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Background and ObjectivesThere is growing evidence that bilingualism can induce neuroplasticity and modulate neural efficiency, resulting in greater resistance to neurologic disease. However, whether bilingualism is beneficial to neural health in the presence of epilepsy is unknown. We tested whether bilingual individuals with temporal lobe epilepsy (TLE) have improved whole-brain structural white matter network organization.MethodsHealthy controls and individuals with TLE recruited from 2 specialized epilepsy centers completed diffusion-weighted MRI and neuropsychological testing as part of an observational cohort study. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory. Global analyses compared network integration (path length) and specialization (transitivity) in TLE vs controls and in a 2 (left vs right TLE) × 2 (bilingual vs monolingual) model. Local analyses compared mean local efficiency of predefined frontal-executive and language (i.e., perisylvian) subnetworks. Exploratory correlations examined associations between network organization and neuropsychological performance.ResultsA total of 29 bilingual and 88 monolingual individuals with TLE matched on several demographic and clinical variables and 81 age-matched healthy controls were included. Globally, a significant interaction between language status and side of seizure onset revealed higher network organization in bilinguals compared with monolinguals but only in left TLE (LTLE). Locally, bilinguals with LTLE showed higher efficiency in frontal-executive but not in perisylvian networks compared with LTLE monolinguals. Improved whole-brain network organization was associated with better executive function performance in bilingual but not monolingual LTLE.DiscussionHigher white matter network organization in bilingual individuals with LTLE suggests a neuromodulatory effect of bilingualism on whole-brain connectivity in epilepsy, providing evidence for neural reserve. This may reflect attenuation of or compensation for epilepsy-related dysfunction of the left hemisphere, potentially driven by increased efficiency of frontal-executive networks that mediate dual-language control. This highlights a potential role of bilingualism as a protective factor in epilepsy, motivating further research across neurologic disorders to define mechanisms and develop interventions.

MR imaging is essential in diagnosing viral encephalitis. Clinical features, cerebrospinal fluid analysis and pathogen confirmation by polymerase chain reaction can be supported by assessing imaging features. MR imaging patterns with typical locations can identify pathogens such as temporal lobe for herpes simplex virus type 1; bilateral thalami for Japanese encephalitis and influenza virus ; and brainstem for enterovirus and rabies. In this article, we have reviewed representative viral encephalitis and its MR imaging patterns. In addition, we also presented acute viral encephalitis without typical MR imaging patterns, such as dengue and varicella-zoster virus encephalitis.

We attempted to explore the common and distinct long- and short-range functional connectivity (FC) patterns of melancholic and non-melancholic major depressive disorder (MDD) and their associations with clinical characteristics.Fifty-nine patients with first-episode drug-naïve MDD, including 31 patients with melancholic features and 28 patients with non-melancholic features, underwent resting-state functional magnetic resonance imaging (fMRI) scanning to examine long- and short-range FC. Thirty-two healthy volunteers were recruited as controls. The support vector machines (SVM) was applied to distinguish the melancholic patients from the non-melancholic patients by using the FC of abnormal brain regions.Compared to healthy volunteers, patients with MDD showed increased long-range positive FC (lpFC) in the right insula/inferior frontal gyrus and left insula. Relative to non-melancholic patients, melancholic patients displayed decreased lpFC in the right lingual gyrus, decreased short-range positive FC (spFC) in the right middle temporal gyrus and right superior parietal lobule, increased lpFC in the left inferior parietal lobule, and increased spFC in the left middle occipital gyrus/inferior occipital gyrus, left cerebellum VII/IX, and bilateral cerebellum CrusII. Increased lpFC in the left inferior parietal lobule in melancholic patients was correlated with the TEPS abstract anticipatory scores. SVM results showed that FCs of five combinations within different brain regions could distinguish melancholic patients from non-melancholic patients.FC abnormalities in the default mode network and parietal-occipital brain regions may underlie the neurobiology of melancholic MDD. An increased lpFC in the left inferior parietal lobule correlated with anhedonia may be a distinctive neurobiological feature of melancholic MDD.

Functional magnetic resonance imaging (fMRI) was used to assess the effect of cognitive training on brain activation as a function of the learning phase and level of education. Forty older adults with subjective cognitive decline (SCD) received 6 1-hour memory training sessions with the method of loci. Brain imaging (N = 29) was measured during word list encoding and retrieval before training (PRE), after 3 training sessions (POST3), and after 6 training sessions (POST6). Participants showed increased activation of the left inferior pre-frontal gyrus from PRE to POST6 during encoding and reduced bilateral frontostriatal activation from PRE to POST3 during retrieval, regardless of education. Activation changes from PRE to POST3 varied as a function of education in 2 regions of the right temporal lobe: participants with lower education showed increased activation, while those with higher education showed decreased activation. These regions were initially less active in people with lower education. Results suggest a strategic shift in people with lower education and expertise building in those with higher education, along with a restoration of initial education-related differences.

Background In the past twenty years, there has been an increasing interest among neuroscientists and physicians in mapping the cortical areas involved in the epileptogenic zone (EZ) through event-related potentials (ERPs) that enable the evaluation of the functional preservation of these areas. The present review is an update on publications on this topic. Objective To investigate the accuracy of the cognitive evoked of the medial temporal lobe P300 (MTL-P300) potential in detecting the EZ in temporal lobe epilepsy (TLE). Methods The systematic review of articles on the PubMed, Embase and Lilacs databases was conducted between February and December 2020. Articles published in English from 1985 to December 2020 were included. Additional studies were identified by searching the references of the selected studies and review articles. The studies were included for the following reasons: in-depth intracranial electroencephalography (iEEG) analysis of hippocampal activity; investigations of patients with TLE; and correlations between regarding the ERP results obtained in the temporal regions (MTL-P300) and the EZ. Results In the three studies analyzed, the authors were able to define the laterality of the EZ during the preoperative investigation through the MTL-P300 results. The sensitivity of this method was of ~ 70% to 80%, and the specificity between 70% and 94.7%. One of the limitations of the present review was the low number of studies. Conclusion There is evidence that the reduced amplitude of the MTL-P300 has high specificity in identifying the EZ, and this is a good marker for diagnosis in unilateral TLE. The low sensitivity and negative likelihood ratios negative that a normal MTL-P300 response does not exclude the epileptogenicity of the hippocampus. Resumo Antecedentes Nos últimos 20 anos, tem havido um crescente interesse de neurocientistas e médicos em mapear áreas corticais envolvidas na zona epileptogênica (ZE) por meio de potenciais relacionados a eventos (PREs), que permitem avaliar a preservação funcional dessas áreas. Esta revisão é uma atualização das publicações sobre esse tema. Objetivo Investigar a acurácia do potencial evocado cognitivo do lobo temporal medial P300 (medial temporal lobe P300, MTL-P300, em inglês) na detecção da ZE em casos de epilepsias do lobo temporal (ELT). Métodos A revisão sistemática de artigos nas bases de dados PubMed, Embase e Lilacs foi realizada entre fevereiro e dezembro de 2020. Foram incluídos artigos publicados em inglês de 1985 a dezembro de 2020. Estudos adicionais foram identificados por meio de busca nas referências dos estudos selecionados e artigos de revisão. Os estudos foram incluídos pelas seguintes razões: análise detalhada por meio de eletroencefalografia intracraniana (iEEG) da atividade hipocampal; investigações de pacientes com ELT; e correlações entre os resultados de ERP obtidos nas regiões temporais (MTL-P300) e na ZE. Resultados Nos três estudos analisados, os autores foram capazes de definir a lateralidade da ZE durante a investigação pré-operatória por meio dos resultados do MTL-P300. A sensibilidade deste método foi de 70% a 80%, e a especificidade, entre 70% e 94.7%. Uma das limitações desta revisão foi o baixo número de estudos. Conclusão Há evidências de que a amplitude reduzida do MTL-P300 tem alta especificidade na identificação da ZE, e este é um bom marcador para o diagnóstico na ELT unilateral. A baixa sensibilidade e a razão de verossimilhança negativa indicam que a resposta MTL-P300 normal não exclui a epileptogenicidade do hipocampo.

To use pre-treatment magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) patients with stage T4/N0-3/M0 within 5 years after radiotherapy.This study retrospectively examined 98 patients (198 temporal lobes) with stage T4/N0-3/M0 NPC. Participants were enrolled into a training cohort or a validation cohort in a ratio of 7:3. Radiomics features were extracted from pre-treatment magnetic resonance imaging that were T1-and T2-weighted. Spearman rank correlation, the t-test and the least absolute shrinkage and selection operator (LASSO) algorithm were used to select significant radiomics features; machine-learning models were used to generate radiomics signatures (Rad-Scores). Rad-Scores and clinical factors were integrated into a nomogram for prediction of RTLI. Nomogram discrimination was evaluated using receiver operating characteristic analysis and clinical benefits were evaluated using decision curve analysis.Participants were enrolled into a training cohort (n = 139) or a validation cohort (n = 59). In total, 3568 radiomics features were initially extracted from T1-and T2-weighted images. Age, DWe developed models for the prediction of RTLI in patients with stage T4/N0-3/M0 NPC using pre-treatment radiomics data and clinical data. Nomograms from these pre-treatment data improved the prediction of RTLI. These results may allow the selection of patients for earlier clinical interventions.

Lateralized processing of orthographic information is a hallmark of proficient reading. However, how this finding obtained for fixed-gaze processing of orthographic stimuli translates to ecologically valid reading conditions remained to be clarified. To address this shortcoming, here we assessed the lateralization of early orthographic processing in fixed-gaze and natural reading conditions using concomitant eye-tracking and EEG data recorded from young adults without reading difficulties. Sensor-space analyses confirmed the well-known left-lateralized negative-going deflection of fixed-gaze EEG activity throughout the period of early orthographic processing. At the same time, fixation-related EEG activity exhibited left-lateralized followed by right-lateralized processing of text stimuli during natural reading. A strong positive relationship was found between the early leftward lateralization in fixed-gaze and natural reading conditions. Using source-space analyses, early left-lateralized brain activity was obtained in lateraloccipital and posterior ventral occipito-temporal cortices reflecting letter-level processing in both conditions. In addition, in the same time interval, left-lateralized source activity was found also in premotor and parietal brain regions during natural reading. While brain activity remained left-lateralized in later stages representing word-level processing in posterior and middle ventral temporal regions in the fixed-gaze condition, fixation-related source activity became stronger in the right hemisphere in medial and more anterior ventral temporal brain regions indicating higher-level processing of orthographic information. Although our results show a strong positive relationship between the lateralization of letter-level processing in the two conditions and suggest lateralized brain activity as a general marker for processing of orthographic information, they also clearly indicate the need for reading research in ecologically valid conditions to identify the neural basis of visuospatial attentional, oculomotor and higher-level processes specific for natural reading.

A number of recent studies have indicated that the medial temporal lobe (MTL) plays a critical role in working memory (WM) and perception, but these results have been highly controversial given the traditional association of MTL with long-term memory. We review the research and highlight important factors that need to be considered in determining the role of MTL in WM including set-size of used stimuli and feature complexity and/or feature conjunctions/bindings embedded in those stimuli. These factors relate to hierarchical and, accordingly, domain-specific theories of functional organization within the temporal lobe. In addition, one must consider process-specific theories too, because two key processes commonly understood to contribute recognition memory, namely, recollection and familiarity, also have robust support from neurophysiological and neuroimaging research as to their functional dissociations within MTL. PFC has long been heavily implicated in WM; however, relatively less is known about how the PFC contributes to recollection and familiarity, although dynamic prefrontal coding models in WM may help to explain their neural mechanisms. The MTL and PFC are heavily interconnected and do not operate independently in underlying WM. We propose that investigation of the interactions between these two regions in WM, particularly their coordinated neural activities, and the modeling of such interactions, will be crucial for the advancing understanding of the neural mechanisms of WM.

Surgical randomized trials are difficult to accomplish. One major problem is recruitment of a sufficient number of patients to address the clinical problem.We review the various ways patient recruitment in surgical RCTs can be promoted. We examine two landmark trials on the surgical treatment of temporal lobe epilepsy (TLE), one that was successful, and one which did not attain the target number of participants.Both designs of the Canadian and American trials of surgery for TLE included a benefit to participants: the Canadian trial gave a chance to have immediate access to investigation and treatment, as compared to a 1 year delay (considered 'standard care' in that center), while the American trial offered free surgical management to both arms. Patients were recruited and treatments randomly allocated prior to knowing for certain whether they were surgical candidates or not. This design choice may have helped circumvent the 'equipoise problem'. The Canadian trial offered participation to drug-resistant patients that were already routinely referred to surgical centers, while the success of the American trial which limited recruitment to the early period of drug resistance was dependent on a change of practice of referring clinicians which did not materialize.The surgical treatment of drug-resistant temporal lobe epilepsy has been validated using RCT methods. Ways to promote participation in surgical trials should be further investigated.

The evaluation ofFifteen AD patients were enrolled in this study. Correlations were evaluated between theA positive correlation was found between the severity of agitation andNeuroinflammation in the medial temporal region and its neighbouring area was shown to be associated with the development of agitation symptoms in AD patients. Our findings extend those of previous studies showing an association between some NPS and inflammation, suggesting that immunologically based interventions for agitation can serve as an alternative treatment for dementia.

Motion opponency, first observed within the primate middle temporal cortex (MT), refers to the suppressing effect of opposite motion directions on neuronal activity. Namely, when opposing motion directional signals stimulate an MT neuron's receptive field, this neuron's response is comparable with that induced by flicker noise. Under such suppression, it is unknown whether any directional information is still represented at MT. In this study, we applied support vector machine (SVM) learning to human functional magnetic resonance imaging data to investigate if any motion defined orientation information was still available from suppressed MT. We found that, at least at the level of ±45° discrimination, such orientation information was still available. Interestingly, after behavioural perceptual learning that improved human discrimination of fine orientation discrimination (e.g. 42° vs. 48°) using the MT-suppressive motion stimuli, the SVM discrimination of ±45° worsened when functional magnetic resonance imaging (fMRI) signals at post-learning MT were used. This result is consistent with findings in Thompson et al. (2013) that, post-perceptual learning, MT suppression was not released, suggesting that motion opponency was perhaps functionally too important for perceptual learning to overcome.

The sylvian fissure stem and its deep cisternal part (SDCP) consist mainly of the orbital gyrus (OG) and anterior medial portion of the temporal lobe. SDCP's adhesion has been found to make a trans-sylvian approach difficult due to the various patterns of adhesion. Thus, in this study, we aim to clarify the morphological features of the SDCP, and to guide a safe trans-sylvian approach. We retrospectively classified the morphology of the SDCP in 81 patients into 3 types (tight, moderate, loose type) according to the degree of adhesion of the arachnoid membrane and analyzed the morphological features of the OG and the temporal lobe using intraoperative video images. In addition, we have retrospectively measured each width of the SDCP's subarachnoid space at the three points (Point A, lateral superior portion; Point B, downward portion; Point C, medial inferior portion of SDCP) and analyzed their relationship to the degree of adhesion using the preoperative coronal three-dimensional computed tomography angiography (3D-CTA) images of 44 patients. As per the results, SDCP's adhesions were determined to be significantly tighter in cases with large OG and young cases. The temporal lobe had four surfaces (posterior, middle, anterior, and medial) that adhered to the OG in various patterns. The tighter the adhesion between the OG and each of the three distal surfaces of the temporal lobe, the narrower the width of the subarachnoid space at each point (A, B, C). Understanding of the morphological features of the SDCP, and estimating its adhesion preoperatively are useful in developing a surgical strategy and obtaining correct intraoperative orientation in the trans-sylvian approach.

Ageing-related pathologies of the brain include neurofibrillary tangles, argyrophilic grains, ageing-related tau astrogliopathy (ARTAG), limbic-predominant age-related TDP-43 encephalopathy-neuropathological change (LATE-NC), vascular pathology and corpora amylacea. This study used an unbiased approach to evaluate a broad range of pathologies in an unselected European community-dwelling ageing cohort of 101 individuals (77-90 years). Pathological alterations observed included neurofibrillary tangles and corpora amylacea in all cases, ARTAG (79%), Thal amyloid-β phase1 (60%), cerebral amyloid angiopathy (39%), Lewy bodies (22%), LATE-NC (21%), oligodendroglial tau-positive coiled bodies (33%), and argyrophilic grains (15%). We demonstrate association of LATE-NC with the previously unappreciated age-related tau oligodendrogliopathy (ARTOG) and highlight the association of LATE-NC with various ARTAG types pointing toward common pathogenic aspects. Only neurofibrillary tangles and LATE-NC were associated with cognitive decline. This study broadens the spectrum of age-related brain pathologies and highlights a novel ageing-related tau pathology in oligodendroglia. Results from this study suggest overlapping pathogenic mechanisms between LATE-NC and glial tau pathologies in the medial temporal lobe.

Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function.

Objective: Ultra long-term monitoring with subcutaneous EEG (sqEEG) offers objective outpatient recording of electrographic seizures as an alternative to self-reported epileptic seizure diaries. This methodology requires an algorithm-based automatic seizure detection to indicate periods of potential seizure activity to reduce the time spent on visual review. The objective of this study was to evaluate the performance of a sqEEG-based automatic seizure detection algorithm. Methods: A multicenter cohort of subjects using sqEEG were analyzed, including nine people with epilepsy (PWE) and 12 healthy subjects, recording a total of 965 days. The automatic seizure detections of a deep-neural-network algorithm were compared to annotations from three human experts. Results: Data reduction ratios were 99.6% in PWE and 99.9% in the control group. The cross-PWE sensitivity was 86% (median 80%, range 69–100% when PWE were evaluated individually), and the corresponding median false detection rate was 2.4 detections per 24 hours (range: 2.0–13.0). Conclusions: Our findings demonstrated that step one in a sqEEG-based semi-automatic seizure detection/review process can be performed with high sensitivity and clinically applicable specificity. Significance: Ultra long-term sqEEG bears the potential of improving objective seizure quantification.

Surgery is an effective treatment for drug-resistant temporal-lobe epilepsy (TLE), but is still underutilized for older patients because of a perceived higher rate of perioperative complications, cognitive decline and worse seizure outcome.We retrospectively screened all patients operated on in our institution for drug-resistant TLE between 2007 and 2019. Data of patients aged ≥50 years versus50 years at surgery were compared. The primary endpoint was freedom from disabling seizure (Engel I) at 2 years postoperatively.In patients aged ≥50 years (n=19), mean age at surgery was 54.9 years and mean disease duration was 36.6 years. At 2 years postoperatively, rates of Engel I seizure outcome were not significantly different between the two groups (73.9% in the50 years group versus 94.4% in the ≥50 years group). Although surgical complications were significantly (47.4%) in the older patients, neurological deficit was permanent in only 5.3% of cases. At 1 year postoperatively, neuropsychological outcome did not significantly differ between the two groups.Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively. Early postoperative complications were more frequent in patients aged ≥50 years but were mostly transient. Cognitive outcome was similar to that in younger patients. These findings strongly suggest that age ≥50 years should not be an exclusion criterion for resective epilepsy surgery in patients with drug-resistant TLE.

The medial temporal lobe (MTL), including the hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC), is central to memory formation. Reward enhances memory through interplay between the HC and substantia nigra/ventral tegmental area (SNVTA). While the SNVTA also innervates the MTL cortex and amygdala (AMY), their role in reward-enhanced memory is unclear. Prior research suggests category specificity in the MTL cortex, with the PRC and PHC processing object and scene memory, respectively. It is unknown, however, whether reward modulates category-specific memory processes. Furthermore, no study has demonstrated clear category specificity in the MTL for encoding processes contributing to subsequent recognition memory. To address these questions, we had 39 healthy volunteers (27 for all memory-based analyses) undergo functional magnetic resonance imaging while performing an incidental encoding task pairing objects or scenes with high or low reward, followed by a next-day recognition test. Behaviorally, high reward preferably enhanced object memory. Neural activity in the PRC and PHC reflected successful encoding of objects and scenes, respectively. Importantly, AMY encoding effects were selective for high-reward objects, with a similar pattern in the PRC. The SNVTA and HC showed no clear evidence of successful encoding. This behavioral and neural asymmetry may be conveyed through an anterior–temporal memory system, including the AMY and PRC, potentially in interplay with the ventromedial prefrontal cortex.

To develop a model based on magnetic resonance imaging (MRI) radiomics and clinical features for predicting radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).Two hundred and sixteen patients with NPC were retrospectively included. Radiomics features were extracted and selected. The logistic regression analysis was performed for prediction models construction. The area under the receiver operating characteristic curve (AUC) was calculated for performance evaluation.Three radiomics features were selected to construct the radiomics signature (AUC of 0.94 and 0.92). The clinical-radiomics model, integrating radiomics signature with T classification, achieved higher predictive performance in the training and validation cohorts (AUC of 0.95 and 0.93), as well as improved accuracy of the classification of RTLI outcomes (net reclassification improvement: 0.711; 95% CI: 0.57-0.86; p 0.001).The clinical-radiomics model and radiomics signature both showed great performance in predicting RTLI in patients with NPC.

Our understanding of post-stroke language function is largely based on older age groups, who show increasing age-related brain pathology and neural reorganisation. To illustrate language outcomes in the young-adult brain, we present the case of A., a 23 y.o. woman with chronic aphasia from a left-hemisphere stroke affecting the temporal lobe. Diffusion MRI-based tractography indicated that A.’s language-relevant white matter structures were severely damaged. Using magnetoencephalography (MEG), we explored A.’s conceptual preparation and word planning abilities. Context-driven and bare picture-naming tasks revealed naming deficits, manifesting as word-finding difficulties and semantic paraphasias about half of the time. Naming was however facilitated by semantically constraining lead-in sentences. Altogether, this pattern indicates relatively spared conceptual preparation but disrupted lexical and phonological retrieval abilities. MEG revealed that A.’s conceptual and naming-related neural responses were supported by the right hemisphere, compared to the typical left-lateralised brain response of a matched control. Differential recruitment of right-hemisphere structures (330-440 ms postpicture onset) was found concurrently during successful naming (right mid-to-posterior temporal lobe) and word-finding attempts (right inferior frontal gyrus). Disconnection of the temporal lobes via corpus callosum was not critical for recruitment of the right hemisphere in visually guided naming, possibly due to neural activity right-lateralising from the outset. We consider that, despite A.’s young age, the presumed strong degree of language lateralisation and extensive structural damage limited her recovery. Although A.’s right hemisphere responded in a timely manner during word planning, its lexical and phonological retrieval abilities remained modest.

Face recognition is a highly developed and efficient human function that involves multiple neural networks. A main pathway links the occipital cortex, where an occipital face area (OFA) has been identified, to a fusiform face area (FFA) in the fusiform gyrus, which plays a critical role in face recognition. This core pathway deals with invariant aspects of the face. Another pathway, including the superior temporal sulcus, is involved in the perception of more changeable aspects of the face such as gaze orientation, face expression and lip movements. It has been defined by some authors as a "third pathway of visual recognition", i.e. a lateral pathway in addition to the "what" and "where" pathways. It deals with sociocognitive aspects of face perception. Many other accessory functional systems are connected to the core system of visual recognition to act in concert with it: the intraparietal sulcus (for the management of spatial attention), the primary auditory cortex (prelexical perception of speech), the amygdala, the insula and the limbic system (perception of emotions), the anterior temporal pole (access to the identity of the individual, his name, biographical information), etc. Functional brain imaging has made remarkable progress in the understanding of face perception, which in the early years was limited to the description of single cases of brain-damaged patients. This progress has made it possible to better analyse the many face recognition disorders, sometimes subtle, other times confusing, observed in human pathology.

When an image is presented twice in succession, neurons in area TE of macaque inferotemporal cortex exhibit repetition suppression, responding less strongly to the second presentation than to the first. Suppression is known to occur if the adapter and the test image are subtly different from each other. However, it is not known whether cross suppression occurs between images that are radically different from each other but that share a subset of features. To explore this issue, we measured repetition suppression using colored shapes. On interleaved trials, the test image might be identical to the adapter, might share its shape or color alone, or might differ from it totally. At the level of the neuronal population as a whole, suppression was especially deep when adapter and test were identical, intermediate when they shared only one attribute, and minimal when they shared neither attribute. At the level of the individual neuron, the degree of suppression depended not only on the properties of the two images but also on the preferences of the neuron. Suppression was deeper when the repeated color or shape was preferred by the neuron than when it was not. This effect might arise from feature-specific adaptation or alternatively from adapter-induced fatigue. Both mechanisms conform to the principle that the degree of suppression is determined by the preferences of the neuron.

Memory consolidation during sleep is thought to depend on the coordinated interplay between cortical slow waves, thalamocortical sleep spindles and hippocampal ripples, but direct evidence is lacking. Here, we implemented real-time closed-loop deep brain stimulation in human prefrontal cortex during sleep and tested its effects on sleep electrophysiology and on overnight consolidation of declarative memory. Synchronizing the stimulation to the active phases of endogenous slow waves in the medial temporal lobe (MTL) enhanced sleep spindles, boosted locking of brain-wide neural spiking activity to MTL slow waves, and improved coupling between MTL ripples and thalamocortical oscillations. Furthermore, synchronized stimulation enhanced the accuracy of recognition memory. By contrast, identical stimulation without this precise time-locking was not associated with, and sometimes even degraded, these electrophysiological and behavioral effects. Notably, individual changes in memory accuracy were highly correlated with electrophysiological effects. Our results indicate that hippocampo-thalamocortical synchronization during sleep causally supports human memory consolidation.

Prior studies in Social Neuroeconomics have consistently reported activation in social cognition regions during interactive economic games, suggesting mentalizing during economic choice. Such mentalizing occurs during active participation in the game, as well as during passive observation of others' interactions. We designed a novel version of the classic false-belief task (FBT) in which participants read vignettes about interactions between agents in the ultimatum and trust games and were subsequently asked to infer the agents' beliefs. We compared activation patterns during the economic games FBT to those during the classic FBT using conjunction analyses. We find significant overlap in the left temporoparietal junction (TPJ) and dorsal medial prefrontal cortex, as well as the temporal pole (TP) during two task phases: belief formation and belief inference. Moreover, generalized Psychophysiological Interaction (gPPI) analyses show that during belief formation, the right TPJ is a target of both the left TPJ and the right TP seed regions, whereas during belief inferences all seed regions show interconnectivity with each other. These results indicate that across different task types and phases, mentalizing is associated with activation and connectivity across central nodes of the social cognition network. Importantly, this is the case for both the novel economic games and the classic FBTs.

(1) Background: The inferior anastomotic vein of Labbé (LV) courses on the temporal lobe, from the sylvian fissure towards the tentorium cerebelli and finishes at the transverse sinus (TS). The importance of the LV topography is related to skull base neurosurgical approaches. Based on the hypothesis of the existence of as yet unidentified anatomical possibilities of the LV, we aimed through this research to document the superficial venous topographic patterns at the lateral and inferior surfaces of the temporal lobe. (2) Methods: A retrospective cohort of 50 computed tomography angiograms (CTAs) of 32 males and 18 females was documented. (3) Results: Absent (type 0) LVs were found in 6% of cases. Anterior (temporal, squamosal–petrosal–mastoid, type 1) LVs were found in 12% of cases. LVs with a posterior, temporoparietal course (type 2) were found to be bilateral in 46% of cases and unilateral in 36% of cases. Type 3 LVs (posterior, parietooccipital) were found to be bilateral in 8% and unilateral in 32% of cases. In 24% of cases, duplicate LVs were found that were either complete or incomplete. A quadruplicate LV was found in a male case. On 78 sides, the LV drained either into a tentorial sinus or into the TS. (4) Conclusions: The anatomy of the vein of Labbé is variable in terms of its course, the number of veins and the modality of drainage; thus, it should determine personalized neurosurgical and interventional approaches. A new classification of the anatomical variations of Labbé’s vein, as detected on the CTAs, is proposed here (types 0–3).

Patients with early Alzheimer’s disease (AD) have difficulty in learning new information and in detecting novel stimuli. The underlying physiological mechanisms are not well known. We investigated the electrophysiological correlates of the early (

The human middle-temporal region MT+ is highly specialized in processing visual motion. However, recent studies have shown that this region is modulated by extraretinal signals, suggesting a possible involvement in processing motion information also from non-visual modalities. Here, we used functional MRI data to investigate the influence of retinal and extraretinal signals on MT+ in a large sample of subjects. Moreover, we used resting-state functional MRI to assess how the subdivisions of MT+ (i.e., MST, FST, MT, and V4t) are functionally connected. We first compared responses in MST, FST, MT, and V4t to coherent vs. random visual motion. We found that only MST and FST were positively activated by coherent motion. Furthermore, regional analyses revealed that MST and FST were positively activated by leg, but not arm, movements, while MT and V4t were deactivated by arm, but not leg, movements. Taken together, regional analyses revealed a visuomotor role for the anterior areas MST and FST and a pure visual role for the anterior areas MT and V4t. These findings were mirrored by the pattern of functional connections between these areas and the rest of the brain. Visual and visuomotor regions showed distinct patterns of functional connectivity, with the latter preferentially connected with the somatosensory and motor areas representing leg and foot. Overall, these findings reveal a functional sensitivity for coherent visual motion and lower-limb movements in MST and FST, suggesting their possible involvement in integrating sensory and motor information to perform locomotion.

The effects of current conduction were researched to confirm that it can decrease focal epileptogenicity in patients with temporal lobe epilepsy (TLE).Data from 13 patients with mesial TLE were collected. After no less than two habitual seizures were captured during stereo-electroencephalogram monitoring, current conduction was measured in the hippocampus to a homemade, zero potential circuit board. The interictal spike, ripple, fast ripple, and ictal epileptogenicity index (EI) changes were analyzed in the hippocampus, amygdala, and anterior and middle temporal neocortex regions.Significant differences were found in the percentage of patients without spikes in the temporal neocortex between pre- and post-current conduction. Significant decreases in average ripple rates were found in the hippocampus and amygdala after current conduction. The percentage of fast ripple rate decrease in the hippocampus and amygdala was significantly higher than that in the temporal neocortex, and significant decreases were found in the fast ripple rate in the hippocampus from post- to pre-current conduction. Significant decreases were found in the EI values after current conduction in the amygdala and middle temporal lobe compared to the EI values before current conduction.After current conduction in patients with TLE, the spike rate decreases in the hippocampus, amygdala, and anterior and middle temporal neocortex, the ripple rate decreases in the hippocampus and amygdala, the fast ripple decreases in the hippocampus, and the EI decreases in the amygdala and middle temporal neocortex. Current conduction can reduce epileptogenicity in the hippocampus in mesial TLE.

The mechanisms underlying accelerated long-term forgetting (ALF) in patients with epilepsy are still under investigation. We examined the contribution of hippocampal subfields and their morphology to long-term memory performance in patients with focal epilepsy.We prospectively assessed long-term memory and performed magnetic resonance imaging in 80 patients with focal epilepsy (61 with temporal lobe epilepsy and 19 with extratemporal lobe epilepsy) and 30 healthy controls. The patients also underwent electroencephalography recording. Verbal and visuospatial memory was tested 30 s, 10 min, and 1 week after learning. We assessed the volumes of the whole hippocampus and seven subfields and deformation of the hippocampal shape. The contributions of the hippocampal volumes and shape deformation to long-term forgetting, controlling for confounding factors, including the presence of interictal epileptiform discharges, were assessed by multiple regression analyses.Patients with focal epilepsy had lower intelligence quotients and route recall scores at 10 min than controls. The focal epilepsy group had smaller volumes of both the right and left hippocampal tails than the control group, but there were no statistically significant group differences for the volumes of the whole hippocampus or other hippocampal subfields. Multiple regression analyses showed a significant association between the left CA1 volume and the 1-week story retention (β = 7.76; Bonferroni-corrected p = 0.044), but this was not found for the whole hippocampus or other subfield volumes. Hippocampal shape analyses revealed that atrophy of the superior-lateral, superior-central, and inferior-medial regions of the left hippocampus, corresponding to CA1 and CA2/3, was associated with the verbal retention rate.Our results suggest that atrophy of the hippocampal CA1 region and its associated structures disrupts long-term memory consolidation in focal epilepsy. Neuronal cell loss in specific hippocampal subfields could be a key underlying cause of ALF in patients with epilepsy.

Neuroimaging, neuropsychological, and psychophysical evidence indicates that concept retrieval selectively engages specific sensory and motor brain systems involved in the acquisition of the retrieved concept. However, it remains unclear which supramodal cortical regions contribute to this process and what kind of information they represent. Here, we used representational similarity analysis of two large fMRI data sets, with a searchlight approach, to generate a detailed map of human brain regions where the semantic similarity structure across individual lexical concepts can be reliably detected. We hypothesized that heteromodal cortical areas typically associated with the “default mode network” encode multimodal experiential information about concepts, consistent with their proposed role as cortical integration hubs. In two studies involving different sets of concepts and different participants (both sexes), we found a distributed, bihemispheric network engaged in concept representation, composed of high-level association areas in the anterior, lateral, and ventral temporal lobe; inferior parietal lobule; posterior cingulate gyrus and precuneus; and medial, dorsal, ventrolateral, and orbital prefrontal cortex. In both studies, a multimodal model combining sensory, motor, affective, and other types of experiential information explained significant variance in the neural similarity structure observed in these regions that was not explained by unimodal experiential models or by distributional semantics (i.e., word2vec similarity). These results indicate that, during concept retrieval, lexical concepts are represented across a vast expanse of high-level cortical regions, especially in the areas that make up the default mode network, and that these regions encode multimodal experiential information.Significance StatementConceptual knowledge includes information acquired through various modalities of experience, such as visual, auditory, tactile, and emotional information. We investigated which brain regions encode mental representations that combine information from multiple modalities when participants think about the meaning of a word. We found that such representations are encoded across a widely distributed network of cortical areas in both hemispheres, including temporal, parietal, limbic, and prefrontal association areas. Several areas not traditionally associated with semantic cognition were also implicated. Our results indicate that the retrieval of conceptual knowledge during word comprehension relies on a much larger portion of the cerebral cortex than previously thought, and that multimodal experiential information is represented throughout the entire network.

Background Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Material and methods In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

High-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA).Whether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP).Low frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix.Overall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites.Our findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.

OBJECTIVE Tailored surgery to extensively resect epileptogenic lesions using intraoperative electrocorticography (ioECoG) may improve seizure outcomes. However, resection of large areas is associated with decreased memory function postoperatively. The authors assessed whether ioECoG could provide useful information on how to minimize the focus resection and obtain better seizure outcomes without memory deterioration. They examined the postoperative seizure-free period and memory alteration in a retrospective cohort of patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) in whom the extent of removal was determined using ioECoG findings. METHODS The authors enrolled 82 patients with TLE associated with HS who were treated surgically. Transsylvian amygdalohippocampectomy was indicated as the first step. When visual inspection identified interictal epileptic discharges from the lateral temporal lobe on ioECoG, anterior temporal lobectomy (ATL) was eventually performed. The patients were divided into the selective amygdalohippocampectomy (SA, n = 40) and ATL (n = 42) groups. Postoperative seizure outcomes were assessed at 1, 2, 3, 5, and 7 years postoperatively using the International League Against Epilepsy classification. The Kaplan-Meier survival analysis was applied to evaluate the period of seizure recurrence between the SA and ATL groups. Factors attributed to seizure recurrence were analyzed using the Cox proportional hazards model, and they were as follows: epileptic focal laterality; age at seizure onset (< 10 or ≥ 10 years old); seizure frequency (more than weekly or less than weekly seizures); history of focal to bilateral tonic-clonic seizure; infectious etiology; and surgical procedure. The Wechsler Memory Scale–Revised was used to evaluate memory function pre- and postoperatively. RESULTS Seizure outcomes were significantly worse in the SA group than in the ATL group at 2 years postoperatively (p = 0.045). The International League Against Epilepsy class 1 outcomes at 7 years postoperatively in the SA and ATL groups were 63% and 81%, respectively. Kaplan-Meier analysis showed that seizure recurred significantly earlier in the SA group than in the ATL group (p = 0.031). The 2-way ANOVA analysis was used to compare the SA and ATL groups in each memory category, and revealed that there was no significant difference regardless of the side of surgery. CONCLUSIONS Visual assessment of ioECoG cannot be used as an indicator to minimize epileptic focus resection in patients with TLE associated with HS. ATL is more effective in obtaining seizure-free outcomes; however, both ATL and SA can preserve memory function.

Risk for schizophrenia peaks during early adulthood, a critical period for brain development. Although several influential theoretical models have been proposed for the developmental relationship between brain pathology and clinical onset, to our knowledge, no study has directly evaluated the predictions of these models for schizophrenia developmental genetic effects on brain structure. To address this question, we introduce a framework to estimate the effects of schizophrenia genetic variation on brain structure phenotypes across the life span. Five-hundred and six participants, including 30 schizophrenia probands, 200 of their relatives (aged 12-85 years) from 32 families with at least two first-degree schizophrenia relatives, and 276 unrelated controls, underwent MRI to assess regional cortical thickness (CT) and cortical surface area (CSA). Genetic variance decomposition analyses were conducted to distinguish among schizophrenia neurogenetic effects that are most salient before schizophrenia peak age-of-risk (i.e., early neurodevelopmental effects), after peak age-of-risk (late neurodevelopmental effects), and during the later plateau of age-of-risk (neurodegenerative effects). Genetic correlations between schizophrenia and cortical traits suggested early neurodevelopmental effects for frontal and insula CSA, late neurodevelopmental effects for overall CSA and frontal, parietal, and occipital CSA, and possible neurodegenerative effects for temporal CT and parietal CSA. Importantly, these developmental neurogenetic effects were specific to schizophrenia and not found with nonpsychotic depression. Our findings highlight the potentially dynamic nature of schizophrenia genetic effects across the lifespan and emphasize the utility of integrating neuroimaging methods with developmental behavior genetic approaches to elucidate the nature and timing of risk-conferring processes in psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Previous brain functional specialization evidence has shown that both aware and unaware visual processing of manipulable objects activate left premotor, parietal, and posterior temporal cortices, which are thought to constitute object-directed action and object-function processing streams. An open question is whether, both under supraliminal and subliminal processing conditions, there is directional spread of activation along these functional streams, leading to causal inter-regional connectivity effects. In this study, we used Dynamic Causal Modelling to estimate the effective connectivity influences within the premotor-parieto-temporal network, as a function of factorial contrasts for Manipulability (manipulable vs non-manipulable objects) and Perceptual Awareness (above vs below perceptual threshold). We modeled forward and backward connections originating from visual area V4, as a region underlying object texture segregation, and spreading through the left premotor-parieto-temporal network. Both above and below perceptual threshold, the visual processing of manipulable objects was associated with a specific increase of reciprocal effective connectivity coupling among left premotor-parieto-temporal regions. Aware and unaware manipulable object processing differed from each other for their distinct patterns of top-down activation enhancement exerted, in the former case, by left premotor-parieto-temporal regions on area V4 and, in the latter case, by left premotor on temporal regions. Although it is only under aware processing conditions that effective connectivity in the action representation system may promote object visual contour segregation in area V4, our results suggest that the encoding of object-action and object-function information can occur through left-hemispheric premotor, parietal, and temporal causal interdependencies, even when the object is not consciously perceived.

Connectivity of the brain at rest can reflect individual differences and impact behavioral outcomes, including memory. The present study investigated how culture influences functional connectivity with regions of the medial temporal lobe. In this study, 46 Americans and 59 East Asians completed a resting state scan after encoding pictures of objects. To investigate cross-cultural differences in resting state functional connectivity, left parahippocampal gyrus (anterior and posterior regions) and left hippocampus were selected as seed regions. These regions were selected, because they were previously implicated in a study of cultural differences during the successful encoding of detailed memories. Results revealed that left posterior parahippocampal gyrus had stronger connectivity with temporo-occipital regions for East Asians compared with Americans and stronger connectivity with parieto-occipital regions for Americans compared with East Asians. Left anterior parahippocampal gyrus had stronger connectivity with temporal regions for East Asians than Americans and stronger connectivity with frontal regions for Americans than East Asians. Although connectivity did not relate to memory performance, patterns did relate to cultural values. The degree of independent self-construal and subjective value of tradition were associated with functional connectivity involving left anterior parahippocampal gyrus. Findings are discussed in terms of potential cultural differences in memory consolidation or more general trait or state-based processes, such as holistic versus analytic processing.

Facial emotion perception can be studied from the point of view of dynamic systems whose output may depend not only on current input but also on prior history — a phenomenon known as hysteresis. In cognitive neuroscience, hysteresis has been described as positive (perceptual persistence) or negative (fatigue of current percept) depending on whether perceptual switching occurs later or earlier than actual physical stimulus changes. However, its neural correlates remain elusive. We used dynamic transitions between emotional expressions and combined behavioral assessment with functional magnetic resonance imaging (fMRI) to investigate the underlying circuitry of perceptual hysteresis in facial emotion recognition. Our findings revealed the involvement of face-selective visual areas — fusiform face area (FFA) and superior temporal sulcus (STS) — in perceptual persistence as well as the right anterior insula. Moreover, functional connectivity analyses revealed an interplay between the right anterior insula and medial prefrontal cortex, which showed to be dependent on the presence of positive hysteresis. Our results support the hypothesis that high-order regions are involved in perceptual stabilization and decision during perceptual persistence (positive hysteresis) and add evidence to the role of the anterior insula as a hub of sensory information in perceptual decision-making.

Selective amygdalohippocampectomy (SelAH) is one of the most common surgical treatments for mesial temporal sclerosis. Microsurgical approaches are associated with the risk of cognitive and visual deficits due to damage to the cortex and white matter (WM) pathways. Our objective is to test the feasibility of an endoscopic approach through the anterior middle temporal gyrus (aMTG) to perform a SelAH.Virtual simulation with MRI scans of ten patients (20 hemispheres) was used to identify the endoscopic trajectory through the aMTG. A cadaveric study was performed on 22 specimens using a temporal craniotomy. The anterior part of the temporal horn was accessed using a tubular retractor through the aMTG after performing a 1.5 cm corticectomy at 1.5 cm posterior to the temporal pole. Then, an endoscope was introduced. SeIAH was performed in each specimen. The specimens underwent neuronavigation-assisted endoscopic SeIAH to confirm our surgical trajectory. WM dissection using Klingler's technique was performed on five specimens to assess WM integrity.This approach allowed the identification of collateral eminence, lateral ventricular sulcus, choroid plexus, inferior choroidal point, amygdala, hippocampus, and fimbria. SelAH was successfully performed on all specimens, and CT neuronavigation confirmed the planned trajectory. WM dissection confirmed the integrity of language pathways and optic radiations.Endoscopic SelAH through the aMTG can be successfully performed with a corticectomy of 15 mm, presenting a reduced risk of vascular injury and damage to WM pathways. This could potentially help to reduce cognitive and visual deficits associated with SelAH.

Frontotemporal dementia corresponds to a heterogenous group of syndromes characterized by progressive changes in behavior and/or language. Approximately 30% of patients with primary progressive aphasia, semantic variant (semantic dementia), present with atrophy in the right cerebral hemisphere, in a rare clinical condition called right temporal variant of frontotemporal dementia (rtvFTD). The objective of the study is to present the main demographic, clinical, neuropsychological, neuroimaging, and pathologic characteristics of rtvFTD patients. A systematic review of the literature was carried out in the PubMed, LILACS, and SCIELO databases between January and March 2022. After the evaluation process, 41 articles were selected, published between 1993 and 2021. We found that rtvFTD presents with severe and progressive prosopagnosia (related to anterior temporal lobe injury) associated with behavioral symptoms-desinibition (51%), apathy (39%), obsessive-compulsive symptoms (37%), changes in eating habits (33%), and depression (28%), which is different from semantic dementia. The most common pathologic pattern is TDP-43, type C. This field of knowledge has few studies (mainly reports and case series) and heterogenous nomenclature, which is a limitation. A multinational longitudinal registry of people with rtvFTD, with standardized assessment and description of symptoms, is necessary to elucidate the characteristics of this entity.

The fusiform gyrus (FG) subserves a range of visual cognitive functions likely arising from its distinct subregions that present different connectivity profiles. Nevertheless, the molecular basis underlying such connectivity variability across FG subregions is still an open question. Resting-state functional magnetic resonance imaging (fMRI) data were collected from a discovery dataset (361 healthy subjects) and two independent cross-race, cross-scanner validation datasets (103 and 329 healthy subjects). We adopted a newly developed standardized pipeline to process gene expression data from the Allen Human Brain Atlas. Fine-grained FG subregions derived from the Human Brainnetome Atlas were utilized to measure seed-based resting-state functional connectivity (rsFC). Then, transcriptome-neuroimaging spatial association analyses were conducted to identify genes related to rsFC of each FG subregion. Results showed that rsFC of the left A37mv was associated with expression measures of 1063 genes, while there were no expression-rsFC correlations for the other subregions. The 1063 genes were mainly enriched for biological functions and pathways related to synaptic transmission, neurons, and neurotransmitter systems as well as for autism spectrum disorder. Specific expression analyses revealed that these rsFC-related genes were specifically expressed in brain tissue, in cortical neurons and immune cells, and during nearly all developmental periods. In addition, these genes were associated with multiple behavioral domains such as vision, language, and sensation. Finally, protein-protein interaction (PPI) analysis demonstrated that the genes could construct a PPI network with 37 hub genes. These findings may offer unique insights into the molecular basis underlying the functional heterogeneity of the FG.

Fear aura has traditionally been considered relevant to epileptic discharges from mesial temporal areas, and few studies have investigated its effect on surgical outcome in drug-resistant epilepsy. We aim to assess the localizing and lateralizing value as well as prognostic significance of fear aura in patients with focal epilepsy.The occurrence of fear aura in relation to epileptogenic origin and its association with postoperative outcome were analyzed in 146 consecutive patients undergoing resective surgery for intractable epilepsy.Ninety-four (64.4%) patients reported auras, and 31 (21.2%) reported fear aura in their seizures. One hundred ten (75.3%) patients had an Engel class I outcome until last follow-up, of whom 24 experienced fear aura preoperatively. Fear aura appeared more frequently during temporal and frontal lobe seizures, but did not lateralize the seizure onset zone. There were no significant baseline differences between patients with and without fear aura. No correlation was found between postoperative outcome and the presence of auras. Occurrence of fear aura failed to show predictive value in surgical outcome whether in pooled or subgroup analysis.This study advances our understanding of the origin of fear aura, and is helpful for presurgical evaluation and outcome prediction. Without lateralizing value, fear aura is more commonly seen with temporal or frontal origin. When taken as a whole, auras do not have a significant impact on seizure outcome in focal epilepsy. Patients with fear aura are no more likely to become seizure-free than those without fear aura.

Understanding the pathogenesis of temporal lobe epilepsy (TLE) is essential for its diagnosis and treatment. The study aimed to explore regional homogeneity (ReHo) and changes in effective connectivity (EC) between brain regions in TLE patients, hoping to discover potential abnormalities in certain brain regions in TLE patients.Resting-state functional magnetic resonance data were collected from 23 TLE patients and 32 normal controls (NC). ReHo was used as a feature of multivariate pattern analysis (MVPA) to explore the ability of its alterations in identifying TLE. Based on the results of the MVPA, certain brain regions were selected as seed points to further explore alterations in EC between brain regions using Granger causality analysis.MVPA results showed that the classification accuracy for the TLE and NC groups was 87.27%, and the right posterior cerebellum lobe, right lingual gyrus (LING_R), right cuneus (CUN_R), and left superior temporal gyrus (STG_L) provided significant contributions. Moreover, the EC from STG_L to right fusiform gyrus (FFG_R) and LING_R and the EC from CUN_R to the right occipital superior gyrus (SOG_R) and right occipital middle gyrus (MOG_R) were altered compared to the NC group.The MVPA results indicated that ReHo abnormalities in brain regions may be an important feature in the identification of TLE. The enhanced EC from STG_L to FFG_R and LING_R indicates a shift in language processing to the right hemisphere, and the weakened EC from SOG_R and MOG_R to CUN_R may reveal an underlying mechanism of TLE.

Responsive neurostimulation is an effective therapy for patients with refractory mesial temporal lobe epilepsy. However, clinical outcomes are variable, few patients become seizure-free, and the optimal stimulation location is currently undefined. The aim of this study was to quantify responsive neurostimulation in the mesial temporal lobe, identify stimulation-dependent networks associated with seizure reduction, and determine if stimulation location or stimulation-dependent networks inform outcomes.We modeled patient-specific volumes of tissue activated and created probabilistic stimulation maps of local regions of stimulation across a retrospective cohort of 22 patients with mesial temporal lobe epilepsy. We then mapped the network stimulation effects by seeding tractography from the volume of tissue activated with both patient-specific and normative diffusion-weighted imaging. We identified networks associated with seizure reduction across patients using the patient-specific tractography maps and then predicted seizure reduction across the cohort.Patient-specific stimulation-dependent connectivity was correlated with responsive neurostimulation effectiveness after cross-validation (p = .03); however, normative connectivity derived from healthy subjects was not (p = .44). Increased connectivity from the volume of tissue activated to the medial prefrontal cortex, cingulate cortex, and precuneus was associated with greater seizure reduction.Overall, our results suggest that the therapeutic effect of responsive neurostimulation may be mediated by specific networks connected to the volume of tissue activated. In addition, patient-specific tractography was required to identify structural networks correlated with outcomes. It is therefore likely that altered connectivity in patients with epilepsy may be associated with the therapeutic effect and that utilizing patient-specific imaging could be important for future studies. The structural networks identified here may be utilized to target stimulation in the mesial temporal lobe and to improve seizure reduction for patients treated with responsive neurostimulation.

Background and ObjectivesWe assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy.MethodsWe studied 499 participants aged 60–88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of β-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education.ResultsIn the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers.DiscussionNovelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity.

Frontotemporal dementia is a neurodegenerative disease characterized by focal degeneration of the frontal and temporal lobes, clinically presenting with disinhibited behavior, personality changes, progressive non-fluent aphasia and/or impaired semantic memory. Research progress has been made in re-organizing the clinical concept of frontotemporal dementia and neuropathological classification based on multiple accumulating proteins. Alongside this progress a list of genetic mutations or variants that are causative or increase the risk of frontotemporal dementia have been identified and some of these gene products are extensively studied. However, there are still a lot of points that need to be overcome, including lack of specific diagnostic biomarker which enable antemortem diagnosis of underlying neurodegenerative process, and lack of disease modifying therapy which could prevent disease progression. Early and precise diagnosis of frontotemporal dementia is urgently required. In this context, how to define prodromal frontotemporal dementia and early differential diagnosis from primary psychiatric disorders are also important issues. In this review we will summarize and discuss current understanding of biological basis and psychiatric symptoms in frontotemporal dementia.

Behavioral flexibility depends on our capacity to build and leverage abstract knowledge about tasks. Recently, two separate lines of research have implicated distinct brain networks in representing abstract task information: a fronto-parietal cortical network, and a network involving the medial temporal lobes (MTL), medial prefrontal, and orbitofrontal cortex (OMPFC). These observations have mostly been made in parallel, with little attempt to understand their relationship. Here, we hypothesize that abstract task representations in these networks differ primarily in format, not content. Namely, that the MTL-OMPFC network maintains task knowledge in a flexible cognitive map, while the fronto-parietal network formats this knowledge as productions that facilitate action selection. We discuss novel implications and predictions for behavioral flexibility arising from this hypothesis.

Few studies have examined how multisensory emotional experiences are processed and encoded into memory. Here, we aimed to determine whether, at encoding, activity within functionally-defined visual- and auditory-processing brain regions discriminated the emotional category (i.e., positive, negative, or neutral) of the multisensory (audio-visual) events. Participants incidentally encoded positive, negative, and neutral multisensory stimuli during event-related functional magnetic resonance imaging (fMRI). Following a 3-hour post-encoding delay, their memory for studied stimuli was tested, allowing us to identify emotion-category-specific subsequent-memory effects focusing on medial temporal lobe regions (i.e., amygdala, hippocampus) and visual- and auditory-processing regions. We used a combination of univariate and multivoxel pattern fMRI analyses (MVPA) to examine emotion-category-specificity in mean activity levels and neural patterning, respectively. Univariate analyses revealed many more visual regions that showed negative-category-specificity relative to positive-category-specificity, and auditory regions only showed negative-category-specificity. These results suggest that negative emotion is more closely tied to information contained within sensory regions, a conclusion that was supported by the MVPA analyses. Functional connectivity analyses further revealed that the visual amplification of category-selective processing is driven, in part, by mean signal from the amygdala. Interestingly, while stronger representations in visuo-auditory regions were related to subsequent-memory for neutral multisensory stimuli, they were related to subsequent-forgetting of positive and negative stimuli. Neural patterning in the hippocampus and amygdala were related to memory for negative multisensory stimuli. These results provide new evidence that negative emotional stimuli are processed with increased engagement of visuosensory regions, but that this sensory engagement—that generalizes across the entire emotion category—is not the type of sensory encoding that is most beneficial for later retrieval.

Numerous studies indicate altered static local and long-range functional connectivity of multiple brain regions in schizophrenia patients with auditory verbal hallucinations (AVHs). However, the temporal dynamics of interhemispheric and intrahemispheric functional connectivity patterns remain unknown in schizophrenia patients with AVHs. We analyzed resting-state functional magnetic resonance imaging data for drug-naïve first-episode schizophrenia patients, 50 with AVHs and 50 without AVH (NAVH), and 50 age- and sex-matched healthy controls. Whole-brain functional connectivity was decomposed into ipsilateral and contralateral parts, and sliding-window analysis was used to calculate voxel-wise interhemispheric and intrahemispheric dynamic functional connectivity density (dFCD). Finally, the correlation analysis was performed between abnormal dFCD variance and clinical measures in the AVH and NAVH groups. Compared with the NAVH group and healthy controls, the AVH group showed weaker interhemispheric dFCD variability in the left middle temporal gyrus (p .01; p .001), as well as stronger interhemispheric dFCD variability in the right thalamus (p .001; p .001) and right inferior temporal gyrus (p .01; p .001) and stronger intrahemispheric dFCD variability in the left inferior frontal gyrus (p .001; p .01). Moreover, abnormal contralateral dFCD variability of the left middle temporal gyrus correlated with the severity of AVHs in the AVH group (r = -.319, p = .024). The findings demonstrate that abnormal temporal variability of interhemispheric and intrahemispheric dFCD in schizophrenia patients with AVHs mainly focus on the temporal and frontal cortices and thalamus that are pivotal components of auditory and language pathways.

Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out at 50 Hz, 0.2 msec, and 1-10 mA current intensity. Common brain regions sampled across all patients were amygdala (AMY), hippocampus (HG), anterior cingulate gyrus (CING), orbitofrontal cortex (OrbF), temporal neocortex (TNC), temporal pole (TP), and entorhinal cortex (ERC). Seven hundred fifty-five stimulations were conducted. Quantitative analysis of breathing signal, that is, changes in breathing rate (BR), depth (TV), and minute ventilation (MV), was carried out during ES using the BreathMetrics breathing waveform analysis toolbox. Electrocardiography, arterial oxygen saturation, end-tidal and transcutaneous carbon dioxide, nasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations.Electrical stimulation of TP and CING (at lower current strengths3 mA) increased TV and MV. At7-10 mA, CING decreased TV and MV. On the other hand, decreased TV and MV occurred with stimulation of mesial temporal structures such as AMY and HG. Breathing changes were dependent on stimulation intensity. Lateral temporal, entorhinal, and orbitofrontal cortices did not affect breathing either way.These findings suggest that breathing responses other than apnea can be induced by ES. Identification of two regions-the temporal pole and anterior cingulate gyrus-for enhancement of breathing may be important in paving the way to future development of strategies for prevention of SUDEP.

To explore dynamic alterations of cortical thickness before and after successful anterior temporal lobectomy (ATL) in patients with unilateral mesial temporal lobe epilepsy (mTLE).High-resolution T1-weighted MRI was obtained in 28 mTLE patients who achieved seizure freedom for at least 24 months after ATL and 29 healthy controls. Patients were scanned at five timepoints, including before surgery, 3, 6, 12 and 24 months after surgery. Preoperative cortical thickness of mTLE patients were compared with healthy controls. Dynamic alterations of cortical thickness before and after surgery were compared among five scans using linear mixed models.Patients with mTLE showed cortical thinning pre-surgically in ipsilateral entorhinal cortex, parahippocampal gyrus, inferior parietal cortex, lateral occipital cortex; contralateral pericalcarine cortex (PCC); and bilateral caudal middle frontal gyrus (cMFG), paracentral lobule, precentral gyrus (PCG), superior parietal cortex. Cortical thickening was observed in contralateral rostral anterior cingulate cortex (rACC). Patients showed postsurgical cortical thinning in ipsilateral temporal lobe, fusiform gyrus, caudal anterior cingulate cortex, lingual gyrus, and insula. Ipsilateral cMFG, PCC, and contralateral PCG showed significant cortical thickening after surgery. In addition, contralateral rACC showed cortical thickening at 3 months follow-up, however, with obvious cortical thinning at 24 months follow-up.Mesial temporal lobe epilepsy patients showed widespread cortical thinning before and after anterior temporal lobectomy. Progressive cortical thinning mainly existed in neighboring regions of resection. Postoperative cortical thickening may indicate cortical remodeling after successful surgery.

Although body image disturbances play a central role in the development, maintenance and relapse of binge eating disorder (BED), studies investigating the neural basis underlying body processing in BED are still missing. To address this gap, we conducted a preregistered (German Clinical Trials Register [Deutsches Register Klinischer Studien; DRKS], Registration DRKS00008107) combined functional magnetic resonance (fMRI)/eye tracking study in which 38 women with BED and 22 healthy controls weight-matched for overall equivalence processed images of their own bodies, an unfamiliar weight-matched body, and visually matched nonbody control stimuli while performing a one-back task. Women with BED responded with higher left fusiform body area (FBA) activity than controls during body image processing. Despite higher levels of self-reported body dissatisfaction, women with BED did not show overactivation in emotion-processing areas in response to their own body. The eye-tracking results indicated that visual attention toward the presented stimuli was associated with increased activity in the extrastriate body area (EBA) and FBA across groups. Our results thus provide evidence for an aberrant neural processing of body images in BED and highlight the importance of controlling for visual attention in future studies assessing neuronal body processing. (PsycInfo Database Record (c) 2022 APA, all rights reserved).