Multiscale chemogenetic dissection of fronto-temporal top-down regulation for object memory in primates.

Visual object memory is a fundamental element of various cognitive abilities, and the underlying neural mechanisms have been extensively examined especially in the anterior temporal cortex of primates. However, both macroscopic large-scale functional network in which this region is embedded and microscopic neuron-level dynamics of top-down regulation it receives for object memory remains elusive. Here, we identified the orbitofrontal node as a critical partner of the anterior temporal node for object memory by combining whole-brain functional imaging during rest and a short-term object memory task in male macaques. Focal chemogenetic silencing of the identified orbitofrontal node downregulated both the local orbitofrontal and remote anterior temporal nodes during the task, in association with deteriorated mnemonic, but not perceptual, performance. Furthermore, imaging-guided neuronal recordings in the same monkeys during the same task causally revealed that orbitofrontal top-down modulation enhanced stimulus-selective mnemonic signal in individual anterior temporal neurons while leaving bottom-up perceptual signal unchanged. Furthermore, similar activity difference was also observed between correct and mnemonic error trials before silencing, suggesting its behavioral relevance. These multifaceted but convergent results provide a multiscale causal understanding of dynamic top-down regulation of the anterior temporal cortex along the ventral fronto-temporal network underpinning short-term object memory in primates.

Occipital-temporal cortical tuning to semantic and affective features of natural images predicts associated behavioral responses.

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

A familiar face and person processing area in the human temporal pole.

How does the brain process the faces of familiar people? Neuropsychological studies have argued for an area of the temporal pole (TP) linking faces with person identities, but magnetic susceptibility artifacts in this region have hampered its study with fMRI. Using data acquisition and analysis methods optimized to overcome this artifact, we identify a familiar face response in TP, reliably observed in individual brains. This area responds strongly to visual images of familiar faces over unfamiliar faces, objects, and scenes. However, TP did not just respond to images of faces, but also to a variety of high-level social cognitive tasks, including semantic, episodic, and theory of mind tasks. The response profile of TP contrasted with a nearby region of the perirhinal cortex that responded specifically to faces, but not to social cognition tasks. TP was functionally connected with a distributed network in the association cortex associated with social cognition, while PR was functionally connected with face-preferring areas of the ventral visual cortex. This work identifies a missing link in the human face processing system that specifically processes familiar faces, and is well placed to integrate visual information about faces with higher-order conceptual information about other people. The results suggest that separate streams for person and face processing reach anterior temporal areas positioned at the top of the cortical hierarchy.

Context-invariant beliefs are supported by dynamic reconfiguration of single unit functional connectivity in prefrontal cortex of male macaques.

Natural behaviors occur in closed action-perception loops and are supported by dynamic and flexible beliefs abstracted away from our immediate sensory milieu. How this real-world flexibility is instantiated in neural circuits remains unknown. Here, we have male macaques navigate in a virtual environment by primarily leveraging sensory (optic flow) signals, or by more heavily relying on acquired internal models. We record single-unit spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and the dorso-lateral prefrontal cortex (dlPFC). Results show that while animals were able to maintain adaptive task-relevant beliefs regardless of sensory context, the fine-grain statistical dependencies between neurons, particularly in 7a and dlPFC, dynamically remapped with the changing computational demands. In dlPFC, but not 7a, destroying these statistical dependencies abolished the area's ability for cross-context decoding. Lastly, correlational analyses suggested that the more unit-to-unit couplings remapped in dlPFC, and the less they did so in MSTd, the less were population codes and behavior impacted by the loss of sensory evidence. We conclude that dynamic functional connectivity between neurons in prefrontal cortex maintain a stable population code and context-invariant beliefs during naturalistic behavior.

Innovative strategies for managing hallucinations by exploring effects of tDCS on source monitoring abilities.

This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual-Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini-Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia.

The representation of noun-verb distinction in left posterior middle temporal gyrus: evidence from representation similarity analyses.

Nouns and verbs are fundamental grammatical building blocks of languages. A key question is whether and where the noun-verb division was represented in the brain. Previous studies mainly used univariate analyses to examine this issue. However, the interpretation of activated brain regions in univariate analyses may be confounded with general cognitive processing and/or confounding variables. We addressed these limitations by using partial representation similarity analysis (RSA) of Chinese nouns and verbs with different levels of imageability. Participants were asked to complete the 1-back grammatical class probe (GCP; an explicit measure) and the 1-back word probe (WP; an implicit measure) tasks while undergoing functional magnetic resonance imaging. RSA results showed that the activation pattern in the left posterior middle temporal gyrus (LpMTG) was significantly correlated with the grammatical class representational dissimilarity matrix in the GCP task after eliminating the potential confounding variables. Moreover, the LpMTG did not overlap with the frontal-parietal regions that were activated by verbs vs. nouns or the task effect (CRP vs. WP) in univariate analyses. These results highlight the role of LpMTG in distinguishing nouns from verbs rather than general cognitive processing.

Gaze and Arrows: Does the Gaze-Following Patch in the Posterior Temporal Cortex Differentiate Social and Symbolic Spatial Cues?

The gaze-following patch (GFP) is located in the posterior temporal cortex and has been described as a cortical module dedicated to processing other people's gaze-direction in a domain-specific manner. Thus, it appears to be the neural correlate of Baron-Cohen's eye direction detector (EDD) which is one of the core modules in his mindreading system-a neurocognitive model for the theory of mind concept. Inspired by Jerry Fodor's ideas on the modularity of the mind, Baron-Cohen proposed that, among other things, the individual modules are domain specific. In the case of the EDD, this means that it exclusively processes eye-like stimuli to extract gaze-direction and that other stimuli, which may carry directional information as well, are processed elsewhere. If the GFP is indeed EDD's neural correlate, it must meet this expectation. To test this, we compared the GFP's BOLD activity during gaze-direction following with the activity during arrow-direction following in the present human fMRI study. Contrary to the expectation based on the assumption of domain specificity, we did not find a differentiation between gaze- and arrow-direction following. In fact, we were not able to reproduce the GFP as presented in the previous studies. A possible explanation is that in the present study-unlike the previous work-the gaze stimuli did not contain an obvious change of direction that represented a visual motion. Hence, the critical stimulus component responsible for the identification of the GFP in the previous experiments might have been visual motion.

Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

Spindle-locked ripples mediate memory reactivation during human NREM sleep.

Memory consolidation relies in part on the reactivation of previous experiences during sleep. The precise interplay of sleep-related oscillations (slow oscillations, spindles and ripples) is thought to coordinate the information flow between relevant brain areas, with ripples mediating memory reactivation. However, in humans empirical evidence for a role of ripples in memory reactivation is lacking. Here, we investigated the relevance of sleep oscillations and specifically ripples for memory reactivation during human sleep using targeted memory reactivation. Intracranial electrophysiology in epilepsy patients and scalp EEG in healthy participants revealed that elevated levels of slow oscillation - spindle activity coincided with the read-out of experimentally induced memory reactivation. Importantly, spindle-locked ripples recorded intracranially from the medial temporal lobe were found to be correlated with the identification of memory reactivation during non-rapid eye movement sleep. Our findings establish ripples as key-oscillation for sleep-related memory reactivation in humans and emphasize the importance of the coordinated interplay of the cardinal sleep oscillations.

Verbal semantic expertise is associated with reduced functional connectivity between left and right anterior temporal lobes.

The left and right anterior temporal lobes (ATLs) encode semantic representations. They show graded hemispheric specialization in function, with the left ATL contributing preferentially to verbal semantic processing. We investigated the cognitive correlates of this organization, using resting-state functional connectivity as a measure of functional segregation between ATLs. We analyzed two independent resting-state fMRI datasets (n = 86 and n = 642) in which participants' verbal semantic expertise was measured using vocabulary tests. In both datasets, people with more advanced verbal semantic knowledge showed weaker functional connectivity between left and right ventral ATLs. This effect was highly specific. It was not observed for within-hemisphere connections between semantic regions (ventral ATL and inferior frontal gyrus (IFG), though it was found for left-right IFG connectivity in one dataset). Effects were not found for tasks probing semantic control, nonsemantic cognition, or face recognition. Our results suggest that hemispheric specialization in the ATLs is not an innate property but rather emerges as people develop highly detailed verbal semantic representations. We speculate that this effect is a consequence of the left ATL's greater connectivity with left-lateralized written word recognition regions, which causes it to preferentially represent meaning for advanced vocabulary acquired primarily through reading.

Basal temporal language area revisited in Japanese language with a language function density map.

We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.

Hypertension is associated with reduced resting-state medial temporal lobe dynamic network flexibility in older African Americans.

Hypertension disproportionately affects African Americans and is a risk factor for Alzheimer's disease (AD). We investigated the relationship of blood pressure (BP) with medial temporal lobe (MTL) dynamic network flexibility (a novel AD biomarker) and cognitive generalization in older African Americans. In a cross-sectional study, 37 normotensive (systolic BP <130 mmHg, 82.5% F, 64.4 ± 4.9 years; 14.3 ± 2.1 years of education) versus 79 hypertensive (systolic BP ≥130 mmHg, 79.5% F, 66.8 ± 4.1 years; 14.0 ± 0.2 years of education) participants were enrolled. All participants completed a 10-min resting-state functional magnetic resonance imaging scan to assess MTL dynamic network flexibility and two generalization tasks to assess cognition. Anthropometrics and aerobic fitness (via 6-min walk test) were also determined. There was no difference in BMI (29.7 ± 6.4 vs. 31.9 ± 6.3 kg/m2, p = 0.083) or aerobic fitness (15.5 ± 2.6 vs. 15.1 ± 2.6 mL/kg/min; p = 0.445) between normotensive and hypertensive groups. However, normotensive participants had higher MTL dynamic network flexibility compared to hypertensive participants (0.42 ± 0.23 vs. 0.32 ± 0.25 mL, p = 0.040), and this was associated with higher mean arterial blood pressure (r = -0.21, p = 0.036). Therefore, hypertensive older African Americans demonstrated lower MTL dynamic network flexibility compared to their normotensive counterparts independent of BMI and aerobic fitness. Further studies are required to determine how blood pressure mediates AD risk in African Americans.

Planum temporale asymmetry in newborn monkeys predicts the future development of gestural communication's handedness.

The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready brain. However, studies have reported a similar structural PT left-asymmetry not only in various adult non-human primates, but also in newborn baboons. Its shared functional links with language are not fully understood. Here we demonstrate using previously obtained MRI data that early detection of PT left-asymmetry among 27 newborn baboons (Papio anubis, age range of 4 days to 2 months) predicts the future development of right-hand preference for communicative gestures but not for non-communicative actions. Specifically, only newborns with a larger left-than-right PT were more likely to develop a right-handed communication once juvenile, a contralateral brain-gesture link which is maintained in a group of 70 mature baboons. This finding suggests that early PT asymmetry may be a common inherited prewiring of the primate brain for the ontogeny of ancient lateralised properties shared between monkey gesture and human language.

The hippocampus supports precise memory for public events regardless of their remoteness.

The necessity of the human hippocampus and surrounding medial temporal lobe structures to semantic memory remains contentious. Impaired semantic memory following hippocampal lesions could arise either due to partially intertwined episodic memories and/or retrograde/anterograde effects. In this study, we tested amnesic individuals with lesions in hippocampus and surrounding medial temporal lobe (n = 7) and age-matched controls (n = 14) on their ability to precisely recall the dates of famous public events that occurred either before (i.e., pre-lifetime) or after participants' birth date (lifetime). We show that deficits in dating precision are greatest for recent lifetime events, consistent with the notion that recent event memory may be particularly intertwined with episodic memory. At the same time, individuals with medial temporal lobe lesions showed more subtle impairments in their ability to date pre-birth and remote lifetime events precisely. Together, these findings suggest that the hippocampus and surrounding medial temporal lobe structures are important for representational precision of semantic memories regardless of their remoteness.

A multimodal interface for speech perception: the role of the left superior temporal sulcus in social cognition and autism.

Multimodal integration is crucial for human interaction, in particular for social communication, which relies on integrating information from various sensory modalities. Recently a third visual pathway specialized in social perception was proposed, which includes the right superior temporal sulcus (STS) playing a key role in processing socially relevant cues and high-level social perception. Importantly, it has also recently been proposed that the left STS contributes to audiovisual integration of speech processing. In this article, we propose that brain areas along the right STS that support multimodal integration for social perception and cognition can be considered homologs to those in the left, language-dominant hemisphere, sustaining multimodal integration of speech and semantic concepts fundamental for social communication. Emphasizing the significance of the left STS in multimodal integration and associated processes such as multimodal attention to socially relevant stimuli, we underscore its potential relevance in comprehending neurodevelopmental conditions characterized by challenges in social communication such as autism spectrum disorder (ASD). Further research into this left lateral processing stream holds the promise of enhancing our understanding of social communication in both typical development and ASD, which may lead to more effective interventions that could improve the quality of life for individuals with atypical neurodevelopment.

Role of the left posterior middle temporal gyrus in shape recognition and its reconstruction during drawing: A study combining transcranial magnetic stimulation and functional near infrared spectroscopy.

There are numerous reports of enhanced or emerged visual arts abilities in patients with semantic impairment. These reports led to the theory that a loss of function on the language side of the brain can result in changes of ability to draw and/or to paint. Further, the left posterior middle temporal gyrus (l-pMTG) has been revealed to contribute to the higher control semantic mechanisms with objects recognition and integration of visual information, within a widely distributed network of the left hemisphere. Nevertheless, the theory has not been fully studied in neural bases. The aim of this study is to examine role of the l-pMTG on shape recognition and its reconstruction within drawing behavior, by using a combining method of the repetitive transcranial magnetic stimulation (rTMS) and functional near-infrared spectroscopy (fNIRS). Eighteen healthy participants received a low frequency inhibitory rTMS to their l-pMTG during the drawing task of the Benton Visual Retention Test (BVRT). There was a significant decrease of the mean accuracy of reproductions in the Complex designs of the BVRT, compared to the Simple and Medium designs. The fNIRS data showed strong negative correlations with the results of the BVRT. Though our hypothesis had a contradiction that rTMS would have inhibited the brain activity in the stimulated site, the results suggest that shape recognition and its reconstruction such as the BVRT require neural activations of the l-TL as well as that of the l-pMTG.

Temporal multiplexing of perception and memory codes in IT cortex.

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

Neural mechanisms underlying improved new-word learning with high-density transcranial direct current stimulation.

Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.