Showing papers on "Temporal cortex published in 2022"

Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1

Abstract: Background: Alzheimer’s disease (AD) is characterized by diffuse amyloid-β (Aβ) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aβ and p-Tau deposition presumably via microglia activation in AD mouse models. Objective: We aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS). Methods: Four participants with mild to moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aβ, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment. Results: No adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aβ as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28. Conclusion: tACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.

More Than the Face: Representations of Bodies in the Inferior Temporal Cortex.

Abstract: Visual representations of bodies, in addition to those of faces, contribute to the recognition of con- and heterospecifics, to action recognition, and to nonverbal communication. Despite its importance, the neural basis of the visual analysis of bodies has been less studied than that of faces. In this article, I review what is known about the neural processing of bodies, focusing on the macaque temporal visual cortex. Early single-unit recording work suggested that the temporal visual cortex contains representations of body parts and bodies, with the dorsal bank of the superior temporal sulcus representing bodily actions. Subsequent functional magnetic resonance imaging studies in both humans and monkeys showed several temporal cortical regions that are strongly activated by bodies. Single-unit recordings in the macaque body patches suggest that these represent mainly body shape features. More anterior patches show a greater viewpoint-tolerant selectivity for body features, which may reflect a processing principle shared with other object categories, including faces. Expected final online publication date for the Annual Review of Vision Science, Volume 8 is September 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Medial Temporal Lobe Networks in Alzheimer's Disease: Structural and Molecular Vulnerabilities

Abstract: The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer's disease (AD), the present study aimed at (1) investigating whether MTL atrophy propagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks (n = 68); (2) longitudinal structural MRI from Alzheimer's disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (PET) data from ADNI3 to evaluate the networks' vulnerability to amyloid and tau (n = 186). Our results suggest that the atrophy of distinct MTL subregions propagates within the AT and PM networks in a dissociable manner. Brodmann area (BA)35 structurally covaried within the AT network while the parahippocampal cortex (PHC) covaried within the PM network. In addition, these networks are differentially associated with relative tau and amyloid burden, with higher tau levels in AT than in PM and higher amyloid levels in PM than in AT. Our results also suggest differences in the relative burden of tau species. The current results provide further support for the notion that two distinct MTL networks display differential alterations in the context of AD. These findings have important implications for disease spread and the cognitive manifestations of AD.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.

Texture is encoded in precise temporal spiking patterns in primate somatosensory cortex

Abstract: Humans are exquisitely sensitive to the microstructure and material properties of surfaces. In the peripheral nerves, texture information is conveyed via two mechanisms: coarse textural features are encoded in spatial patterns of activation that reflect their spatial layout, and fine features are encoded in highly repeatable, texture-specific temporal spiking patterns evoked as the skin moves across the surface. Here, we examined whether this temporal code is preserved in the responses of neurons in somatosensory cortex. We scanned a diverse set of everyday textures across the fingertip of awake macaques while recording the responses evoked in individual cortical neurons. We found that temporal spiking patterns are highly repeatable across multiple presentations of the same texture, with millisecond precision. As a result, texture identity can be reliably decoded from the temporal patterns themselves, even after information carried in the spike rates is eliminated. However, the combination of rate and timing is more informative than either code in isolation. The temporal precision of the texture response is heterogenous across cortical neurons and depends on the submodality composition of their input and on their location along the somatosensory neuraxis. Furthermore, temporal spiking patterns in cortex dilate and contract with decreases and increases in scanning speed, respectively, and this systematic relationship between speed and patterning may contribute to the observed perceptual invariance to speed. Finally, we find that the quality of a texture percept can be better predicted when these temporal patterns are taken into consideration. We conclude that high-precision spike timing complements rate-based signals to encode texture in somatosensory cortex.

High-Order Areas and Auditory Cortex Both Represent the High-Level Event Structure of Music

Abstract: Recent fMRI studies of event segmentation have found that default mode regions represent high-level event structure during movie watching. In these regions, neural patterns are relatively stable during events and shift at event boundaries. Music, like narratives, contains hierarchical event structure (e.g., sections are composed of phrases). Here, we tested the hypothesis that brain activity patterns in default mode regions reflect the high-level event structure of music. We used fMRI to record brain activity from 25 participants (male and female) as they listened to a continuous playlist of 16 musical excerpts and additionally collected annotations for these excerpts by asking a separate group of participants to mark when meaningful changes occurred in each one. We then identified temporal boundaries between stable patterns of brain activity using a hidden Markov model and compared the location of the model boundaries to the location of the human annotations. We identified multiple brain regions with significant matches to the observer-identified boundaries, including auditory cortex, medial prefrontal cortex, parietal cortex, and angular gyrus. From these results, we conclude that both higher-order and sensory areas contain information relating to the high-level event structure of music. Moreover, the higher-order areas in this study overlap with areas found in previous studies of event perception in movies and audio narratives, including regions in the default mode network.

Hippocampus and temporal pole functional connectivity is associated with age and individual differences in autobiographical memory

Abstract: Significance Autobiographical memory includes the recollection of both episodic and semantic content, which has been shown to engage the default network. The present study examines how regions associated with the coordinated retrieval of different types of details are intrinsically connected to the default network and how these connectivity patterns in turn relate to autobiographical recall in younger and older adults. Connectivity within this circuit scaled with the tendency to recall one’s personal past with a balance of episodic and semantic detail. Young adults showed a distinct signature of connectivity related to more detailed recollection overall. Our findings provide a high-resolution map of connectivity within the default network and evidence for how variation in this map is sensitive to individual differences in autobiographical recollection.

Representations of Temporal Community Structure in Hippocampus and Precuneus Predict Inductive Reasoning Decisions

Abstract: Our understanding of the world is shaped by inferences about underlying structure. For example, at the gym, you might notice that the same people tend to arrive around the same time and infer that they are friends that work out together. Consistent with this idea, after participants are presented with a temporal sequence of objects that follows an underlying community structure, they are biased to infer that objects from the same community share the same properties. Here, we used fMRI to measure neural representations of objects after temporal community structure learning and examine how these representations support inference about object relationships. We found that community structure learning affected inferred object similarity: When asked to spatially group items based on their experience, participants tended to group together objects from the same community. Neural representations in perirhinal cortex predicted individual differences in object grouping, suggesting that high-level object representations are affected by temporal community learning. Furthermore, participants were biased to infer that objects from the same community would share the same properties. Using computational modeling of temporal learning and inference decisions, we found that inductive reasoning is influenced by both detailed knowledge of temporal statistics and abstract knowledge of the temporal communities. The fidelity of temporal community representations in hippocampus and precuneus predicted the degree to which temporal community membership biased reasoning decisions. Our results suggest that temporal knowledge is represented at multiple levels of abstraction, and that perirhinal cortex, hippocampus, and precuneus may support inference based on this knowledge.

Distinct roles for the anterior temporal lobe and angular gyrus in the spatiotemporal cortical semantic network

Abstract: Semantic knowledge is supported by numerous brain regions, but the spatiotemporal configuration of the network that links these areas remains an open question. The hub-and-spokes model posits that a central semantic hub coordinates this network. In this study, we explored distinct aspects that define a semantic hub, as reflected in the spatiotemporal modulation of neural activity and connectivity by semantic variables, from the earliest stages of semantic processing. We used source-reconstructed electro/magnetoencephalography, and investigated the concreteness contrast across three tasks. In a whole-cortex analysis, the left anterior temporal lobe (ATL) was the only area that showed modulation of evoked brain activity from 100 ms post-stimulus. Furthermore, using Dynamic Causal Modeling of the evoked responses, we investigated effective connectivity amongst the candidate semantic hub regions, that is, left ATL, supramarginal/angular gyrus (SMG/AG), middle temporal gyrus, and inferior frontal gyrus. We found that models with a single semantic hub showed the highest Bayesian evidence, and the hub region was found to change from ATL (within 250 ms) to SMG/AG (within 450 ms) over time. Our results support a single semantic hub view, with ATL showing sustained modulation of neural activity by semantics, and both ATL and AG underlying connectivity depending on the stage of semantic processing.

Loss of Cholinergic Receptor Muscarinic 1 (CHRM1) Protein in the Hippocampus and Temporal Cortex of a Subset of Individuals with Alzheimer's Disease, Parkinson's Disease, or Frontotemporal Dementia: Implications for Patient Survival.

Abstract: BACKGROUND Dysfunction of cholinergic neurotransmission is a hallmark of Alzheimer's disease (AD); forming the basis for using acetylcholine (ACh) esterase (AChE) inhibitors to mitigate symptoms of ACh deficiency in AD. The Cholinergic Receptor Muscarinic 1 (CHRM1) is highly expressed in brain regions impaired by AD. Previous analyses of postmortem AD brains revealed unaltered CHRM1 mRNA expression compared to normal brains. However, the CHRM1 protein level in AD and other forms of dementia has not been extensively studied. Reduced expression of CHRM1 in AD patients may explain the limited clinical efficacy of AChE inhibitors. OBJECTIVE To quantify CHRM1 protein in the postmortem hippocampus and temporal cortex of AD, Parkinson's disease (PD), and frontotemporal dementia (FTD) patients. METHODS Western blotting was performed on postmortem hippocampus (N = 19/73/7/9: unaffected/AD/FTD/PD) and temporal cortex (N = 9/74/27: unaffected/AD/PD) using a validated anti-CHRM1 antibody. RESULTS Quantification based on immunoblotting using a validated anti-CHRM1 antibody revealed a significant loss of CHRM1 protein level (<50%) in the hippocampi (78% AD, 66% PD, and 85% FTD) and temporal cortices (56% AD and 42% PD) of dementia patients. Loss of CHRM1 in the temporal cortex was significantly associated with early death (<65-75 years) for both AD and PD patients. CONCLUSION Severe reduction of CHRM1 in a subset of AD and PD patients can explain the reported low efficacy of AChE inhibitors as a mitigating treatment for dementia patients. Based on this study, it can be suggested that future research should prioritize therapeutic restoration of CHRM1 protein levels in cholinergic neurons.

Aligning Model and Macaque Inferior Temporal Cortex Representations Improves Model-to-Human Behavioral Alignment and Adversarial Robustness

Abstract: While some state-of-the-art artificial neural network systems in computer vision are strikingly accurate models of the corresponding primate visual processing, there are still many discrepancies between these models and the behavior of primates on object recognition tasks. Many current models suffer from extreme sensitivity to adversarial attacks and often do not align well with the image-by-image behavioral error patterns observed in humans. Previous research has provided strong evidence that primate object recognition behavior can be very accurately predicted by neural population activity in the inferior temporal (IT) cortex, a brain area in the late stages of the visual processing hierarchy. Therefore, here we directly test whether making the late stage representations of models more similar to that of macaque IT produces new models that exhibit more robust, primate-like behavior. We conducted chronic, large-scale multi-electrode recordings across the IT cortex in six non-human primates (rhesus macaques). We then use these data to fine-tune (end-to-end) the model “IT” representations such that they are more aligned with the biological IT representations, while preserving accuracy on object recognition tasks. We generate a cohort of models with a range of IT similarity scores validated on held-out animals across two image sets with distinct statistics. Across a battery of optimization conditions, we observed a strong correlation between the models’ IT-likeness and alignment with human behavior, as well as an increase in its adversarial robustness. We further assessed the limitations of this approach and find that the improvements in behavioral alignment and adversarial robustness generalize across different image statistics, but not to object categories outside of those covered in our IT training set. Taken together, our results demonstrate that building models that are more aligned with the primate brain leads to more robust and human-like behavior, and call for larger neural data-sets to further augment these gains.

The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study

Abstract: Abstract Objective Autistic traits are associated with alterations in brain morphology. However, the anatomic location of these differences and their developmental trajectories are unclear. The primary objective of this longitudinal study was to explore the bidirectional relationship between autistic traits and brain morphology from childhood to adolescence. Method Participants were drawn from a population-based cohort. Cross-sectional and longitudinal analyses included 1950 (mean age 13.5) and 304 participants (mean ages 6.2 and 13.5), respectively. Autistic traits were measured with the Social Responsiveness Scale. Global brain measures and surface-based measures of gyrification, cortical thickness and surface area were obtained from T 1 -weighted MRI scans. Cross-sectional associations were assessed using linear regression analyses. Cross-lagged panel models were used to determine the longitudinal bidirectional relationship between autistic traits and brain morphology. Results Cross-sectionally, higher levels of autistic traits in adolescents are associated with lower gyrification in the pars opercularis, insula and superior temporal cortex; smaller surface area in the middle temporal and postcentral cortex; larger cortical thickness in the superior frontal cortex; and smaller cerebellum cortex volume. Longitudinally, both autistic traits and brain measures were quite stable, with neither brain measures predicting changes in autistic traits, nor vice-versa. Limitations Autistic traits were assessed at only two time points, and thus we could not distinguish within- versus between-person effects. Furthermore, two different MRI scanners were used between baseline and follow-up for imaging data acquisition. Conclusions Our findings point to early changes in brain morphology in children with autistic symptoms that remain quite stable over time. The observed relationship did not change substantially after excluding children with high levels of autistic traits, bolstering the evidence for the extension of the neurobiology of autistic traits to the general population.

The role of temporal cortex in the control of attention

Abstract: Attention is an indispensable component of active vision. Contrary to the widely accepted notion that temporal cortex processing primarily focusses on passive object recognition, a series of very recent studies emphasize the role of temporal cortex structures, specifically the superior temporal sulcus (STS) and inferotemporal (IT) cortex, in guiding attention and implementing cognitive programs relevant for behavioral tasks. The goal of this theoretical paper is to advance the hypothesis that the temporal cortex attention network (TAN) entails necessary components to actively participate in attentional control in a flexible task-dependent manner. First, we will briefly discuss the general architecture of the temporal cortex with a focus on the STS and IT cortex of monkeys and their modulation with attention. Then we will review evidence from behavioral and neurophysiological studies that support their guidance of attention in the presence of cognitive control signals. Next, we propose a mechanistic framework for executive control of attention in the temporal cortex. Finally, we summarize the role of temporal cortex in implementing cognitive programs and discuss how they contribute to the dynamic nature of visual attention to ensure flexible behavior.

The central autonomic system revisited – Convergent evidence for a regulatory role of the insular and midcingulate cortex from neuroimaging meta-analyses

Abstract: The autonomic nervous system regulates dynamic body adaptations to internal and external environment changes. Capitalizing on two different algorithms (that differ in empirical assumptions), we scrutinized the meta-analytic convergence of human neuroimaging studies investigating the neural basis of peripheral autonomic signal processing. Among the selected studies, we identified 42 records reporting 44 different experiments and testing 758 healthy individuals. The results of the two different algorithms converge in identifying the bilateral dorsal anterior insula and midcingulate cortex as the critical areas of the central autonomic system (CAN). Applying an unbiased approach, we were able to identify a single condition-independent functional circuit that supports CAN activity. Partially overlapping with the salience network this functional circuit includes the bilateral insular cortex and midcingulate cortex as well as the bilateral inferior parietal lobules. Remarkably, the critical regions of the CAN observed in this meta-analysis overlapped with the salience network as well as regions commonly reported across different cognitive and affective neuroimaging paradigms and regions being dysregulated across different mental and neurological disorders.

Resting-state fMRI in depressive and (hypo)manic mood states in bipolar disorders: A systematic review.

Abstract: Objective Abnormalities in spontaneous brain activity, measured with resting-state functional magnetic resonance imaging (rs-fMRI), may be key biomarkers for bipolar disorders. This systematic review compares rs-fMRI findings in people experiencing a bipolar depressive or (hypo)manic episode to bipolar euthymia and/or healthy participants. Methods Medline, Web of Science and Embase were searched up until April 2021. Studies without control group, or including minors, neurological co-morbidities or mixed episodes, were excluded. Qualitative synthesis was used to report results and risk of bias was assessed using the National Heart, Lung and Blood Institute tool for case-control studies. Results Seventy-one studies were included (3167 bipolar depressed/706 (hypo)manic). In bipolar depression, studies demonstrated default-mode (DMN) and frontoparietal network (FPN) dysfunction, altered baseline activity in the precuneus, insula, striatum, cingulate, frontal and temporal cortex, and disturbed regional homogeneity in parietal, temporal and pericentral areas. Functional connectivity was altered in thalamocortical circuits and between the cingulate cortex and precuneus. In (hypo)mania, studies reported altered functional connectivity in the amygdala, frontal and cingulate cortex. Finally, rs-fMRI disturbances in the insula and putamen correlate with depressive symptoms, cerebellar resting-state alterations could evolve with disease progression and altered amygdala connectivity might mediate lithium effects. Conclusions Our results suggest DMN and FPN dysfunction in bipolar depression, whereas local rs-fMRI alterations might differentiate mood states. Future studies should consider controlling rs-fMRI findings for potential clinical confounding factors such as medication. Considerable heterogeneity of methodology between studies limits conclusions. Standardised clinical reporting and consistent analysis approaches would increase coherence in this promising field.

Dynamic Predictive Coding: A New Model of Hierarchical Sequence Learning and Prediction in the Cortex

Abstract: We introduce dynamic predictive coding, a hierarchical model of spatiotemporal prediction and sequence learning in the cortex. The model assumes that higher cortical levels modulate the temporal dynamics of lower levels, correcting their predictions of dynamics using prediction errors. As a result, lower levels form representations that encode sequences at shorter timescales (e.g., a single step) while higher levels form representations that encode sequences at longer timescales (e.g., an entire sequence). We tested this model using a two-level neural network, where the top-down modulation is implemented as a low-dimensional mixture of possible temporal dynamics. When trained on natural videos, the lower-level model neurons developed space-time receptive fields similar to those of simple cells in the primary visual cortex while the higher-level responses spanned longer timescales, mimicking temporal response hierarchies in the cortex. Additionally, the network’s hierarchical sequence representation exhibited both predictive and postdictive effects resembling those observed in visual motion processing in humans (e.g., the flash-lag illusion). When coupled with an associative memory mimicking the role of the hippocampus, the model allowed episodic memories to be stored and retrieved, supporting cue-triggered recall of an input sequence similar to activity recall in the visual cortex. Taken together, our results suggest that cortical processing and learning of sequences can be interpreted as dynamic predictive coding based on a hierarchical spatiotemporal generative model of the visual world.

Tau positron emission tomography in preclinical Alzheimer's disease.

Abstract: Rates of tau accumulation in cognitively unimpaired older adults are subtle with magnitude and spatial patterns varying in recent reports. Regional accumulation also likely varies in the degree to which accumulation is amyloid β-dependent. Thus, there is a need to evaluate the pattern and consistency of tau accumulation across multiple cognitively unimpaired cohorts, and how these patterns relate to amyloid burden, in order to design optimal tau endpoints for clinical trials. Using three large cohorts of cognitively unimpaired older adults, the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and companion study, Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (N = 447), the Alzheimer's Disease Neuroimaging Initiative (N = 420), and the Harvard Aging Brain Study (N = 190), we attempt to identify regions with high rates of tau accumulation and estimate how these rates evolve over a continuous spectrum of baseline amyloid deposition. Optimal combinations of regions, tailored to multiple ranges of baseline amyloid burden as hypothetical clinical trial inclusion criteria, were tested and validated. The inferior temporal cortex, fusiform gyrus and middle temporal cortex had the largest effect sizes of accumulation in both longitudinal cohorts, when considered individually. When tau regions of interest were combined to find composite weights to maximize the effect size of tau change over time, both longitudinal studies exhibited a similar pattern - inferior temporal cortex, almost exclusively, was optimal for participants with mildly elevated amyloid β levels. For participants with highly elevated baseline amyloid β levels, combined optimal composite weights were 53% inferior temporal cortex, 31% amygdala, and 16% fusiform. At mildly elevated levels of baseline amyloid β, a sample size of 200/group required a treatment effect of 0.40-0.45 (40-45% slowing of tau accumulation), to power an 18-month trial using the optimized composite. Neither a temporal lobe composite nor a global composite reached 80% power with 200/group with an effect size under 0.5. The focus of early tau accumulation on the medial temporal lobe has resulted from the observation that the entorhinal cortex is the initial site to show abnormal levels of tau with age. However, these abnormal levels do not appear to be the result of a high rate of accumulation in the short term, but possibly a more moderate rate occurring early with respect to age. While the entorhinal cortex plays a central role in the early appearance of tau, it may be the inferior temporal cortex that is the critical region for rapid tau accumulation in preclinical Alzheimer's disease.

Developmental experiences alter the temporal processing characteristics of the visual cortex: Evidence from deaf and hearing native signers

Abstract: To date, the extent to which early experience shapes the functional characteristics of neural circuits is still a matter of debate. In the present study, we tested whether congenital deafness and/or the acquisition of a sign language alter the temporal processing characteristics of the visual system. Moreover, we investigated whether, assuming cross‐modal plasticity in deaf individuals, the temporal processing characteristics of possibly reorganised auditory areas resemble those of the visual cortex. Steady‐state visual evoked potentials (SSVEPs) were recorded in congenitally deaf native signers, hearing native signers, and hearing nonsigners. The luminance of the visual stimuli was periodically modulated at 12, 21, and 40 Hz. For hearing nonsigners, the optimal driving rate was 12 Hz. By contrast, for the group of hearing signers, the optimal driving rate was 12 and 21 Hz, whereas for the group of deaf signers, the optimal driving rate was 21 Hz. We did not observe evidence for cross‐modal recruitment of auditory cortex in the group of deaf signers. These results suggest a higher preferred neural processing rate as a consequence of the acquisition of a sign language.

Sex and APOE ɛ4 modify the effect of cardiovascular risk on tau in cognitively normal older adults

Abstract: Abstract The interaction between APOE ɛ4 and vascular risk factors on cognitive function is stronger in women than in men. These effects may be mediated by the amount of tau pathology in the brain. Therefore, we examined whether APOE ɛ4 and sex modify cross-sectional associations between cardiovascular risk and tau deposition in cognitively normal older adults from the Alzheimer’s Disease Neuroimaging Initiative. We calculated the Framingham Heart Study cardiovascular disease risk score for 141 participants (74 women, 47 APOE ɛ4 carriers) with complete medical history data, processed tau-PET data and a Clinical Dementia Rating global score of 0.0 at the time of the tau-PET scan, implying no significant cognitive or functional impairment. We used linear regression models to examine the effects of sex, APOE ɛ4, cardiovascular risk and their interactions on tau deposition in the entorhinal cortex, inferior temporal cortex and a composite meta-region of interest of temporal lobe areas. We found a significant three-way interaction among sex, APOE ɛ4 status and cardiovascular disease risk on tau deposition in the entorhinal cortex (β = 0.04; 95% CI, 0.01–0.07; P = 0.008), inferior temporal cortex (β = 0.02; 95% CI, 0.0–0.05; P = 0.029) and meta-region (β = 0.02; 95% CI, 0.0–0.04; P = 0.042). After stratifying by APOE ɛ4 status to examine interactions between sex and cardiovascular disease risk on tau in APOE ɛ4 carriers and non-carriers, we found a significant two-way interaction between sex and cardiovascular disease risk on tau in the entorhinal cortex (β = 0.05; 95% CI, 0.02–0.08; P = 0.001), inferior temporal cortex (β = 0.03; 95% CI, 0.01–0.05; P =0.009) and meta-region (β = 0.02; 95% CI, 0.01–0.04; P = 0.008) only among APOE ɛ4 carriers. In analyses stratified by sex, higher cardiovascular risk scores were associated with higher levels of tau in the entorhinal cortex (β = 0.05; 95% CI, 0.02–0.08; P = 0.002), inferior temporal cortex (β = 0.02; 95% CI, 0.0–0.05; P = 0.023) and meta-region (β = 0.02; 95% CI, 0.01–0.04; P = 0.013) in female APOE ɛ4 carriers but not in male carriers. Our findings suggest that cognitively normal older women carrying at least one APOE ɛ4 allele, may be particularly vulnerable to the effects of cardiovascular disease risk on early tau deposition.

OUP accepted manuscript

Abstract: The interaction between APOE ɛ4 and vascular risk factors on cognitive function is stronger in women than in men. These effects may be mediated by the amount of tau pathology in the brain. Therefore, we examined whether APOE ɛ4 and sex modify cross-sectional associations between cardiovascular risk and tau deposition in cognitively normal older adults from the Alzheimer's Disease Neuroimaging Initiative. We calculated the Framingham Heart Study cardiovascular disease risk score for 141 participants (74 women, 47 APOE ɛ4 carriers) with complete medical history data, processed tau-PET data and a Clinical Dementia Rating global score of 0.0 at the time of the tau-PET scan, implying no significant cognitive or functional impairment. We used linear regression models to examine the effects of sex, APOE ɛ4, cardiovascular risk and their interactions on tau deposition in the entorhinal cortex, inferior temporal cortex and a composite meta-region of interest of temporal lobe areas. We found a significant three-way interaction among sex, APOE ɛ4 status and cardiovascular disease risk on tau deposition in the entorhinal cortex (β = 0.04; 95% CI, 0.01-0.07; P = 0.008), inferior temporal cortex (β = 0.02; 95% CI, 0.0-0.05; P = 0.029) and meta-region (β = 0.02; 95% CI, 0.0-0.04; P = 0.042). After stratifying by APOE ɛ4 status to examine interactions between sex and cardiovascular disease risk on tau in APOE ɛ4 carriers and non-carriers, we found a significant two-way interaction between sex and cardiovascular disease risk on tau in the entorhinal cortex (β = 0.05; 95% CI, 0.02-0.08; P = 0.001), inferior temporal cortex (β = 0.03; 95% CI, 0.01-0.05; P =0.009) and meta-region (β = 0.02; 95% CI, 0.01-0.04; P = 0.008) only among APOE ɛ4 carriers. In analyses stratified by sex, higher cardiovascular risk scores were associated with higher levels of tau in the entorhinal cortex (β = 0.05; 95% CI, 0.02-0.08; P = 0.002), inferior temporal cortex (β = 0.02; 95% CI, 0.0-0.05; P = 0.023) and meta-region (β = 0.02; 95% CI, 0.01-0.04; P = 0.013) in female APOE ɛ4 carriers but not in male carriers. Our findings suggest that cognitively normal older women carrying at least one APOE ɛ4 allele, may be particularly vulnerable to the effects of cardiovascular disease risk on early tau deposition.

The role of the anterior temporal cortex in action: evidence from fMRI multivariate searchlight analysis during real object grasping

Abstract: Intelligent manipulation of handheld tools marks a major discontinuity between humans and our closest ancestors. Here we identified neural representations about how tools are typically manipulated within left anterior temporal cortex, by shifting a searchlight classifier through whole-brain real action fMRI data when participants grasped 3D-printed tools in ways considered typical for use (i.e., by their handle). These neural representations were automatically evocated as task performance did not require semantic processing. In fact, findings from a behavioural motion-capture experiment confirmed that actions with tools (relative to non-tool) incurred additional processing costs, as would be suspected if semantic areas are being automatically engaged. These results substantiate theories of semantic cognition that claim the anterior temporal cortex combines sensorimotor and semantic content for advanced behaviours like tool manipulation.

Corticofugal Modulation of Temporal and Rate Representations in the Inferior Colliculus of the Awake Marmoset.

Abstract: Temporal processing is crucial for auditory perception and cognition, especially for communication sounds. Previous studies have shown that the auditory cortex and the thalamus use temporal and rate representations to encode slowly and rapidly changing time-varying sounds. However, how the primate inferior colliculus (IC) encodes time-varying sounds at the millisecond scale remains unclear. In this study, we investigated the temporal processing by IC neurons in awake marmosets to Gaussian click trains with varying interclick intervals (2-100 ms). Strikingly, we found that 28% of IC neurons exhibited rate representation with nonsynchronized responses, which is in sharp contrast to the current view that the IC only uses a temporal representation to encode time-varying signals. Moreover, IC neurons with rate representation exhibited response properties distinct from those with temporal representation. We further demonstrated that reversible inactivation of the primary auditory cortex modulated 17% of the stimulus-synchronized responses and 21% of the nonsynchronized responses of IC neurons, revealing that cortico-colliculus projections play a role, but not a crucial one, in temporal processing in the IC. This study has significantly advanced our understanding of temporal processing in the IC of awake animals and provides new insights into temporal processing from the midbrain to the cortex.

A modality-independent proto-organization of human multisensory areas

Abstract: Abstract The processing of multisensory information is based upon the capacity of brain regions, such as the superior temporal cortex, to combine information across modalities. However, it is still unclear whether the representation of coherent auditory and visual events requires any prior audiovisual experience to develop and function. Here we measured brain synchronization during the presentation of an audiovisual, audio-only or video-only version of the same narrative in distinct groups of sensory-deprived (congenitally blind and deaf) and typically developed individuals. Intersubject correlation analysis revealed that the superior temporal cortex was synchronized across auditory and visual conditions, even in sensory-deprived individuals who lack any audiovisual experience. This synchronization was primarily mediated by low-level perceptual features, and relied on a similar modality-independent topographical organization of slow temporal dynamics. The human superior temporal cortex is naturally endowed with a functional scaffolding to yield a common representation across multisensory events.

Serotonin Receptor Expression in Hippocampus and Temporal Cortex of TLE Patients by PGES Duration.

Abstract: OBJECTIVE Prolonged postictal generalized EEG suppression (PGES) is a potential biomarker for sudden unexpected death in epilepsy (SUDEP), which may be associated with dysfunctional autonomic responses and serotonin signaling. To better understand molecular mechanisms, PGES duration was correlated to 5HT1A and 5HT2A receptor protein expression and RNAseq from resected hippocampus and temporal cortex of temporal lobe epilepsy (TLE) patients with seizures recorded in preoperative evaluation. METHODS Analyses included 36 cases (range: age 14-64 years, epilepsy onset 0-51, epilepsy duration 2-53, PGES 0-93 seconds), with 13 cases in all hippocampal analyses. 5HT1A and 5HT2A protein was evaluated by western blot and histologically in hippocampus (n=16) and temporal cortex (n=9). We correlated PGES duration to our previous RNAseq dataset for serotonin receptor expression and signaling pathways, as well as weighted gene correlation network analysis (WGCNA) to identify correlated gene clusters. RESULTS In hippocampus, 5HT2A protein by western blot positively correlated with PGES duration (p=0.0024, R2 =0.52) but 5HT1A did not (p=0.87, R2 =0.0020). In temporal cortex, 5HT1A and 5HT2A had lower expression and did not correlate with PGES duration. Histologically, PGES duration did not correlate with 5HT1A or 5HT2A expression in hippocampal CA4, dentate gyrus, or temporal cortex. RNAseq identified two serotonin receptors with expression that correlated to PGES duration in an exploratory analysis: HTR3B negatively correlated (p=0.043, R2 =0.26) and HTR4 positively correlated (p=0.049, R2 =0.25). WGCNA identified 4 modules correlated to PGES duration, including positive correlation to synaptic transcripts (p=0.040, corr.=0.52), particularly potassium channels (KCNA4, KCNC4, KCNH1, KCNIP4, KCNJ3, KCNJ6, KCNK1). No modules were associated with serotonin receptor signaling. SIGNIFICANCE Higher hippocampal 5HT2A receptor protein and potassium channel transcripts may reflect underlying mechanisms contributing to or resulting from prolonged PGES. Future studies with larger cohorts should assess functional analyses and additional brain regions to elucidate mechanisms underlying PGES and SUDEP risk.

The representation of shape and texture in category‐selective regions of ventral‐temporal cortex

Abstract: Neuroimaging studies using univariate and multivariate approaches have shown that the fusiform face area (FFA) and parahippocampal place area (PPA) respond selectively to images of faces and places. The aim of this study was to determine the extent to which this selectivity to faces or places is based on the shape or texture properties of the images. Faces and houses were filtered to manipulate their texture properties, while preserving the shape properties (spatial envelope) of the images. In Experiment 1, multivariate pattern analysis (MVPA) showed that patterns of fMRI response to faces and houses in FFA and PPA were predicted by the shape properties, but not by the texture properties of the image. In Experiment 2, a univariate analysis (fMR‐adaptation) showed that responses in the FFA and PPA were sensitive to changes in both the shape and texture properties of the image. These findings can be explained by the spatial scale of the representation of images in the FFA and PPA. At a coarser scale (revealed by MVPA), the neural selectivity to faces and houses is sensitive to variation in the shape properties of the image. However, at a finer scale (revealed by fMR‐adaptation), the neural selectivity is sensitive to the texture properties of the image. By combining these neuroimaging paradigms, our results provide insights into the spatial scale of the neural representation of faces and places in the ventral‐temporal cortex.