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

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

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

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

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

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

BackgroundSeizure detection is challenging outside the clinical environment due to the lack of comfortable, reliable, and practical long-term neurophysiological monitoring devices. We developed a novel, discreet, unobstructive in-ear sensing system that enables long-term electroencephalography (EEG) recording. This is the first study we are aware of that systematically compares the seizure detection utility of in-ear EEG with that of simultaneously recorded intracranial EEG. In addition, we present a similar comparison between simultaneously recorded in-ear EEG and scalp EEG.MethodsIn this foundational research, we conducted a clinical feasibility study and validated the ability of the ear-EEG system to capture focal-onset seizures against 1255 hrs of simultaneous ear-EEG data along with scalp or intracranial EEG in 20 patients with refractory focal epilepsy (11 with scalp EEG, 8 with intracranial EEG, and 1 with both).ResultsIn a blinded, independent review of the ear-EEG signals, two epileptologists were able to detect 86.4% of the seizures that were subsequently identified using the clinical gold standard EEG modalities, with a false detection rate of 0.1 per day, well below what has been reported for ambulatory monitoring. The few seizures not detected on the ear-EEG signals emanated from deep within the mesial temporal lobe or extra-temporally and remained very focal, without significant propagation. Following multiple sessions of recording for a median continuous wear time of 13 hrs, patients reported a high degree of tolerance for the device, with only minor adverse events reported by the scalp EEG cohort.ConclusionsThese preliminary results demonstrate the potential of using ear-EEG to enable routine collection of complementary, prolonged, and remote neurophysiological evidence, which may permit real-time detection of paroxysmal events such as seizures and epileptiform discharges. This study suggests that the ear-EEG device may assist clinicians in making an epilepsy diagnosis, assessing treatment efficacy, and optimizing medication titration.

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimers disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.

Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1-3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Accurate and scalable quantification of amyloid-β (Aβ) pathology is crucial for deeper disease phenotyping and furthering research in Alzheimer Disease (AD). This multidisciplinary study addresses the current limitations on neuropathology by leveraging a machine learning (ML) pipeline to perform a granular quantification of Aβ deposits and assess their distribution in the temporal lobe. Utilizing 131 whole-slide-images from consecutive autopsied cases at the University of California Davis Alzheimer Disease Research Center, our objectives were threefold: (1) Validate an automatic workflow for Aβ deposit quantification in white matter (WM) and gray matter (GM); (2) define the distributions of different Aβ deposit types in GM and WM, and (3) investigate correlates of Aβ deposits with dementia status and the presence of mixed pathology. Our methodology highlights the robustness and efficacy of the ML pipeline, demonstrating proficiency akin to experts' evaluations. We provide comprehensive insights into the quantification and distribution of Aβ deposits in the temporal GM and WM revealing a progressive increase in tandem with the severity of established diagnostic criteria (NIA-AA). We also present correlations of Aβ load with clinical diagnosis as well as presence/absence of mixed pathology. This study introduces a reproducible workflow, showcasing the practical use of ML approaches in the field of neuropathology, and use of the output data for correlative analyses. Acknowledging limitations, such as potential biases in the ML model and current ML classifications, we propose avenues for future research to refine and expand the methodology. We hope to contribute to the broader landscape of neuropathology advancements, ML applications, and precision medicine, paving the way for deep phenotyping of AD brain cases and establishing a foundation for further advancements in neuropathological research.

• We investigated if postural instability can induce motor resonance. • The unstable, compared to stable, display dampened left temporal theta activity. • The unstable display enhanced left temporal-prefrontal connectivity. • Biological and scramble stimuli differently modulated temporal cortex. • Observed postural (in)stability is encoded in cortical theta oscillations. This study investigates whether postural equilibration follows the same principles of motor resonance as goal-oriented actions, namely, whether an individual activates the same neuronal substrates when experiencing postural perturbation as when observing another individual in this condition. To address this question, we examined electroencephalographic dynamics while subjects observed point-light displays featuring an unstable human display, a stable human display, and their respective scrambled counterparts lacking shape information and biological motion. We focused on theta band (4–7 Hz), which is a fundamental frequency for modulating brain activity during challenging balance tasks and reflects postural stability monitoring. Rather than mirroring activity, our findings suggest an inhibitory response to postural instability. Theta event-related synchronization in the left temporal cortex was dampened for the unstable display as compared to its scramble counterpart and to the stable display. This low theta response coincided with an increase in left temporal-prefrontal connectivity, compatible with top-down inhibitory mechanisms. By contrast, the stronger theta response to the stable display as compared to the unstable one could be due to the difficulty of recognizing low-motion biological stimuli, or alternatively, to a facilitation of stimulus processing and strengthening of the mirroring response. The response facilitation for stable posture, coupled with a diminished response to the unstable display, could contribute to a broader mechanism mitigating postural threats and ensuring stable balance. Future investigations should leverage these findings to explore how posture-related responses correlate with perceptual and motor expertise, and to more clearly define these mechanisms during dynamic social interactions. [ABSTRACT FROM AUTHOR]

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network whilemacaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Comparedwith distractors, fixations on targets reduced spike--LFP coherence within the temporal cortex. Importantly, targetinduced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks. [ABSTRACT FROM AUTHOR]

• Diffusion in subarachnoid space was more isotropic with aging in young adults. • Other brain regions did not show an age-related decline of diffusion anisotropy. • Diffusion anisotropy in subarachnoid space was highest in the temporal lobe. • Reduced anisotropy may be relevant to reduced glymphatic transport with aging. The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. For instance, the SAS around the middle cerebral artery is known to be highly involved in glymphatic influx. While diffusion tensor imaging has been used for studying the glymphatic system, there has been limited exploration of age-related changes in diffusion anisotropy within SAS and their regional variations. Given the narrow and heterogeneous morphology of SAS, the fractional anisotropy (FA) in diverse brain regions may be more relevant to glymphatic transport than mean diffusivity (MD). The goal of this study was to investigate FA in SAS to observe age-related changes across different brain regions and to interpret the results based on the glymphatic transport. We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport. [ABSTRACT FROM AUTHOR]

• We propose a model to detect the spatial locus of a listener's auditory attention. • EEG is modeled as a graph with node features based on time-frequency feature fusion. • Graph convolution can take advantage of local brain neuroanatomical connectivity. • Global attention mechanism is adopted to learn global brain effective connectivity. • Right-lateralized frontotemporal activation and connectivity exist in spatial hearing. Auditory spatial attention detection (ASAD) aims to decipher the spatial locus of a listener's selective auditory attention from electroencephalogram (EEG) signals. However, current models may exhibit deficiencies in EEG feature extraction, leading to overfitting on small datasets or a decline in EEG discriminability. Furthermore, they often neglect topological relationships between EEG channels and, consequently, brain connectivities. Although graph-based EEG modeling has been employed in ASAD, effectively incorporating both local and global connectivities remains a great challenge. To address these limitations, we propose a new ASAD model. First, time-frequency feature fusion provides a more precise and discriminative EEG representation. Second, EEG segments are treated as graphs, and the graph convolution and global attention mechanism are leveraged to capture local and global brain connections, respectively. A series of experiments are conducted in a leave-trials-out cross-validation manner. On the MAD-EEG and KUL datasets, the accuracies of the proposed model are more than 9% and 3% higher than those of the corresponding state-of-the-art models, respectively, while the accuracy of the proposed model on the SNHL dataset is roughly comparable to that of the state-of-the-art model. EEG time-frequency feature fusion proves to be indispensable in the proposed model. EEG electrodes over the frontal cortex are most important for ASAD tasks, followed by those over the temporal lobe. Additionally, the proposed model performs well even on small datasets. This study contributes to a deeper understanding of the neural encoding related to human hearing and attention, with potential applications in neuro-steered hearing devices. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Broca's aphasia is a crushing syndrome after stroke. Although there are multiple therapies, the recovery of a considerable number of patients is still not ideal. Repetitive transcranial magnetic stimulation (rTMS) combined with speech and language therapy has been a promising combination regimen in recent years. However, the efficacy and persistent effects thereof remain unclear. We aimed to determine the immediate and long-term effects of rTMS combined with speech and language therapy on subacute stroke patients with Broca's aphasia and explore relevant mechanisms in the picture-naming task via functional near-infrared spectroscopy (fNIRS). Materials and methods: This was a prospective clinical study. In accordance with the inclusion criteria, 18 patients with post-stroke were recruited and randomly divided into either the rTMS group or the sham-rTMS group. Patients in both groups received low-frequency rTMS therapy for 20 min a day and then speech and language therapy for 30 min a day, 5 days a week, for a total of 4 weeks. Two groups of patients underwent the Western Aphasia Battery Revised (WAB-R), the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39), and non-language-based cognitive assessment (NLCA) before treatment and at 2 weeks, 4 weeks, and 3 months after treatment. Meanwhile, we collected fNIRS task state data while naming images before and after 4 weeks of treatment. The primary outcome was WAB-R changes. The secondary outcomes include the SAQOL-39, NLCA, as well as the difference in activation status of brain regions in the cortical language function network. Results: For the index scores of the two groups, the results of repeated-measures ANOVA indicated an increasing trend at three time points, i.e., after 2 weeks of treatment, 4 weeks after treatment, and 3 months after the end of treatment (p < 0.001); in terms of intergroup effects, there was a statistically significant difference between the two groups in WAB naming scores (F = 4.865, p = 0.042); and the aphasia quotient (AQ), listening comprehension, and naming scores of the two groups had interactive effects (F AQ = 11.316, P AQ = 0.000; F listening = 8.205, P listening = 0.002; F naming = 27.46, P naming = 0.000). Independent sample t-tests also showed that until 4 weeks after the end of treatment, there were significant differences in information volume and naming scores between the two groups (t information = 2.352, P information = 0.032; t naming = 3.164, P naming = 0.006). Three months after the end of treatment, there were significant differences in information volume, naming, AQ and repetition scores (t information = 2.824, P information = 0.012; t naming = 5.090, P naming = 0.000; t AQ = 2.924, P AQ = 0.010; t repetition = 2.721, P repetition = 0.015). In the picture-naming task, fNIRS analysis found that in the rTMS group after treatment, the activation in the left superior temporal gyrus (STG), middle temporal gyrus (MTG), premotor cortex (PM), supplementary motor area (SMA), pars triangularis Broca's area, and dorsolateral prefrontal lobe (DLPFC) decreased (p < 0.05). Conclusion: The language function of patients was improved after 4 weeks of treatment, and there was a long-term effect (3 months follow-up), especially in naming gains. Moreover, by analyzing cortical activation during a picture-naming task with fNIRS, we found that rTMS could downgrade the activation level in the left MTG, STG, PM and SMA, DLPFC, and pars triangularis Broca's area, whereas the sham-rTMs group only showed downgraded activation levels in the right PM and SMA. This demonstrates the unique mechanism of rTMS. Clinical trial registration : ChiCTR.org.cn, identifier, ChiCTR2300067703. [ABSTRACT FROM AUTHOR]

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information involved in sublexical information processing. However, a comprehensive spatiotemporal neural network for sublexical processing remains to be fully elucidated due to the low temporal or spatial resolutions of previous neuroimaging studies. In this study, we recorded stereoelectroencephalography signals with high spatial and temporal resolutions from a large sample of 39 epilepsy patients (both sexes) during a Chinese character oral reading task. We explored the activated brain regions and their connectivity related to three sublexical effects: phonological regularity (whether the whole character's pronunciation aligns with its phonetic radical), phonological consistency (whether characters with the same phonetic radical share the same pronunciation), and semantic transparency (whether the whole character's meaning aligns with its semantic radical). The results revealed that sublexical effects existed in the inferior frontal gyrus, precentral and postcentral gyri, temporal lobe, and middle occipital gyrus. Additionally, connectivity from the middle occipital gyrus to the postcentral gyrus and from postcentral gyrus to the fusiform gyrus was associated with the sublexical effects. These findings provide valuable insights into the spatiotemporal dynamics of sublexical processing and object recognition in the brain. [ABSTRACT FROM AUTHOR]

Estimating the direction of functional connectivity (FC) can help further elucidate complex brain function. However, the estimation of directed FC at the voxel level in fMRI data, and evaluating its performance, has yet to be done. We therefore developed a novel directed seed-based connectivity analysis (SCA) method based on normalized pairwise Granger causality that provides greater detail and accuracy over ROI-based methods. We evaluated its performance against 145 cortical retrograde tracer injections in male and female marmosets that were used as ground truth cellular connectivity on a voxel-by-voxel basis. The receiver operating characteristic (ROC) curve was calculated for each injection, and we achieved area under the ROC curve of 0.95 for undirected and 0.942 for directed SCA in the case of high cell count threshold. This indicates that SCA can reliably estimate the strong cellular connections between voxels in fMRI data. We then used our directed SCA method to analyze the human default mode network (DMN) and found that dlPFC (dorsolateral prefrontal cortex) and temporal lobe were separated from other DMN regions, forming part of the languagenetwork that works together with the core DMN regions. We also found that the cerebellum (Crus I-II) was strongly targeted by the posterior parietal cortices and dlPFC, but reciprocal connections were not observed. Thus, the cerebellum may not be a part of, but instead a target of, the DMN and language-network. Summarily, our novel directed SCA method, visualized with a new functional flat mapping technique, opens a new paradigm for whole-brain functional analysis. [ABSTRACT FROM AUTHOR]

In this study, we examined the relatively unexplored realm of face perception, investigating the activities within human brain face-selective regions during the observation of faces at both subordinate and superordinate levels. We recorded intracranial EEG signals from the ventral temporal cortex in neurosurgical patients implanted with subdural electrodes during viewing of face subcategories (human, mammal, bird, and marine faces) as well as various non-face control stimuli. The results revealed a noteworthy correlation in response patterns across all face-selective areas in the ventral temporal cortex, not only within the same face category but also extending to different face categories. Intriguingly, we observed a systematic decrease in response correlation coupled with an increased response onset time from human face to mammalian face, bird face and marine faces. Our result aligns with the notion that distinctions at the basic level category (e.g., human face versus non-human face) emerges earlier than those at the superordinate level (e.g., animate versus inanimate). This indicates response gradient in the representation of facial images within human face-sensitive regions, transitioning progressively from human faces to non-face stimuli. Our findings provide insights into spatiotemporal dynamic of face representations which varies spatially and at different timescales depending on the face subcategory represented. [ABSTRACT FROM AUTHOR]

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non‐functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full‐text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer‐reviewed journal. The full‐text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case–control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre‐operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

ABSTRACT This article focuses on familiarity, the form of memory allowing humans to recognize stimuli that have been encountered before. We aim to emphasize its complex nature which includes representational and phenomenological dimensions. The former implies that its neural correlates depend on the type and complexity of the cue stimulus, as different classes of stimuli are represented in distributed ventral visual and medial temporal regions. The second dimension relates to the subjective feeling of familiarity, which results from a fluency signal that is attributed to past encounters with the stimulus. We review mnemonic and non‐mnemonic sources of fluency that can induce a sense of familiarity, as well as cases where fluency is not attributed to memory, among which the phenomenological experience of déjà‐vu. Across these two dimensions, we highlight key questions to be answered by future studies to improve our understanding of the underpinnings of this form of memory and contribute to building an integrative neurocognitive model of familiarity. Essential to this aim is the clarification of the computational, cognitive, and neural mechanisms involved, namely global matching, fluency attribution, and sharpening. Furthermore, future research is needed to unravel the relationships between these mechanisms. We argue that to achieve these goals, researchers must use appropriate behavioral paradigms and clearly define which dimension of familiarity they investigate. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Anterior temporal lobe resection (ATLR) is an effective treatment for drug‐resistant temporal lobe epilepsy (TLE), although language deficits may occur after both left and right ATLR. Functional reorganization of the language network has been observed in the ipsilateral and contralateral hemispheres within 12 months after ATLR, but little is known of longer‐term plasticity effects. Our aim was to examine the plasticity of language functions up to a decade after ATLR, in relation to cognitive profiles.We examined 24 TLE patients (12 left [LTLE]) and 10 controls across four time points: pre‐surgery, 4 months, 12 months, and ~9 years post‐ATLR. Participants underwent standard neuropsychological assessments (naming, phonemic, and categorical fluency tests) and a verbal fluency functional magnetic resonance imaging (fMRI) task. Using a flexible factorial design, we analyzed longitudinal fMRI activations from 12 months to ~9 years post‐ATLR, relative to controls, with separate analyses for people with hippocampal sclerosis (HS). Change in cognitive profiles was correlated with the long‐term change in fMRI activations to determine the “efficiency” of reorganized networks.LTLE patients had increased long‐term engagement of the left extra‐temporal and contralateral temporal regions, with better language performance linked to bilateral activation. Those with HS exhibited more widespread bilateral activations. RTLE patients showed plasticity in the left extra‐temporal regions, with better language outcomes associated with these areas. Both groups of patients achieved cognitive stability over 9 years, with more than 50% of LTLE patients improving. Older age, longer epilepsy duration, and lower pre‐operative cognitive reserve negatively affected long‐term language performance.Neuroplasticity continues for up to ~9 years post‐epilepsy surgery in LTLE and RTLE, with effective language recovery linked to bilateral engagement of temporal and extra‐temporal regions. This adaptive reorganization is associated with improved cognitive outcomes, challenging the traditional view of localized surgery effects. These findings emphasize the need for early intervention, tailored pre‐operative counseling, and the potential for continued cognitive gains with extended post‐ATLR rehabilitation. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Different types of physical training can lead to changes in brain activity and function, and these changes can vary depending on the type of training. However, it remains unclear whether there are commonalities in how different types of training affect brain activity and function. The purpose of this study is to compare the brain activity states of professional athletes with those of ordinary university students and to explore the relationship between training and differences in brain activity states.This study primarily utilizes resting‐state MRI and the degree centrality metric to investigate spontaneous brain activity in 86 high‐level athletes with extensive training and 74 age‐ and gender‐matched nonathletes. Additionally, a correlation analysis between brain activity in relevant regions and years of training was conducted.The analysis revealed that, compared to nonathletes, high‐level athletes exhibited reduced activity in the Calcarine (a visual area) and Middle Temporal Gyrus. Furthermore, changes in the activity of the Calcarine and Middle Temporal Gyrus were significantly correlated with the number of years of professional training.The study results indicate that long‐term physical training is associated with changes in brain activity in athletes, providing insights into the neural mechanisms underlying behavioral performance in professional athletes. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). Methods: The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. Results: T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P =0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. Conclusions: T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD. [ABSTRACT FROM AUTHOR]

Background: Functional magnetic resonance imaging has been used in many studies to explore the neural mechanism of acupuncture in patients with post-stroke motor dysfunction. Inconsistent results have been found in these studies, however. This activation likelihood estimation (ALE) meta-analysis was designed to quantitatively integrate changes in brain activity and the neurological effects of acupuncture on patients with motor dysfunction after stroke. Methods: We searched PubMed, Embase, Web of Science, the Cochrane Library, China Science and Technology Journal Database, the China Biology Medicine, the China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform for literature from the establishment of the database until March 21, 2024. Research papers were selected, data extracted, and quality assessment was done independently by two researchers. The GingerALE software was used for meta-analysis, and Jackknife sensitivity analysis was employed to assess result robustness. Results: We ended up analyzing 14 studies that included 235 patients and 100 healthy people. ALE meta-analysis showed that Compared with healthy people, the enhanced brain region in poststroke patients with motor dysfunction was located in the left posterior lobe of the cerebellum, the left inferior frontal gyrus, and the left precuneus (p < 0.001). After acupuncture, the activated regions were mainly located in the left posterior lobe of the cerebellum, the right lentiform nucleus putamen, the right medial frontal gyrus, the right inferior frontal gyrus, the left precuneus, the right middle temporal gyrus, the left claustrum, the left cerebellar tonsil, the right superior marginal gyrus, the inactivated area is located in the right medial frontal gyrus the left precentral gyrus and the right precuneus (p < 0.001). Conclusion: Acupuncture can reestablish motor function by causing extensive changes in the brain function of patients with stroke, which may be the neurological effect of acupuncture therapy on stroke patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024526263. [ABSTRACT FROM AUTHOR]

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) reveals diverse neural activity patterns in cervical spondylosis (CS) patients. However, the reported results are inconsistent. Therefore, our objective was to conduct a meta-analysis to synthesize the findings from existing rs-fMRI studies and identify consistent patterns of neural brain activity alterations in patients with CS. Materials and methods: A systematic search was conducted across PubMed, Web of Knowledge, Embase, Google Scholar, and CNKI for rs-fMRI studies that compared CS patients with healthy controls (HCs), up to January 28, 2024. Significant cluster coordinates were extracted for comprehensive analysis. Results: We included 16 studies involving 554 CS patients and 488 HCs. CS patients demonstrated decreased brain function in the right superior temporal gyrus and left postcentral gyrus, and increased function in the left superior frontal gyrus. Jackknife sensitivity analysis validated the robustness of these findings, and Egger's test confirmed the absence of significant publication bias (p > 0.05). Meta-regression showed no significant impact of age or disease duration differences on the results. Conclusion: This meta-analysis confirms consistent alterations in specific brain regions in CS patients, highlighting the potential of rs-fMRI to refine diagnostic and therapeutic strategies. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42024496263. [ABSTRACT FROM AUTHOR]

Background: New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. Methods: The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. Results: T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. Conclusions: Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Lesions causing refractory epilepsy, often associated with temporal lobe epilepsy (TLE), can be undetectable on standard magnetic resonance imaging (MRI) in dogs. Automated brain volumetry, widely used in human medicine, can now be applied in veterinary medicine because of the availability of brain atlases.This study aimed to develop an automatic volumetry method, translate the outcomes into the assessment of temporal lobe volumes in dogs with idiopathic epilepsy, and correlate the results with the electroencephalography (EEG) data of epileptiform discharges (EDs).Thirty‐one dogs of various breeds with dominant temporal lobe discharge.Retrospective, observational study. The MRI and EEG examination results of dogs referred for neurological diagnosis data between 2016 and 2021 were retrospectively analyzed. An automated volumetry method was developed, which allowed the evaluation of temporal lobe volumes of the dogs. The asymmetric ratio (AR) was then estimated, and the results were correlated with the EEG EDs.12/31 (38%; 95% CI: 21.8%‐57.8%) dogs had an asymmetric ratio >6%. Among them, reduction in temporal lobe volumes correlated with the side of the EEG EDs in 7 cases. There was no statistical correlation between temporal lobe volume changes and ED location.Preliminary volumetric analysis of the temporal lobes indicates the presence of volume differences between the lobes in some dogs with idiopathic epilepsy. Diagnosis of TLE in dogs based on MRI volumetry in correlation with EEG examination, especially for dogs with drug‐resistant epilepsy, can influence the development of new therapeutic options, such as surgery. [ABSTRACT FROM AUTHOR]

Food is fundamental to survival, and our brains are highly attuned to rapidly process food stimuli. Neural signals show that foods can be discriminated as edible or inedible as early as 85 ms after stimulus onset, 1 distinguished as processed or unprocessed beginning at 130 ms, 2 and as high or low density from 165 ms. 3 Recent evidence revealed specialized processing of food stimuli in the ventral visual pathway, 4,5,6 an area that underlies perception of faces and other important objects. For many visual objects, perception can be biased toward recent perceptual history (known as serial dependence 7,8). We examined serial dependence for food in two large samples (n > 300) who rated sequences of food images for either "appeal" or "calories." Ratings for calories were highly correlated between participants and were similar for males and females. Appeal ratings varied considerably between participants, consistent with the idiosyncratic nature of food preferences, and tended to be higher for males than females. High-calorie ratings were associated with high appeal, especially in males. Importantly, response biases showed clear positive serial dependences: higher stimulus values in the previous trials led to positive biases, and vice versa. The effects were similar for males and females and for calories and appeal ratings and were remarkably consistent across participants. These findings square with recently found food selectively in the visual temporal cortex, reveal a new mechanism influencing food decision-making, and suggest a new sensory-level component that could complement cognitive strategies in diet intervention. • Ratings of food images for calories or appeal are not serially independent • Both rating types show an "attraction" bias toward the previously seen food • For appeal ratings, the bias declined with hunger and age and increased with BMI • This perceptual bias in food appraisal could augment existing clinical interventions Alais et al. show that ratings of food images for appeal or calories are biased toward foods previously seen, with current ratings being higher after a highly rated food (and vice versa). Many visual stimuli show this bias, thought to arise at sensory levels. This bias could be used to nudge sensory food responses higher or lower to moderate food behaviors. [ABSTRACT FROM AUTHOR]

Mental time travel (MTT), a cornerstone of human cognition, enables individuals to mentally project themselves into their past or future. It was shown that this self-projection may extend beyond the temporal domain to the spatial and social domains. What about higher cognitive domains? Twenty-eight participants underwent functional magnetic resonance imaging (fMRI) while self-projecting to different political, moral and temporal perspectives. For each domain, participants were asked to judge their relationship to various people (politicians, moral figures, personal acquaintances) from their actual or projected self-location. Findings showed slower, less accurate responses during self-projection across all domains. fMRI analysis revealed self-projection elicited brain activity at the precuneus, medial and dorsolateral prefrontal cortex, temporoparietal junction and anterior insula, bilaterally and right lateral temporal cortex. Notably, 23.5% of active voxels responded to all three domains and 27% to two domains, suggesting a shared brain system for self-projection. For ordinality judgement (self-reference), 52.5% of active voxels corresponded to the temporal domain specifically. Self-projection activity overlapped mostly with the frontoparietal control network, followed by the default mode network, while self-reference showed a reversed pattern, demonstrating MTT's implication in spontaneous brain activity. MTT may thus be regarded as a 'mental-experiential travel', with self-projection as a domain-general construct and self-reference related mostly to time. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'. [ABSTRACT FROM AUTHOR]

The clinical manifestation of Parkinson's disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson's disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration. We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning algorithm that combined disease progression modelling with clustering methods, to cortical and subcortical neurodegeneration visible on 3 T structural MRI of a large cross-sectional sample of 504 patients and 279 healthy controls. Serial longitudinal data were available for a subset of 178 patients at the 2-year follow-up and for 140 patients at the 4-year follow-up. In a subset of 210 patients, concomitant Alzheimer's disease pathology was assessed by evaluating amyloid-β concentrations in the CSF or via the amyloid-specific radiotracer 18F-flutemetamol with PET. The SuStaIn analysis revealed three distinct subtypes, each characterized by unique patterns of spatiotemporal evolution of brain atrophy: neocortical, limbic and brainstem. In the neocortical subtype, a reduction in brain volume occurred in the frontal and parietal cortices in the earliest disease stage and progressed across the entire neocortex during the early stage, although with relative sparing of the striatum, pallidum, accumbens area and brainstem. The limbic subtype represented comparative regional vulnerability, which was characterized by early volume loss in the amygdala, accumbens area, striatum and temporal cortex, subsequently spreading to the parietal and frontal cortices across disease stage. The brainstem subtype showed gradual rostral progression from the brainstem extending to the amygdala and hippocampus, followed by the temporal and other cortices. Longitudinal MRI data confirmed that 77.8% of participants at the 2-year follow-up and 84.0% at the 4-year follow-up were assigned to subtypes consistent with estimates from the cross-sectional data. This three-subtype model aligned with empirically proposed subtypes based on age at onset, because the neocortical subtype demonstrated characteristics similar to those found in the old-onset phenotype, including older onset and cognitive decline symptoms (P < 0.05). Moreover, the subtypes correspond to the three categories of the neuropathological consensus criteria for symptomatic patients with Lewy pathology, proposing neocortex-, limbic- and brainstem-predominant patterns as different subgroups of α-synuclein distributions. Among the subtypes, the prevalence of biomarker evidence of amyloid-β pathology was comparable. Upon validation, the subtype model might be applied to individual cases, potentially serving as a biomarker to track disease progression and predict temporal evolution. [ABSTRACT FROM AUTHOR]

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, whereas semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE and 60 age- and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient-mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, in both the MTL and neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, in contrast, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, whereas hippocampal functional topographies were unaffected. Furthermore, leveraging MRI proxies of MTL pathology, we observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic memory, but again not in semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, whereas episodic processes are supported by a network involving both the hippocampus and the neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE. [ABSTRACT FROM AUTHOR]

Background and Purpose: In recent years, there has been a growing interest in the study of resting neural networks in different neurological and mental disorders. While previous studies suggest that the default mode network (DMN) may be altered in dyscalculia, the study of resting‐state networks in the development of numerical skills, especially in children with developmental dyscalculia (DD), is scarce and relatively recent. Based on this, this study examines differences in resting‐state functional connectivity (rs‐FC) data of children with DD using functional connectivity multivariate pattern analysis (fc‐MVPA), a data‐driven methodology that summarizes properties of the entire connectome. Methods: We performed fc‐MVPA on resting‐state images of a sample composed of a group of children with DD (n = 19, 8.06 ± 0.87 years) and an age‐ and sex‐matched control group of typically developing children (n = 23, 7.76 ± 0.46 years). Results: Analysis of fc‐MVPA showed significant differences between group connectivity profiles in two clusters allocated in both the right and left medial temporal gyrus. Post hoc effect size results revealed a decreased rs‐FC between each temporal pole and the DMN in children with DD and an increased rs‐FC between each temporal pole and the sensorimotor network. Conclusions: Our results suggest an aberrant information flow between resting‐state networks in children with DD, demonstrating the importance of these networks for arithmetic development. [ABSTRACT FROM AUTHOR]

Purpose: A relevant aspect of listening is the effort required during speech processing, which can be assessed by pupillometry. Here, we assessed the pupil dilation response of normal-hearing (NH) and hard of hearing (HH) individuals during listening to clear sentences and masked or degraded sentences. We combined this assessment with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of the pupil dilation response. Method: Seventeen NH participants (Mage = 46 years) were compared to 17 HH participants (Mage = 45 years) who were individually matched in age and educational level. Participants repeated sentences that were presented clearly, that were distorted, or that were masked. The sentence intelligibility level of masked and distorted sentences was 50% correct. Silent baseline trials were presented as well. Performance measures, pupil dilation responses, and fMRI data were acquired. Results: HH individuals had overall poorer speech reception than the NH participants, but not for noise-vocoded speech. In addition, an interaction effect was observed with smaller pupil dilation responses in HH than in NH listeners for the degraded speech conditions. Hearing impairment was associated with higher activation across conditions in the left superior temporal gyrus, as compared to the silent baseline. However, the region of interest analysis indicated lower activation during degraded speech relative to clear speech in bilateral frontal regions and the insular cortex, for HH compared to NH listeners. Hearing impairment was also associated with a weaker relation between the pupil response and activation in the right inferior frontal gyrus. Overall, degraded speech evoked higher frontal activation than clear speech. Conclusion: Brain areas associated with attentional and cognitive-control processes may be increasingly recruited when speech is degraded and are related to the pupil dilation response, but this relationship is weaker in HH listeners. [ABSTRACT FROM AUTHOR]

Memory is notoriously fallible and susceptible to misinformation. Yet little is known about the underlying cognitive and neural mechanisms that render individuals vulnerable to this type of false memory. The current experiments take an individual differences approach to examine whether susceptibility to misinformation reflects stable underlying factors related to memory retrieval. In Study 1, we report for the first time the existence of substantial individual variability in susceptibility to misinformation in the context of repeated memory retrieval, when the misinformation effect is most pronounced. This variability was not related to an individual's tendency to adopt an episodic retrieval style during remembering (trait mnemonics). In Study 2, we next examined whether susceptibility to misinformation is related to intrinsic functional connectivity in medial temporal lobe (MTL) networks known to coordinate memory reactivation during event retrieval. Stronger resting-state functional connectivity between the MTL and cortical areas associated with visual memory reactivation (occipital cortex) was associated with better protection from misinformation. Together, these results reveal that while memory distortion is a universal property of our reconstructive memory system, susceptibility to misinformation varies at the individual level and may depend on one's ability to reactivate visual details during memory retrieval. [ABSTRACT FROM AUTHOR]

Symmetrical lesions in the temporal poles and external capsules on brain MRI are known as radiological markers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); however, similar imaging findings have also been reported in neuromyelitis optica spectrum disorder (NMOSD), and this study investigated the frequency of such findings. The study included 55 NMOSD patients who met the 2015 international NMO diagnosis panel (IPND) criteria and were positive for aquaporin-4 antibodies (AQP4-Ab). Images were evaluated based on the consensus of two neuroradiologists, and brain lesions were detected in 33 patients, of whom 2 (6%) had symmetrical lesions in both the temporal poles and external capsules, and 1 (3%) had symmetrical lesions confined to the external capsules. Therefore, when symmetrical lesions in the temporal poles and external capsules are observed on MRI, NMOSD should be considered in the differential diagnosis. [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]

STUDY QUESTION Are there neurobiological changes induced by endometriosis? SUMMARY ANSWER Women with endometriosis demonstrate specific neurobiological changes distinct from those in patients with chronic pelvic pain (CPP) in the absence of endometriosis. WHAT IS KNOWN ALREADY Endometriosis is a chronic disease affecting women of reproductive age that presents with pain and infertility often accompanied by comorbid mental disorders. Only one study with a number of limitations has investigated changes in gray matter volumes and functional connectivity in a small group of patients with endometriosis. STUDY DESIGN, SIZE, DURATION This prospective study recruited 53 women undergoing a laparoscopy due to suspicion of symptomatic endometriosis and 25 healthy, pain-free women. Clinical and psychological characteristics, thermal pain perception, and voxel- and surface-based morphology were assessed in all study participants. Thereafter, the patients underwent a laparoscopy, where endometriosis was either histologically confirmed and removed, or ruled out. Correspondingly, patients were assigned into the group with endometriosis (n = 27) or with endometriosis-independent CPP (n = 26) and compared to the pain-free controls. PARTICIPANTS/MATERIALS, SETTING, METHODS The study groups were generally representative for the population of women with endometriosis. Sociodemographic, medical, clinical, and psychological characteristics were collected using various questionnaires and a structured clinical interview. Thermal pain perception and voxel- and surface-based morphometry were assessed using thermode and MRI, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Despite comparable pain intensity and burden of mental disorders, both patient groups demonstrated distinct neurobiological patterns. Women with endometriosis exhibited increased gray matter volume (GMV) in the left cerebellum, lingual gyrus and calcarine gyrus, compared to those with endometriosis-independent CPP. Patients with CPP had decreased GMV in the right cerebellum as compared to controls. Dysmenorrhoea severity correlated positively with GMV in the left inferior parietal lobule, whereas depressive symptoms were associated with decreased GMV in the right superior medial gyrus across patient groups. Dyspareunia correlated negatively with cortical thickness in the left inferior temporal gyrus and left middle temporal gyrus. LIMITATIONS, REASONS FOR CAUTION The study groups differed in a few baseline-characteristics, including educational levels, smoking and BMI. While measuring pain perception thresholds, we did not attempt to mimic CPP by placement of the thermode on the abdominal wall. WIDER IMPLICATIONS OF THE FINDINGS Changes in gray matter volume associated with endometriosis differ from those observed in women with endometriosis-independent CPP. Our results underline an involvement of the cerebellum in pain perception and the pathogenesis of pain associated with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the START Program of the Faculty of Medicine, RWTH Aachen, Germany, and supported by the International Research Training Group (IRTG 2150) of the German Research Foundation (DFG)—269953372/GRK2150, Germany. S.T. was supported by postdoctoral fellowship of the Faculty of Medicine, RWTH Aachen, Germany. There are no conflicts of interest. TRIAL REGISTRATION NUMBER DRKS00021236 [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole‐brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD‐FOG) and 8 without FOG (PD‐nFOG), and 10 healthy controls were enrolled. High‐resolution 3D T1‐weighted and resting‐state functional MRI (rs‐fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs‐fMRI FC using seed‐based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs‐fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = −0.82, P <.001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD‐nFOG group. PD‐FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD‐nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD‐FOG and distinguishing between PD subtypes. [ABSTRACT FROM AUTHOR]

Cochlear implants (CIs) are the most successful neural prostheses, enabling individuals with severe to profound hearing loss to access sounds and understand speech. While CI has demonstrated success, speech perception outcomes vary largely among CI listeners, with significantly reduced performance in noise. This review paper summarizes prior findings on speech-evoked cortical activities in adult CI listeners using functional near-infrared spectroscopy (fNIRS) to understand (a) speech-evoked cortical processing in CI listeners compared to normal-hearing (NH) individuals, (b) the relationship between these activities and behavioral speech recognition scores, (c) the extent to which current fNIRS-measured speech-evoked cortical activities in CI listeners account for their differences in speech perception, and (d) challenges in using fNIRS for CI research. Compared to NH listeners, CI listeners had diminished speech-evoked activation in the middle temporal gyrus (MTG) and in the superior temporal gyrus (STG), except one study reporting an opposite pattern for STG. NH listeners exhibited higher inferior frontal gyrus (IFG) activity when listening to CI-simulated speech compared to natural speech. Among CI listeners, higher speech recognition scores correlated with lower speech-evoked activation in the STG, higher activation in the left IFG and left fusiform gyrus, with mixed findings in the MTG. fNIRS shows promise for enhancing our understanding of cortical processing of speech in CI listeners, though findings are mixed. Challenges include test-retest reliability, managing noise, replicating natural conditions, optimizing montage design, and standardizing methods to establish a strong predictive relationship between fNIRS-based cortical activities and speech perception in CI listeners. [ABSTRACT FROM AUTHOR]

In healthy vision, bright slow-motion stimuli are processed primarily by the regions of the visual system that receive input from the central part of the scene, whereas processing of dark fast-motion stimuli is more dependent on peripheral visual input. We tested 31 retinitis pigmentosa (RP) patients with long-term loss of peripheral photoreceptors and healthy controls with temporarily limited peripheral vision. We measured motion-based acuity using random-dot kinematograms, establishing individual thresholds for differentiating a circle from an ellipse. Participants subsequently performed a functional magnetic resonance imaging (fMRI) task set at a constant level of difficulty. The results showed that limiting vision did not affect motion-acuity thresholds in control participants but did cause different brain activations than those in RP patients, indicating prompt implementation of the strategy that would be perceptually successful. Compared with controls with both full and limited vision, impaired motion acuity in RP patients led to decreased brain activation, particularly in the primary peripheral visual areas V1-3. Importantly, compared with controls in full vision, matched decreased activation in MT+/V5, salience-processing cortices and the superior temporal cortex were detected in RP patients and in controls with limited peripheral vision, revealing brain networks that compensate for the loss of peripheral vision. [ABSTRACT FROM AUTHOR]

Unitization – the fusion of objects into a single unit through an action/consequence sequence – can mitigate relational memory impairments, but the circumstances under which unitization is effective are unclear. Using transverse patterning (TP), we compared unitization (and its component processes of fusion, motion, and action/consequence) with extended practice on relational learning and transfer in older adults and neuropsychological cases with lesions (to varying extents) in the medial prefrontal cortex (mPFC) or hippocampus/medial temporal lobe (HC/MTL). The latter included a person with bilateral HC lesions primarily within the dentate gyrus. For older adults, TP accuracy increased, and transfer benefits were observed, with extended practice and unitization. Broadly, the lesion cases did not benefit from either extended practice or unitization, suggesting the mPFC and dentate gyrus play important roles in relational memory and in unitization. The results suggest that personalized strategy interventions must align with the cognitive and neural profiles of the user. [ABSTRACT FROM AUTHOR]

To explore changes in cerebral cortex activation and functional connectivity during resting-state and verbal fluency tasks in patients with different types of dementia. We recorded oxygenated hemoglobin concentration (HbO) signals detected by functional near-infrared spectroscopy (fNIRS) from the prefrontal cortex, partial parietal cortex, and cortex of the temporal lobe in four groups of participants: mild cognitive impairment (MCI), Lewy body dementia (LBD), Alzheimer's disease (AD), and cognitively normal (CN). The study recruited 120 older adults with MCI (n = 30), LBD (n = 28), AD (n = 30), or CN (n = 32). The mean functional connectivity of the frontal and temporal lobe in resting state was significantly less in the AD (0.19 ± 0.11) group than in the MCI (0.23 ± 0.11), LBD (0.29 ± 0.12), and CN (0.40 ± 0.11) groups (p < 0.001). Further, the mean HbO concentrations in the brain regions and channels were significantly lower in the AD group than in the LBD and MCI groups (p < 0.001). Cognitive levels correlated significantly with the mean HbO concentrations in the resting state and verbal fluency task conditions. The fNIRS HbO signals significantly differed in the cerebral cortex regions in participants with different types of dementia. These findings suggest that fNIRS can effectively enhance the differential diagnosis and assessment of dementia. [ABSTRACT FROM AUTHOR]

Major depression disorder (MDD) exhibits a high global incidence; however, its pathogenesis remains elusive. In this prospective study, we employed diffusion kurtosis imaging (DKI) to investigate changes in brain function among patients with MDD both pre- and post-electroconvulsive therapy (ECT). We divided a sample of 22 MDD patients into ECT group, which received six treatments over a span of two weeks, and control group (n = 12). DKI scanning was performed before and after treatment. The Hamilton Depression Rating Scale (HAMD) and Life Satisfaction Rating Scale (LSRS) were administered to assess depressive symptoms at baseline, on the 14th day, and at month three. Significant differences were found between group, time and time × group in terms of HAMD score and LSRS score. In the ECT group compared to pre- ECT measurement, changes in mean diffusivity (MD), fractional Anisotropy (FA), mean kurtosis (MK), radial kurtosis (RK), FA of kurtosis (KA), and anxia kurtosis (AK) value were detected in specific regions such as the frontal, temporal lobe, and hippocampus. In the control group only MD and RK value increased in a limited number of area. ECT holds the potential to elicit neuroplasticity in the brain, facilitating rapid structural modifications and amelioration of depressive symptoms in patients with MDD. [ABSTRACT FROM AUTHOR]

Background: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language deficits. The main variants of PPA – semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA) – can be challenging to distinguish. Limb apraxia often co-occurs with PPA, but it is unclear whether PPA variants are associated with different gesture deficits. Prior evidence from stroke indicates that temporal lobe lesions are associated with reduced benefit from meaning in gesture performance. Temporal lesions are also associated with greater deficits in hand postures compared to arm kinematics in gesture imitation. Aims: We tested the hypothesis that svPPA, who primarily exhibit temporal lobe atrophy, would differentially show this pattern. In addition, we predicted that as a group, individuals with PPA would more accurately produce meaningful than meaningless gestures and kinematic components than hand postures, as found in neurotypical adults and individuals with stroke. Methods & Procedures: Participants with PPA completed meaningful and meaningless gesture imitation tasks. Performance was scored for hand posture and arm kinematic components. Bayesian mixed-effect models examined trial-level gesture imitation accuracy, while controlling for dementia severity and random effects of subjects and items. Fixed effects included an interaction between PPA variant, task condition/meaning, and gesture component. Outcomes & Results: We found a critical interaction between PPA variant, meaning, and gesture component. In particular, unlike lvPPA and nfvPPA, svPPA subjects' hand postures failed to benefit from gesture meaning. This preliminary research extends prior findings on the role of the temporal lobe in action representations associated with manipulable objects, and is among the first to demonstrate distinct gesture imitation patterns between PPA variants. Conclusions: Characterizing gesture deficits in PPA may help inform diagnostics, compensatory communication strategies, and models of praxis. [ABSTRACT FROM AUTHOR]

It has been hypothesized that differential processing occurs along the longitudinal (anterior–posterior) axis of the hippocampus. One hypothesis is that spatial memory (during both encoding and retrieval) is associated with the posterior hippocampus. An alternative hypothesis is that memory encoding (either spatial or nonspatial) is associated with the anterior hippocampus and memory retrieval is associated with the posterior hippocampus. Of importance, during spatial memory encoding, the spatial–posterior hypothesis predicts posterior hippocampal involvement, whereas the encoding–retrieval hypothesis predicts anterior hippocampal involvement. To distinguish between these hypotheses, we conducted a coordinate‐based fMRI activation likelihood estimation (ALE) meta‐analysis of 26 studies (with a total of 435 participants) that reported hippocampal activity during spatial memory encoding and/or spatial memory retrieval. Both spatial memory encoding and spatial memory retrieval produced extensive activity along the longitudinal axis of the hippocampus as well as the entorhinal cortex, the perirhinal cortex, and the parahippocampal cortex. Critically, the contrast of spatial memory encoding and spatial memory retrieval produced activations in both the anterior hippocampus and the posterior hippocampus. That spatial memory encoding produced activity in both the anterior and posterior hippocampus can be taken to reject strict forms of the spatial–posterior hypothesis, which stipulates that all forms of spatial memory produce activity in the posterior hippocampus, and the encoding–retrieval hypothesis, which stipulates that all forms of encoding versus retrieval produce activity in only the anterior hippocampus. Our results indicate that spatial memory encoding can involve the anterior hippocampus and the posterior hippocampus. [ABSTRACT FROM AUTHOR]

The recent development of methods for constructing directly comparable white matter atlases in primate brains from diffusion MRI allows us to probe specializations unique to humans, great apes, and other primate taxa. Here, we constructed the first white matter atlas of a lesser ape using an ex vivo diffusion-weighted scan of a brain from a young adult (5.5 years) male lar gibbon. We find that white matter architecture of the gibbon temporal lobe suggests specializations that are reminiscent of those previously reported for great apes, specifically, the expansion of the arcuate fasciculus and the inferior longitudinal fasciculus in the temporal lobe. Our findings suggest these white matter expansions into the temporal lobe were present in the last common ancestor to hominoids approximately 16 million years ago and were further modified in the great ape and human lineages. White matter atlases provide a useful resource for identifying neuroanatomical differences and similarities between humans and other primate species and provide insight into the evolutionary variation and stasis of brain organization. [ABSTRACT FROM AUTHOR]

Making sense of natural language and narratives requires building and manipulating a situation model by adding incoming information to the model and using the context stored in the model to comprehend subsequent details and events. Situation model maintenance is supported by the default mode network (DMN), but comprehension of the individual moments in the narrative relies on access to the conceptual store within the semantic system. The present study examined how these systems are engaged by different narrative content to investigate whether highly informative, or semantic, content is a particularly strong driver of semantic system activation compared with contextually driven content that requires using the situation model, which might instead engage DMN regions. The study further investigated which subregions of the graded semantic hub in the left anterior temporal lobe (ATL) were engaged by the type of narrative content. To do this, we quantified the semantic, pragmatic, social, ambiguous, and emotional content for each sentence in a complete narrative, the English translation of The Little Prince. Increased activation in the transmodal hub in the ventral ATL was only observed for high semantic (i.e., informative) relative to low semantic sentences. Activation in the dorsolateral and ventrolateral ATL subregions was observed for both high relative to low semantic and social content sentences, but the ventrolateral ATL effects were more extensive in the social condition. There was high correspondence between the social and pragmatic content results, particularly in the ventrolateral ATL. We argue that the ventrolateral ATL may be particularly engaged by internal, or endogenous, processing demands, aided by functional connections between the anterior middle temporal gyrus and the DMN. Pragmatic and social content may have driven endogenous processing given the pervasive and plot-progressing nature of this content in the narrative. We put forward a revised account of how the semantic system is engaged in naturalistic contexts, a critical step toward better understanding real-world semantic and social processing. [ABSTRACT FROM AUTHOR]

Although the role of the medial temporal lobe (MTL) and the hippocampus in episodic memory is well established, there is emerging evidence that these regions play a broader role in cognition, specifically in temporal processing. However, despite strong evidence that the hippocampus plays a critical role in sequential processing, the involvement of the MTL in timing per se is poorly understood. In the present study, we investigated whether patients with MTL damage exhibit differential performance on a temporal distance memory task. Critically, we manipulated context shifts, or boundaries, which have been shown to interfere with associative binding, leading to increases in subjective temporal distance. We predicted that patients with MTL damage would show impaired binding across boundaries and thus fail to show temporal expansion. Consistent with this hypothesis, unilateral patients failed to show a temporal expansion effect, and bilateral patients actually exhibited the reverse effect, suggesting a critical role for the MTL in binding temporal information across boundaries. Furthermore, patients were impaired overall on both the temporal distance memory task and recognition memory, but not on an independent, short-timescale temporal perception task. Interestingly, temporal distance performance could be independently predicted by performance on recognition memory and the short temporal perception task. Together, these data suggest that distinct mnemonic and temporal processes may influence long interval temporal memory and that damage to the MTL may impair the ability to integrate episodic and temporal information in memory. [ABSTRACT FROM AUTHOR]