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Objective: The aim of our research was to evaluate the demographic and clinical features, treatment characteristics, and responses of the patients who presented to the Ege University Neurology Headache Outpatient Clinic with headaches lasting less than 4 hours. Another primary goal was to compare the characteristics mentioned above of patients with and without cranial autonomic symptoms. Materials and Methods: Our study was retrospective and cross-sectional. The findings were based on the data collected at our tertiary headache center. Headache disorder diagnoses were made in accordance with the International Classification of Headache Disorders-3 guideline. We reviewed the patients’ charts and recorded the information on a standardized form. The patients’ clinical features, and treatment responses were noted. The patients were divided into two groups as those with and without autonomic findings, and the above-mentioned features were compared. Treatment responses of patients with trigeminal autonomic cephalgia (TAC) and patients with trigeminal neuralgia (TN) were analyzed via logistic regression analysis. Values of p

Objectives: To detect seed-based functional connectivity (FC) between various cortical sub-regions and the thalamus in lifelong premature ejaculation (LPE) patients and explore whether specific thalamocortical networks are significantly altered in PE patients compared to healthy controls (HCs) Methods: Fifty non-medicated LPE patients and 40 age-matched HCs underwent a resting-state functional MRI. FC was adopted to identify specific thalamocortical connectivity between the thalamus and six cortical regions of interest (i.e. the motor cortex/supplementary motor, the prefrontal cortex, the temporal lobe, the posterior parietal cortex, the somatosensory cortex and the occipital lobe). In LPE patients, regression analysis was subsequently conducted to assess relationships of thalamocortical connectivity with the Premature Ejaculation Diagnostic Tool (PEDT) score and the Intravaginal Ejaculatory Latency Time (IELT). Results: LPE patients had significantly decreased FC between the motor cortex and bilateral ventral thalamus, between the prefrontal cortex and left dorsomedial thalamus, as well as between the temporal cortex and bilateral ventromedial thalamus. In LPE patients, PEDT score was significantly positively associated with the thalamus-posterior parietal cortex FC, and negatively associated with the thalamus-temporal cortex FC, while IELT was positively associated with the thalamus-temporal cortex and thalamus-motor cortex FC. Conclusion: These results enrich the imaging evidence for the understanding of the neurobiological mechanisms and/or consequences of LPE.

Background and ObjectivesTo examine associations between indicators of estrogen exposure from women's reproductive history and brain MRI biomarkers of Alzheimer disease (AD) in midlife.MethodsWe evaluated 99 cognitively normal women 52 ± 6 years of age and 29 men 52 ± 7 years of age with reproductive history data, neuropsychological testing, and volumetric MRI scans. We used multiple regressions to examine associations among reproductive history indicators, voxel-wise gray matter volume (GMV), and memory and global cognition scores, adjusting for demographics and midlife health indicators. Exposure variables were menopause status, age at menarche, age at menopause, reproductive span, hysterectomy status, number of children and pregnancies, and use of menopause hormonal therapy (HT) and hormonal contraceptives (HC).ResultsAll menopausal groups exhibited lower GMV in AD-vulnerable regions compared to men, with perimenopausal and postmenopausal groups also exhibiting lower GMV in temporal cortex compared to the premenopausal group. Reproductive span, number of children and pregnancies, and use of HT and HC were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus, independent of age, APOE ε4 status, and midlife health indicators. Although reproductive history indicators were not directly associated with cognitive measures, GMV in temporal regions was positively associated with memory and global cognition scores.DiscussionReproductive history events signaling more estrogen exposure such as premenopausal status, longer reproductive span, higher number of children, and use of HT and HC were associated with larger GMV in women in midlife. Further studies are needed to elucidate sex-specific biological pathways through which reproductive history influences cognitive aging and AD risk.

Background: Posture Instability (PI) is known to be a severe complication in Parkinson’s Disease (PD), and its mechanism remains poorly understood. Our study aims to explore the changes of brain network in PI of PD, and further investigate the role of peripheral inflammation on activities of different brain regions in PD with PI. Methods: 167 individuals were recruited, including 36 PD cases with PI and 131 ones without PI. We carefully assessed the status of motor and cognitive function, measured serum inflammatory factors, and detected the dopaminergic pathways and the metabolism of different brain regions by Positron Emission Tomography (PET). Data analysis was conducted by variance, univariate analysis, chi-square analysis, logistic regression, and partial correlation. Result: No difference was found for age or onset age between the two groups (P>0.05). Female patients were susceptible to posture impairment and had a 2.14-fold risk for PI compared with male patients in PD (P Conclusion: Female patients were susceptible to posture instability and had a 2.14-fold risk for PI of PD. Patients with PI had more severe impairments of motor and cognitive function for a longer duration than those without PI. PI was associated with a dopamine drop of the nigrostriatal system and lower activities of the limbic cortex in PD. Peripheral inflammation may be involved in degeneration of the cerebral cortex in PD combined with PI.

Whilst functional neuroimaging has been used to investigate cortical processing of degraded speech in adults, much less is known about how these signals are processed in children. An enhanced understanding of cortical correlates of poor speech perception in children would be highly valuable to oral communication applications, including hearing devices. We utilised vocoded speech stimuli to investigate brain responses to degraded speech in 29 normally hearing children aged 6–12 years. Intelligibility of the speech stimuli was altered in two ways by (i) reducing the number of spectral channels and (ii) reducing the amplitude modulation depth of the signal. A total of five different noise-vocoded conditions (with zero, partial or high intelligibility) were presented in an event-related format whilst participants underwent functional near-infrared spectroscopy (fNIRS) neuroimaging. Participants completed a word recognition task during imaging, as well as a separate behavioural speech perception assessment. fNIRS recordings revealed statistically significant sensitivity to stimulus intelligibility across several brain regions. More intelligible stimuli elicited stronger responses in temporal regions, predominantly within the left hemisphere, while right inferior parietal regions showed an opposite, negative relationship. Although there was some evidence that partially intelligible stimuli elicited the strongest responses in the left inferior frontal cortex, a region previous studies have suggested is associated with effortful listening in adults, this effect did not reach statistical significance. These results further our understanding of cortical mechanisms underlying successful speech perception in children. Furthermore, fNIRS holds promise as a clinical technique to help assess speech intelligibility in paediatric populations.

Language dysfunction is common in Alzheimer’s disease. There is increasing interest in the preclinical or asymptomatic phase of Alzheimer’s disease. Here we examined in 35 cognitively intact older adults (age range 52–78 years at baseline, 17 male) in a longitudinal study design the association between accumulation of amyloid over a 5–6-year period, measured using PET, and functional changes in the language network measured over the same time period using task-related functional MRI. In the same participants, we also determined the association between the longitudinal functional MRI changes and a cross-sectional measure of tau load as measured with 18F-AV1451 PET. As predicted, the principal change occurred in posterior temporal cortex. In the cortex surrounding the right superior temporal sulcus, the response amplitude during the associative-semantic versus visuo-perceptual task increased over time as amyloid load accumulated (Pcorrected = 0.008). In a whole-brain voxel-wise analysis, amyloid accumulation was also associated with a decrease in response amplitude in the left inferior frontal sulcus (Pcorrected = 0.009) and the right dorsomedial prefrontal cortex (Pcorrected = 0.005). In cognitively intact older adults, cross-sectional tau load was not associated with longitudinal changes in functional MRI response amplitude. Our findings confirm the central role of the neocortex surrounding the posterior superior temporal sulcus as the area of predilection within the language network in the earliest stages of Alzheimer’s disease. Amyloid accumulation has an impact on cognitive brain circuitry in the asymptomatic phase of Alzheimer’s disease., Using fMRI and amyloid PET in a longitudinal multimodal study, Reinartz et al. reveal functional changes in the language network occurring with increasing amyloid accumulation in an early asymptomatic phase of Alzheimer's disease.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER, "Otra manera de hacer Europa", "Investing in your future"); Red Española de Esclerosis Múltiple (REEM - RD16/0015/0002, RD16/0015/0003, RD12/0032/0002, RD12/0060/01-02); TEVA Spain; Fundación Merck Salud (Ayudas Merck de Investigación 2017); Proyecto Societat Catalana Neurologia 2017; CIBERNED program (Program 1, Alzheimer Disease and SIGNAL study); National Institutes of Health (NIA grants 1R01AG056850-01A1, R21AG056974, R01AG061566;, Fundació La Marató de TV3 (20142030, 20141210); Fundació Catalana Síndrome de Down; Fundació Víctor Grífols i Lucas; Generalitat de Catalunya (SLT006/17/00119); Universitat de Barcelona (APIF Pre-doctoral grant); Hospital Clinic Emili Letang). The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5-15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage.

Some of the most impressive functional specializations in the human brain are found in the occipitotemporal cortex (OTC), where several areas exhibit selectivity for a small number of visual categories, such as faces and bodies, and spatially cluster based on stimulus animacy. Previous studies suggest this animacy organization reflects the representation of an intuitive taxonomic hierarchy, distinct from the presence of face- and body-selective areas in OTC. Using human functional magnetic resonance imaging, we investigated the independent contribution of these two factors-the face-body division and taxonomic hierarchy-in accounting for the animacy organization of OTC and whether they might also be reflected in the architecture of several deep neural networks that have not been explicitly trained to differentiate taxonomic relations. We found that graded visual selectivity, based on animal resemblance to human faces and bodies, masquerades as an apparent animacy continuum, which suggests that taxonomy is not a separate factor underlying the organization of the ventral visual pathway.SIGNIFICANCE STATEMENT Portions of the visual cortex are specialized to determine whether types of objects are animate in the sense of being capable of self-movement. Two factors have been proposed as accounting for this animacy organization: representations of faces and bodies and an intuitive taxonomic continuum of humans and animals. We performed an experiment to assess the independent contribution of both of these factors. We found that graded visual representations, based on animal resemblance to human faces and bodies, masquerade as an apparent animacy continuum, suggesting that taxonomy is not a separate factor underlying the organization of areas in the visual cortex. ispartof: JOURNAL OF NEUROSCIENCE vol:41 issue:33 pages:7103-7119 ispartof: location:United States status: published

Objective Surgical techniques to achieve complete resection of mesial–basal temporal tumors should be pursued by neurosurgical oncologists. We describe the anatomical subpial amygdalohippocampectomy (SpAH) technique for tumor resection. Methods The key anatomical landmarks and critical steps of the SpAH technique were outlined and emphasized with medical illustrations and intraoperative photographs. The senior author's 90-day surgical outcomes with this approach were reviewed. Results Twenty-five patients (men, 17 [68%]; women, 8 [32%]; median [range] age, 59 [23–80] years) with temporal tumors involving the amygdalohippocampal region were included. SpAH was performed selectively in 8 [32%] patients, whereas 17 [68%] patients underwent SpAH in conjunction with an anterior temporal lobectomy due to tumor involvement of the anterolateral temporal cortex. The subpial resection of the amygdala protected the critical structures of the suprasellar cistern and sylvian fissure. Identifying the choroidal fissure as the superior-most aspect of hippocampal resection protected the optic tract and the thalamus. Subpial resection of the parahippocampal gyrus inferiorly protected the brainstem and critical structures of the ambient cistern. Tumors in the amygdalohippocampal region were anatomically and completely resected in all 25 patients. Of the 15 patients who presented with seizures, 13 (87%) were seizure-free at the 90-day postsurgical follow-up. Permanent neurologic deficits occurred in 3 patients (12%). Conclusions The SpAH technique permits complete resection of mesial–basal temporal tumors with an acceptable morbidity profile. An in-depth understanding of temporal lobe anatomy combined with a refined microsurgical technique allows for reproducible resection of tumor in the amygdalohippocampal region while protecting critical neurovascular structures.

International audience; Limited studies in humans and in animal models have investigated the neurotoxic risks related to a gestational exposure to diesel exhaust particles (DEP) on the embryonic brain, especially those regarding monoaminergic systems linked to neurocognitive disorders. We previously showed that exposure to DEP alters monoaminergic neurotransmission in fetal olfactory bulbs and modifies tissue morphology along with behavioral consequences at birth in a rabbit model. Given the anatomical and functional connections between olfactory and central brain structures, we further characterized their impacts in brain regions associated with monoaminergic neurotransmission. At gestational day 28 (GD28), fetal rabbit brains were collected from dams exposed by nose-only to either a clean air or filtered DEP for 2 h/day, 5 days/week, from GD3 to GD27. HPLC dosage and histochemical analyses of the main monoaminergic systems, i.e., dopamine (DA), noradrenaline (NA), and serotonin (5-HT) and their metabolites were conducted in microdissected fetal brain regions. DEP exposure increased the level of DA and decreased the dopaminergic metabolites ratios in the prefrontal cortex (PFC), together with sex-specific alterations in the hippocampus (Hp). In addition, HVA level was increased in the temporal cortex (TCx). Serotonin and 5-HIAA levels were decreased in the fetal Hp. However, DEP exposure did not significantly modify NA levels, tyrosine hydroxylase, tryptophan hydroxylase or AChE enzymatic activity in fetal brain. Exposure to DEP during fetal life results in dopaminergic and serotonergic changes in critical brain regions that might lead to detrimental potential short-term neural disturbances as precursors of long-term neurocognitive consequences.

The human hippocampus is involved in forming new memories: damage impairs memory. The dual stream model suggests that object “what” representations from ventral stream temporal cortex project to the hippocampus via the perirhinal and then lateral entorhinal cortex, and spatial “where” representations from the dorsal parietal stream via the parahippocampal gyrus and then medial entorhinal cortex. The hippocampus can then associate these inputs to form episodic memories of what happened where. Diffusion tractography was used to reveal the direct connections of hippocampal system areas in humans. This provides evidence that the human hippocampus has extensive direct cortical connections, with connections that bypass the entorhinal cortex to connect with the perirhinal and parahippocampal cortex, with the temporal pole, with the posterior and retrosplenial cingulate cortex, and even with early sensory cortical areas. The connections are less hierarchical and segregated than in the dual stream model. This provides a foundation for a conceptualization for how the hippocampal memory system connects with the cerebral cortex and operates in humans. One implication is that prehippocampal cortical areas such as the parahippocampal TF and TH subregions and perirhinal cortices may implement specialized computations that can benefit from inputs from the dorsal and ventral streams.

Alzheimer's disease (AD) is a devastating disease characterized by loss of synapses and neurons in the elderly. Accumulation of the β-amyloid peptide (Aβ) in the brain is thought to be central to the pathogenesis of AD. ApoE plays a key role in normal and physiological clearance of Aß, since it facilitates the peptide intra- and extracellular proteolytic degradation. Besides the cognitive deficit, AD patients also show alterations in their circadian rhythms. The objective of this study was to investigate the effects of an i.c.v. injection of Aβ (1-42) peptide on the 24 h rhythms of Apo E, BMAL1, RORα, Bdnf and trkB mRNA and Aβ levels in the rat temporal cortex. We found that an i.c.v. injection of Aβ aggregates phase shifts daily Bdnf expression as well as Apo E, BMAL1, RORα, Aβ and decreased the mesor of TrkB rhythms. Thus, elevated Aβ peptide levels might modify the temporal patterns of cognition-related factors, probably; by affecting the clock factors rhythms as well as in the 24 h rhythms of Apo E.

Background Adolescents are at increased risk of developing major depressive disorder (MDD) than many other age groups. Although the neural correlates of MDD in adults have been studied prospectively, such adolescent depression studies are mainly cross-sectional. We extracted data regarding the relationship between cortical thickness and later development of adolescent MDD from a national community study that uses an accelerated longitudinal design to examine the psychological, environmental, and neural differences related to drinking and brain development. Methods 692 subjects (age 12–21 years; 50% female) without a history of MDD were assessed with structural neuroimaging at baseline. We compared those 101 subjects who transitioned to MDD by 1-year follow-up to those who remained non-depressed over the same time period. FreeSurfer's autosegmentation process estimated vertex-wide cortical thicknesses and its Query, Design, Estimate, Contrast (Qdec) application investigated cortical thickness between those who later developed MDD and those who remained without MDD (Monte Carlo corrected for multiple comparisons, vertex-wise cluster threshold of 1.3, p Results Those who transitioned in the next year to MDD had, at baseline, thinner cortices in the superior frontal cortex, precentral and postcentral regions, and superior temporal cortex, above and beyond effects attributable to age and sex. No cortical thickness sex differences or sex-by-depression interactions were observed. Limitations A larger sample size could improve statistical power and future investigations will be needed to confirm our results. Conclusions Thinner cortices over frontal and temporal regions may be linked to enhanced vulnerability for future depression during the adolescent–young adulthood transition.

Background: Eating disorders (ED) in dementia represent a significant impairment affecting patients’ and caregivers’ lives. In frontotemporal dementia (FTD), ED include overeating, sweet food preference, stereotypical eating, and hyperorality, while in Alzheimer’s disease (AD), anorexia and appetite loss are the most common ED. Objective: The aim of our study was to highlight Brodmann areas (BAs) implicated specifically in the appearance of ED in FTD and AD. Methods: We studied 141 patients, 75 with FTD and 66 with AD. We used the NeuroGamTM software on the reconstructed single photon emission computed tomography-SPECT data for the automated comparison of BAs perfusion on the left (L) and right (R) hemisphere with perfusion in corresponding BAs of a normal database. Results: The FTD group included 27 men and 48 women, age (mean±SD) 65.8±8.5 years, duration of disease 3.4±3.3 years, Mini-Mental State Examination (MMSE) 17.9±8.6, ED score on Neuropsychiatric Inventory (NPI) 4.7±8.5. ED in FTD were correlated with hypoperfusion in right anterior and dorsolateral prefrontal cortices (BAs 10R, 46R), left orbitofrontal cortex (BA 12L), orbital part of the right inferior frontal gyrus (BA 47R), and left parahippocampal gyrus (BA 36L). The AD group included 21 men and 45 women, age (mean±SD) 70.2±8.0 years, duration of disease 3.3±2.4 years, MMSE 20.2±6, ED-NPI score 2.7±3.9. ED in AD were correlated with hypoperfusion in left inferior temporal cortex (BA 20L). Conclusion: SPECT imaging with automated mapping of brain cortex could contribute to the understanding of the neural networks involved in the manifestation of ED in dementia.

Objective To determine if long interspersed element-1 (L1) retrotransposons convey risk for idiopathic temporal lobe epilepsy (TLE). Methods Surgically resected temporal cortex from individuals with TLE (N = 33) and postmortem temporal cortex from individuals with no known neurological disease (N = 33) were analyzed for L1 content by Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq). Expression of three KCNIP4 splice variants was assessed by droplet digital PCR (ddPCR). Protein ANalysis THrough Evolutionary Relationships (PANTHER) was used to determine ontologies and pathways for lists of genes harboring L1 insertions. Results We identified novel L1 insertions specific to individuals with TLE, and others specific to controls. Although there were no statistically significant differences between cases and controls in the numbers of known and novel L1 insertions, PANTHER analyses of intragenic L1 insertions showed statistically significant enrichments for epilepsy-relevant gene ontologies in both cases and controls. Gene ontologies "neuron projection development" and "calcium ion transmembrane transport" were among those found only in individuals with TLE. We confirmed novel L1 insertions in several genes associated with seizures/epilepsy, including a de novo somatic L1 retrotransposition in KCNIP4 that occurred after neural crest formation in one patient. However, ddPCR results suggest this de novo L1 did not alter KCNIP4 mRNA expression. Significance Given current data from this small cohort, we conclude that L1 elements, either rare heritable germline insertions or de novo somatic retrotranspositions, may contribute only minimally to overall genetic risk for idiopathic TLE. We suggest that further studies in additional patients and additional brain regions are warranted.

Background: Olfactory impairment is evident in Alzheimer’s disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. Objective: To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. Methods: Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ42). Results: Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p

In humans, brain oscillations support critical features of memory formation. However, understanding the molecular mechanisms underlying this activity remains a major challenge. Here, we measured memory-sensitive oscillations using intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. When these patients subsequently underwent resection, we employed transcriptomics on the temporal cortex to link gene expression with brain oscillations and identified genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated oscillatory signature-specific modules associated with neuropsychiatric disorders and ion channel activity, with highly correlated genes exhibiting strong connectivity within these modules. Using single-nucleus transcriptomics, we further revealed that these modules are enriched for specific classes of both excitatory and inhibitory neurons, and immunohistochemistry confirmed expression of highly correlated genes. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding.

Background Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. Method We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. Results Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case–control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. Limitations We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. Conclusions Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms.

Research in functional neuroimaging has suggested that category-selective regions of visual cortex, including the ventral temporal cortex (VTC), can be reactivated endogenously through imagery and recall. Face representation in the monkey face-patch system has been well studied and is an attractive domain in which to explore these processes in humans. The VTCs of 8 human subjects (4 female) undergoing invasive monitoring for epilepsy surgery were implanted with microelectrodes. Most (26 of 33) category-selective units showed specificity for face stimuli. Different face exemplars evoked consistent and discriminable responses in the population of units sampled. During free recall, face-selective units preferentially reactivated in the absence of visual stimulation during a 2 s window preceding face recall events. Furthermore, we show that in at least 1 subject, the identity of the recalled face could be predicted by comparing activity preceding recall events to activity evoked by visual stimulation. We show that face-selective units in the human VTC are reactivated endogenously, and present initial evidence that consistent representations of individual face exemplars are specifically reactivated in this manner.SIGNIFICANCE STATEMENTThe role of “top-down” endogenous reactivation of native representations in higher sensory areas is poorly understood in humans. We conducted the first detailed single-unit survey of ventral temporal cortex (VTC) in human subjects, showing that, similarly to nonhuman primates, humans encode different faces using different rate codes. Then, we demonstrated that, when subjects recalled and imagined a given face, VTC neurons reactivated with the same rate codes as when subjects initially viewed that face. This suggests that the VTC units not only carry durable representations of faces, but that those representations can be endogenously reactivated via “top-down” mechanisms.

The decrease in response with stimulus repetition is a common property observed in many sensory brain areas. This repetition suppression (RS) is ubiquitous in neurons of macaque inferior temporal (IT) cortex, the end-stage of the ventral visual pathway. The neural mechanisms of RS in IT are still unclear, and one possibility is that it is inherited from areas upstream to IT that show also RS. Since neurons in IT have larger receptive fields compared with earlier visual areas, we examined the inheritance hypothesis by presenting adapter and test stimuli at widely different spatial locations along both vertical and horizontal meridians and across hemifields. RS was present for distances between adapter and test stimuli up to 22° and when the two stimuli were presented in different hemifields. Also, we examined the position tolerance of the stimulus selectivity of adaptation by comparing the responses to a test stimulus following the same (repetition trial) or a different (alternation trial) adapter at a position different from the test stimulus. Stimulus-selective adaptation was still present and consistently stronger in the later phase of the response for distances up to 18°. Finally, we observed stimulus-selective adaptation in repetition trials even without a measurable excitatory response to the adapter stimulus. To accommodate these and previous data, we propose that at least part of the stimulus-selective adaptation in IT is based on short-term plasticity mechanisms within IT and/or reflects top-down activity from areas downstream to IT.

Human visual cortex contains many retinotopic and category-specific regions. These brain regions have been the focus of a large body of functional magnetic resonance imaging research, significantly expanding our understanding of visual processing. As studying these regions requires accurate localization of their cortical location, researchers perform functional localizer scans to identify these regions in each individual. However, it is not always possible to conduct these localizer scans. Here, we developed and validated a functional region of interest (ROI) atlas of early visual and category-selective regions in human ventral and lateral occipito-temporal cortex. Results show that for the majority of functionally defined ROIs, cortex-based alignment results in lower between-subject variability compared to nonlinear volumetric alignment. Furthermore, we demonstrate that 1) the atlas accurately predicts the location of an independent dataset of ventral temporal cortex ROIs and other atlases of place selectivity, motion selectivity, and retinotopy. Next, 2) we show that the majority of voxel within our atlas is responding mostly to the labeled category in a left-out subject cross-validation, demonstrating the utility of this atlas. The functional atlas is publicly available (download.brainvoyager.com/data/visfAtlas.zip) and can help identify the location of these regions in healthy subjects as well as populations (e.g., blind people, infants) in which functional localizers cannot be run.

Highlights • Semantic task demands affect activity and connectivity at different processing stages. • Earliest task modulations occurred in posterior visual brain regions. • ATL, PTC and IFG effects reflect task-relevant retrieval of multimodal information. • ATL effects are left-lateralised for activation but bilateral for functional connectivity. • Dynamic evoked and connectivity data are essential to study semantic networks., How does brain activity in distributed semantic brain networks evolve over time, and how do these regions interact to retrieve the meaning of words? We compared spatiotemporal brain dynamics between visual lexical and semantic decision tasks (LD and SD), analysing whole-cortex evoked responses and spectral functional connectivity (coherence) in source-estimated electroencephalography and magnetoencephalography (EEG and MEG) recordings. Our evoked analysis revealed generally larger activation for SD compared to LD, starting in primary visual area (PVA) and angular gyrus (AG), followed by left posterior temporal cortex (PTC) and left anterior temporal lobe (ATL). The earliest activation effects in ATL were significantly left-lateralised. Our functional connectivity results showed significant connectivity between left and right ATL, PTC and right ATL in an early time window, as well as between left ATL and IFG in a later time window. The connectivity of AG was comparatively sparse. We quantified the limited spatial resolution of our source estimates via a leakage index for careful interpretation of our results. Our findings suggest that the different demands on semantic information retrieval in lexical and semantic decision tasks first modulate visual and attentional processes, then multimodal semantic information retrieval in the ATLs and finally control regions (PTC and IFG) in order to extract task-relevant semantic features for response selection. Whilst our evoked analysis suggests a dominance of left ATL for semantic processing, our functional connectivity analysis also revealed significant involvement of right ATL in the more demanding semantic task. Our findings demonstrate the complementarity of evoked and functional connectivity analysis, as well as the importance of dynamic information for both types of analyses.

Epub 2022 May 2 hMT+/V5 is a region in the middle occipitotemporal cortex that responds preferentially to visual motion in sighted people. In cases of early visual deprivation, hMT+/V5 enhances its response to moving sounds. Whether hMT+/V5 contains information about motion directions and whether the functional enhancement observed in the blind is motion specific, or also involves sound source location, remains unsolved. Moreover, the impact of this cross-modal reorganization of hMT+/V5 on the regions typically supporting auditory motion processing, like the human planum temporale (hPT), remains equivocal. We used a combined functional and diffusion-weighted MRI approach and individual in-ear recordings to study the impact of early blindness on the brain networks supporting spatial hearing in male and female humans. Whole-brain univariate analysis revealed that the anterior portion of hMT+/V5 responded to moving sounds in sighted and blind people, while the posterior portion was selective to moving sounds only in blind participants. Multivariate decoding analysis revealed that the presence of motion direction and sound position information was higher in hMT+/V5 and lower in hPT in the blind group. While both groups showed axis-of-motion organization in hMT+/V5 and hPT, this organization was reduced in the hPT of blind people. Diffusion-weighted MRI revealed that the strength of hMT+/V5-hPT connectivity did not differ between groups, whereas the microstructure of the connections was altered by blindness. Our results suggest that the axis-of-motion organization of hMT+/V5 does not depend on visual experience, but that congenital blindness alters the response properties of occipitotemporal networks supporting spatial hearing in the sighted.SIGNIFICANCE STATEMENT Spatial hearing helps living organisms navigate their environment. This is certainly even more true in people born blind. How does blindness affect the brain network supporting auditory motion and sound source location? Our results show that the presence of motion direction and sound position information was higher in hMT+/V5 and lower in human planum temporale in blind relative to sighted people; and that this functional reorganization is accompanied by microstructural (but not macrostructural) alterations in their connections. These findings suggest that blindness alters cross-modal responses between connected areas that share the same computational goals. The project was funded in part by a European Research Council starting grant MADVIS (Project 337573) awarded to O.C., the Belgian Excellence of Science (EOS) program (Project 30991544) awarded to O.C., a Flagship ERA-NET grant SoundSight (FRS-FNRS PINT-MULTI R.8008.19) awarded to O.C., and by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 701250 awarded to V.O. Computational resources have been provided by the supercomputing facilities of the Université catholique de Louvain (CISM/UCL) and the Consortium des Équipements de Calcul Intensif en Fédération Wallonie Bruxelles (CÉCI) funded by the Fond de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under convention 2.5020.11 and by the Walloon Region. A.G.-A. is supported by the Wallonie Bruxelles International Excellence Fellowship and the FSR Incoming PostDoc Fellowship by Université Catholique de Louvain. O.C. is a research associate, C.B. is postdoctoral researcher, and M.R. is a research fellow at the Fond National de la Recherche Scientifique de Belgique (FRS-FNRS).

Studies have shown that particulate matter (PM) induces the expression of the aryl hydrocarbon receptor (Ahr) leading to the activation of the oxidative stress response. This study is aimed at characterizing the specific impact of fine PM on the expression profile of the Ahr and oxidative stress response in the primary auditory cortex. PM2.5 ( n = 14 per group), respectively. One week after intracranial injection, the temporal cortex was harvested. Transmission electron microscopy was performed to evaluate the distribution of PM2.5 within the temporal cortex. Additionally, the mRNA and protein expression levels of cytochrome P450 1A1 (CYP1A1), CYP1B1, inducible nitric oxide synthase (iNOS), Ahr, and brevican mRNA and protein were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) or western blotting, respectively. Finally, the protein expression levels of the receptor for advanced glycation end products (RAGE) were estimated using enzyme-linked immunosorbent assay (ELISA). PM2.5 was observed in intracellular vesicles within the temporal cortex following intracranial injection. Levels of oxidative stress molecules (i.e., CYP1A1, CYP1B1, and iNOS), Ahr, Brevican, and RAGE were higher in the PM2.5 group compared with the control group. Intracranial administration of PM2.5 led to increased levels of Ahr and markers of an oxidative stress response in the temporal cortex. The oxidative stress response-mediated increases in the levels of brevican and RAGE.

Previous research has shown that social-conceptual associations, such as stereotypes, can influence the visual representation of faces and neural pattern responses in ventral temporal cortex (VTC) regions, such as the fusiform gyrus (FG). Current models suggest that this social-conceptual impact requires medial orbitofrontal cortex (mOFC) feedback signals during perception. Backward masking can disrupt such signals, as it is a technique known to reduce functional connectivity between VTC regions and regions outside VTC. During functional magnetic resonance imaging (fMRI), subjects passively viewed masked and unmasked faces, and following the scan, perceptual biases and stereotypical associations were assessed. Multi-voxel representations of faces across the VTC, and in the FG and mOFC, reflected stereotypically biased perceptions when faces were unmasked, but this effect was abolished when faces were masked. However, the VTC still retained the ability to process masked faces and was sensitive to their categorical distinctions. Functional connectivity analyses confirmed that masking disrupted mOFC–FG connectivity, which predicted a reduced impact of stereotypical associations in the FG. Taken together, our findings suggest that the biasing of face representations in line with stereotypical associations does not arise from intrinsic processing within the VTC and FG alone, but instead it depends in part on top-down feedback from the mOFC during perception.

Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers. Interpretation: A subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.

INTRODUCTION Hyperactivity of the sympathetic nervous system is considered as an important component involved in the pathological mechanisms of premature ejaculation (PE). However, the neural mechanisms of PE with high sympathetic activity are still not well understood. METHODS The activity of the sympathetic innervations in the penis was evaluated by the sympathetic skin response of the penis (PSSR) with an electromyograph and evoked potential equipment. Resting-state functional magnetic resonance imaging (fMRI) data were acquired from 18 PE patients with high sympathetic activity (sPE), 17 PE patients with normal sympathetic activity (nsPE), and 24 healthy controls (HC). We investigated the neural basis of sPE based on the measure of regional homogeneity (ReHo). Moreover, the correlations between brain regions with altered ReHo and PEDT scores and PSSR latencies in the patient group were explored. RESULTS Altered ReHo values among three groups were found in the temporal, cingulated, and parietal cortex in the default mode network (DMN), as well as the temporal cortex in the auditory network (AUD). Compared with HC, Patients with sPE had increased ReHo values of brain regions in DMN, AUD, and decreased ReHo values of brain regions in DMN. In addition, increased ReHo values were found in DMN of patients with nsPE, while decreased ReHo values were found in DMN and the attention network (AN). Moreover, sPE patients had increased ReHo values in AUD and decreased ReHo values in DMN when compared with nsPE patients. Finally, altered ReHo values of brain regions in DMN and AUD were associated with PEDT scores and PSSR latencies in the patient group. CONCLUSION Our results suggested that PE patients had abnormal ReHo values in DMN, AUD, and AN. Patients with sPE were characterized by increased neuronal activity in AUD and decreased activity in DMN. This highlighted the significances of DMN, AUD, and AN in the pathophysiology of PE and also provided potential neuroimaging biomarkers for distinguishing sPE from nsPE and HC.

Impulsivity refers to a set of traits that are generally negatively related to critical domains of adaptive functioning and are core features of numerous psychiatric disorders. The current study examined the gray and white matter correlates of five impulsive traits measured using an abbreviated version of the UPPS-P (Urgency, (lack of) Premeditation, (lack of) Perseverance, Sensation-Seeking, Positive Urgency) impulsivity scale in children aged 9 to 10 (N = 11,052) from the Adolescent Brain and Cognitive Development (ABCD) study. Linear mixed effect models and elastic net regression were used to examine features of regional gray matter and white matter tractography most associated with each UPPS-P scale; intraclass correlations were computed to examine the similarity of the neuroanatomical correlates among the scales. Positive Urgency showed the most robust association with neuroanatomy, with similar but less robust associations found for Negative Urgency. Perseverance showed little association with neuroanatomy. Premeditation and Sensation Seeking showed intermediate associations with neuroanatomy. Critical regions across measures include the dorsolateral prefrontal cortex, lateral temporal cortex, and orbitofrontal cortex; critical tracts included the superior longitudinal fasciculus and inferior fronto-occipital fasciculus. Negative Urgency and Positive Urgency showed the greatest neuroanatomical similarity. Some UPPS-P traits share neuroanatomical correlates, while others have distinct correlates or essentially no relation to neuroanatomy. Neuroanatomy tended to account for relatively little variance in UPPS-P traits (i.e., Model R2 < 1%) and effects were spread throughout the brain, highlighting the importance of well powered samples. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BackgroundThe heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological etiologies, genetics, neural systems, neurocognitive attributes and clinical subtypes or phenotypes has been observed across individuals with ASD.MethodsIn this study, we aim to investigate the heterogeneity in ASD from a multimodal brain imaging perspective. The Autism Diagnostic Observation Schedule (ADOS) was used as a reference to guide functional and structural MRI fusion. DSM-IV-TR diagnosed Asperger’s disorder (n = 79), pervasive developmental disorder-not otherwise specified [PDD-NOS] (n = 58) and Autistic disorder (n = 92) from ABIDE II were used as discovery cohort, and ABIDE I (n = 400) was used for replication.ResultsDorsolateral prefrontal cortex and superior/middle temporal cortex are the primary common functional–structural covarying cortical brain areas shared among Asperger’s, PDD-NOS and Autistic subgroups. Key differences among the three subtypes are negative functional features within subcortical brain areas, including negative putamen–parahippocampus fractional amplitude of low-frequency fluctuations (fALFF) unique to the Asperger’s subtype; negative fALFF in anterior cingulate cortex unique to PDD-NOS subtype; and negative thalamus–amygdala–caudate fALFF unique to the Autistic subtype. Furthermore, each subtype-specific brain pattern is correlated with different ADOS subdomains, with social interaction as the common subdomain. The identified subtype-specific patterns are only predictive for ASD symptoms manifested in the corresponding subtypes, but not the other subtypes.ConclusionsAlthough ASD has a common neural basis with core deficits linked to social interaction, each ASD subtype is strongly linked to unique brain systems and subdomain symptoms, which may help to better understand the underlying mechanisms of ASD heterogeneity from a multimodal neuroimaging perspective.LimitationsThis study is male based, which cannot be generalized to the female or the general ASD population.

Long‐term hearing loss in postlingually deaf (PD) adults may lead to brain structural changes that affect the outcomes of cochlear implantation. We studied 94 PD patients who underwent cochlear implantation and 37 patients who were MRI‐scanned within 2 weeks after the onset of sudden hearing loss and expected with minimal brain structural changes in relation to deafness. Compared with those with sudden hearing loss, we found lower gray matter (GM) probabilities in bilateral thalami, superior, middle, inferior temporal cortices as well as the central cortical regions corresponding to the movement and sensation of the lips, tongue, and larynx in the PD group. Among these brain areas, the GM in the middle temporal cortex showed negative correlation with disease duration, whereas the other areas displayed positive correlations. Left superior, middle temporal cortical, and bilateral thalamic GMs were the most accurate predictors of post‐cochlear implantation word recognition scores (mean absolute error [MAE] = 10.1, r = .82), which was superior to clinical variables used (MAE: 12.1, p, Our findings suggest that the cross‐modal plasticity allowing the superior temporal cortex and thalamus to process other modal sensory inputs reverses the initially lower volume when deafness becomes persistent. The middle temporal cortex processing higher‐level language comprehension shows persistent negative correlations with disease duration, suggesting this area's association with degraded speech comprehensions due to long‐term deafness. Morphological features combined with clinical variables might play a key role in predicting outcomes of cochlear implantation.

Stressful events are often vividly remembered. Although generally adaptive to survival, this emotional-memory enhancement may contribute to stress-related disorders. We tested here whether the enhanced memory for stressful events is due to the expectancy violation evoked by these events. Ninety-four men and women underwent a stressful or control episode. Critically, to manipulate the degree of expectancy violation, we gave participants either detailed or minimal information about the stressor. Although the subjective and hormonal stress responses were comparable in informed and uninformed participants, prior information about the stressor abolished the memory advantage for core features of the stressful event, tested 7 days later. Using functional near-infrared spectroscopy, we further linked the expectancy violation and memory formation under stress to the inferior temporal cortex. These data are the first to show that detailed information about an upcoming stressor and, by implication, a reduced expectancy violation attenuates the memory for stressful events.

The evolution and development of anatomical–functional relationships in the cerebral cortex is of major interest in neuroscience. Here, we leveraged the fact that a functional region selective for visual scenes is located within a sulcus in the medial ventral temporal cortex (VTC) in both humans and macaques to examine the relationship between sulcal depth and place selectivity in the medial VTC across species and age groups. To do so, we acquired anatomical and functional magnetic resonance imaging scans in 9 macaques, 26 human children, and 28 human adults. Our results revealed a strong structural–functional coupling between sulcal depth and place selectivity across age groups and species in which selectivity was strongest near the deepest sulcal point (the sulcal pit). Interestingly, this coupling between sulcal depth and place selectivity strengthens from childhood to adulthood in humans. Morphological analyses suggest that the stabilization of sulcal–functional coupling in adulthood may be due to sulcal deepening and areal expansion with age as well as developmental differences in cortical curvature at the pial, but not the white matter surfaces. Our results implicate sulcal features as functional landmarks in high-level visual cortex and highlight that sulcal–functional relationships in the medial VTC are preserved between macaques and humans despite differences in cortical folding.

Schizophrenic patients often experience visual hallucinations (VHs) and auditory hallucinations (AHs); however, brain aberrations associated with combined VH and AH in schizophrenic patients remains poorly documented. Changes to the brain and cognition during the first episode of untreated schizophrenic patients (FUSCH) with both VHs and AHs (FUSCHVA) were evaluated. One-hundred and fifty-seven patients were enrolled that had FUSCH (1) with VHs but not AHs (FUSCHV), and (2) with AHs but not VHs (FUSCHA), plus FUSCHVA and healthy controls (n = 30). Gray matter volume (GMV) and MATRICS Consensus Cognitive Battery (MCCB) was measured to reflect impairments to the brain and cognition, respectively. FUSCHVA patients had the severest cognitive impairment for all components of the MCCB, followed by FUSCHV and FUSCHA patients. Compared to healthy patients, FUSCHVA patients had reduced GMV in the occipital, parietal, frontal, and temporal cortex, and increased GMV in the hippocampus and striatum. Compared to FUSCHV patients, FUSCHVA patients had reduced GMV in the occipital cortex and postcentral gyrus, and increased GMV in the posterio-parietal lobe. Compared to patients with FUSCHA, the GMV in patients with FUSCHVV was reduced in the occipital cortex and posterio parietal lobe. In conclusion, visual and auditory hallucinations appear to deteriorate reciprocally in FUSCHVA patients, accompanied with sever cognitive impairments. Compared to AHs, VHs might be accompanied with severe GMV impairment in the brain, especially in the primary visual cortex and higher perception integration cortex (posterio parietal lobe) in patients with FUSCH.

Loss of function mutations within the vesicular trafficking protein Ras analogy in brain 39B (RAB39B) are associated with rare X‐linked Parkinson’s disease (PD). Physiologically, RAB39B is localized to Golgi vesicles and recycling endosomes and is required for glutamatergic receptor maturation but also for alpha‐Synuclein (aSyn) homeostasis and the inhibition of its aggregation. Despite evidence linking RAB39B to neurodegeneration, the involvement of the protein in idiopathic neurodegenerative diseases remains undetermined. Here, analysis of the spatial distribution and expression of RAB39B was conducted in post‐mortem human brain tissue from cases of dementia with Lewy bodies (DLB, n = 10), Alzheimer’s disease (AD, n = 12) and controls (n = 12). Assessment of cortical RAB39B immunoreactivity using tissue microarrays revealed an overall reduction in the area of RAB39B positive gray matter in DLB cases when compared to controls and AD cases. Strikingly, RAB39B co‐localized with beta‐amyloid (Aβ) plaques in all cases examined and was additionally present in a subpopulation of Lewy bodies (LBs) in DLB. Biochemical measures of total RAB39B levels within the temporal cortex were unchanged between DLB, AD and controls. However, upon subcellular fractionation, a reduction of RAB39B in the cytoplasmic pool was found in DLB cases, alongside an increase of phosphorylated aSyn and Aβ in whole tissue lysates. The reduction of cytoplasmic RAB39B is consistent with an impaired reserve capacity for RAB39B‐associated functions, which in turn may facilitate LB aggregation and synaptic impairment. Collectively, our data support the involvement of RAB39B in the pathogenesis of DLB and the co‐aggregation of RAB39B with Aβ in plaques suggests that age‐associated cerebral Aβ pathology may be contributory to the loss of RAB39B. Thus RAB39B, its associated functional pathways and its entrapment in aggregates may be considered as future targets for therapeutic interventions to impede the overall pathological burden and cellular dysfunction in Lewy body diseases.

Objective To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. Methods Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. Results Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. Significance The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the “attention to detail” subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.

Introduction Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer's disease (AD) cases. Methods We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [Aβ40], Aβ42, tau, p-tau, and apolipoprotein E) in the temporal cortex were assessed by ELISA. Results Higher levels of soluble tau, insoluble p-tau, and apolipoprotein E (apoE) were independently correlated with lower levels of endothelial tight junction proteins CLDN5 and OCLN in AD brains. Although high Aβ40 levels, APOE e4, and male sex were predominantly associated with exacerbated CAA severity, those factors did not influence tight junction protein levels. Discussion Refining the molecular mechanisms connecting tau, Aβ, and apoE with cerebrovascular pathologies is critical for greater understanding of AD pathogenesis and establishing effective therapeutic interventions for the disease.

Social behavior is transmitted cross-generationally through coordinated behavior within attachment bonds. Parental depression and poor parental care are major risks for disruptions of such coordination and are associated with offspring’s psychopathology and interpersonal dysfunction. Given the key role of the cortico-basal ganglia (CBG) circuits in social communication, we examined similarities (concordance) of parent–offspring CBG white matter (WM) connections and how parental history of major depressive disorder (MDD) and early parental care moderate these similarities. We imaged 44 parent–offspring dyads and investigated WM connections between basal-ganglia seeds and selected regions in temporal cortex using diffusion tensor imaging (DTI) tractography. We found significant concordance in parent–offspring strength of CBG WM connections, moderated by parental lifetime-MDD and care. The results showed diminished neural concordance among dyads with a depressed parent and that better parental care predicted greater concordance, which also provided a protective buffer against attenuated concordance among dyads with a depressed parent. Our findings provide the first neurobiological evidence of concordance between parents-offspring in WM tracts and that concordance is diminished in families where parents have lifetime-MDD. This disruption may be a risk factor for intergenerational transmission of psychopathology. Findings emphasize the long-term role of early caregiving in shaping the neural concordance among at-risk and affected dyads.

Spinal cord injury (SCI) is a common cause of disability, which often leads to sensorimotor cortex dysfunction above the spinal injury site. However, the cerebral regional effects on metabolic information after SCI have been little studied. Here, adult Sprague-Dawley rats were divided into acute and chronic treatment groups and sham groups with day-matched periods. The Basso, Beatte, and Bresnahan scores method were utilized to evaluate the changes in behaviors during the recovery of the animals, and the metabolic information was measured with the 1 H-observed/13 C-edited NMR method. Total metabolic concentrations in every region were almost similar in both treated groups. However, the metabolic kinetics in most regions in the acute group were significantly altered (P < .05), particularly in the cortical area, thalamus and medulla (P < .01). After long-term recovery, some metabolic kinetics were recovered, especially in the temporal cortex, occipital cortex, and medulla. The metabolic kinetic changes revealed the alteration of metabolism and neurotransmission in different brain regions after SCI, which present evidence for the alternation of brain glucose oxidation. Therefore, this shows the significant influence of SCI on cerebral function and neuroscience research. This study also provides the theoretical basis for clinical therapy after SCI, such as mitochondrial transplantation. \ud \ud Keywords: NMR; brain regions; metabolic kinetics; neurotransmitters; spinal cord injury.

The complex multifactorial nature of AD pathogenesis has been highlighted by evidence implicating additional neurodegenerative mechanisms, beyond that of amyloid-β (Aβ) and tau. To provide insight into cause and effect, we here investigated the temporal profile and associations of pathological changes in synaptic, endoplasmic reticulum (ER) stress and neuro-inflammatory markers. Quantifications were established via immunoblot and immunohistochemistry protocols in post-mortem lateral temporal cortex (n = 46). All measures were assessed according to diagnosis (non-AD vs. AD), neuropathological severity (low (Braak ≤ 2) vs. moderate (3–4) vs. severe (≥ 5)) and individual Braak stage, and were correlated with Aβ and tau pathology and cognitive scores. Postsynaptic PSD-95, but not presynaptic synaptophysin, was decreased in AD cases and demonstrated a progressive decline across disease severity and Braak stage, yet not with cognitive scores. Of all investigated ER stress markers, only phospho-protein kinase RNA-like ER kinase (p-PERK) correlated with Braak stage and was increased in diagnosed AD cases. A similar relationship was observed for the astrocytic glial fibrillary acidic protein (GFAP); however, the associated aquaporin 4 and microglial Iba1 remained unchanged. Pathological alterations in these markers preferentially correlated with measures of tau over those related to Aβ. Notably, GFAP also correlated strongly with Aβ markers and with all assessments of cognition. Lateral temporal cortex-associated synaptic, ER stress and neuro-inflammatory pathologies are here determined as late occurrences in AD progression, largely associated with tau pathology. Moreover, GFAP emerged as the most robust indicator of disease progression, tau/Aβ pathology, and cognitive impairment. Electronic supplementary material The online version of this article (10.1007/s12035-020-01950-1) contains supplementary material, which is available to authorized users.

Research using functional and structural magnetic resonance imaging has identified areas of reduced brain activation and gray matter volume in children and adults with reading disability, but associations between cortical structure and individual differences in reading in typically developing children remain underexplored. Furthermore, the majority of research linking gray matter structure to reading ability quantifies gray matter in terms of volume, and cannot specify unique contributions of cortical surface area and thickness to these relationships. Here, we applied a continuous analytic approach to investigate associations between distinct surface-based properties of cortical structure and individual differences in reading-related skills in a sample of typically developing young children. Correlations between cortical structure and reading-related skills were conducted using a surface-based vertex-wise approach. Cortical thickness in the left superior temporal cortex was positively correlated with word and pseudoword reading performance. The observed positive correlation between cortical thickness in the left superior temporal cortex and reading may have implications for the patterns of brain activation that support reading.

See Ware et al. (doi:10.1093/brain/awaa166) for a scientific commentary on this article. Using a modified MRI-based method that can detect subtle, region-specific blood-brain barrier dysfunction, Veksler et al. reveal slow blood-to-brain transport in a subset of amateur American football players. MRI may allow early detection of microvascular pathology in patients at risk for chronic traumatic encephalopathy., Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood–brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood–brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies.

We have an amazing ability to categorize objects in the world around us. Nevertheless, how cortical regions in human ventral temporal cortex (VTC), which is critical for categorization, support this behavioral ability, is largely unknown. Here, we examined the relationship between neural responses and behavioral performance during the categorization of morphed silhouettes of faces and hands, which are animate categories processed in cortically adjacent regions in VTC. Our results reveal that the combination of neural responses from VTC face- and body-selective regions more accurately explains behavioral categorization than neural responses from either region alone. Furthermore, we built a model that predicts a person’s behavioral performance using estimated parameters of brain–behavior relationships from a different group of people. Moreover, we show that this brain–behavior model generalizes to adjacent face- and body-selective regions in lateral occipitotemporal cortex. Thus, while face- and body-selective regions are located within functionally distinct domain-specific networks, cortically adjacent regions from both networks likely integrate neural responses to resolve competing and perceptually ambiguous information from both categories.

Background Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. Methods Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. Results We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. Conclusion In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.

Rodent and human studies examining the relationship between aerobic exercise, brain structure, and brain function indicate that the hippocampus, a brain region critical for episodic memory, demonstrates striking plasticity in response to exercise. Beyond the hippocampal memory system, human studies also indicate that aerobic exercise and cardiorespiratory fitness (CRF) are associated with individual differences in large-scale brain networks responsible for broad cognitive domains. Examining network activity in large-scale resting-state brain networks may provide a link connecting the observed relationships between aerobic exercise, hippocampal plasticity, and cognitive enhancement within broad cognitive domains. Previously, CRF has been associated with increased functional connectivity of the default mode network (DMN), specifically in older adults. However, how CRF relates to the magnitude and directionality of connectivity, or effective connectivity, between the hippocampus and other DMN nodes remains unknown. We used resting-state fMRI and conditional Granger Causality Analysis (CGCA) to test the hypothesis that CRF positively predicts effective connectivity between the hippocampus and other DMN nodes in healthy young adults. Twenty-six participants (ages 18-35 years) underwent a treadmill test to determine CRF by estimating its primary determinant, maximal oxygen uptake ([Formula: see text]), and a 10-minute resting-state fMRI scan to examine DMN effective connectivity. We identified the DMN using Group Independent Component Analysis and examined effective connectivity between nodes using CGCA. Linear regression analyses demonstrated that CRF significantly predicts causal influence from the hippocampus to the ventromedial prefrontal cortex, posterior cingulate cortex, and lateral temporal cortex and to the hippocampus from the dorsomedial prefrontal cortex. The observed relationship between CRF and hippocampal effective connectivity provides a link between the rodent literature, which demonstrates a relationship between aerobic exercise and hippocampal plasticity, and the human literature, which demonstrates a relationship between aerobic exercise and CRF and the enhancement of broad cognitive domains including, but not limited to memory.

We present the case of a patient with an atypical course of frontotemporal lobar degeneration (FTLD) complicated by the use of an anticholinergic drug. A 70-year-old patient, followed by psychiatrists for depression and behavioral disorders, received a diagnosis of dementia with Lewy bodies (DLB) at another Center due to auditory hallucinations, gait impairment, and tendency to fall. He was then admitted to our Memory Clinic Unit for behavioral disturbances, such as delusional thinking, auditory hallucinations, and memory complaints. At that time, the patient's therapy included Lorazepam, Quetiapine, Promazine, and Biperiden. The latter was immediately suspended for the absence of extrapyramidal signs and to avoid the anticholinergic cognitive side effects. A 18F-FDG PET showed a derangement of cortical metabolism with diffusely reduced activity, and limited areas of hyperactivity involving lateral frontal and lateral temporal inferior regions bilaterally. The patient underwent a series of exams, including neuropsychological tests, 123I-MIBG scintigraphy, cerebrospinal fluid examination, and genetic analysis. A second 18F-FDG PET showed an extensive remodulation of metabolic activity: relative higher concentration of the tracer in the prefrontal and inferior temporal cortex was no more detectable. Similarly, the diffuse reduced metabolic activity could not be traced anymore. Nonetheless, the metabolic activity still appeared reduced in the frontal lobe, in the anterior cingulate bilaterally, and in the anterior part of the hemispheric fissure. Taken together, clinical and neuroimaging features would point to a FTLD-like form. Furthermore, the diagnostic work-up was likely confounded by the anticholinergic drug on 18F-FDG PET, highlighting the importance of carefully checking the patient's pharmacology during the diagnostic process.

ObjectiveTo assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau.MethodsFrom the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly ≥65 years of age with both AV-1451 tau-PET and Pittsburgh compound B (PiB)-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the entorhinal and inferior temporal cortices as our regions of interest (ROIs) because they are highly susceptible to tau accumulation. PET signal was scaled to the cerebellum crus to calculate standardized uptake value ratio (SUVR). We fit linear models to assess the association between regional tau and witnessed apneas while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global PiB.ResultsForty-three participants (14.7%) were found to have witnessed apneas during sleep. The report of witnessed apneas was associated with higher tau-PET SUVR elevation in our ROIs: 0.049 SUVR (95% confidence interval [CI] 0.010–0.087, p = 0.015) in the entorhinal cortex and 0.037 SUVR (95% CI 0.006–0.067, p = 0.019) in the inferior temporal cortex after controlling for confounders.ConclusionWe identified a significant association between witnessed apneas in CU elderly and elevated tau-PET signal in tau-susceptible brain regions. These results suggest a plausible mechanism that could contribute to cognitive impairment and the development of Alzheimer disease. Longitudinal observations are necessary to determine direction of causality.

Current theories of automatic or preattentive change detection suggest a regularity or prediction violation mechanism involving functional connectivity between the inferior frontal cortex (IFC) and the superior temporal cortex (STC). By disrupting the IFC function with transcranial magnetic stimulation (TMS) and recording the later STC mismatch response with event‐related optical signal (EROS), previous study demonstrated a causal IFC‐to‐STC functional connection in detecting a pitch or physical change. However, physical change detection can be achieved by memory comparison of the physical features and may not necessarily involve regularity/rule extraction and prediction. The current study investigated the IFC–STC functional connectivity in detecting rule violation (i.e., an abstract change). Frequent standard tone pairs with a constant relative pitch difference, but varying pitches, were presented to establish a pitch interval rule. This abstract rule was violated by deviants with reduced relative pitch intervals. The EROS STC mismatch response to the deviants was abolished by the TMS applied at the IFC 80 ms after deviance onset, but preserved in the spatial (TMS on vertex), auditory (TMS sound), and temporal (200 ms after deviance onset) control conditions. These results demonstrate the IFC–STC connection in preattentive abstract change detection and support the regularity or prediction violation account.