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Purpose: The monoacylglycerol lipase (MAGL) plays a pivotal role in modulating the endocannabinoid system and is considered an attractive therapeutic target for diseases in both the central nervous system and periphery. The current study aimed to develop and evaluate a suitable carbon-11 labeled tracer for imaging MAGL in preclinical studies. Methods: (R)-YH168 was synthesized via a multi-step pathway and its half-maximal inhibitory concentration (IC50) values were measured using an enzymatic assay. Radiosynthesis of (R)-[11C]YH168 was accomplished by 11C-methylation via Suzuki cross-coupling of a pinacol boron precursor. In vitro autoradiography was performed using brain tissues from MAGL knockout and the corresponding wild-type mice. The metabolic stability of (R)-[11C]YH168 in mouse brain and plasma was assessed 5 min after injection. Dynamic PET scans were conducted on anesthetized mice and rhesus monkey. For studies in non-human primates, arterial blood samples were analyzed to obtain the input function for kinetic modeling. Blocking studies with the irreversible MAGL inhibitor PF-06795071 were performed to assess the binding specificity of (R)-[11C]YH168. Results: (R)-[11C]YH168 was synthesized via Suzuki coupling of the phenyl boronic ester with [11C]CH3I in the presence of palladium catalyst. In vitro autoradiography revealed a heterogeneous distribution pattern of (R)-[11C]YH168 with higher binding to MAGL-rich brain regions in wild-type mouse brain slices compared to that of MAGL knockout mice. Dynamic PET imaging in wild-type and MAGL knockout mice confirmed its high specificity and selectivity in mouse brains. In the rhesus monkey, (R)-[11C]YH168 displayed good brain permeability. High levels of radioactivity uptake were seen in the cingulate cortex, frontal cortex, cerebellum, occipital cortex, and hippocampus, consistent with MAGL expression. The one-tissue compartment model was appropriate for fitting the regional time-activity curves and provided reliable volume of distribution values across all brain regions. Pretreatment with PF-06795071 (0.1 mg/kg) resulted in almost complete blockade (> 95%) of radioactivity uptake, demonstrating binding specificity of (R)-[11C]YH168 to MAGL in the non-human primate brain. The regional non-displaceable binding potential follows the rank order of cingulate cortex ~ frontal cortex ~ insula > putamen > temporal cortex > caudate ~ occipital cortex ~ thalamus > nucleus accumbens ~ hippocampus ~ cerebellum ~ globus pallidus > substantia nigra > amygdala. Conclusion: (R)-[11C]YH168 is a promising PET probe for imaging and quantifying MAGL in the brains of mice and non-human primates. This 11C-labeled tracer holds great potential for translation into human subjects and offers the possibility of performing multiple PET scans on the same subject within a single day. [ABSTRACT FROM AUTHOR]

The three clap test (TCT) is a simple bedside test that can elicit the so-called applause sign (AS), manifesting with more than three claps after the examiner's instruction to clap three times. Although the AS was originally described as a useful sign differentiating patients with progressive supranuclear palsy (PSP) from patients with Parkinson's disease (PD) and frontotemporal dementia (FTD), it is also known to be present in PD, Alzheimer's disease and several other diseases. It reflects the so-called stopping impulsivity and cognitive and frontal lobe dysfunction. In addition to the AS, the TCT can also elicit the non-applause sign, linked with the apathy subtype of behavioural variant of FTD and the jumping the gun sign, a sign of waiting impulsivity, also seen in PSP. This review summarizes the up-to-date clinical aspects and pathophysiology of all these signs and discuss the benefit of using the TCT in the routine clinical praxis. [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]

Background: Brain intraparenchymal schwannoma is a rare clinical entity, generally curable with adequate resection. Methods and results: We describe a case in a male patient first presenting at 19 months of age, the youngest reported age for this lesion. It also appears to be the first case connected to a germline TSC2 p.1510del mutation in a patient with autism-like symptoms. Although tuberous sclerosis is generally not associated with increased risk of schwannoma, mTORC1 activity, which is inhibited by intact TSC1/TSC2 complex, is involved in schwannoma progression. This patient's tumor also harbored a CHD7::VGLL3 fusion consistent with its genomic DNA methylation classification of CNS Schwannoma, VGLL-fused. The Hippo pathway, mTORC1, and VGLL3 all negatively regulate the YAP1/TEAD cotranscriptional complex. We hypothesize that this schwannoma may have arisen because of increased VGLL3 functional activity from the CHD7::VGLL3 fusion and, perhaps, increased mTORC1 activity due to TSC2 mutation, and their combined effects on the balance between YAP1/TEAD- and VGLL3/TEAD-mediated transcriptional programs. Conclusions: We present a frontal lobe intra-axial parenchymal schwannoma containing a CHD7::VGLL3 gene fusion presenting in a 19 month-old male, the youngest patient yet reported for this lesion. [ABSTRACT FROM AUTHOR]

In 2022, para-fluorofentanyl (pFF) rose to the 6th most reported drug and the most reported fentanyl analog in the United States according to the Drug Enforcement Administration (DEA). pFF differs from fentanyl by the addition of a single fluorine group. To date, pFF has not been extensively evaluated in vivo and is frequently seen in combination with fentanyl. In the present study, the pharmacodynamic (PD) and pharmacokinetic (PK) properties and brain region-specific concentrations of pFF were evaluated in male Sprague–Dawley rats and compared to fentanyl. A 300 μg/kg subcutaneous dose of fentanyl or pFF was administered to assess PD and PK parameters as well as brain region concentrations. PD parameters were evaluated via a tail flick test to evaluate analgesia and core body temperature to measure hypothermia, a surrogate marker of overall opioid toxicity. Fentanyl and pFF were found to be equally active at the tested dose in terms of tail flick response with both compounds producing an analgesic response that lasted up to 240 min post-drug treatment. pFF induced a significantly greater hypothermic effect compared to fentanyl with a maximum temperature decrease of −5.6 ℃. Plasma PK parameters (T1/2, AUC, etc.) did not differ between fentanyl and pFF. However, pFF concentrations in the medulla, hippocampus, frontal cortex and striatum were more than two times the fentanyl concentrations. The increase in brain concentrations and greater hypothermic effect suggests that pFF is potentially more dangerous than fentanyl. [ABSTRACT FROM AUTHOR]

Objectives: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. Methods: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. Results: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. Conclusion: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. Clinical relevance statement: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. Key Points: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems. [ABSTRACT FROM AUTHOR]

Memory for words that are drawn or sketched by the participant, rather than written, during encoding is typically superior. While this drawing benefit has been reliably demonstrated in recent years, there has yet to be an investigation of its neural basis. Here, we asked participants to either create drawings, repeatedly write, or list physical characteristics depicting each target word during encoding. Participants then completed a recognition memory test for target words while undergoing functional magnetic resonance imaging (fMRI). Behavioural results showed memory was significantly higher for words drawn than written, replicating the typical drawing effect. Memory for words whose physical characteristics were listed at encoding was also higher than for those written repeatedly, but lower than for those drawn. Voxel-wise analyses of fMRI data revealed two distributed sets of brain regions more active for items drawn relative to written, the left angular gyrus (BA 39) and bilateral frontal (BA 10) regions, suggesting integration and self-referential processing during retrieval of drawn words. Brain-behaviour correlation analyses showed that the size of one's memory benefit for words drawn relative to written at encoding was positively correlated with activation in brain regions linked to visual representation and imagery (BA 17 and cuneus) and motor planning (premotor and supplementary motor areas; BA 6). This study suggests that drawing benefits memory by coactivating multiple sensory traces. Target words drawn during encoding are subsequently remembered by re-engaging visual, motoric, and semantic representations. [ABSTRACT FROM AUTHOR]

A central tenet of cognitive neuroscience is that humans build an internal model of the external world and use mental simulation of the model to perform physical inferences. Decades of human experiments have shown that behaviors in many physical reasoning tasks are consistent with predictions from the mental simulation theory. However, evidence for the defining feature of mental simulation – that neural population dynamics reflect simulations of physical states in the environment – is limited. We test the mental simulation hypothesis by combining a naturalistic ball-interception task, large-scale electrophysiology in non-human primates, and recurrent neural network modeling. We find that neurons in the monkeys' dorsomedial frontal cortex (DMFC) represent task-relevant information about the ball position in a multiplexed fashion. At a population level, the activity pattern in DMFC comprises a low-dimensional neural embedding that tracks the ball both when it is visible and invisible, serving as a neural substrate for mental simulation. A systematic comparison of different classes of task-optimized RNN models with the DMFC data provides further evidence supporting the mental simulation hypothesis. Our findings provide evidence that neural dynamics in the frontal cortex are consistent with internal simulation of external states in the environment. Mental simulation is key to flexible inference and other cognitive functions. Here the authors show that the frontal cortex recursively updates the internal state of objects over short time intervals, supporting the simulation hypothesis. [ABSTRACT FROM AUTHOR]

Integrating spatial and temporal information is essential for our sensory experience. While psychophysical evidence suggests spatial dependencies in duration perception, few studies have directly tested the neural link between temporal and spatial processing. Using ultra-high-field functional MRI and neuronal-based modeling, we investigated how and where the processing and the representation of a visual stimulus duration is linked to that of its spatial location. Our results show a transition in duration coding: from monotonic and spatially-dependent in early visual cortex to unimodal and spatially-invariant in frontal cortex. Along the dorsal visual stream, particularly in the intraparietal sulcus (IPS), neuronal populations show common selective responses to both spatial and temporal information. In the IPS, spatial and temporal topographic organizations are also linked, although duration maps are smaller, less clustered, and more variable across participants. These findings help identify the mechanisms underlying human perception of visual duration and characterize the functional link between time and space processing, highlighting the importance of their interactions in shaping brain responses. Common organizational principles of spatial and temporal information processing are not fully understood. This study shows that the duration coding of brief visual events transforms along the human cortical hierarchy, and that duration and spatial processing interact through common neural responses and linked topographic representations. [ABSTRACT FROM AUTHOR]

It is well established that monitoring one's memory performance involves engaging in metacognitive monitoring and activating the frontal cortex. Judgments of Learning (JOLs) are individuals' assessments of the likelihood of remembering a specific item on a future test, usually occurring after learning and before testing. An ongoing debate exists regarding whether participants' metacognitive monitoring is based on a single process or two distinct processes when making JOLs. In this study, we investigated the electrophysiological correlates of JOLs induced by an episodic memory task in 38 adult participants. Participants completed a word pairs memory task and rated their memory performance after remembered whole items. We observed that participants with high judgments of learning had faster reaction times compared to those with low judgments of learning. The electrophysiological results revealed that low judgments of learning were associated with a more negative frontal-central N400-600 amplitude, while high judgments of learning were associated with a larger frontal-parietal slow wave amplitude. Furthermore, low judgments of learning exhibited greater theta band event-related synchronization (θ-ERS) and beta band event-related desynchronization (β-ERD) during the metacognitive monitoring phase compared to high judgments of learning. Brain-behavior correlations also indicated a relationship between the 600–1000 component and behavioral performance, highlighting differential effects between high and low JOLs when making metacognitive monitoring ratings. These findings extend previous research and suggest that the formation of JOL ratings involves two distinct stages: the first stage involves obtaining retrieval fluency cues (frontal-central N400-600 amplitude), while the second stage involves utilizing these cues for metacognitive monitoring (frontal-parietal slow wave amplitude). Varying item familiarity and degrees of retrieval familiarity contribute to differences in JOL ratings. In summary, this study provides compelling evidence for a two-stage process in metacognitive monitoring ratings from both neurophysiological and brain-behavior correlation perspectives. [ABSTRACT FROM AUTHOR]

A prominent tripartite model proposes that parent role modeling of emotion regulation, emotion socialization behaviors, and the emotional climate of the family are important for young people's emotional development. However, limited research has examined the neural mechanisms at play. Here, we examined the associations between family and parenting factors, the neural correlates of emotional reactivity and regulation, and internalizing symptoms in early adolescent girls. Sixty-four female adolescents aged 10–12 years with elevated internalizing symptoms completed emotional reactivity, implicit (affect labeling) and explicit (cognitive reappraisal) emotion regulation tasks during functional magnetic resonance imaging. Positive family emotional climate was associated with greater activation in the anterior cingulate and middle temporal cortices during emotional reactivity. Maternal emotion regulation difficulties were associated with increased frontal pole and supramarginal gyrus activation during affect labeling, whereas supportive maternal emotion socialization and positive family emotional climate were associated with activation in prefrontal regions, including inferior frontal and superior frontal gyri, respectively, during cognitive reappraisal. No mediating effects of brain function were observed in the associations between family/parenting factors and adolescent symptoms. These findings highlight the role of family and parenting behaviors in adolescent emotion regulation neurobiology, and contribute to prominent models of adolescent emotional development. [ABSTRACT FROM AUTHOR]

Intracranial lesions in children often have good prognoses, allowing long-term survival. Cognitive functions, crucial for life quality, need more attention. Previous research has focused on adults, with pediatric studies limited by varied lesions and complex treatments. This study aims to evaluate cognitive and brain network changes in children with frontal lobe lesions, which significantly impact cognitive function, using a before-and-after comparison. The study enrolled 20 children with frontal lesions who underwent fMRI and cognitive tests before and after surgery, with only surgical treatment initially. Brain network changes were evaluated using functional metrics, and cognitive shifts were measured through test scores. Correlations were analyzed to explore brain mechanisms behind cognitive changes. Additionally, 20 healthy children underwent the same assessments for baseline data. Preliminary evidence of cognitive recovery, notably in social cognition, was observed about three months post-surgery, potentially linked to increased functional connectivity between the right lingual gyrus and right middle temporal gyrus. Children with frontal lobe lesions have demonstrated short-term postoperative cognitive improvement and associated reorganization and repair of brain networks, though this capacity for repair may diminish over time. This underscores the importance of timely rehabilitation interventions. This study offers unique insights into cognitive neuroscience and potential rehabilitation targets. [ABSTRACT FROM AUTHOR]

There are pronounced differences in the degree to which individuals experience music-induced pleasure which are linked to variations in structural connectivity between auditory and reward areas. However, previous studies exploring the link between white matter structure and music reward sensitivity (MRS) have relied on standard diffusion tensor imaging methods, which present challenges in terms of anatomical accuracy and interpretability. Further, the link between MRS and connectivity in regions outside of auditory-reward networks, as well as the role of musical training, have yet to be investigated. Therefore, we investigated the relation between MRS and structural connectivity in a large number of directly segmented and anatomically verified white matter tracts in musicians (n = 24) and non-musicians (n = 23) using state-of-the-art tract reconstruction and fixel-based analysis. Using a manual tract-of-interest approach, we additionally tested MRS-white matter associations in auditory-reward networks seen in previous studies. Within the musician group, there was a significant positive relation between MRS and fiber density and cross section in the right middle longitudinal fascicle connecting auditory and inferior parietal cortices. There were also positive relations between MRS and fiber-bundle cross-section in tracts connecting the left thalamus to the ventral precentral gyrus and connecting the right thalamus to the right supplementary motor area, however, these did not survive FDR correction. These results suggest that, within musicians, dorsal auditory and motor networks are crucial to MRS, possibly via their roles in top-down predictive processing and auditory-motor transformations. [ABSTRACT FROM AUTHOR]

Spinal manipulative therapy (SMT) has been shown to significantly alleviate pain in patients with lumbar disc herniation (LDH), with its effects closely associated with brain function modulation. This study investigates the neural biomarkers linked to pain relief efficacy following a complete SMT treatment cycle in LDH patients. A total of 59 LDH patients were randomized into two groups: SMT treatment (Group 1, n = 28) and sham treatment (ST) (Group 2, n = 31). A matched healthy control group (Group 3, n = 28) was also included. Functional magnetic resonance imaging (fMRI) was performed on LDH patients at two time points (TPs)—before (TP1) and after (TP2) treatment—while healthy controls were scanned once. Clinical assessments were conducted using the Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association (JOA) scale. Post-treatment results indicated significant improvements in both VAS and JOA scores for Group 1, while the improvement was limited to VAS scores for Group 2. Graph properties analysis revealed notable differences in brain network connectivity between LDH patients and healthy controls, particularly between the left precentral gyrus (left PreCG) and left inferior frontal gyrus, opercular part (left IFGoperc). Enhanced functional connectivity (FC) was observed in Group 1, notably between the right angular gyrus (right ANG) and the left middle orbital gyrus (left ORBmid), with right ANG showing a significant positive correlation with clinical scores. This study identifies the sensorimotor network—salience network are significantly activated in chronic pain among LDH patients. The default mode network—dorsal attention network may serve as key neural biomarkers for the efficacy of SMT treatment in alleviating pain in LDH. [ABSTRACT FROM AUTHOR]

SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain. Therefore, the aim of this study was to examine the distribution of SMOC1 in human AD brain tissue and to determine if SMOC1 influenced amyloid beta (Aβ) aggregation. The distribution of SMOC1 in human brain tissue was assessed in 3 brain regions (temporal cortex, hippocampus, and frontal cortex) using immunohistochemistry in a cohort of 73 cases encompassing advanced AD, mild cognitive impairment (MCI), preclinical AD, and cognitively normal controls. The Aβ- and phosphorylated tau-interaction with SMOC1 was assessed in control, MCI, and advanced AD human brain tissue using co-immunoprecipitation, and the influence of SMOC1 on Aβ aggregation kinetics was assessed using Thioflavin-T assays and electron microscopy. SMOC1 strongly colocalized with a subpopulation of amyloid plaques in AD (43.8 ± 2.4%), MCI (32.8 ± 5.4%), and preclinical AD (28.3 ± 6.4%). SMOC1 levels in the brain strongly correlated with plaque load, irrespective of disease stage. SMOC1 also colocalized with a subpopulation of phosphorylated tau aggregates in AD (9.6 ± 2.6%). Co-immunoprecipitation studies showed that SMOC1 strongly interacted with Aβ in human MCI and AD brain tissue and with phosphorylated tau in human AD brain tissue. Thioflavin-T aggregation assays showed that SMOC1 significantly delayed Aβ aggregation in a dose-dependent manner, and electron microscopy confirmed that the Aβ fibrils generated in the presence of SMOC1 had an altered morphology. Overall, our results emphasize the importance of SMOC1 in the onset and progression of AD and suggest that SMOC1 may influence pathology development in AD. [ABSTRACT FROM AUTHOR]

Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to in vivo tau PET signals is still unclear. Therefore, we performed a translational study using a broad spectrum of advanced methodologies to investigate the sources of [18F]PI-2620 tau PET signals in individuals with 4R-tauopathies, including a pilot PET autopsy study in patients. First, we conducted a longitudinal [18F]PI-2620 PET/MRI study in a 4-repeat-tau mouse model (PS19) and detected elevated [18F]PI-2620 PET signals in the presence of high levels of neuronal tau. An innovative approach involving cell sorting after radiotracer injection in vivo revealed higher tracer uptake in single neurons than in the astrocytes of PS19 mice. Regional [18F]PI-2620 tau PET signals during the lifetime correlated with the abundance of fibrillary tau and with autoradiography signal intensity in PSP patients and disease controls who underwent autopsy 2–63 months after tau PET. In autoradiography, tau-positive neurons and oligodendrocytes with a high AT8 density, but not tau-positive astrocytes, were the drivers of [18F]PI-2620 autoradiography signals in individuals with PSP. The high tau abundance in oligodendrocytes at the boundary of gray and white matter facilitated the identification of an optimized frontal lobe target region to detect the tau burden in patients with PSP. In summary, neuronal and oligodendroglial tau constitutes the dominant source of tau PET radiotracer binding in 4-repeat-tauopathies, translating to an in vivo signal. [ABSTRACT FROM AUTHOR]

This study delves into the claustrum's role in modulating spontaneous and sensory-evoked network activity across cortical regions. Using mesoscale calcium imaging and Gi and Gq DREADDs in anesthetized mice, we show that decreasing claustral activity enhances prefrontal cortical activity, while activation reduces prefrontal cortical activity. This claustrum modulation also caused changes to the brain's large-scale functional networks, emphasizing the claustrum's ability to influence long-range functional connectivity in the cortex. Claustrum inhibition increased the local coupling between frontal cortex areas, but reduced the correlation between anterior medial regions and lateral/posterior regions, while also enhancing sensory-evoked responses in the visual cortex. These findings indicate the claustrum can participate in orchestrating neural communication across cortical regions through modulation of prefrontal cortical activity. These insights deepen our understanding of the claustrum's impact on prefrontal connectivity, large-scale network dynamics, and sensory processing, positioning the claustrum as a key node modulating large-scale cortical dynamics. Chemogenetic modulation of claustro-cortical neurons alters cortical activity and functional connectivity as measured by mesoscale calcium fluorescence imaging in mice. [ABSTRACT FROM AUTHOR]

Neuroeconomics theories propose that the value associated with diverse rewards or reward-predicting stimuli is encoded along a common reference scale, irrespective of their sensory properties. However, in a dynamic environment with changing stimulus-reward pairings, the brain must also represent the sensory features of rewarding stimuli. The mechanism by which the brain balances these needs—deriving a common reference scale for valuation while maintaining sensitivity to sensory contexts—remains unclear. To investigate this, we conducted an fMRI study with human participants engaged in a dynamic foraging task, which required integrating the reward history of auditory or visual choice options and updating the subjective value for each sensory modality. Univariate fMRI analysis revealed modality-specific value representations in the orbitofrontal cortex (OFC) and modality-general value representations in the ventromedial prefrontal cortex (vmPFC), confirmed by an exploratory multivariate pattern classification approach. Crucially, modality-specific value representations were absent when the task involved instruction-based rather than value-based choices. Effective connectivity analysis showed that modality-specific value representations emerged from selective bidirectional interactions across the auditory and visual sensory cortices, the corresponding OFC clusters, and the vmPFC. These results illustrate how the brain enables a valuation process that is sensitive to the sensory context of rewarding stimuli. Model-based fMRI study shows how context-sensitive valuation arises from modality-specific and general reward value coding in the orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (vmPFC), through dynamic interactions with sensory cortices. [ABSTRACT FROM AUTHOR]

Introduction: Multiple system atrophy (MSA), a rare neurodegenerative disease, is usually accompanied by brain morphological alterations. However, the causal relationships between progressive gray matter atrophy in MSA parkinsonian (MSA-P) subtype remain unknown. Methods: In total, thirty-five MSA-P patients and thirty-five healthy controls (HC) underwent three-dimensional high-resolution T1-weighted structural imaging and voxel-based morphometry analysis. The causal structural covariance network (CaSCN) of gray matter was assessed to explore the causal relationships in MSA-P. Results: With greater illness duration, the reduction of gray matter was originated from right cerebellum and progressed to bilateral cerebellum, fusiform gyrus, insula, putamen, caudate nucleus, frontal lobe, right angular gyrus, right precuneus, left middle occipital lobe and left inferior temporal lobe, then expanded to midbrain, bilateral para-hippocampus, thalamus, temporal lobe, inferior parietal lobule (IPL), precentral gyrus, postcentral gyrus and middle cingulate cortex. The right cerebellum was revealed to be the core node of the directional network and projected positive causal effects to bilateral cerebellum, caudate nucleus and left IPL. Conclusion: MSA-P patients showed progression of gray matter atrophy over time, with the right cerebellum probably as a primary hub. Furthermore, the early structural vulnerability of cerebellum in MSA-P may play a pivotal role in the modulation of motor and non-motor circuits at the structural level. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease (sCJD) is a frequent differential diagnostic consideration in patients with rapidly progressive dementia (RPD). Fortunately, in the last 2 decades there has been substantial cumulative improvements in sCJD biomarkers, particularly those based on imaging and cerebrospinal fluid (CSF) interrogation. Brain MRI is a very frequently employed investigation in patients with RPD, often utilized quite early in the evaluation and thereby offering a potentially key role in prompting initial concerns for sCJD. Extant conventional MRI criteria for sCJD diagnosis are relatively stringent, requiring fluid attenuated inversion recovery (FLAIR) or diffusion weighted imaging (DWI) high signal changes in 2 or more cortical regions (excluding frontal) or in both the caudate and putamen. Challenging these conventional criteria, a recent publication described improved sensitivity and unchanged specificity if MRI criteria were arguably less rigorous, requiring DWI high signal changes in only 1 or more of 7 discrete brain regions: frontal, parietal, occipital or temporal cortices, as well as the caudate, putamen or thalamus. The aim of the current study was to test the diagnostic performance of this proposed change in MRI criteria in the Australian context and compare it with conventional criteria, as well as 2 other stringent sets of criteria, predicting that a similar improved sensitivity with unchanged specificity would be observed when the proposed criteria were utilized. Sixty-five definite sCJD cases were compared with 63 age- and sex-matched controls. Radiological review of all MRIs applying the different sets of MRI criteria was undertaken by a blinded neuroradiologist, very experienced in CJD interpretation, with independent assessment of 71 MRIs performed by a second blinded neuroradiologist less experienced in sCJD imaging findings. Our study found the sensitivity of the recently proposed MRI criteria (92.3%) to be comparable to that originally reported (90–95%) and also equivalent to the conventional MRI diagnostic criteria (92.3%), while the specificities were also quite similar between the conventional MRI criteria (87.3%) and proposed criteria (85.7%), with the latter lower than previously reported. Negative predictive values and positive predictive values were also very similar between the conventional and proposed MRI criteria. Other MRI criteria assessed were associated with unacceptably low sensitivity for clinical use. Inter-rater reliability as assessed by intra-class correlation coefficients (ICC) revealed moderate reliability for the conventional and proposed MRI criteria, modestly better in the former and when the frontal lobe was retained versus excluded in comparisons. [ABSTRACT FROM AUTHOR]

This study investigated differences in electroencephalography (EEG) activity within motor-related brain areas during three phases of a single-leg squat (SLS)—i.e., descending, holding, and ascending phases. Specifically, utilizing advanced magnetic resonance imaging guided EEG source localization techniques and markerless motion capture technology, we explored the interplay between concurrently recorded lower-extremity biomechanics and brain activity. Among the phases of a nondominant leg SLS, differences in contralateral brain activity (right hemisphere) were found in the activity of the precentral gyrus, the postcentral gyrus, and the sensory motor area. Alternatively, during the dominant SLS leg, differences among the three SLS phases in contralateral brain activity were fewer. Hemispheric dependent brain activity also significantly correlated with participants' knee valgus angle range of motion (right hemisphere) and peak knee valgus angles (left hemisphere). In addition to the novel brain and biomechanical findings, this study sheds light on the technical feasibility of recording EEG during complex multi-joint movements and its potential applications in understanding sensorimotor behavior. [ABSTRACT FROM AUTHOR]

The significance of biomechanical analyses for forensic time since death estimations has recently been demonstrated. Previous biomechanical analyses successfully discriminated post-mortem brain tissue from tissue with a post-mortem interval of at least one day when held at 20 °C. However, the practical utility of such analyses beyond day one at 20 °C was limited. This study investigates the storage, loss, and complex shear modulus of various brain regions in sheep stored at 4 °C in 24-hour intervals over four days post-mortem using rheometry tests. The aim is to identify the critical biomechanical tissue property values to predict post-mortem time and assess the temperature sensitivity of the rheometry method by comparing results to recent findings at 20 °C. Thirty sheep brains were examined, including the frontal lobe, parietal lobe, anterior and posterior deep brain, superior colliculi, pons, medulla, and cerebellum. Rheometry tests were conducted, and receiver operator characteristic analyses were employed to establish cut-off values. At 4 °C storage, all investigated biomechanical properties of the examined brain regions remained stable for at least one day post-mortem. Using cerebellar samples stored at 4 °C, a post-mortem interval of at least two days could be determined with excellent diagnostic ability. Complex shear modulus values below 1435 Pa or storage modulus values below 1313 Pa allowed prediction of two or more days post-mortem. Comparisons between 4 °C and 20 °C revealed brain region-specific results. For instance, the complex shear moduli of the anterior deep brain at 4 °C were significantly higher on all individual testing days when compared to 20 °C. In contrast, the combined medulla and pons samples were similar on each day. Rheometry testing of brain tissue consistently stored at 4 °C since death proved valuable for forensic time since death estimations starting from two days after death. [ABSTRACT FROM AUTHOR]

Purpose: Craniopharyngioma is a tumor derived from the squamous epithelium of Rathke's pouch. Despite successful excision, recurrence is common, typically occurring at the original tumor site. More rarely, recurrences can manifest at distant locations. This article reports on three distinct types of ectopic recurrence and reviews the existing literature. Methods: We reviewed clinical records and neuroimaging data of craniopharyngioma patients at our institution, identifying three cases of ectopic recurrence. Additionally, we conducted a literature review of similar cases published between 1975 and 2023, focusing on historical background, pathophysiology, clinical and radiological features, and treatment options. Results: We identified nineteen articles detailing ectopic recurrence of craniopharyngiomas in pediatric patients. The right frontal lobe was the most frequently reported site of recurrence. The shortest interval to recurrence was 11 months, while the longest was 14 years. Most cases were managed with surgical resection, yielding positive outcomes. In our cases, the recurrence sites were temporal intraparenchymal, intraosseous orbital, and occipital intraventricular. All were successfully treated with surgery, with no subsequent recurrences. Conclusion: Although craniopharyngiomas are histologically benign, they can recur locally and, more rarely, at distant sites. Surgical intervention is generally well-tolerated. Further research into tumor cell dissemination mechanisms is essential to develop strategies for preventing ectopic recurrence. [ABSTRACT FROM AUTHOR]

Rationale: Neuroinflammation may inhibit oligodendrocyte and astrocyte differentiation, which causes demyelination and synaptic degeneration. The myelin component nervonic acid (NA) may improve demyelinating and neurodegenerative diseases. Objectives: This study firstly explored relationships between glial cell dysfunction and demyelination or synaptic degeneration in schizophrenia patients, and secondly determined nervonic acid therapeutic effects in a preclinical schizophrenia model of mice. Methods: Plasma samples were collected from 18 male healthy controls and 18 male schizophrenic patients (diagnosed by DSM-V) at aged 18–55. Mouse brain samples were collected from a maternal immune activation (MIA) model of schizophrenia via injecting 5 mg/kg polyinosinic-polycytidylic acid. Male mouse offspring (age 2.5 months, n = 12) were treated by clozapine (15 mg/kg/day) or fed 0.5% NA for 6 weeks. Cytokine and dopamine (DA) concentrations, and glial phenotypes and myelin markers were measured in both human plasma and mouse brain samples. Results: In patient plasma, increased proinflammatory cytokines were associated with reactive microglia (Iba-1) up-regulation, while decreased anti-inflammatory cytokines were related to microglia (CD206) downregulation. Decreased astrocyte marker (p11) concentrations were accompanied by reduced concentrations of oligodendrocyte and synaptic markers. However, NA and DA contents were increased. Compared with control mice, SZ-like behaviors appeared in MIA male mice. Changes in microglia and astrocytes markers, and cytokine concentrations in the frontal cortex were consistent with those observed in patients' plasma. Hippocampal oligodendrocyte and synaptic marker expression were also decreased. DA content and DA/metabolite (DAPOC) were increased in MIA mouse brains. Most of these changes were normalized by both clozapine and NA. Even though some NA effects were more pronounced than clozapine, only clozapine restored cytokine function. Conclusion: The data suggest a possible therapeutic route for schizophrenia patients. [ABSTRACT FROM AUTHOR]

The subdivisions of the extended cingulate cortex of the human brain are implicated in a number of high-level behaviors and affected by a range of neuropsychiatric disorders. Its anatomy, function, and response to therapeutics are often studied using non-human animals, including the mouse. However, the similarity of human and mouse frontal cortex, including cingulate areas, is still not fully understood. Some accounts emphasize resemblances between mouse cingulate cortex and human cingulate cortex while others emphasize similarities with human granular prefrontal cortex. We use comparative neuroimaging to study the connectivity of the cingulate cortex in the mouse and human, allowing comparisons between mouse 'gold standard' tracer and imaging data, and, in addition, comparison between the mouse and the human using comparable imaging data. We find overall similarities in organization of the cingulate between species, including anterior and midcingulate areas and a retrosplenial area. However, human cingulate contains subareas with a more fine-grained organization than is apparent in the mouse and it has connections to prefrontal areas not present in the mouse. Results such as these help formally address between-species brain organization and aim to improve the translation from preclinical to human results. [ABSTRACT FROM AUTHOR]

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V–VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes. [ABSTRACT FROM AUTHOR]

The research of mechanisms regulating aggressive behavior is one of the main problems of neurogenetics. Tame and highly aggressive strains of rats (Rattus norvegicus) obtained through long-term selective breeding are a useful model for studying the mechanisms of genetically determined defensive behavior. The neurotransmitter serotonin (5-HT) controls many forms of behavior, including aggression. The activity of the brain 5-HT system is regulated not only by its own elements, such as 5-HT1A and 5-HT7 receptors, but also by various modulators. Among their variety, trace amines attract special attention. The main receptor of trace amines, TAAR1, is localized on 5-HT neurons pre- and postsynaptically. NO is also a perspective modulator, it's synthesis in the brain is activated predominantly by neuronal NO-synthase (NOS1). Here, NOS1 and TAAR1 expression levels in comparison with the level of 5-HT, its main metabolite (5-HIAA) and mRNA of 5-HT receptors (Htr1a, Htr7), as well as the expression and activity of TPH2 in the midbrain, hippocampus, hypothalamus and frontal cortex of tame and aggressive rats was analyzed. In the midbrain and hypothalamus in the aggressive rats compared to tame ones was detected a decrease in the Htr1a mRNA level, while in the frontal cortex there was an increase in the expression level of the Htr7 gene. However, no interstrain differences in the TAAR1 protein level were detected in the investigated brain structures. Moreover, in highly aggressive rats, an increase in the Taar1 mRNA level was detected in the midbrain and hippocampus, while in the hypothalamus and frontal cortex Taar1 expression was not detected, regardless of the aggressiveness degree. The most significant changes in the 5-HT system of aggressive rats were found in the frontal cortex; an increase in the 5-HT metabolism index was revealed due to an increase in the 5-HIAA level. There was an inverse correlation between the 5-HT metabolism index and NOS1 expression. We hypothesized that the NOS1/NO system is an indicator of the 5-HT system functional activity in the genetically determined aggression conditions. [ABSTRACT FROM AUTHOR]

Background: The objective of frontal lobe disconnection (FD) is to isolate the frontal lobe without removing brain parenchyma, to achieve epilepsy outcomes comparable to those for frontal lobectomy but with fewer complications, since a large post-operative cavity is not created. Method: Main surgical steps include "Identification of the central sulcus" to ensure the preservation of motor function, and "Frontal lobe disconnection" comprising: 1) fronto-parietal disconnection; 2) fronto-basal disconnection; 3) anterior corpus callosotomy; and 4) insula and basal ganglia disconnection. Conclusion: In performing FD, consideration of the disconnection boundary based on an anatomical understanding of white matter tracts is essential. [ABSTRACT FROM AUTHOR]

Perceptual segregation of complex sounds such as speech and music simultaneously emanating from multiple sources is a remarkable ability that is common in humans and other animals alike. Unlike animal physiological experiments with simplified sounds or human investigations with spatially broad imaging techniques, this study combines insights from animal single-unit recordings with segregation of speech-like sound mixtures. Ferrets are trained to attend to a female voice and detect a target word, both in presence and absence of a concurrent equally salient male voice. Recordings are made in primary and secondary auditory cortical fields, and in frontal cortex. During task performance, representation of the female words becomes enhanced relative to the male in all, but especially in higher cortical regions. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings underscore the role of the principle of temporal coherence whereby attention to a target voice binds together all neural responses coherently modulated with the target, thus ultimately forming and extracting a common auditory stream. Ferrets learned to attend and react to words of a female voice embedded in a speech mixture with a male. Recordings in auditory cortex reveal rapidly enhanced responses to the attended female voice and a simultaneous suppression of the male distractor. [ABSTRACT FROM AUTHOR]

Introduction: Learning is a long-term memory process heavily influenced by the control processes implemented by working memory, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. Aim: The aim of this study is to investigate the verbal learning strategies of patients affected by a tumor in the left frontal lobe to highlight the role of area 9. Method: Ten patients with frontal low-grade gliomas and ten healthy control subjects, matched for age, sex and education, were recruited and then evaluated with a two-part verbal learning test: multi-trial word list learning in free recall, and multi-trial word list learning preceded by an explicit semantic strategy cue. Frontal patients were divided into two groups: those either with frontal lesions involving or sparing area 9. Results: In comparison to healthy control subjects, frontal patients with lesions involving area 9 memorized fewer words and displayed difficulty in using semantic strategies. When the strategy was suggested by the examiner, their performance improved, but to a lesser extent than the healthy control. Conversely, frontal patients with lesions sparing area 9 showed similar results to healthy control subjects. Conclusion: The results suggested that, while the identification of the categorical criterion requires the integrity of the entire dorsolateral prefrontal area, only area 9, and not the surrounding areas, could be responsible for the effective use of semantic strategies in learning tasks. [ABSTRACT FROM AUTHOR]

The debate surrounding nature versus nurture remains a central question in neuroscience, psychology, and in psychiatry, holding implications for both aging processes and the etiology of mental illness. Epigenetics can serve as a bridge between genetic predisposition and environmental influences, thus offering a potential avenue for addressing these questions. Epigenetic clocks, in particular, offer a theoretical framework for measuring biological age based on DNA methylation signatures, enabling the identification of disparities between biological and chronological age. This structured review seeks to consolidate current knowledge regarding the relationship between mental disorders and epigenetic age within the brain. Through a comprehensive literature search encompassing databases such as EBSCO, PubMed, and ClinicalTrials.gov, relevant studies were identified and analyzed. Studies that met inclusion criteria were scrutinized, focusing on those with large sample sizes, analyses of both brain tissue and blood samples, investigation of frontal cortex markers, and a specific emphasis on schizophrenia and depressive disorders. Our review revealed a paucity of significant findings, yet notable insights emerged from studies meeting specific criteria. Studies characterized by extensive sample sizes, analysis of brain tissue and blood samples, assessment of frontal cortex markers, and a focus on schizophrenia and depressive disorders yielded particularly noteworthy results. Despite the limited number of significant findings, these studies shed light on the complex interplay between epigenetic aging and mental illness. While the current body of literature on epigenetic aging in mental disorders presents limited significant findings, it underscores the importance of further research in this area. Future studies should prioritize large sample sizes, comprehensive analyses of brain tissue and blood samples, exploration of specific brain regions such as the frontal cortex, and a focus on key mental disorders. Such endeavors will contribute to a deeper understanding of the relationship between epigenetic aging and mental illness, potentially informing novel diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

People often reflect on how things end up and imagine how they could have turned out differently. The pervasive cognitive process of imagining alternative scenarios of actual events is termed counterfactual thinking (CT). Though evidence has been established linking CT and personality, little is known about the association between CT and trait anxiety and its underpinning neural substrates. This study leveraged multi-modality fMRI to address these issues. We conducted voxel-based morphometry analyses and functional connectivity analyses using a relatively large sample (n = 85) to explore the neural basis of the relationship between upward CT and trait anxiety. The behavioral data revealed a positive correlation between upward CT and trait anxiety. The VBM results found that upward CT was negatively associated with the GMV in the left precentral gyrus. Further, functional results revealed functional connectivities of the left precentral gyrus-dmPFC positively predicted upward CT. Finally, the impact of trait anxiety on upward CT was mediated by this functional connectivity. The results suggest that the somatosensory and monitoring network play vital roles in the influence of trait anxiety on upward CT. [ABSTRACT FROM AUTHOR]

Patients with meningiomas frequently exhibit impairments in executive functioning. There are few studies specifically examining the role of frontal meningioma localization in executive functioning impairments. This study examines whether frontally located meningiomas are specifically associated with executive functioning impairments in a large sample of meningioma patients before treatment, using an axis-wise and lobe-based approach to meningioma localization. We retrospectively examined cognitive performances in 353 patients with frontal, frontally-involved and non-frontal meningiomas on a battery of tests including tests of executive functioning. We applied an axis-based approach to meningioma location, in addition to qualitative lobe-based localization. We examined the association between meningioma coordinates on an anterior-posterior axis and continuous cognitive performance scores in univariate correlations and linear regression analyses. We also examined the association between meningioma coordinates on an anterior-posterior axis with cognitive impairments in multivariable logistic regression analyses. Meningioma position on the anterior-posterior axis was only univariately associated with mean performance on the Stroop test Interference ratio and Symbol Digit Coding task. There was no (multivariable) association with impairments on tests of executive or non-executive domains. Increased odds of impairment on executive functioning tasks were associated with left-localization (Verbal Fluency) and larger meningioma volumes (Shifting Attention). We did not find a specific relation between a frontal meningioma location and executive functioning impairments, which may be explained by widespread organization of executive functioning throughout the brain, diffuse cognitive effects of the mass of meningiomas, functional reorganization due to neuroplasticity, or functional involvement of less-anteriorly located frontal areas. [ABSTRACT FROM AUTHOR]

At present, researches on brain fatigue recognition are still in the stage of single task and simple brain region network features, while researches on high-order brain functional network features and brain region state mechanisms during fatigue in multi-task scenarios are still insufficient, making it difficult to meet the needs of fatigue recognition under complex conditions. Therefore, this study utilized functional near-infrared spectroscopy (fNIRS) technology to explore the correlation and differences in the low-order and high-order brain functional network attributes of three task induced mental fatigue, and to explore the brain regions that have a major impact on mental fatigue. Self-training algorithms were used to identify the three levels of brain fatigue. The results showed that during the fatigue development, the overall connection strength of the endothelial cell metabolic activity and neural activity frequency bands of the low-order brain functional network first decreased and then increased, while the myogenic activity and heart rate activity frequency bands showed the opposite pattern. Network topology analysis indicated that from no fatigue to mild fatigue, the clustering coefficient of endothelial cell metabolic activity and myogenic activity frequency bands significantly decreased, while the characteristic path length of myogenic activity significantly increased; when experiencing severe fatigue, the small-world attribute of the neural frequency band significantly weakened. However, each frequency band maintained its small-world attribute, reflecting the self-optimization and adaptability of the network during the fatigue process. During mild fatigue, neuronal activity bands' node degree, cluster coefficient, and efficiency rose in high-order brain networks, while low-order networks showed no significant changes. As fatigue progressed, the myogenic activity bands of high-order network properties dominated, but neural bands gained prominence in mild fatigue, approaching the level of myogenic bands in severe fatigue, indicating that brain fatigue orchestrated a shift from myogenic to neural dominance in frequency bands. In addition, during the process of fatigue, the four network attributes of the high-order network cluster composed of low-order nodes related to the prefrontal cortex region, left anterior motor region, motor assist region, and left frontal lobe eye movement region significantly increased, indicating that these brain regions had a significant impact on brain fatigue status. The accuracy of using both high-order and low-order features to identify fatigue levels reached 88.095%, indicating that the combined network features of both high-order and low-order fNIRS signals could effectively detect multi-level mental fatigue, providing innovative ideas for fatigue warning. [ABSTRACT FROM AUTHOR]

Resection of a glioma from the dorsomedial frontal lobe, including the supplementary motor area (SMA), can result in postoperative SMA syndrome. SMA syndrome may occur during awake craniotomies. However, it is often difficult to intraoperatively distinguish between motor dysfunction due to pyramidal tract damage from that due to SMA syndrome. Patients with suspected intraoperative SMA syndrome are indifferent to their surroundings, have stiff facial muscles, and maintain a fixed gaze. We defined this condition as "apathetic look." The present study aimed to investigate whether intraoperative "apathetic look" is useful for identifying intraoperative SMA syndrome in patients with glioma close to motor-related areas, including the SMA, during awake craniotomy. This study included 33 consecutive patients with glioma included in the SMA. We excluded patients whose tumors extended to motor-related areas. We also assessed whether intraoperative SMA syndrome occurred in each patient. We evaluated the correlation between the occurrence of intraoperative SMA syndrome and various clinical factors, including intraoperative "apathetic look." Of the 33 patients, 12 had intraoperative SMA syndrome. Intraoperative "apathetic look" showed strong correlation with intraoperative SMA syndrome (p < 0.0001). Additionally, higher extent of resection (EOR) and resection of the corpus callosum showed a significantly higher incidence of intraoperative "apathetic look." All 12 patients with intraoperative SMA syndrome showed intraoperative "apathetic look" and recovered from SMA syndrome with high EOR. In conclusion, intraoperative "apathetic look" shows strong correlation with intraoperative SMA syndrome. Therefore, "apathetic look" may be a valuable indicator of intraoperative SMA syndrome during awake craniotomy. [ABSTRACT FROM AUTHOR]

Neural consequences of social disparities are not yet rigorously investigated. How socioeconomic conditions influence children's connectome development remains unknown. This paper endeavors to gauge how precisely the connectome structure of the brain can predict an individual's social environment, thereby inversely assessing how social influences are engraved in the neural development of the Adolescent brain. Utilizing Adolescent Brain and Cognition Development (ABCD) data (9099 children residing in the United States), we found that social conditions both at the household and neighborhood levels are significantly associated with specific neural connections. Solely with brain connectome data, we train a linear support vector machine (SVM) to predict socio-economic conditions of those adolescents. The classification performance generally improves when the thresholds of the advantageous and disadvantageous environments compartmentalize the extreme cases. Among the tested thresholds, the 20th and 80th percentile thresholds using the dual combination of household income and neighborhood education yielded the highest Area Under the Precision-Recall Curve (AUPRC) of 0.8224. We identified 8 significant connections that critically contribute to predicting social environments in the parietal lobe and frontal lobe. Insights into social factors that contribute to early brain connectome development is critical to mitigate the disadvantages of children growing up in unfavorable neighborhoods. [ABSTRACT FROM AUTHOR]

Cortical neurons exhibit temporally irregular spiking patterns and heterogeneous firing rates. These features arise in model circuits operating in a 'fluctuation-driven regime', in which fluctuations in membrane potentials emerge from the network dynamics. However, it is still debated whether the cortex operates in such a regime. We evaluated the fluctuation-driven hypothesis by analyzing spiking and sub-threshold membrane potentials of neurons in the frontal cortex of mice performing a decision-making task. We showed that while standard fluctuation-driven models successfully account for spiking statistics, they fall short in capturing the heterogeneity in sub-threshold activity. This limitation is an inevitable outcome of bombarding single-compartment neurons with a large number of pre-synaptic inputs, thereby clamping the voltage of all neurons to more or less the same average voltage. To address this, we effectively incorporated dendritic morphology into the standard models. Inclusion of dendritic morphology in the neuronal models increased neuronal selectivity and reduced error trials, suggesting a functional role for dendrites during decision-making. Our work suggests that, during decision-making, cortical neurons in high-order cortical areas operate in a fluctuation-driven regime. Whether the cortex operates in a fluctuation-driven regime remains unclear. Here, the authors found that standard models explain spiking but not sub-threshold statistics; however, this was resolved by adding dendritic morphology, suggesting a functional role for dendrites in decision-making. [ABSTRACT FROM AUTHOR]

Episodic memory is essential for forming and retaining personal experiences, representing a fundamental aspect of human cognition. Traditional studies of episodic memory have typically used static analysis methods, viewing the brain as an unchanging entity and overlooking its dynamic properties over time. In this study, we utilized dynamic functional connectivity analysis on fMRI data from healthy adults performing an episodic memory task. We quantified integration and recruitment metrics and examined their correlation with memory performance using Pearson correlation. During encoding, integration across the entire brain, especially within the frontoparietal subnetwork, was significantly correlated with memory performance. During retrieval, recruitment becomes significantly associated with memory performance in visual subnetwork, somatomotor subnetwork, and ventral attention subnetwork. At the nodal level, a significant negative correlation was observed between memory scores and integration of the anterior cingulate gyrus, precentral gyrus, and inferior frontal gyrus within the frontoparietal network during encoding task. During retrieval task, a significant negative correlation was found between memory scores and recruitment in the left progranular cortex and right transverse gyral ventral, whereas positive correlations were seen in the right posterior inferior temporal, left middle temporal, right frontal operculum, and left operculum nodes. Moreover, the dynamic reconfiguration of the functional network was predictive of predict memory performance, as demonstrated by a significant correlation between actual and predicted memory scores. These findings advance our understanding network mechanisms underlying memory processes and developing intervention approaches for memory-related disorders as they shed light on critical factors involved in cognitive processes and provide a deeper understanding of the underlying mechanisms driving cognitive function. [ABSTRACT FROM AUTHOR]

Introduction: FTLD-FET is a newly described subtype of frontotemporal lobar degeneration (FTLD characterized by pathologic inclusions of FET proteins: fused in sarcoma (FUS), Ewing sarcoma, and TATA-binding protein-associated factor 2N (TAF15)). Severe caudate volume loss on MRI has been linked to FTLD-FUS, yet glucose hypometabolism in FTLD-FET has not been studied. We assessed [18F] fluorodeoxyglucose PET (FDG-PET) hypometabolism in FTLD-FET subtypes and compared metabolism to FTLD-tau and FTLD-TDP. Methods: We retrospectively reviewed medical records of 26 autopsied FTLD patients (six FTLD-FET, ten FTLD-Tau, and ten FTLD-TDP) who had completed antemortem FDG-PET. We evaluated five regions, caudate nucleus, medial frontal cortex, lateral frontal cortex, and medial temporal using a 0–3 visual rating scale and validated our findings quantitatively using CORTEX-ID suite Z scores. Results: Of the six FTLD-FET cases (three females) with median age at onset = 36, three were atypical FTLD-U (aFTLD-U) and three were neuronal intermediate filament inclusion disease (NIFID). bvFTD was the most common presentation. Four of the six FTLD cases (3 aFTLD-U + 1 NIFID) showed prominent caudate hypometabolism relatively early in the disease course. FTLD-tau and FTLD-TDP did not show early prominent caudate hypometabolism. Hypometabolism in medial and lateral temporal cortex was associated with FTLD-TDP, while FTLD-tau had normal-minimal regional metabolism. Discussion: Prominent caudate hypometabolism, especially early in the disease course, appears to be a hallmark feature of the aFTLD-U subtype of FTLD-FET. Assessing caudate and temporal hypometabolism on FDG-PET will help to differentiate FTLD-FET from FTLD-tau and FTLD-TDP. [ABSTRACT FROM AUTHOR]

Background: Reactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer's dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R. We report the radiosynthesis of both [3H]1 and [11C]1. The PET imaging properties of [11C]1 in mice and baboon were investigated. [3H]1 was studied in Bmax measurement in post-mortem autoradiography in the frontal cortex, inferior parietal cortex and hippocampus from donors diagnosed with AD and age-matched controls. In vitro binding affinity of 1 was measured commercially. Nor-methyl-1 precursor was radiolabeled with [11C]iodomethane or [3H]iodomethane to produce [11C]1 and [3H]1, respectively. Ex vivo brain biodistribution of [11C]1 was compared in normal mice versus lipopolysaccharide-administered (LPS) murine model of neuroinflammation. Dynamic PET imaging was performed in a healthy male Papio anubis baboon. Post-mortem autoradiography with [3H]1 was performed in frozen sections using a standard saturation binding technique. Results: Compound 1 exhibits a high in vitro CSF1R binding affinity (0.59 nM). [11C]1 was synthesized with high yield. [3H]1 was synthesized similarly (commercially). Biodistribution of [11C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [11C]1 was ~ 50% specific for CSF1R. PET/CT [11C]1 study in baboon revealed low brain uptake (0.36 SUV) of [11C]1. Autoradiography with [3H]1 gave significantly elevated Bmax values in AD frontal cortex versus control (47.78 ± 26.80 fmol/mg vs. 12.80 ± 5.30 fmol/mg, respectively, P = 0.023) and elevated, but not significantly different binding in AD hippocampus grey matter and inferior parietal cortex (IPC) white matter. Conclusions: Compound 1 exhibits a high in vitro CSF1R binding affinity. [11C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood–brain barrier in baboon PET. [3H]1 specifically labels CSF1R in post-mortem human brain. The binding of [3H]1 is significantly higher in the post-mortem frontal cortex of AD versus control subjects. [ABSTRACT FROM AUTHOR]

A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals. [ABSTRACT FROM AUTHOR]

We elucidated the molecular fingerprint of vulnerable excitatory neurons within select cortical lamina of individuals with Down syndrome (DS) for mechanistic understanding and therapeutic potential that also informs Alzheimer's disease (AD) pathophysiology. Frontal cortex (BA9) layer III (L3) and layer V (L5) pyramidal neurons were microisolated from postmortem human DS and age- and sex-matched controls (CTR) to interrogate differentially expressed genes (DEGs) and key biological pathways relevant to neurodegenerative programs. We identified > 2300 DEGs exhibiting convergent dysregulation of gene expression in both L3 and L5 pyramidal neurons in individuals with DS versus CTR subjects. DEGs included over 100 triplicated human chromosome 21 genes in L3 and L5 neurons, demonstrating a trisomic neuronal karyotype in both laminae. In addition, thousands of other DEGs were identified, indicating gene dysregulation is not limited to trisomic genes in the aged DS brain, which we postulate is relevant to AD pathobiology. Convergent L3 and L5 DEGs highlighted pertinent biological pathways and identified key pathway-associated targets likely underlying corticocortical neurodegeneration and related cognitive decline in individuals with DS. Select key DEGs were interrogated as potential hub genes driving dysregulation, namely the triplicated DEGs amyloid precursor protein (APP) and superoxide dismutase 1 (SOD1), along with key signaling DEGs including mitogen activated protein kinase 1 and 3 (MAPK1, MAPK3) and calcium calmodulin dependent protein kinase II alpha (CAMK2A), among others. Hub DEGs determined from multiple pathway analyses identified potential therapeutic candidates for amelioration of cortical neuron dysfunction and cognitive decline in DS with translational relevance to AD. [ABSTRACT FROM AUTHOR]

Overall, 28 participants took part in a comparative neuroaesthetic study in the conditions of a visit to the mono-exhibition of M. Vrubel (Russian Museum, St. Petersburg) (30–70 years old, 12 men, and 16 women; 10 artists and 18 non-artists). During the visit (~60 min), electroencephalograms (EEGs) were recorded. From 30 s to 3 min subjects examined each of the painting and by series of clicks (from 1 to 10) on the mark button evaluated the subjective aesthetic "attractiveness" of the canvases. Spectral power in the α1 (8–10 Hz), α2 (10–13 Hz), β1 (13–18 Hz), and β2 (13–30 Hz) EEG bands was analyzed during viewing the most famous paintings by M. Vrubel ("Bogatyr," "Swan Princess," "Sitting Demon," "Demon Flying," "Pan," etc.); and event-related EEG synchronization/desynchronization regarding subjective emotional-aesthetic assessment of canvases by artists and non-artists were analyzed. Artists had lower EEG spectral power values in α1 (F3, C3, T4, Pz leads) and α2 (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4 leads) frequency bands in the frontal, central, and parietal regions. Also, artists revealed lower power values in β1,2-frequency bands in the frontal (F3, F4, C3) and larger ones in the occipital (O1, O2—β1, β2) and posterior temporal regions (β2) of the cortex when compared with a group of subjects without special art education. The decision on the high emotional and aesthetic attractiveness of the paintings among artists compared to non-artists was accompanied by an increase in the event-related EEG synchronization in the frequency band of 11.5–27 Hz in the frontal and central cortex regions 580–360 ms before the answer (1st button press). Whereas a low emotional and aesthetic assessment was characterized in artists by a greater desynchronization of the EEG compared to non-artists in the frequency band of 9–27 Hz, starting 60 ms before the start of the response and lasting up to 440 ms after it in the posterior temporal and parietal regions. Differences in the frontal cortex zones can be associated with a greater involvement of the reward system in the perception of aesthetically pleasing canvases, and differences in parietal and posterior temporal zones with ongoing visual synthesis and reanalysis (longer visual attention) in the perception of subjectively less attractive paintings by artists compared to non-artists. [ABSTRACT FROM AUTHOR]

Background: The frontal cortex, relevant to global cognition and motor function, is recruited to compensate for mobility dysfunction in older adults. However, the in vivo neurophysiological (e.g., neurometabolites) underpinnings of the frontal cortex compensation for mobility dysfunction remain poorly understood. The purpose of this study was to investigate the relationships among frontal cortex neurophysiology, mobility, and cognition in healthy older adults. Methods: Magnetic Resonance Spectroscopy (MRS) quantified N-acetylasparate (tNAA) and total choline (tCho) concentrations and ratios in the frontal cortex in 21 older adults. Four inertial sensors recorded the Timed Up & Go (TUG) test. Cognition was assessed using the Flanker Inhibitory Control and Attention Test which requires conflict resolution because of response interference from flanking distractors during incongruent trials. Congruent trials require no conflict resolution. Results: tNAA concentration significantly related to the standing (p = 0.04) and sitting (p = 0.03) lean angles. tCho concentration (p = 0.04) and tCho ratio (p = 0.02) significantly related to TUG duration. tCho concentration significantly related to incongruent response time (p = 0.01). tCho ratio significantly related to both congruent (p = 0.009) and incongruent (p < 0.001) response times. Congruent (p = 0.02) and incongruent (p = 0.02) Flanker response times significantly related to TUG duration. Conclusions: Altered levels of frontal cortex neurometabolites are associated with both mobility and cognitive abilities in healthy older adults. Identifying neurometabolites associated with frontal cortex compensation of mobility dysfunction could improve targeted therapies aimed at improving mobility in older adults. [ABSTRACT FROM AUTHOR]

Hermann Oppenheim (1858–1919) was a German neurologist without an academic career, who in his productive period around 1900 made a name for himself during his lifetime as a major player in the history of German neurology with his many contributions to multiple sclerosis, syphilis and the controversial study of traumatic neurosis; however, it is almost unknown that in 1890 he introduced the term "witzelsucht", which is still used internationally today. Moritz Jastrowitz dealt with behavioral abnormalities due to frontal brain injuries 1 year earlier and used the term "moria" for a form of mental disorder associated with a kind of childish behavior and inappropriate jocularity. Oppenheim was critical of this and differentiated his "witzelsucht" from this. With this term he wanted to describe humoristic feeble-mindedness in a much narrower sense, which stands in striking contrast to the usual symptoms in cases of cerebral tumors. Oppenheim recognized the frontal brain, particularly the right brain, to be an important functional unit for humorous behavior. Modern research has confirmed that the processing of humor requires a complex interaction of multiple brain regions. Damage to the right frontal lobe or to connecting structures can lead to the disorder "witzelsucht". Whether a simultaneous damage to the left hemisphere must be present or if this is dependent on the individual dominant hemisphere, needs further research. [ABSTRACT FROM AUTHOR]

Introduction: Stereoelectroencephalography (SEEG) is valuable for delineating the seizure onset zone (SOZ) in pharmacoresistant epilepsy when non-invasive presurgical techniques are inconclusive. Secondary epilepsy surgery after initial failure is challenging and there is limited research on SEEG following failed epilepsy surgery in children. Objective: The objective of this manuscript is to present the outcomes of children who underwent SEEG after failed epilepsy surgery. Methods: In this single-institution retrospective study, demographics, previous surgery data, SEEG characteristics, management, and follow-up were analyzed for pediatric patients who underwent SEEG after unsuccessful epilepsy surgery between August 2016 and February 2023. Results: Fifty three patients underwent SEEG investigation during this period. Of this, 13 patients were identified who had unsuccessful initial epilepsy surgery (24%). Of these 13 patients, six patients (46%) experienced unsuccessful resective epilepsy surgery that targeted the temporal lobe, six patients (46%) underwent surgery involving the frontal lobe, and one patient (8%) had laser interstitial thermal therapy (LITT) of the right insula. SEEG in two thirds of patients (4/6) with initial failed temporal resections revealed expanded SOZ to include the insula. All 13 patients (100%) had a subsequent surgery after SEEG which was either LITT (54%) or surgical resection (46%). After the subsequent surgery, a favorable outcome (Engel class I/II) was achieved by eight patients (62%), while five patients experienced an unfavorable outcome (Engel class III/IV, 38%). Of the six patients with secondary surgical resection, four patients (67%) had favorable outcomes, while of the seven patients with LITT, two patients (29%) had favorable outcomes (Engel I/II). Average follow-up after the subsequent surgery was 37 months ±23 months. Conclusion: SEEG following initial failed resective epilepsy surgery may help guide next steps at identifying residual epileptogenic cortex and is associated with favorable seizure control outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential therapeutic effects of cerebellar transcranial magnetic stimulation (TMS) on balance and limb motor impairments in stroke patients. A meta-analysis of randomized controlled trials was conducted to assess the effects of cerebellar TMS on balance and motor impairments in stroke patients. Additionally, an activation likelihood estimation (ALE) meta-analysis was performed on resting-state functional magnetic resonance imaging (fMRI) studies to compare spontaneous neural activity differences between stroke patients and healthy controls using measures including the amplitude of low frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). The analysis included 10 cerebellar TMS studies and 18 fMRI studies. Cerebellar TMS treatment demonstrated significant improvements in the Berg Balance Scale score (p < 0.0001) and the Fugl-Meyer Assessment lower extremity score (p < 0.0001) compared to the control group in stroke patients. Additionally, spontaneous neural activity alterations were identified in motor-related regions after stroke, including the precentral gyrus, putamen, thalamus, and paracentral lobule. Cerebellar TMS shows promise as a therapeutic intervention to enhance balance and lower limb motor function in stroke patients. It is easy for clinical application and addresses the limitations of insufficient direct stimulation depth on the leg area of the cortex. However, further research combining neuroimaging outcomes with clinical measurements is necessary to validate these findings. [ABSTRACT FROM AUTHOR]

The morphometric characteristics of brain tissue were studied based on autopsy material from 49 deceased newborns divided into 7 groups based on the time after death. Samples were taken from the upper (frontal lobe) and lower (occipital lobe) regions relative to the supine position of the body. Paraffin sections were prepared from these samples and stained with hematoxylin and eosin. Histological preparations were analyzed using an image analysis system to determine the area of gliocyte nuclei, cross-cut blood vessels, and expanded area around them in the white matter of the brain. Based on these data, severity indices were calculated for both cellular (pericellular) and vascular (perivascular) expansion. The dynamics of changes in morphometric parameters within the range of cellular and vascular alterations on brain tissue specimens, which reflect the development of postmortem hypostasis and autolysis in this organ, can be used to estimate the duration of the postmortem interval. At the same time, these changes, when combined with other non-specific postmortem findings, should be distinguished from long-term pathological processes and diseases that may have occurred during life. [ABSTRACT FROM AUTHOR]

The behavioral effects of α-synuclein oligomers were studied at various times after its chronic intranasal administration to 75-day-old C57BL/6J mice in comparison with the dynamics of changes in the transcriptional activity of caspases genes (Casp9, Casp8, and Casp3) in the hippocampus, frontal cortex, and cerebellum. The negative effects of α-synuclein oligomers on exploratory activity and short-term memory in the novel object recognition test were most pronounced after 90 days from the end of administration, while after 1 and 270 days, partial compensation of the studied cognitive functions was observed. Analysis of the expression of caspase genes suggests that early compensatory mechanisms are associated with suppression of the effector caspase-3 gene expression along with increased activity of the genes encoding initiator caspases-9 and -8. Late compensation processes are associated with a decrease in the activity of initiator caspases in the frontal cortex and cerebellum. [ABSTRACT FROM AUTHOR]

Background: In adults, moyamoya disease (MMD) often presents with slight neurocognitive impairment, which may result from frontal lobe hemodynamic insufficiency. Methods: In this study, we performed revascularization surgery by superficial temporal artery–anterior cerebral artery (ACA) direct bypass in 20 adults with MMD with poor anterograde ACA flow (Group M). The pre- and postoperative neurocognitive test results of these patients were retrospectively analyzed. The comparative group (Group C) included 23 patients with unruptured aneurysms or brain tumors who underwent craniotomy, as well as the same neurocognitive tests as Group M. We calculated the compositive frontal lobe function index (CFFI) based on the results of seven neurocognitive tests for each patient, and the difference between the pre- and postoperative CFFI values (CFFI Post − Pre) was compared between the two groups. Results: Frontal perfusion improved postoperatively in all patients in Group M. The CFFI Post − Pre was significantly higher in Group M than in Group C (0.23 ± 0.44 vs. − 0.20 ± 0.32; p < 0.001). After adjusting for postoperative age, sex, preoperative non-verbal intelligence quotient, and preoperative period of stress, Group M had a significantly higher CFFI Post − Pre than Group C in the multiple regression analysis (t value = 4.01; p < 0.001). Conclusion: Improving frontal lobe hemodynamics might be the key for improving neurocognitive dysfunction in adults with MMD. The surgical indication and method should be considered from the perspective of both stroke prevention and neurocognitive improvement or protection. [ABSTRACT FROM AUTHOR]