Brain Regions Research Articles

Effects of growth hormone and sex steroid therapy on brain structure and pituitary function in turner syndrome

Introduction: Turner syndrome (TS) is a chromosomal disorder affecting approximately 1 in 2,500 live female births, characterized by the partial or complete absence of one X chromosome. This genetic anomaly leads to physical, cognitive, and endocrine abnormalities, including short stature, gonadal dysgenesis, and structural brain anomalies. Cognitive deficits in TS involve visuospatial processing, memory, and executive function, often linked to structural brain changes. Magnetic resonance imaging (MRI) has revealed significant alterations in gray and white matter volumes in various brain regions. Growth hormone (GH) and sex steroid therapies, such as estrogen and progesterone, are used to address growth and developmental delays in TS. However, their impact on brain structure and pituitary function remains an area of active research. Aim of the Review: To systematically review and synthesize findings on the effects of GH and sex steroid therapy on brain structure and pituitary function in patients with Turner syndrome. Methods: A comprehensive literature review was conducted to identify studies examining the effects of GH and sex steroid therapy on brain structure and pituitary function in TS. Data from various sources were compiled, focusing on MRI-based structural brain changes. Key parameters analyzed included sample size, findings from MRI and fMRI studies, and clinical associations. Studies were summarized and presented in a structured table format. Results: Estrogen-progesterone treatment was found to suppress pituitary gonadotropin release more effectively than estrogen alone, indicating a feedback interaction between pituitary gonadotropin release and sex steroids. MRI studies showed that TS patients exhibit smaller volumes in the hippocampus, caudate, lenticular, thalamic nuclei, and parieto-occipital brain matter, correlating with cognitive deficits. GH-IGF axis abnormalities are modulated by body composition and physical fitness, with sex hormone replacement normalizing the GH-IGF axis and improving body composition. Although GH therapy alone did not significantly improve cognitive functions, the combination of GH with oxandrolone improved working memory. Estrogen deficiency and TS are associated with slower growth in parieto-occipital regions and enhanced volume growth in basal ganglia and cerebellar areas during adolescence, underscoring the importance of estrogen replacement in brain development. Discussion: GH and sex steroid therapies significantly impact brain structure, pituitary function, and clinical outcomes in TS. GH therapy, often combined with sex steroids, improves growth and cognitive functions, particularly working memory. However, GH alone does not significantly impact overall cognitive function. The timing and combination of these therapies are crucial for optimizing outcomes. Regular monitoring and individualized treatment plans are essential to address the complex needs of TS patients. Further research is needed to explore the long-term impacts of these therapies and develop optimal treatment regimens. Conclusion: GH and sex steroid therapies are vital in managing TS contributing to improved growth, body composition, and cognitive enhancements. A multifaceted therapeutic approach and regular monitoring are crucial for optimizing treatment outcomes and quality of life for TS patients.

Scalp acupuncture targets for neurological disorders：evidence from neuroimaging studies (part 2).

Scalp acupuncture is a method of treating diseases by dividing and stimulating the corresponding function-oriented cortical scalp areas. It is a commonly used therapy for neurological disorders. However, the specific target selection for scalp acupuncture remains to be explored. This manuscript aims to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings and noninvasive brain stimulation. Neurosynth-based meta-analysis of neuroimaging studies was conducted to identify brain stimulation targets of neurological disorders. The identified target regions were further projected to the scalp. The traditional acupoints and 10-20 EEG system were referenced for the localization of these targets. In this study, the "mild cognitive impairment" (MCI), "Alzheimer's disease" (AD) and "dementia" were used as the retrieval terms respectively, and a unity detection method was used to generate brain maps, with the default FDR (false discovery rate, P<0.01) threshold of Neurosynth set for subsequent exploration of various disease-related brain regions. The literature search was conducted on July 30, 2022. The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets for MCI, AD, and dementia were introduced in the present paper (part 2). Here are 3 target examples for each of these 3 diseases due to word limitation. 1) MCI：Based on the 81 papers retrieved, we identified 6 potential scalp acupuncture points for MCI, their corresponding brain regions, brain functions and the possible resultant effects of the scalp target acupoint stimulation respectively are as below. MCI1：the orbital part of the left inferior frontal gyrus (left Brodmann area ［BA］47), related to semantic coding, working memory and episodic memory, improving semantic coding and memory function；MCI2：the anterior motor area/left anterior central gyrus (left BA6), the motor center area, improving MCI motor function；MCI3：the left medial temporal gyrus (left BA21), related to the processing of speech, visual space, language and word understanding, improving language and memory. 2) AD：Based on the 196 papers retrieved, we found 6 potential scalp acupuncture targets for AD, their corresponding brain regions and brain functions of the 3 example targets respectively are as below. AD1：the left medial temporal gyrus (left BA21), participating in language and semantic processing, sentence and word generation, intent expression, deductive reasoning；AD2：the left angular gyrus (left BA39), related to semantic processing, word reading and comprehension, memory retrieval, attention and spatial cognition, reasoning, etc.；AD3：the left fusiform/suboccipital gyrus (left BA37), related to semantic classification, text generation, sign language, phonology processing, etc. 3) Dementia：Based on the 142 papers retrieved, we found 4 potential scalp acupuncture targets for dementia, their corresponding brain regions, brain functions and the possible targets of the proposed scalp stimulation respectively are as below. D1 and D2：the left inferior frontal gyrus (i.e., left BA46, and left BA47, respectively), being closely related to working memory, emotional response regulation, melody and other processing processes, may be suitable for treating memory decline and advanced executive dysfunction in patients with dementia；D3：the left medial temporal gyrus (left BA21), an important brain region for various sensory integration, cognitive processing and memory functions, and emotional processing, may be suitable for temporal dementia. We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging findings and noninvasive brain stimulation. The proposed targets may also be used for treating these disorders using nerve/brain stimulation methods.

Bypassing Striatal Learning Mechanisms Using Delayed Feedback to Circumvent Learning Deficits in Traumatic Brain Injury.

Feedback facilitates learning by guiding and modifying behaviors through an action-outcome contingency. As the majority of existing studies have focused on the immediate presentation of feedback, the impact of delayed feedback on learning is understudied. Prior work demonstrated that learning from immediate and delayed feedback employed distinct brain regions in healthy individuals, and compared to healthy individuals, individuals with traumatic brain injury (TBI) are impaired in learning from immediate feedback. The goal of the current investigation was to assess the effects of delayed vs immediate feedback on learning in individuals with TBI and examine brain networks associated with delayed and immediate feedback processing. Nonprofit research organization. Twenty-eight individuals with moderate-to-severe TBI. Participants completed a paired-associate word learning task while undergoing magnetic resonance imaging. During the task, feedback was presented either immediately, after a delay, or not at all (control condition). Learning performance accuracy, confidence ratings, post-task questionnaire, and blood oxygen level-dependent signal. Behavioral data showed that delayed feedback resulted in better learning performance than immediate feedback and no feedback. In addition, participants reported higher confidence in their performance during delayed feedback trials. During delayed vs immediate feedback processing, greater activation was observed in the superior parietal and angular gyrus. Activation in these areas has been previously associated with successful retrieval and greater memory confidence. The observed results might be explained by delayed feedback processing circumventing the striatal dopaminergic regions responsible for learning from immediate feedback that are impaired in TBI. In addition, delayed feedback evokes less of an affective reaction than immediate feedback, which likely benefited memory performance. Indeed, compared to delayed feedback, positive or negative immediate feedback was more likely to be rated as rewarding or punishing, respectively. The findings have significant implications for TBI rehabilitation and suggest that delaying feedback during rehabilitation might recruit brain regions that lead to better functional outcomes.

Grey matter ageing-related tau astrogliopathy: associations with brain pathologies and cognitive decline.

Grey matter ARTAG pathology is common in aged brains and detected in multiple brain regions. However, the associations of grey matter ARTAG with Alzheimer's disease (AD) and other common age-related proteinopathies, as well as clinical phenotypes including Alzheimer's dementia and cognitive decline remain unclear. We examined 442 decedents (mean age-at-death=90 years, males=32%) from three longitudinal community-based clinical-pathological studies. Using AT8 immunohistochemistry, grey matter ARTAG pathology was counted in the the superior frontal, anterior temporal tip, and amygdala and summarized as a severity score from 0 (none) to 6 (severe). AD and other common age-related neuropathologies were also evaluated. The diagnosis of Alzheimer's dementia was based on clinical evaluations; annual tests of cognitive performance were summarized as global cognition and five cognitive domains. Multivariable logistic regression tested the associations of grey matter ARTAG pathology with an array of age-related neuropathologies. To evaluate associations of grey matter ARTAG pathology with Alzheimer's dementia and cognitive decline, we employed logistic regression and linear mixed effect models. Grey matter ARTAG pathology was seen in 324 (73%) participants, of which 303 (68%) participants had ARTAG in the amygdala, 246 (56%) in the anterior temporal tip, and 137 (31%) in the superior frontal region. Grey matter ARTAG pathology from each of the three regions was associated with pathologic diagnosis of AD and LATE-NC but not with vascular pathology. In fully adjusted models that controlled for demographics, AD, and common age-related pathologies, an increase in severity of grey matter ARTAG pathology in the superior frontal cortex, but not in the amygdala or the anterior temporal tip, was associated with higher odds of Alzheimer's dementia and faster decline in global cognition, episodic memory, and semantic memory. These results provide compelling evidence that grey matter ARTAG, specifically in the superior frontal cortex contributes to Alzheimer's dementia and cognitive decline in old age.

Intergenerational effects of racism on amygdala and hippocampus resting state functional connectivity

Racism is an insidious problem with far-reaching effects on the lives of Black, Indigenous, and People of Color (BIPOC). The pervasive negative impact of racism on mental health is well documented. However, less is known about the potential downstream impacts of maternal experiences of racism on offspring neurodevelopment. This study sought to examine evidence for a biological pathway of intergenerational transmission of racism-related trauma. This study examined the effects of self-reported maternal experiences of racism on resting state functional connectivity (rsFC) in n = 25 neonates (13 female, 12 male) birthed by BIPOC mothers. Amygdala and hippocampus are brain regions involved in fear, memory, and anxiety, and are central nodes in brain networks associated with trauma-related change. We used average scores on the Experiences of Racism Scale as a continuous, voxel-wise regressor in seed-based, whole-brain connectivity analysis of anatomically defined amygdala and hippocampus seed regions of interest. All analyses controlled for infant sex and gestational age at the 2-week scanning session. More maternal racism-related experiences were associated with (1) stronger right amygdala rsFC with visual cortex and thalamus; and (2) stronger hippocampus rsFC with visual cortex and a temporo-parietal network, in neonates. The results of this research have implications for understanding how maternal experiences of racism may alter neurodevelopment, and for related social policy.

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model.

Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. Preliminary findings using the JPM support the development and adoption of a universal scale for tau-PET quantification. Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed "CenTauRs". Tested a Centiloid-like linear regression approach. Using five cohorts with head-to-head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Association of sarcopenia with regional brain atrophy and white matter lesions in a general older population: the Hisayama Study.

Sarcopenia has been reported to be associated with cognitive decline and the risk of dementia. However, few studies have addressed the association between sarcopenia and brain morphological changes in the general population. A total of 1373 community-dwelling participants aged ≥ 65years underwent brain MRI. Sarcopenia was defined based on the Asian Working Group for Sarcopenia's criteria. The pattern of regional gray matter volume loss associated with sarcopenia were assessed using a voxel-based morphometry (VBM) analysis. Regional brain volumes, intracranial volumes (ICV), and white matter lesions volumes (WMLV) were also measured using FreeSurfer. An analysis of covariance was used to examine the associations of sarcopenia with regional brain volumes in proportion to ICV. Of the participants, 112 had sarcopenia. The participants with sarcopenia had significantly lower total brain volume/ICV and total gray matter volume/ICV and higher WMLV/ICV than those without sarcopenia after adjusting for confounders. In VBM, sarcopenia was associated with lower gray matter volume in the frontal lobe, insula, cingulate gyrus, hippocampus, amygdala, and basal ganglia. Using FreeSurfer, we confirmed that the participants with sarcopenia had significantly lower frontal, insular, cingulate, and hippocampal volumes than those without sarcopenia. The current study showed that participants with sarcopenia had significantly lower volume in the frontal lobe, insula, cingulate, and hippocampus and higher WMLV than participants without sarcopenia. As these brain regions are likely to play an important role in cognitive function, these changes may suggest a shared underlying mechanism for the progression of sarcopenia and cognitive decline.

Neural and behavioral markers of inhibitory control predict symptom improvement during internet-delivered cognitive behavioral therapy for depression

Poor inhibitory control contributes to deficits in emotion regulation, which are often targeted by treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT). Brain regions that contribute to inhibitory control and emotion regulation overlap; thus, inhibitory control might relate to response to CBT. In this study, we examined whether baseline inhibitory control and resting state functional connectivity (rsFC) within overlapping emotion regulation-inhibitory control regions predicted treatment response to internet-based CBT (iCBT). Participants with MDD were randomly assigned to iCBT (N = 30) or a monitored attention control (MAC) condition (N = 30). Elastic net regression was used to predict post-treatment Patient Health Questionnaire-9 (PHQ-9) scores from baseline variables, including demographic variables, PHQ-9 scores, Flanker effects (interference, sequential dependency, post-error slowing), and rsFC between the dorsal anterior cingulate cortex, bilateral anterior insula (AI), and right temporoparietal junction (TPJ). Essential prognostic predictor variables retained in the elastic net regression included treatment group, gender, Flanker interference response time (RT), right AI-TPJ rsFC, and left AI-right AI rsFC. Prescriptive predictor variables retained included interactions between treatment group and baseline PHQ-9 scores, age, gender, Flanker RT, sequential dependency effects on accuracy, post-error accuracy, right AI-TPJ rsFC, and left AI-right AI rsFC. Inhibitory control and rsFC within inhibitory control-emotion regulation regions predicted reduced symptom severity following iCBT, and these effects were stronger in the iCBT group than in the MAC group. These findings contribute to a growing literature indicating that stronger inhibitory control at baseline predicts better outcomes to psychotherapy, including iCBT.

Aberrant hippocampal Ca2+ microwaves following synapsin-dependent adeno-associated viral expression of Ca2+ indicators.

Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca2+ microwaves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7, or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer in a titre-dependent fashion. Ca2+ microwaves developed in hippocampal CA1 and CA3, but not dentate gyrus nor neocortex, were typically first observed at 4 wk after viral transduction, and persisted up to at least 8 wk. The phenomenon was robust and observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca2+ microwaves depend on the promoter and viral titre of the GECI, density of expression, as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artefact. The results show that commonly used Ca2+-indicator AAV transduction procedures can produce artefactual Ca2+ responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca2+ microwaves, and we provide a potential solution.

Multi-Modal Diagnosis of Alzheimer's Disease using Interpretable Graph Convolutional Networks.

The interconnection between brain regions in neurological disease encodes vital information for the advancement of biomarkers and diagnostics. Although graph convolutional networks are widely applied for discovering brain connection patterns that point to disease conditions, the potential of connection patterns that arise from multiple imaging modalities has yet to be fully realized. In this paper, we propose a multi-modal sparse interpretable GCN framework (SGCN) for the detection of Alzheimer's disease (AD) and its prodromal stage, known as mild cognitive impairment (MCI). In our experimentation, SGCN learned the sparse regional importance probability to find signature regions of interest (ROIs), and the connective importance probability to reveal disease-specific brain network connections. We evaluated SGCN on the Alzheimer's Disease Neuroimaging Initiative database with multi-modal brain images and demonstrated that the ROI features learned by SGCN were effective for enhancing AD status identification. The identified abnormalities were significantly correlated with AD-related clinical symptoms. We further interpreted the identified brain dysfunctions at the level of large-scale neural systems and sex-related connectivity abnormalities in AD/MCI. The salient ROIs and the prominent brain connectivity abnormalities interpreted by SGCN are considerably important for developing novel biomarkers. These findings contribute to a better understanding of the network-based disorder via multi-modal diagnosis and offer the potential for precision diagnostics. The source code is available at https://github.com/Houliang-Zhou/SGCN.

Labeling of the serotonergic neuronal circuits emerging from the raphe nuclei via some retrograde tracers.

Serotonin (5-hydroxytryptamine, 5-HT) is a very important neurotransmitter emerging from the raphe nuclei to several brain regions. Serotonergic neuronal connectivity has multiple functions in the brain. In this study, several techniques were used to trace serotonergic neurons in the dorsal raphe (DR) and median raphe (MnR) that project toward the arcuate nucleus of the hypothalamus (Arc), dorsomedial hypothalamic nucleus (DM), lateral hypothalamic area (LH), paraventricular hypothalamic nucleus (PVH), ventromedial hypothalamic nucleus (VMH), fasciola cinereum (FC), and medial habenular nucleus (MHb). Cholera toxin subunit B (CTB), retro-adeno-associated virus (rAAV-CMV-mCherry), glycoprotein-deleted rabies virus (RV-ΔG), and simultaneous microinjection of rAAV2-retro-Cre-tagBFP with AAV-dio-mCherry in C57BL/6 mice were used in this study. In addition, rAAV2-retro-Cre-tagBFP was microinjected into Ai9 mice. Serotonin immunohistochemistry was used for the detection of retrogradely traced serotonergic neurons in the raphe nuclei. The results indicated that rAAV2-retro-Cre-tagBFP microinjection in Ai9 mice was the best method for tracing serotonergic neuron circuits. All of the previously listed nuclei exhibited serotonergic neuronal projections from the DR and MnR, with the exception of the FC, which had very few projections from the DR. The serotonergic neuronal projections were directed toward the Arc by the subpeduncular tegmental (SPTg) nuclei. Moreover, the RV-ΔG tracer revealed monosynaptic non-serotonergic neuronal projections from the DR that were directed toward the Arc. Furthermore, rAAV tracers revealed monosynaptic serotonergic neuronal connections from the raphe nuclei toward Arc. These findings validate the variations in neurotropism among several retrograde tracers. The continued discovery of several novel serotonergic neural circuits is crucial for the future discovery of the functions of these circuits. RESEARCH HIGHLIGHTS: Various kinds of retrograde tracers were microinjected into C57BL/6 and Ai9 mice. The optimum method for characterizing serotonergic neuronal circuits is rAAV2-retro-Cre-tagBFP microinjection in Ai9 mice. The DR, MnR, and SPTg nuclei send monosynaptic serotonergic neuronal projections toward the arcuate nucleus of the hypothalamus. Whole-brain quantification analysis of retrograde-labeled neurons in different brain nuclei following rAAV2-retro-Cre-tagBFP microinjection in the Arc, DM, LH, and VMH is shown. Differential quantitative analysis of median and dorsal raphe serotonergic neurons emerging toward the PVH, DM, LH, Arc, VMH, MHb, and FC is shown.

Preclinical investigation of the effect of stress on the binding of [18F]F13640, a 5-HT1A radiopharmaceutical

Background[18F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT1A receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT1A receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [18F]FDG and then proceeded to test for effects of this model on the cerebral binding of [18F]F13640, a 5-HT1A receptors PET radiopharmaceutical. MethodsFour groups of male Sprague-Dawley were used to identify the optimal model: “stressed group” (n = 10), “post-traumatic stress disorder (PTSD) group” (n = 9) and “restraint group” (n = 8), compared with a control group (n = 8). All rats performed neuroimaging [18F]FDG μPET-CT to decipher which model was the most appropriate to test effects of stress on radiotracer binding. Subsequently, a group of rats (n = 10) underwent two PET imaging acquisitions (baseline and PTSD condition) using the PET radiopharmaceutical [18F]F13640 to assess influence of stress on its binding. Voxel-based analysis was performed to assess [18F]FDG or [18F]F13640 changes. ResultsIn [18F]FDG experiments, the PTSD group showed a pattern of cerebrometabolic activation in various brain regions previously implicated in stress (amygdala, perirhinal cortex, olfactory bulb and caudate). [18F]F13640 PET scans showed increased radiotracer binding in the PTSD condition in caudate nucleus and brainstem. ConclusionsThe present study demonstrated stress-induced cerebrometabolic activation or inhibition of various brain regions involved in stress model. Applying this model to our radiotracer, [18F]F13640 showed few influence of stress on its binding. This will enable to rule out any confounding effect of stress during imaging studies.

Subthalamic nucleus deep brain stimulation induces functional deficits in norepinephrinergic neurotransmission in a Parkinson’s disease model

BackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) is a successful treatment option in Parkinson’s disease (PD) for different motor and non-motor symptoms, but has been linked to postoperative cognitive impairment. AimSince both dopaminergic and norepinephrinergic neurotransmissions play important roles in symptom development, we analysed STN-DBS effects on dopamine and norepinephrine availability in different brain regions and morphological alterations of catecholaminergic neurons in the 6-hydroxydopamine PD rat model. MethodsWe applied one week of continuous unilateral STN-DBS or sham stimulation, respectively, in groups of healthy and 6-hydroxydopamine-lesioned rats to quantify dopamine and norepinephrine contents in the striatum, olfactory bulb and dentate gyrus. In addition, we analysed dopaminergic cell counts in the substantia nigra pars compacta and area tegmentalis ventralis and norepinephrinergic neurons in the locus coeruleus after one and six weeks of STN-DBS. ResultsIn 6-hydroxydopamine-lesioned animals, one week of STN-DBS did not alter dopamine levels, while striatal norepinephrine levels were decreased. However, neither one nor six weeks of STN-DBS altered dopaminergic neuron numbers in the midbrain or norepinephrinergic neuron counts in the locus coeruleus. Dopaminergic fibre density in the dorsal and ventral striatum also remained unchanged after six weeks of STN-DBS. In healthy animals, one week of STN-DBS resulted in increased dopamine levels in the olfactory bulb and decreased contents in the dentate gyrus, but had no effects on norepinephrine availability. ConclusionsSTN-DBS modulates striatal norepinephrinergic neurotransmission in a PD rat model. Additional behavioural studies are required to investigate the functional impact of this finding.

Eye size does not change with artificial selection on relative telencephalon size in guppies (Poecilia reticulata).

Variation in eye size is sometimes closely associated with brain morphology. Visual information, detected by the retina, is transferred to the optic tectum to coordinate eye and body movements towards stimuli, and thereafter distributed into other brain regions for further processing. The telencephalon is an important visual processing region in many vertebrate species and a highly developed region in visually dependent species. Yet, the existence of a coevolutionary relationship between telencephalon size and eye size remains relatively unknown. Here, we use male and female guppies artificially selected for small- and large-relative-telencephalon-size to test if artificial selection on telencephalon size results in changes in eye size. In addition, we performed an optomotor test as a proxy for visual acuity. We found no evidence that eye size changes with artificial selection on telencephalon size. Eye size was similar in both absolute and relative terms between the two selection regimes, but was larger in females. This is most likely because of the larger body size in females, but it could also reflect their greater need for visual capacity due to sex-specific differences in foraging and mating behaviour. Although the optomotor response was stronger in guppies with a larger telencephalon, we found no evidence for differences in visual acuity between the selection regimes. Our study suggests that eye size and visual perception in guppies does not change rapidly with strong artificial selection on telencephalon size.

Intermittent fasting alleviates postoperative cognitive dysfunction by reducing neuroinflammation in aged mice

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated the exacerbating effect of sevoflurane anesthesia on neuroinflammation, which can further deteriorate the condition of POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and has been demonstrated to ameliorate cognitive dysfunction induced by neuropathic inflammation. We subjected 18-month-old male mice to 16hours of fasting and 8hours of unrestricted eating over a 24-hour period for 0, 1, 2, and 4 weeks, followed by abdominal exploration under sevoflurane anesthesia. In this study, we aim to explore the potential impact of IF on postoperative cognitive function in aged mice undergoing sevoflurane surgery through the preoperative implementation of IF measures. The findings indicate two weeks of IF leads to a significant enhancement of learning and memory capabilities in mice following surgery. The cognitive performance, as determined by the novel object recognition and Morris water maze tests, as well as the synaptic plasticity, as measured by in vivo electrophysiological recordings, has demonstrated marked improvements. Furthermore, the administration of IF markedly enhances the expression of synaptic-associated proteins in hippocampal neurons, concomitant with a decreasing expression of pro-inflammatory factors and a reduced density of microglial cells within the hippocampal brain region. To summarize, the results of this study indicate that IF may mitigate inflammation in the hippocampal area of the brain. Furthermore, IF appears to provide a safeguard against cognitive impairment and synaptic plasticity impairment brought on by sevoflurane anesthesia.

The Brominated Flame Retardant Hexabromocyclododecane Causes Systemic Changes in Polyunsaturated Fatty Acid Incorporation in Mouse Lipids.

Brominated flame retardants are used in many household products to reduce flammability, but often leach into the surrounding environment over time. Hexabromocyclododecane (HBCD) is one brominated flame retardant detected in human blood across the world. HBCD exposure can result in neurological problems and altered lipid metabolism, but to date the two remain unlinked. As lipids constitute ∼50% of brain dry weight, lipid metabolism plays a critical role in neuronal function and homeostasis. To determine the effect of HBCD exposure on brain lipid metabolism, young adult male C57BL/6 mice were exposed to 1 mg/kg HBCD every 3 days for 28 days. Major lipid classes were found to change across brain regions, including the membrane glycerolipids phosphatidylcholine and phosphatidylethanolamine, and sphingolipids such as hexosylceramide. In addition, saturated, monounsaturated, and polyunsaturated fatty acids were enriched within brain lipid species. To understand the source of the brain lipidomic alterations, the blood and liver lipidomes and the cecal microbiome were evaluated. The liver and blood demonstrated changes amongst multiple lipid classes, including triacylglycerol suppression, as well as altered esterified fatty acid content. Significant alterations were also detected in the cecal microbiome, with decreases in the Firmicutes to Bacteriodetes ratio, changes in beta diversity, and pathway alterations associated with metabolic pathways and amino acid biosynthesis. These data demonstrate that HBCD can induce lipidomic alterations across brain regions and organs and supports a potential role of the microbiome in these alterations.

Ageing-related tau astrogliopathy severely affecting the substantia nigra.

Astrocytic tau pathology is a major feature of tauopathies and ageing-related tau astrogliopathy (ARTAG). The substantia nigra (SN) is one of the important degenerative areas in tauopathies with parkinsonism. Nigral tau pathology is usually reported as neuronal predominant with less prominent astrocytic involvement. We aimed to identify cases with prominent astrocytic tau pathology in the SN. We use the term nigral tau-astrogliopathy (NITAG) to describe cases showing an unusually high density of ARTAG with less neuronal tau pathology in the SN. We collected clinical information and studied the distribution of tau pathology, morphological features and immunostaining profiles in three cases. Three cases, all males with parkinsonism, were identified with the following clinicopathological diagnoses: (i) atypical parkinsonism with tau pathology reminiscent to that in postencephalitic parkinsonism (69-year-old); (ii) multiple system atrophy (73-year-old); (iii) traumatic encephalopathy syndrome/chronic traumatic encephalopathy (84-year-old). Double-labelling immunofluorescence confirmed co-localization of GFAP and phosphorylated tau in affected astrocytes. Staining profiles of NITAG revealed immunopositivity for various phosphorylated tau antibodies. Some astrocytic tau lesions were also seen in other brainstem regions and cerebral grey matter. We propose NITAG is a rare neuropathological feature, and not a distinct disease entity, in the frame of multiple system ARTAG, represented by abundant tau-positive astrocytes in various brain regions but having the highest density in the SN. The concept of NITAG allows the stratification of cases with various background pathologies to understand its relevance and contribution to neuronal dysfunction.

Unfolded protein response markers Grp78 and eIF2alpha are upregulated with increasing alpha-synuclein levels in Lewy body disease.

Endoplasmic reticulum stress followed by the unfolded protein response is one of the cellular mechanisms contributing to the progression of α-synuclein pathology in Parkinson's disease and other Lewy body diseases. We aimed to investigate the activation of endoplasmic reticulum stress and its correlation with α-synuclein pathology in human post-mortem brain tissue. We analysed brain tissue from 45 subjects-14 symptomatic patients with Lewy body disease, 19 subjects with incidental Lewy body disease, and 12 healthy controls. The analysed brain regions included the medulla, pons, midbrain, striatum, amygdala and entorhinal, temporal, frontal and occipital cortex. We analysed activation of endoplasmic reticulum stress via levels of the unfolded protein response-related proteins (Grp78, eIF2α) and endoplasmic reticulum stress-regulating neurotrophic factors (MANF, CDNF). We showed that regional levels of two endoplasmic reticulum-localised neurotrophic factors, MANF and CDNF, did not change in response to accumulating α-synuclein pathology. The concentration of MANF negatively correlated with age in specific regions. eIF2α was upregulated in the striatum of Lewy body disease patients and correlated with increased α-synuclein levels. We found the upregulation of chaperone Grp78 in the amygdala and nigral dopaminergic neurons of Lewy body disease patients. Grp78 levels in the amygdala strongly correlated with soluble α-synuclein levels. Our data suggest a strong but regionally specific change in Grp78 and eIF2α levels, which positively correlates with soluble α-synuclein levels. Additionally, MANF levels decreased in dopaminergic neurons in the substantia nigra. Our research suggests that endoplasmic reticulum stress activation is not associated with Lewy pathology but rather with soluble α-synuclein concentration and disease progression.

Sensitivity and specificity of the action observation network to kinematics, target object, and gesture meaning.

Hierarchical models have been proposed to explain how the brain encodes actions, whereby different areas represent different features, such as gesture kinematics, target object, action goal, and meaning. The visual processing of action-related information is distributed over a well-known network of brain regions spanning separate anatomical areas, attuned to specific stimulus properties, and referred to as action observation network (AON). To determine the brain organization of these features, we measured representational geometries during the observation of a large set of transitive and intransitive gestures in two independent functional magnetic resonance imaging experiments. We provided evidence for a partial dissociation between kinematics, object characteristics, and action meaning in the occipito-parietal, ventro-temporal, and lateral occipito-temporal cortex, respectively. Importantly, most of the AON showed low specificity to all the explored features, and representational spaces sharing similar information content were spread across the cortex without being anatomically adjacent. Overall, our results support the notion that the AON relies on overlapping and distributed coding and may act as a unique representational space instead of mapping features in a modular and segregated manner.

Efferent pathways from the suprachiasmatic nucleus to the horizontal limbs of diagonal band promote NREM sleep during the dark phase in mice

The regulation of circadian rhythms and the sleep–wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep–wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN–HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non–rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN–HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep–wake states regulation.