing rates. These data provide direct neural evidence for a functional role of phase precession in human episodic memory.

Early stages of Alzheimer's disease (AD) are associated with volume reductions in specific subregions of the medial temporal lobe (MTL). Using a manual segmentation method-the Olsen-Amaral-Palombo (OAP) protocol-previous work in healthy older adults showed that reductions in grey matter volumes in MTL subregions were associated with lower scores on the Montreal Cognitive Assessment (MoCA), suggesting atrophy may occur prior to diagnosis of mild cognitive impairment, a condition that often progresses to AD. However, current "gold standard" manual segmentation methods are labour intensive and time consuming. Here, we examined the utility of Automatic Segmentation of Hippocampal Subfields (ASHS) to detect volumetric differences in MTL subregions of healthy older adults who varied in cognitive status as determined by the MoCA. We trained ASHS on the OAP protocol to create the ASHS-OAP atlas and then examined how well automated segmentation replicated manual segmentation. Volumetric measures obtained from the ASHS-OAP atlas were also contrasted against those from the ASHS-PMC atlas, a widely used atlas provided by the ASHS team. The pattern of volumetric results was similar between the ASHS-OAP atlas and manual segmentation for anterolateral entorhinal cortex and perirhinal cortex, suggesting that ASHS-OAP is a viable alternative to current manual segmentation methods for detecting group differences based on cognitive status. Although ASHS-OAP and ASHS-PMC produced varying volumes for most regions of interest, they both identified early signs of neurodegeneration in CA2/CA3/DG and identified marginal differences in entorhinal cortex. Our findings highlight the utility of automated segmentation methods but still underscore the need for a unified and harmonized MTL segmentation atlas.

Despite promising advancements, closed-loop neurostimulation for drug-resistant epilepsy (DRE) still relies on manual tuning and produces variable outcomes, while automated predictable algorithms remain an aspiration. As a fundamental step towards addressing this gap, here we study predictive dynamical models of human intracranial EEG (iEEG) response under parametrically rich neurostimulation. Using data from n = 13 DRE patients, we find that stimulation-triggered switched-linear models with ~300 ms of causal historical dependence best explain evoked iEEG dynamics. These models are highly consistent across different stimulation amplitudes and frequencies, allowing for learning a generalizable model from abundant STIM OFF and limited STIM ON data. Further, evoked iEEG in nearly all subjects exhibited a distance-dependent pattern, whereby stimulation directly impacts the actuation site and nearby regions (≲ 20 mm), affects medium-distance regions (20 ~ 100 mm) through network interactions, and hardly reaches more distal areas (≳ 100 mm). Peak network interaction occurs at 60 ~ 80 mm from the stimulation site. Due to their predictive accuracy and mechanistic interpretability, these models hold significant potential for model-based seizure forecasting and closed-loop neurostimulation design.

Hippocampal seizures mimicking mesial temporal lobe epilepsy cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive neural stem cells, React-NSCs) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division, and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here, using a mouse model of mesial temporal lobe epilepsy, we show that the epidermal growth factor receptor (EGFR) signaling pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signaling pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis.

Both navigation abilities and gait can be affected by the atrophy in the medial temporal cortex. This study aimed to determine whether navigation abilities could differentiate seniors with and without medial temporal lobe atrophy who complained about their cognitive status. The participants, classified to either the medial temporal atrophy group (n = 23) or the control group (n = 22) underwent neuropsychological assessment and performed a spatial navigation task while their gait parameters were recorded. The study showed no significant differences between the two groups in memory, fluency, and semantic knowledge or typical measures of navigating abilities. However, gait parameters, particularly the propulsion index during certain phases of the navigation task, distinguished between seniors with and without medial temporal lobe lesions. These findings suggest that the gait parameters in the navigation task may be a valuable tool for identifying seniors with cognitive complaints and subtle medial temporal atrophy. [ABSTRACT FROM AUTHOR]

IntroductionAlthough frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.MethodsRetrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.ResultsCommon symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.DiscussionThis study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.HighlightsThis project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

In everyday life, people need to respond appropriately to many types of emotional stimuli. Here, we investigate whether human occipital-temporal cortex (OTC) shows co-representation of the semantic category and affective content of visual stimuli. We also explore whether OTC transformation of semantic and affective features extracts information of value for guiding behavior. Participants viewed 1620 emotional natural images while functional magnetic resonance imaging data were acquired. Using voxel-wise modeling we show widespread tuning to semantic and affective image features across OTC. The top three principal components underlying OTC voxel-wise responses to image features encoded stimulus animacy, stimulus arousal and interactions of animacy with stimulus valence and arousal. At low to moderate dimensionality, OTC tuning patterns predicted behavioral responses linked to each image better than regressors directly based on image features. This is consistent with OTC representing stimulus semantic category and affective content in a manner suited to guiding behavior.

A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli1. Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code2-4. Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here we examined how familiar faces are encoded in the IT anterior medial face patch (AM), perirhinal face patch (PR) and temporal pole face patch (TP). In AM and PR we observed that the encoding axis for familiar faces is rotated relative to that for unfamiliar faces at long latency; in TP this memory-related rotation was much weaker. Contrary to previous claims, the relative response magnitude to familiar versus unfamiliar faces was not a stable indicator of familiarity in any patch5-11. The mechanism underlying the memory-related axis change is likely intrinsic to IT cortex, because inactivation of PR did not affect axis change dynamics in AM. Overall, our results suggest that memories of familiar faces are represented in AM and perirhinal cortex by a distinct long-latency code, explaining how the same cell population can encode both the percept and memory of faces.

• Decreased brain activities and functional connectivity associated with pED. • SVM classification model demonstrated notable capability in detecting pED. • These findings provided potential neuroimaging biomarkers for diagnosis of pED. Psychogenic erectile dysfunction (pED) is often accompanied by abnormal brain activities. This study aimed to develop an automatic classifier to distinguish pED from healthy controls (HCs) by identified brain-based characteristics. Resting-state functional magnetic resonance imaging data were acquired from 45 pED patients and 43 HCs. Regional homogeneity (ReHo) and functional connectivity (FC) values were calculated and compared between groups. Moreover, based on altered ReHo and FC values, support vector machine (SVM) classifier, incorporating recursive feature elimination (RFE), an SVM-RFE diagnostic model was established using leave-one-out cross-validation. Patients demonstrated reduced ReHo values in the left middle temporal gyrus (had decreased FC values with the left medial superior frontal gyrus and cuneus), orbital part of inferior frontal gyrus (had decreased FC values within the same region), triangular part of inferior frontal gyrus, anterior cingulate gyrus (had decreased FC values with the left inferior temporal gyrus, anterior cingulate gyrus, cuneus and right supplementary motor area) and middle frontal gyrus. The right calcarine fissure displayed increased ReHo values. The diagnostic model demonstrated excellent performance, achieving an accuracy rate of 90.80%. This study identified altered regional activity and FC in specific brain regions of pED patients, which might be related to the development of pED. The application of machine learning confirmed the distinctive characteristics of these functional changes in the brain. The high accuracy of our diagnostic model suggested a promising direction for developing objective diagnostic tools for psychological disorders. [ABSTRACT FROM AUTHOR]

• In individuals with ADHD during resting state, hypoperfusion was frequently observed in the right orbitofrontal gyrus, temporal cortex, basal ganglia and putamen. On the contrary, hyperperfusion was noted in frontal lobes, left postcentral gyrus, and occipital lobes. • During cognitive tasks, hyperperfusion was observed in frontal areas, temporal regions, cingulate cortex and the precuneus. • The administration of methylphenidate was associated with increased CBF in striatal and posterior periventricular regions, the right thalamus, and the precentral gyrus. • There seems a need of longitudinal studies to reinforce the knowledge on the topic. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent and disabling neurodevelopmental disorders. Recent research on cerebral blood flow (CBF) has enhanced understanding of the underlying pathophysiology in neuropsychiatric disorders. This systematic review aims to synthesize the existing literature on CBF anomalies among individuals with ADHD in comparison to controls. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, a systematic literature search was conducted using PubMed, PsycInfo, and Web of Science to identify relevant studies on CBF in ADHD. Twenty studies, encompassing a total of 1652 participants with ADHD and 580 controls, were included, employing measurements from SPECT (n = 9), ASL (n = 6), PET (n = 4), and BOLD-derived quantitative maps (n = 1). In individuals with ADHD during resting state, hypoperfusion was frequently observed in the right orbitofrontal gyrus, temporal cortex, basal ganglia and putamen. Conversely, hyperperfusion was noted in frontal lobes, left postcentral gyrus, and occipital lobes. During cognitive tasks, hyperperfusion was observed in frontal areas, temporal regions, cingulate cortex and the precuneus. Furthermore, the administration of methylphenidate was associated with increased CBF in striatal and posterior periventricular regions, the right thalamus, and the precentral gyrus. This review highlights diverse CBF anomalies in ADHD. The most consistently reported findings suggest hypoperfusion during resting state in prefrontal and temporal areas, along with the basal ganglia, while there is a hyperperfusion in frontal, parietal and occipital regions. Further research, including longitudinal studies, is essential to develop a comprehensive understanding of CBF implications in ADHD. [ABSTRACT FROM AUTHOR]

Differentiating between patients with bipolar disorder (BD) and major depressive disorder (MDD) is clinically challenging. This study aimed to explore the potential of radiomic textural features for discriminating BD and MDD. A total 253 subjects (114 patients with BD, 139 patients with MDD) with T1-weighted MRI data were recruited. Radiomics features and gray matter volume (GMV) features were extracted from each brain region. A novel high-level MSN_II feature method based on radiomic features was proposed. And a total of 21 MSN features (5 MSN_I and 16 MSN_II) based on different combinations of the 5 types of radiomic textural feature were calculated. Classification models were constructed using various combinations of MSNs or GMV, and their performance and stability was evaluated through 2000 repeated experiments. The model built with combined features (GMV and GMV + MSN_II_GLCM_GLSZM_NGTDM) showed the best classification performance (AUC = 0.896 ± 0.058, ACC = 0.831 ± 0.064) in the validation cohort. After MANOVA analysis and FDR correlation, the MSN_II_GLCM_GLSZM_NGTDM values in 4 regions (right rectus gyrus, right temporal pole: middle temporal gyrus, Vermis3 and Vermis10) showed significant difference between BD and MDD. The main limitation of this study is that the data is derived from a single center without an external independent test set. Incorporating the high-level MSN_II based on radiomics features can improve the classification performance compared to models solely relying on GMV features alone. This result implied the potential application of the proposed high level MSN method and radiomics textural features on the MDD and BD clinical studies. • A novel high-order MSN feature based on radiomic texture features was proposed. • The proposed feature can discriminate MDD patients from BD patients. • The proposed feature can enhance the performance of GMV-only classification models. • The proposed features identified four brain regions where MDD and BD differ. [ABSTRACT FROM AUTHOR]

[Display omitted] • Excitatory amino acid transporter 1 (EAAT1) labeling density increases in Alzheimer's disease tissue compared to control. • EAAT1 is visibly associated with astrocytic processes in Alzheimer's disease. • A significant correlation was observed between EAAT1 density and case age in Alzheimer's. • The EAAT1 staining density increase in Alzheimer's has implications for glutamate signalling, needing further exploration. Alzheimer's disease (AD) is a growing health problem worldwide, particularly in the developed world due to an ageing population. Glutamate excitotoxicity plays a major role in the pathophysiology of AD, and glutamate re-uptake is controlled by excitatory amino acid transporters (EAATs). The EAAT2 isoform is the predominant transporter involved in glutamate reuptake, therefore EAAT1 has not been the focus of AD research. We investigated the layer-specific expression of EAAT1 in human medial temporal lobe regions such as the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus, using fluorescent immunohistochemistry and laser scanning confocal microscopy in human post-mortem tissue. We observed low EAAT1 immunoreactivity in control cases, but upregulated labeling in AD across several brain regions of the medial temporal lobe. Significantly higher integrated density in AD cases was observed in the str. oriens and str. radiatum of the CA2 region, the str. pyramidale of CA3, and the str. moleculare and str. granulosum of the DG. Labeling of EAAT1 appeared astrocytic in nature, showing close association with astrocytic processes in AD cases. We also report that a higher EAAT1 density was positively correlated with the age of AD cases, but this relationship was not observed in control cases. Overall, our results indicate an upregulation of EAAT1 across several hippocampal subregions and layers in AD cases, indicating a potential physiological role for this transporter that needs further investigation. [ABSTRACT FROM AUTHOR]

The training of temporal action localization models relies heavily on a large amount of manually annotated data. Video annotation is more tedious and time-consuming compared with image annotation. Therefore, the semi-supervised method that combines labeled and unlabeled data for joint training has attracted increasing attention from academics and industry. This study proposes a method called pseudo-label refining (PLR) based on the teacher-student framework, which consists of three key components. First, we propose pseudo-label self-refinement which features in a temporal region interesting pooling to improve the boundary accuracy of TAL pseudo label. Second, we design a module named boundary synthesis to further refined temporal interval in pseudo label with multiple inference. Finally, an adaptive weight learning strategy is tailored for progressively learning pseudo labels with different qualities. The method proposed in this study uses ActionFormer and BMN as the detector and achieves significant improvement on the THUMOS14 and ActivityNet v1.3 datasets. The experimental results show that the proposed method significantly improve the localization accuracy compared to other advanced SSTAL methods at a label rate of 10% to 60%. Further ablation experiments show the effectiveness of each module, proving that the PLR method can improve the accuracy of pseudo-labels obtained by teacher model reasoning. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionsThe prodromal phase preceding the onset of First Episode Psychosis (FEP) is associated with an increased risk of Suicidal Behaviors (SBs). The aim of this study was to identify specific structural brain abnormalities linked to SBs that occur prior to the onset of FEP.Voxel-based morphometry analyses were used to investigate differences in brain Grey Matter (GM) volume using the CAT12 toolbox within SPM12. Covariates, including gender, age, handedness, intracranial volume, depression severity, and global cognitive functioning, were controlled for as confounding factors.Significant reductions in GM were observed in the left superior temporal gyrus, dorsal posterior cingulate cortex, precuneus, cuneus, anterior cerebellum (p-FWE corrected < 0.05, k > 50) as well as in the right amygdala (0.96 ± 0.06 vs. 1.01 ± 0.05; F = 4.78; p < 0.05) and left amygdala (0.97 ± 0.06 vs. 1.02 ± 0.05; F = 8.97; p = 0.01).History of SB prior to the onset of the psychotic disorder was related to wider and more widespread brain GM alterations. The regions identified are involved in cognitive and emotional processes such as emotional regulation, social cognition, perseverative thinking, and pain tolerance. These findings suggest that structural brain abnormalities related to SB occurring before FEP onset may serve as early biomarkers for identifying individuals at increased risk of suicide. [ABSTRACT FROM AUTHOR]

Dissociative experiences commonly occur alongside adverse childhood experiences (ACE), yet research on their neurofunctional biomarkers has overlooked their unique association with dimensions of childhood abuse and neglect. We investigated interactions between dissociative experiences and childhood abuse, anticipating anti-correlations between the right-lateralized anterior middle frontal gyrus (raMFG) and the medial temporal lobe, as well as the temporal gyri. Examining resting-state functional connectivity in 91 participants with a history of ACE, we employed seed-to-voxel analyses seeding the raMFG. Multiple linear regression and post-hoc moderation/mediation models explored interactions and individual effects of dissociation and dimensions of ACE. The Dissociative Experiences Scale (DES) and Childhood Trauma Questionnaire (CTQ) quantified dissociation and dimensions of ACE. A DES by CTQ-A (childhood abuse) interaction predicted an anti-correlation between the raMFG and right hippocampus, moderated by CTQ-A. The CTQ revealed negative connectivity between the raMFG and right anterior cingulate cortex. CTQ-N (childhood neglect) indicated that both the right supplementary motor area and right insula related positively to the raMFG. Our findings underscore a distinct neural signature of childhood abuse-related dissociative experiences, potentially linked to dissociated memories. [ABSTRACT FROM AUTHOR]

Both sleep alterations and epileptiform activity are associated with the accumulation of amyloid-β and tau pathology and are currently investigated for potential therapeutic interventions in Alzheimer's disease. However, a bidirectional intertwining relationship between sleep and neuronal hyperexcitability might modulate the effects of Alzheimer's disease pathology on the corresponding associations. To investigate this, we performed multiple day simultaneous foramen ovale (FO) plus scalp EEG and polysomnography recordings and acquired 18F-MK6240 tau PET-MR in three patients in the prodromal stage of Alzheimer's disease and in two patients with mild and moderate dementia due to Alzheimer's disease, respectively. As an eligibility criterion for the present study, subjects either had a history of a recent seizure (n = 2) or subclinical epileptiform activity (SEA) on a previous scalp EEG taken in a research context (n = 3). The 18F-MK6240 standard uptake value ratio (SUVR) and asymmetry index (AI) were calculated in a priori -defined volumes of interest. Linear mixed-effects models were used to study associations between interictal epileptiform discharges (IEDs), polysomnography parameters and 18F-MK6240 SUVR. Epileptiform activity was bilateral but asymmetrically present on FO electrodes in all patients and ≥95% of IEDs were not visible on scalp EEG. In one patient, two focal seizures were detected on FO electrodes, both without visual scalp EEG correlate. We observed lateralized periodic discharges, brief potentially ictal rhythmic discharges and lateralized rhythmic delta activity on FO electrodes in four patients. Unlike scalp EEG, intracranial electrodes showed a lateralization of epileptiform activity. Although the amount of IEDs on intracranial electrodes was not associated to the 18F-MK6240 SUVR binding in different volumes of interest, there was a congruent asymmetry of the 18F-MK6240 binding towards the most epileptic hemisphere for the mesial (P = 0.007) and lateral temporal cortex (P = 0.006). IEDs on intracranial electrodes were most abundant during slow wave sleep (SWS) (92/h) and non-REM sleep 2 (N2, 81/h), followed by non-REM sleep 1 (N1, 33/h) and least frequent during wakefulness (17/h) and REM sleep (9/h). The extent of IEDs during sleep was not reflected in the relative time in each sleep stage spent [REM% (P = 0.415), N1% (P = 0.668), N2% (P = 0.442), SWS% (P = 0.988)], and not associated with the arousal index (P = 0.317), apnoea-hypopnoea index (P = 0.846) or oxygen desaturation index (P = 0.746). Together, our observations suggest a multi-directional interaction between sleep, epileptiform activity and tau pathology in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Patients with obstructive sleep apnea (OSA) experience chronic intermittent hypoxia and sleep fragmentation, leading to brain ischemia and neurological dysfunction. Therefore, it is important to identify features that can differentiate patients with OSA from healthy controls (HC) and provide insights into the underlying brain alterations associated with OSA. This study aimed to distinguish patients with OSA from healthy individuals and predict clinical symptom alterations using cerebellum-whole-brain static and dynamic functional connectivity (sFC and dFC, respectively), with the cerebellum as the seed region. Sixty male patients with OSA and 60 male HC matched for age, education level, and sex were included. Using 27 cerebellar seeds, sliding-window analysis was performed to calculate sFC and dFC between the cerebellum and the whole brain. The sFC and dFC values were then combined and used in multiple machine-learning models to distinguish patients with OSA from HC and predict the clinical symptoms of patients with OSA. Patients with OSA showed increased dFC between cerebellar subregions and the superior and middle temporal gyri and decreased dFC with the middle frontal gyrus. Conversely, increased sFC was observed between cerebellar subregions and the cerebellar lobule VI, cingulate gyrus, middle frontal gyrus, inferior parietal lobules, insula, and superior temporal gyrus. Combined dynamic-static FC features demonstrated superior classification performance with a support vector machine in discriminating OSA from HC. In clinical symptom prediction, FC alterations contributed up to 30.11 % to cognitive impairment, 55.96 % to excessive sleepiness, and 27.94 % to anxiety and depression. Combining cerebrocerebellar sFC and dFC analyses enables high-precision classification and prediction of OSA. Aberrant FC patterns reflect compensatory brain reorganization and disrupted cognitive network integration, highlighting potential neuroimaging markers for OSA. • Combined dFC-sFC features have superior classification performance using a support vector machine. • Combining cerebrocerebellar sFC and dFC analyses enables high-precision classification and prediction of OSA. • Aberrant FC patterns reflect compensatory brain reorganization and disrupted cognitive network integration. [ABSTRACT FROM AUTHOR]

The question of whether cognitive control is specific to certain domains or domain-general remains an extensively debated question at both cognitive and neural levels. This study examined the neural substrates associated with resistance to interference (RI) in phonological, semantic, and visual domains by using strictly matched tasks and determining the domain-general or domain-specific manner in which aging affects the neural substrates associated with RI. In an fMRI experiment, young and older participants performed a similarity judgment task with phonological, semantic, or visual interference buildup. For both age groups, domain-specific RI effects were observed at the univariate level, with increased involvement in the phonological domain of the right angular gyrus and the right lingual gyrus, in the semantic domain of the bilateral inferior frontal gyrus, the bilateral superior parietal and angular gyri and the left middle temporal gyrus, and in the visual domain of the middle/superior frontal gyri and occipital gyri. At the multivariate level, although RI effects could be decoded from neural patterns in the bilateral inferior frontal gyrus for all domains and age groups, between-domain prediction of RI conditions was associated with Bayesian evidence for the null hypothesis. This study supports the domain specificity of neural substrates associated with RI while stressing its age independency. [ABSTRACT FROM AUTHOR]

The insula has a significant impact on interoception and depression. This study aims to explore the role of the insula in mediating treatment responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC). Twenty-five patients with either bipolar disorder (BD, n = 15) or major depressive disorder (MDD, n = 10) were recruited. All subjects were aged between 20 and 70, with a minimum score of 18 on the 24-item Hamilton Rating Scale for Depression (HDRS-24). Each patient received 12 sessions of rTMS treatment using a figure-eight-shaped coil at 10 Hz high-frequency stimulation intensity, targeted to the left DLPFC. Resting-state functional magnetic resonance imaging was conducted before and after the rTMS treatment to assess changes in insula-seeded functional connectivity. Both BD and MDD patients experienced significant reductions in depressive symptoms following rTMS therapy. The respective response rates at weeks 4, 8 and 12 were 64.0 %, 64.0 % and 68.0 % and remission rates were 40.0 %, 36.0 % and 44.0 %. Decreases in functional connectivity between the right anterior insula and right calcarine were significantly larger in the remitters than in the non-remitters (p = 0.013). Additionally, a higher baseline functional connectivity between the right anterior insula and right superior temporal gyrus correlated with better treatment outcome. The small sample size of 25 participants is small. Our findings highlight the potential role of the insula in depression and suggest that insula-seeded functional connectivity could serve as a predictive biomarker for rTMS efficacy. • rTMS reduces depressive symptoms in BD and MDD patients for at least 12 weeks. • Decreases in insula and calcarine connectivity correlate with symptom improvement after rTMS. • Higher baseline connectivity of insula and superior temporal gyrus predicts better rTMS outcome. • Insula connectivity can serve as a predictive biomarker to optimize rTMS treatment. [ABSTRACT FROM AUTHOR]

Background: Tourette syndrome (TS) is a prevalent neurodevelopmental disorder with an uncertain etiology. Numerous neuroimaging studies have investigated patients with TS, but their conclusions remain inconsistent. The current study attempted to provide an unbiased statistical meta-analysis of published neuroimaging studies of TS. Methods: A comprehensive literature search was conducted to identify voxel-based whole-brain morphology (VBM) and functional magnetic resonance imaging (fMRI) studies related to TS. Two separate meta-analyses of neurofunctional activation and gray matter volume (GMV) were performed using a seed-point-based d-mapping software package, followed by joint and subgroup analyses. Results: 11 VBM studies and 18 fMRI studies were included in this study. We found that grey matter volumes were significantly decreased in the right anterior cingulate/paracingulate gyri and the left postcentral gyrus; while the cerebellum, bilateral cortico-spinal projections, and striatum showed increased GMV in patients with TS. In fMRI studies, patients with TS showed overactivation in the right superior frontal gyrus and right superior temporal gyrus, and significant hypoactivation in left SMA. In the multimodal studies, TS patients showed that there was an overlap between decreased GMV and hypoactivation in the right median cingulate/paracingulate gyri. Conclusion: Abnormal alterations in the structure and function of the brain regions may play a role in the pathogenesis of TS in patients, and may be used as an imaging indicator for patients with TS to be diagnosed. [ABSTRACT FROM AUTHOR]

Background: Repeat neurological assessment is standard in cases of severe acute brain injury. However, conventional measures rely on overt behavior. Unfortunately, behavioral responses may be difficult or impossible for some patients. As a result, patients who recover consciousness before the ability to express so may go undetected. Recent studies have demonstrated the efficacy of incorporating functional neuroimaging into clinical assessment protocols. The objective of the current study is to assess the feasibility of a multi-task, multimodal bedside technique to evaluate sensory and cognitive function in behaviorally non-responsive patients. Methods: We deployed a novel assessment paradigm to evaluate sensory and cognitive processing in one 63-year-old unresponsive patient with acute motor sensory axonal neuropathy (AMSAN). We collected parallel bedside EEG-fNIRS activity during hierarchical auditory processing, movie listening, and motor imagery. Results: We found appropriate hemodynamic activation in the patient's middle and superior temporal gyri to simple sounds and activation in their superior temporal gyrus, left angular and precentral gyri during speech. During movie listening, the patient produced patterns of EEG and fNIRS activity that were statistically indistinguishable from healthy controls. The patient also showed appropriate fNIRS and source-localized EEG activation of motor areas during motor imagery. Upon recovering, the patient correctly recalled multiple aspects of our assessment procedures. Conclusion: In sum, our assessment protocol effectively captures neural markers of sensory and cognitive function in behaviorally non-responsive patients. Crucially, while AMSAN is distinct from brain injury, the patient's assumed dissociation between behavior and awareness provided an ideal test case to validate our protocol. [ABSTRACT FROM AUTHOR]

Context Changes in verbal memory have been reliably reported across the menopause transition. To understand the role of endogenous estrogens in verbal memory performance, this study assessed the associations of endogenous estradiol and estrone with brain network connectivity during a verbal memory fMRI task. Objective Determine associations of endogenous estrogens with memory systems in the postmenopausal brain and evaluate clinical significance. Methods In the MsBrain cohort (n = 199, mean age 59.3 ± 3.9 years, 83.9% White), we examined the cross-sectional association of serum estradiol (E2) and estrone (E1), measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS), during a functional magnetic resonance imaging (fMRI) task of word encoding and recognition. To characterize the clinical significance of those associations, we examined the magnitude of activation in relation to a neuropsychological measures of memory and affect. Results Endogenous E2 was positively associated with activation in temporal and frontal cortices during encoding and negatively associated with one prefrontal region during recognition (P <.05). Activation in the left inferior frontal gyrus was associated with memory performance (β [SE] = 0.004 [0.002]; P <.05), and anxiety (β [SE] = −0.100 [0.050]; P <.05). The left middle frontal gyrus was associated with memory performance (β [SE] = 0.006 [0.002]; P <.01), depression, and anxiety. The left superior temporal gyrus (STG) was associated with depression (β [SE] = −0.083 [0.036]; P <.05) and anxiety (β [SE] = −0.134 [0.058]; P <.05). E1 was positively associated with activation in a range of brain areas including bilateral STG and right superior frontal gyrus during encoding (P <.05). Activation of the left insula and precentral gyrus were associated with symptoms of depression and anxiety. None related to memory. Conclusion The function of brain areas critical to memory performance varies with estrogen levels in the postmenopause, even though those levels are low. Higher levels of E2 may facilitate memory performance through enhanced function of temporal and frontal cortices during encoding of verbal material. [ABSTRACT FROM AUTHOR]

• Subacute subcortical aphasia patients exhibited rCrus II hypoactivity. • FC was reduced between rCrus II and multiple language-related cortical areas. • Stronger rCrus II–LIFG rsFC predicted superior recovery of language function. • The right cerebellum may be an effective target for aphasia treatment. Loss of language function (aphasia) is a common complication after stroke, and post-stroke recovery remains highly unpredictable due to the absence of reliable neurobiomarkers. Growing evidence points to involvement of the cerebellum in language processing; however, it is unclear if abnormal cerebellar activity and altered functional connectivity (FC) to language-related regions of cerebral cortex are underlying neural mechanisms for subcortical aphasia. In this longitudinal observational study, we used resting-state functional magnetic resonance imaging to examine potential abnormalities in spontaneous cerebellar activity and resting-state (rs)FC with language networks among post-stroke patients with subacute subcortical aphasia (n = 19) compared to healthy controls (HCs, n = 18). In addition, correlations between rsFC variables and language performance metrics were examined at post-stroke baseline and at follow-up. Compared to HCs, patients with subacute subcortical aphasia exhibited significantly reduced fractional amplitude of low frequency fluctuations, a measure of spontaneous activity, in the right cerebellar Crus II (rCrus II) region and reduced rsFC between rCrus II and left inferior frontal gyrus (LIFG), left angular gyrus (LAG), and left middle temporal gyrus (LMTG). Both rCrus II–LAG and rCrus II–LMTG rsFC values were positively correlated with Aphasia Battery of Chinese scores at baseline. Baseline rCrus II–LIFG rsFC was also positively correlated with spontaneous speech and naming scores at follow-up. A stronger baseline rCrus II–LIFG rsFC predicted superior recovery of language function post-stroke. We conclude that the right cerebellum may be an effective therapeutic target for subcortical aphasia. [ABSTRACT FROM AUTHOR]

Background and purpose: Asymptomatic carotid stenosis (ACS) is an independent risk factor for ischemic stroke and vascular cognitive impairment, affecting cognitive function across multiple domains. This study aimed to explore differences in static and dynamic intrinsic functional connectivity and temporal dynamics between patients with ACS and those without carotid stenosis. Methods: We recruited 30 patients with unilateral moderate-to-severe (stenosis ≥ 50%) ACS and 30 demographically-matched healthy controls. All participants underwent neuropsychological testing and 3.0T brain MRI scans. Resting-state functional MRI (rs-fMRI) was used to calculate both static and dynamic functional connectivity. Dynamic independent component analysis (dICA) was employed to extract independent circuits/networks and to detect time-frequency modulation at the circuit level. Further imaging-behavior associations identified static and dynamic functional connectivity patterns that reflect cognitive decline. Results: ACS patients showed altered functional connectivity in multiple brain regions and networks compared to controls. Increased connectivity was observed in the inferior parietal lobule, frontal lobe, and temporal lobe. dICA further revealed changes in the temporal frequency of connectivity in the salience network. Significant differences in the temporal variability of connectivity were found in the fronto-parietal network, dorsal attention network, sensory-motor network, language network, and visual network. The temporal parameters of these brain networks were also related to overall cognition and memory. Conclusions: These results suggest that ACS involves not only changes in the static large-scale brain network connectivity but also dynamic temporal variations, which parallel overall cognition and memory recall. [ABSTRACT FROM AUTHOR]

Interpersonal interaction is essential to romantic couples. Understanding how gender impacts an individual's brain activities during intimate interaction is crucial. The present study examined gender differences in oxyhemoglobin (oxy-Hb) changes during real-time drawing interactions between members of romantic couples using non-invasive functional near-infrared spectroscopy (fNIRS). We analyzed the oxy-Hb concentrations of romantic couples engaged in interactive (i.e., chase and escape) and non-interactive (i.e., individual) drawing sessions. Our findings indicated that males (vs. females) exhibited more pronounced oxy-Hb concentrations in Broca's area, motor area, sensorimotor cortex, and temporal lobe areas than women in an interactive drawing task, suggesting a heightened goal-oriented engagement in social interaction. Significant positive correlations were found between oxy-Hb volumes of the temporal area and the Quality of Relationship Index (QRI), underscoring the impact of interpersonal dynamics on brain function during interactive tasks. This study deepens the understanding of gender differences in neural mechanisms in social interaction tasks and provides important insights for intimacy research. [ABSTRACT FROM AUTHOR]

We appraise other people's emotions by combining multiple sources of information, including somatic facial/body reactions and the surrounding context. Wealthy literature revealed how people take into account contextual information in the interpretation of facial expressions, but the mechanisms mediating such influence still need to be duly investigated. Across two experiments, we mapped the neural representations of distinct (but comparably unpleasant) negative states, pain, and disgust, as conveyed by naturalistic facial expressions or contextual sentences. Negative expressions led to shared activity in the fusiform gyrus and superior temporal sulcus. Instead, pain contexts recruited the supramarginal, postcentral, and insular cortex, whereas disgust contexts triggered the temporoparietal cortex and hippocampus/amygdala. When pairing the two sources of information together, we found a higher likelihood of classifying an expression according to the sentence preceding it. Furthermore, networks specifically involved in processing contexts were re-enacted whenever a face followed said context. Finally, the perigenual medial prefrontal cortex (mPFC) showed increased activity for consistent (vs inconsistent) face-context pairings, suggesting that it integrates state-specific information from the two sources. Overall, our study reveals the heterogeneous nature of face-context information integration, which operates both according to a state-general and state-specific principle, with the latter mediated by the perigenual medial prefrontal cortex. [ABSTRACT FROM AUTHOR]

Objective: To investigate the altered characteristics of cortical morphology and individual-based morphological brain networks in type 2 diabetes mellitus (T2DM), as well as the neural network mechanisms underlying cognitive impairment in T2DM. Methods: A total of 150 T2DM patients and 130 healthy controls (HCs) were recruited in this study. The study used voxel- and surface-based morphometric analyses to investigate morphological alterations (including gray matter volume, cortical thickness, cortical surface area, and localized gyrus index) in the brains of T2DM patients. Then two methods, Jensen-Shannon divergence-based similarities (JSDs) and Kullback–Leibler divergence-based similarities (KLDs), were used to construct individual morphometric brain networks based on gray matter volume, to discover altered features of the topological network and extract abnormal key brain regions. Subsequently, partial correlation analyses were performed to explore the relationship between clinical biochemical indices, neuropsychological test scores, and altered cortical morphology and network indices. Results: Brain regions with reduced gray matter volume and cortical thickness in T2DM patients were mainly concentrated in the frontal lobe, temporal lobe, parietal lobe, anterior cingulate gyrus, insula, lingual gyrus, and cerebellar hemispheres. The global attributes of the Individual-based morphological brain network were significantly reduced (Cp, Eloc, σ), with an increase in the nodal efficiency of the hippocampus and the nodal local efficiency of the anterior cingulate gyrus, and the nodal local efficiency of the parahippocampal gyrus and transverse temporal gyrus were reduced. There was a correlation between these node attributes and cognitive scale scores. Conclusion: This study demonstrated that patients with T2DM exhibit generalized cortical atrophy and damage to individual morphologic brain networks. It also identified overlapping and cognitively relevant key brain regions, primarily within the limbic/paralimbic network (especially the hippocampus and cingulate gyrus), which may serve as imaging markers for identifying cognitive deficits in T2DM. These findings offer new insights into the neural network mechanisms underlying T2DM-associated brain damage and cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: This study aims to observe the effect of enrichment rehabilitation (ER) on cognitive function in post-stroke patients and to clarify its underlying mechanism. Methods: Forty patients with post-stroke cognitive impairment (PSCI) meeting the inclusion criteria were randomly assigned to two groups: conventional medical rehabilitation (CM group) and ER intervention (ER group). All patients underwent assessments of overall cognitive function, attention function, and executive function within 24 h before the start of training and within 24 h after the 8 weeks of training. We investigated the altered resting-state functional connectivity (RSFC) with the right dorsolateral prefrontal cortex (DLPFC) in patients with PSCI following ER training through functional magnetic resonance imaging (fMRI). Additionally, twenty people undergoing routine physical examinations in the outpatient department of our hospital were selected as the healthy control (HC) group. Results: Before training, both groups of PSCI patients exhibited significant impairment in overall cognitive function, attention function, and executive function compared to the HC group. However, there was no significant difference between the two PSCI patient groups. Following 8 weeks of treatment, both PSCI patient groups demonstrated substantial improvement in overall cognitive function, attention function, and executive function. Moreover, the ER group exhibited greater improvement after training compared to the CM group. Despite the improvements, the cognitive behavioral performance assessment scores of both PSCI patient groups remained lower than those of the HC group. RSFC analysis in the ER group revealed strengthened positive functional connectivity between the right DLPFC and the left superior frontal gyrus (SFG) and left anterior cingulate gyrus (ACG), along with decreased functional connectivity between the right DLPFC and the right superior temporal gyrus (STG) and right precentral gyrus post-ER intervention. Conclusion: ER intervention is more effective than conventional medical rehabilitation in improving the cognitive function of PSCI patients, potentially by augmenting the FC between the right DLPFC and dominant cognitive brain regions, such as the left SFG and left ACG while attenuating the FC between the right DLPFC and non-dominant hemisphere areas including the STG and precentral gyrus within the right hemisphere. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between urban living and borderline personality disorder (BPD) through neuroplasticity, highlighting the impact of the physical environment on the development and treatment of BPD. It emphasizes the adverse effects of urban environments on brain regions associated with BPD, such as the amygdala, hippocampus, and cortex, leading to maladaptive neuroplasticity outcomes. The article calls for collaborative efforts between therapists, public health policymakers, urban planners, architects, and interior designers to prevent triggering BPD and improve treatment outcomes through environmental interventions. The importance of addressing the physical environment in BPD care pathways is underscored, with recommendations for incorporating environmental factors into treatment strategies. [Extracted from the article]

It is estimated that the incidence of first episode psychotic disorder is about 33 people out of 100,000 each year. Beyond primary psychotic illness (e.g., schizophrenia, schizophreniform disorder), some of these patients will develop psychotic disorder due to a complex interplay of genetics, anatomical variations, traumatic brain injury (TBI), environment, substance use, and/or other causes. A small subset of patients will develop psychotic disorder due to a structural anatomic lesion, such as a CNS tumor. Here we present a 35-year-old male with worsening auditory hallucinations after surgical resection and radiation of a right temporal lobe astrocytoma in the setting of co-morbid methamphetamine usage. This case report helps illustrate how a neuroimaging work-up is important for the first incidence of psychotic disorder and how a tumor can produce a psychotic disorder that persists after oncologic treatment. This paper adds to the literature on the presentation and treatment of post-resection tumor-induced psychotic disorder. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant impairments in social interaction, often manifested in facial recognition deficits. These deficits hinder individuals with ASD from recognizing facial identities and interpreting emotions, further complicating social communication. This review explores the neural mechanisms underlying these deficits, focusing on both functional anomalies and anatomical differences in key brain regions such as the fusiform gyrus (FG), amygdala, superior temporal sulcus (STS), and prefrontal cortex (PFC). It has been found that the reduced activation in the FG and atypical activation of the amygdala and STS contribute to difficulties in processing facial cues, while increased reliance on the PFC for facial recognition tasks imposes a cognitive load. Additionally, disrupted functional and structural connectivity between these regions further exacerbates facial recognition challenges. Future research should emphasize longitudinal, multimodal neuroimaging approaches to better understand developmental trajectories and design personalized interventions, leveraging AI and machine learning to optimize therapeutic outcomes for individuals with ASD. [ABSTRACT FROM AUTHOR]

Background: Pediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAFV600E alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAFV600E altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAFV600E altered pLGG. Methods: A single institution retrospective chart review analysis was performed on patients, 0 to 21 years of age, with newly diagnosed and/or progressive BRAFV600E mutated pLGGs (WHO Grade 1 or 2) at Children's Healthcare of Atlanta treated off-study with BRAF inhibitor monotherapy between 2013-2023. 2-year progression free survival (PFS) and objective tumor response was evaluated. All toxicities possibly associated with BRAF inhibition therapy were evaluated and described according to Common Terminology Criteria for Adverse Events version 5 (CTCAEv5). MRI brain imaging data at baseline and best response was evaluated to identify patterns that may predict response to BRAF inhibition monotherapy. Results: Fifteen patients diagnosed with BRAFV600E mutated pLGG, treated with monotherapy BRAF inhibition, were identified. Median age of diagnosis: 3.8 years (0.2 –18.1). Histologic diagnosis: pilocytic astrocytoma (PA) (N=4); ganglioglioma (GGL) (N=3); GGL, atypical (N=3); pleomorphic xanthroastrocytoma (PXA) (N=2); low-grade neuroepithelial tumor (N=1); infiltrating glioma (N=1); and LGG (NOS) (N=1). Tumor locations included: hypothalamus/optic chiasm (N=6); brainstem (N=4); third ventricle/thalamus (N=2); parietal/temporal lobe (N=2); and spinal cord (N=1). Mean duration of BRAF inhibitor monotherapy: 38.41 months (range 3.9-83.7). Median follow-up: 32.6 months (16 - 78.1). Two-year PFS for patients on BRAFi monotherapy for at least 10 months: 90% (95% CI: 73.2%-100%). Objective Response (OR) for 15 evaluable patients on BRAF inhibitor (BRAFi) therapy: 73% (0/15 CR + 6/15 PR + 5/15 MR) with Overall Response Rate (ORR=CR+PR): 40%. Overall, patients tolerated treatment well with Grade 1 rash being the most common toxicity. Two of 15 patients (13%) discontinued therapy due to toxicities, and 2 other patients switched within drug class from vemurafenib to dabrafenib due to toxicities. Discussion: In this small cohort of incompletely resected BRAFV600E mutated pLGGs, BRAFi monotherapy was effective and well tolerated with an ORR comparable to published prospective outcomes of dual MEK/BRAF inhibitor therapy. This promising monotherapy treatment should be considered when choosing treatment for incompletely resected BRAFV600E-altered pLGGs. [ABSTRACT FROM AUTHOR]

Purpose: Tinnitus is considered a neurological disorder affecting both auditory and nonauditory networks. This study aimed to investigate the structural brain covariance network in tinnitus patients and analyze its altered topological properties. Materials: Fifty three primary tinnitus patients and 67 age- and sex-matched healthy controls (HCs) were included. Gray matter volume (GMV) of each participant was extracted using voxel-based morphometry, a group-level structural covariance network (SCN) was constructed based on the GMV of each participant, and graph theoretic analyses were performed using graph analysis toolbox (GAT). The differences in the topological properties of SCN between both groups were compared and analyzed. Results: Both groups exhibited small-world attributes. Compared with HCs, tinnitus patients had significantly higher characteristic path length, lambda, transitivity, and assortativity (p < 0.05), and significantly lower global efficiency (p < 0.05). Tinnitus patients had higher clustering coefficient and reduced gamma and modularity, but neither was remarkable. The hubs in tinnitus network focused on the temporal lobe. In addition, the tinnitus network was found to be reduced in robustness to targeted attacks compared with HCs. Besides, a significant negative correlation between Tinnitus Handicap Inventory (THI) score and GMV in the left angular gyrus (r = −0.283, p = 0.040) as well as left superior temporal pole (r = −0.282, p = 0.041) were identified. Conclusion: Tinnitus patients showed reduced small-world properties, altered hub nodes, and reduced ability to respond to targeted attacks in brain network. The GMV in the left angular gyrus and left superior temporal pole showed significant negative correlation with tinnitus distress (THI score), indicating potential therapeutic target. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner. Here, we hypothesized that neuronal hyperactivity and hypersynchronicity, resulting in functional connectivity increases, constitute a crucial mechanism by which Aβ facilitates the spreading of tau pathology. By combining Aβ positron emission tomography (PET), resting-state functional magnetic resonance imaging, and longitudinal tau-PET in 69 cognitively normal amyloid-negative controls and 140 amyloid-positive patients covering the AD spectrum, we confirmed that Aβ induces hyperconnectivity of temporal lobe tau epicenters to posterior brain regions that are vulnerable to tau accumulation in AD. This was replicated in an independent sample of 55 controls and 345 individuals with preclinical AD and low cortical tau-PET uptake, suggesting that the emergence of Aβ-related hyperconnectivity precedes neocortical tau spreading. Last, using longitudinal tau-PET and mediation analysis, we confirmed that these Aβ-related connectivity increases in tau epicenters to typical tau-vulnerable brain regions in AD mediated the effect of Aβ on faster tau accumulation, unveiling increased connectivity as a potential causal link between the two AD hallmark pathologies. Together, these findings suggest that Aβ promotes tau spreading by eliciting neuronal hyperconnectivity and that targeting Aβ-related neuronal hyperconnectivity may attenuate tau spreading in AD. Editor's summary: The "amyloid cascade model" of Alzheimer's disease suggests that plaques of amyloid-β (Aβ) precede and trigger other pathological changes such as the spread of abnormal tau protein. How amyloid pathology influences tau pathology remains incompletely understood. Here, Roemer-Cassiano et al. analyzed Aβ positron emission tomography (PET), functional magnetic resonance imaging, and tau-PET data from the Alzheimer's Disease Neuroimaging Initiative and show that the spread of tau is in part mediated by Aβ-related increases in connectivity between tau epicenters and brain regions that are vulnerable to tau accumulation. These results highlight an intricate connection between amyloid and tau pathology. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]

Minimally invasive parafascicular surgery (MIPS) with the use of tubular retractors achieve a safe resection in deep seated tumours. Diffusion changes noted on postoperative imaging; the significance and clinical correlation of this remains poorly understood. Single centre retrospective cohort study of neuro-oncology patients undergoing MIPS. The impact of surgical approach—transsulcal (TS) versus transgyral (TG) – and respective entry points in clinical and imaging outcomes was assessed. 82 patients (35 male; 47 female, average age 43.94 ± 22.85 years) were included. 84% presented with neurological deficit and glioblastoma was the commonest diagnosis (38.24%). Surgical approach was not relevant for the number of patients that showed postoperative peritubular injury (TS: 20 (37.74%) versus TG: 8 (27.59%), p = 0.354) or its volume (TS: 0.95 ± 1.82 cc versus TG: 0.43 ± 1.32 cc, p = 0.1435). When adjusted for preoperative volume and depth of tumour, TS approach was associated with less diffusion restriction (p = 0.030). Temporal lobe access points had the highest volume of diffusion restriction (temporal lobe—2.50 ± 3.54 cc versus frontal lobe – 1.15 ± 1.53 versus parietal lobe—0.51 ± 0.91 cc, p = 0.0096), particularly in the TS approach (p = 0.0152). Superior motor outcomes were demonstrated in the TS versus the TG approach (postoperative improvement: TS: 14.63% versus TG: 6.9%, p = 0.015), especially for parietal approaches (p = 0.039). TS approach was related with a significantly decreased length of stay (TS—11.67 ± 14.19 days versus TG – 23.97 ± 18.01 days, p = 0.001). Transsulcal approach demonstrated a better motor outcome profile, particularly in parietal lobe, and shorter length of stay. The superior temporal sulcus was more susceptible to ischaemic changes. Therefore, transgyral route can be considered in temporal lobe MIPS. [ABSTRACT FROM AUTHOR]

Introduction: Recent research revealed that Tau plays critical roles in various neuronal functions. We previously demonstrated that destabilization and nuclear delocalization of Tau alter the expression of glutamatergic genes, mediating early neuronal damage. Methods: In this study, we discovered that changes in Tau availability are linked to global alterations in gene expression that affect multiple neuronal pathways. Comparison with the human temporal region showed that the Tau-dependent modulation of gene expression closely resembles the intermediate stages of Alzheimer's disease (AD) that precede the definitive pathological condition. Results: Furthermore, we identified the chromatin remodeling pathway as being significantly affected by Tau in both our cellular model and AD brains, with reductions in heterochromatin markers. Our findings indicate that Tau is able to globally affect the neuronal transcriptome and that its subcellular unbalance changes gene expression in the intermediate stages of AD development. In addition, we found that the chromatin architecture is affected by Tau during the progression of AD. Discussion: These results provide new insights into the molecular mechanisms underlying early stages of AD development and highlight the central role of Tau and the contribution of nuclear Tau in this process. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is considered as a network disorder of interacting brain regions. The propagation of local epileptic activity from the seizure onset zone (SOZ) along neuronal networks determines the semiology of seizures. However, in highly interconnected brain regions such as the insula, the association between the SOZ and semiology is blurred necessitating invasive stereoelectroencephalography (SEEG). Normative connectomes on MRI data enable to link different symptoms and lesion locations to a common functional network. The present study applied connectomics to disentangle epilepsy networks from insular SEEG recordings and to describe their relationship to seizure semiology. Methods: We retrospectively extracted functional networks by normative connectome analysis from 118 insular contacts depicting epileptic discharges during SEEG in 20 epilepsy patients. The resulting epilepsy networks were correlated to the corresponding semiology by voxel-wise regression and multivariate analyses of variances. Results: Epileptic foci were found in the posterior insula for somatosensory, other sensory and motor seizures, while cognitive and autonomic symptoms were related to the anterior insula. We identified insular connections to the superior temporal gyrus and heschl gyrus in sensory seizures and projections to the somatosensory cortex in somatosensory seizures. Insula-basal ganglia pathways were found in cognitive seizure manifestations, while insular connectivity to fronto-basal regions were strongest in patients with autonomic seizures. Conclusion: The semiology of seizures is mirrored in the functional connectivity of insular epileptic discharges. Combining SEEG and connectomics could provide additional information about seizure propagation within the epilepsy network and might enable new treatment options in the future like deep brain stimulation. [ABSTRACT FROM AUTHOR]

In light of the growing interest in the bidirectional relationship between epilepsy and dementia, this review aims to provide an overview of the role of hyperphosphorylated tau (pTau) in cognition in human epilepsy. A literature search identified five relevant studies. All of them examined pTau burden in surgical biopsy specimens from patients with temporal lobe epilepsy. The prevalence of pTau reported across the five studies, encompassing a total of 142 patients, ranged from 3.5% to 95%. Findings also varied regarding the location of pTau in the hippocampus and/or temporal cortex. Two of five studies (40%) demonstrated an inverse relationship between pTau burden and cognitive performance, one study with regard to executive functions and the other with regard to naming and verbal short-term memory. The only longitudinal study found a significant link between pTau and cognitive decline in verbal learning and memory, and in part also in naming, from the pre- to the postoperative assessment and from three to 12 months postoperatively. Given the heterogeneity of the study cohorts and the neuropsychological and neuropathological methodologies and findings, no clear picture emerges regarding the association between pTau and cognition in temporal lobe epilepsy. Added to this is the multifactorial etiology of cognitive impairment in epilepsy, including the active epilepsy, the underlying and sometimes dynamic pathology, and anti-seizure medication. Some of these factors may affect pTau expression. Further research should aim to investigate pTau longitudinally and noninvasively on a whole-brain level, using targeted neuropsychological outcome measures and controlling for age and other factors potentially influencing cognitive trajectories in epilepsy. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have reported extensive resting-state functional connectivity (rsFC) abnormalities in the default mode network (DMN) in patients with obsessive-compulsive disorder (OCD), but findings are inconsistent. DMN can be divided into three subsystems: core, dorsal medial prefrontal cortex (dMPFC), and medial temporal lobe (MTL). This study aimed to explore abnormalities in rsFC strength within and between DMN subsystems in OCD patients, and their relationship with clinical symptoms. This study recruited 39 OCD patients and 45 healthy controls (HCs). OCD symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). The seed-to-seed method was used to construct rsFC matrix. The rsFC strength within and between the three DMN subsystems were calculated. Compared to the HC group, the OCD group exhibited reduced rsFC strength within core subsystem (F = 7.799, p = 0.007, Bonferroni corrected p = 0.042). Further, this reduction was also observed in the unmedicated OCD group (n = 19), but not in the medicated OCD group (n = 18). In addition, rsFC strength within core subsystem was negatively correlated with the obsession subscale of YBOCS in the OCD group (r = −0.512, p = 0.004, Bonferroni corrected p = 0.008). Further, this correlation was also significant in the unmedicated OCD group, but not in the medicated OCD group. Our findings suggest that reduced rsFC strength within core subsystem is a feature of OCD patients and may serve as a potential biomarker of obsession severity. Moreover, pharmacological treatments may affect rsFC strength in DMN. • OCD patients showed reduced rsFC strength within core subsystem. • rsFC strength within core subsystem was strongly negatively correlated with the obsession severity. • rsFC strength within core subsystem was reduced in the unmedicated OCD group, but not in the medicated OCD group. [ABSTRACT FROM AUTHOR]

Prospective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship remains uncertain. To clarify this, we utilized Mendelian randomization (MR) to assess the causal effects of common gastrointestinal disorders on cortical structures. Genome-wide association study (GWAS) data was gathered for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) from European populations numbering 329,262, 16,792, and 602,604, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR–Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy. FD significantly decreases the TH in the rostral anterior cingulate cortex (β TH = −0.022 mm; 95%CI: −0.035 mm to −0.009 mm2; P TH = 6.89 × 10−4), and IBS significantly decreases the SA of the pars triangularis (β SA = −21.91 mm2; 95%CI: −32.99 mm to −10.83 mm2; P SA = 1.06 × 10−4), precuneus (β SA = −47.53 mm2; 95%CI: −73.57 mm to-21.48 mm2; P SA = 3.48 × 10−4) and superior frontal regions (β SA = −78.70 mm2; 95%CI: −122.61 mm to −34.78 mm2; P SA = 4.4 × 10−4). At the local functional level, GERD significantly increases the SA of the inferior temporal region (β SA = −113.58 mm2, 95%CI: −113.58 mm to −39.01 mm2, P SA = 6.05 × 10−5). FD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, potentially increasing the risks of mental illness and cognitive impairment. • Functional dyspepsia, irritable bowel syndrome and gastroesophageal reflux disease affects cortical structure of the brain. • FD can significantly decrease the thickness of the rostral anterior cingulate. lBS can significantly decrease the surface area of pars triangularis, precuneus, and superior frontal. GERD can significantly increases the surface area of inferior temporal. [ABSTRACT FROM AUTHOR]

Background: To investigate the alterations in spontaneous brain activity and the similarities and differences between monocular deprivation amblyopia and binocular deprivation amblyopia. Methods: Twenty children with binocular deprivation amblyopia, 26 children with monocular deprivation amblyopia and 20 healthy controls underwent resting-state functional magnetic resonance imaging. The evaluation of altered spontaneous brain activity was conducted using fractional amplitude of low-frequency fluctuations (fALFF). One-way analysis of variance was employed to analyze fALFF values among the three groups. Additionally, the relationship between fALFF values and best corrected visual acuity (BCVA) was analyzed via correlation analysis. Results: Compared to healthy controls, children with binocular deprivation amblyopia presented increased fALFF values in the left medial superior frontal gyrus, left middle frontal gyrus, left anterior cingulate cortex, left postcentral gyrus and bilateral precentral gyrus, and decreased fALFF values in the right fusiform gyrus. Compared to healthy controls, children with monocular deprivation amblyopia presented increased fALFF values in the right lingual gyrus, right superior frontal gyrus, right middle frontal gyrus, left superior temporal gyrus, triangular part of the left inferior frontal gyrus and bilateral middle temporal gyrus, and decreased fALFF values in the right precuneus. Compared with monocular deprivation amblyopia, fALFF values of binocular deprivation amblyopia were decreased in the triangular part of the left inferior frontal gyrus, right lingual gyrus and right cuneus, and increased in the left precentral gyrus and left postcentral gyrus. No significant correlations were found between the fALFF values of identified regions and the BCVA of amblyopic eyes for either type of amblyopia. Conclusions: Children with deprivation amblyopia presented alterations in spontaneous activity in multiple brain regions, and these alterations differed between monocular amblyopia and binocular amblyopia. These abnormal spontaneous activities may reflect dysfunctions and compensation related to amblyopia. [ABSTRACT FROM AUTHOR]

Meningoencephaloceles (MEC) of the skull base commonly result from head trauma, or congenital malformation, or may arise spontaneously due to increased intracranial pressure, leading to a bony defect and subsequent herniation of brain parenchyma. Spontaneous MEC at orbital and temporal locations are rare, with only a few cases reported in the literature. Brain MRI is typically used for diagnosis, and treatment may be medical or surgical, depending on the size of the bony defect. We present an unusual case of a 69-year-old woman with spontaneous orbital and temporal MEC, resulting in proptosis, strabismus, and seizures secondary to idiopathic intracranial hypertension (IIH). This condition was managed medically, with a favourable outcome. This report aims to describe and analyse the case, reviewing the literature on spontaneous MEC in adult patients at different locations caused by IIH and their management, emphasizing the critical role of imaging in diagnosing this etiology. [ABSTRACT FROM AUTHOR]

Human visual cortex contains regions selectively involved in perceiving and recognizing ecologically important visual stimuli such as people and places. Located in the ventral temporal lobe, these regions are organized consistently relative to cortical folding, a phenomenon thought to be inherited from how centrally or peripherally these stimuli are viewed with the retina.While this eccentricity theory of visual cortex has been one of the best descriptions of its functional organization, whether or not it accurately describes visual processing in all category-selective regions is not yet clear. Through a combination of behavioral and functional MRI measurements in 27 participants (17 females), we demonstrate that a limb-selective region neighboring well-studied face-selective regions shows tuning for the visual periphery in a cortical region originally thought to be centrally biased. We demonstrate that the spatial computations performed by the limb-selective region are consistent with visual experience and in doing so, make the novel observation that there may in fact be two eccentricity gradients, forming an eccentricity reversal across high-level visual cortex. These data expand the current theory of cortical organization to provide a unifying principle that explains the broad functional features of many visual regions, showing that viewing experience interacts with innate wiring principles to drive the location of cortical specialization. [ABSTRACT FROM AUTHOR]