Biology subjects

Petrides, M.

Publications and source records attributed to Petrides, M..

8 recordsLinked to original sources

bioRxiv2024

Right posterior theta reflects human parahippocampal phase resetting by salient cues during goal-directed navigation

Animal and computational work indicate that phase resetting of theta oscillations (4-12 Hz) in the parahippocampal gyrus (PHG) by salient events (e.g., reward, landmarks) facilitates the encoding of goal-oriented information during navigation. Although well-studied in animals, this mechanism has not been empirically substantiated in humans. In the present article, we present data from two studies (Study 1: asynchronous EEG-MEG | Study 2: simultaneous EEG-fMRI) to investigate theta phase resetting and its relationship to PHG BOLD activation in healthy adults (aged 18-34 years old) navigating a virtual T-maze to find rewards. In the first experiment, both EEG and MEG data revealed a burst of theta power over right-posterior scalp locations following feedback onset (termed right-posterior theta, RPT), and RPT power and measures of phase resetting were sensitive to the subjects spatial trajectory. In Experiment 2, we used probabilistic tractography data from the human connectome project to segment the anterior and posterior PHG based on differential connectivity profiles to other brain regions. This analysis resulted in a PHG subdivision consisting of four distinct anterior and two posterior PHG clusters. Next, a series of linear mixed effects models based on simultaneous EEG-fMRI data revealed that single-trial RPT peak power significantly predicted single-trial hemodynamic responses in two clusters within the posterior PHG and one in the anterior PHG. This coupling between RPT power and PHG BOLD was exclusive to trials performed during maze navigation, and not during a similar task devoid of the spatial context of the maze. These findings highlight a role of PHG theta phase resetting for the purpose of encoding salient information during goal-directed spatial navigation. Taken together, RPT during virtual navigation integrates experimental, computational, and theoretical research of PHG function in animals with human cognitive electrophysiology studies and clinical research on memory-related disorders such as Alzheimers disease.

neuroscience↗

bioRxiv2023

Structures of LIG1 active site mutants reveal the importance of DNA end rigidity for mismatch discrimination

ATP-dependent DNA ligases catalyze phosphodiester bond formation in the conserved three-step chemical reaction of nick sealing. Human DNA ligase I (LIG1) finalizes almost all DNA repair pathways following DNA polymerase-mediated nucleotide insertion. We previously reported that LIG1 discriminates mismatches depending on the architecture of the 3-terminus at a nick, however the contribution of conserved active site residues to faithful ligation remains unknown. Here, we comprehensively dissect the nick DNA substrate specificity of LIG1 active site mutants carrying Ala(A) and Leu(L) substitutions at Phe(F)635 and Phe(F)F872 residues and show completely abolished ligation of nick DNA substrates with all 12 non-canonical mismatches. LIG1EE/AA structures of F635A and F872A mutants in complex with nick DNA containing A:C and G:T mismatches demonstrate the importance of DNA end rigidity, as well as uncover a shift in a flexible loop near 5-end of the nick, which causes an increased barrier to adenylate transfer from LIG1 to the 5-end of the nick. Furthermore, LIG1EE/AA/8oxoG:A structures of both mutants demonstrated that F635 and F872 play critical roles during steps 1 or 2 of the ligation reaction depending on the position of the active site residue near the DNA ends. Overall, our study contributes towards a better understanding of the substrate discrimination mechanism of LIG1 against mutagenic repair intermediates with mismatched or damaged ends and reveals the importance of conserved ligase active site residues to maintain ligation fidelity.

biochemistry↗

bioRxiv2022

Non-necessary neural activity in the primate cortex

When neuroscientists record neural activity from the brain, they often conclude that neural responses observed during task performance are indicative of the functional role of the brain area(s) studied. In humans and nonhuman primates, it is often hard to combine recordings and causal techniques within the same experiment, leaving the possibility that the activity recorded may be epiphenomenal rather than reflecting a specific functional role. Currently, the prevalence of epiphenomenal neural activity in the cortex is unknown. To estimate the extent of such activity in primates, we chronically recorded neural activity in the prefrontal cortex of the same monkeys using the same neural implants during the performance of four different cognitive tasks. The four tasks were carefully selected such that only one of them causally depends on the brain area recorded, as demonstrated by previous double dissociation studies. Using the four most common single neuron analyses methods in the field, we found that the prevalence and strength of neural correlates were just as high across all four tasks, including for the three tasks that do not depend on this brain area. These results suggest that the probability of observing epiphenomenal activity in primate cortex is high, which can mislead investigators relying on neural recording or imaging to map brain function. One-Sentence SummaryTremblay, Testard and colleagues show that inferring a brain areas function from neural recordings alone could be misleading.

neuroscience↗

bioRxiv2022

Neural cognitive signals during spontaneous movements in the macaque

The single neuron basis of cognitive processing in primates has mostly been studied in laboratory settings where movements are severely restricted. It is unclear, therefore, how natural movements might affect neural signatures of cognition in the brain. Moreover, studies in mice indicate that body movements, when measured, account for most of the neural dynamics in the cortex. To examine this issue, we recorded from single neuron ensembles in the prefrontal cortex in moving monkeys performing a cognitive task and characterized eyes, head, and body movements using video tracking. Despite significant trial-to-trial movement variability, single neuron tuning could be precisely measured and decision signals accurately decoded on a single-trial basis. Creating or abolishing spontaneous movements through head restraint and task manipulations had no measurable impact on neural responses. However, encoding models showed that uninstructed movements explained as much neural variance as task variables, with most of them aligned to task events. These results demonstrate that cognitive signals in the cortex are robust to natural movements, but also that unmeasured movements are potential confounds in cognitive neurophysiology experiments.

neuroscience↗

bioRxiv2020

Morphological and functional variability in central and subcentral motor cortex of the human brain

There is a long-established link between anatomy and function in the somatomotor system in the mammalian cerebral cortex. The morphology of the central sulcus is predictive of the location of functional activation peaks relating to movement of different effectors in individuals. By contrast, morphological variation in the subcentral region and its relationship to function is, as yet, unknown. Investigating the subcentral region is particularly important in the context of speech, since control of the larynx during human speech production is related to activity in this region. Here, we examined the relationship between morphology in the central and subcentral region and the location of functional activity during movement of the hand, lips, tongue, and larynx at the individual participant level. We provide a systematic description of the sulcal patterns of the subcentral and adjacent opercular cortex, including the inter-individual variability in sulcal morphology. We show that, in the majority of participants, the anterior subcentral sulcus is not continuous, but consists of two distinct segments. A robust relationship between morphology of the central and subcentral sulcal segments and movement of different effectors is demonstrated. Inter-individual variability of underlying anatomy might thus explain previous inconsistent findings, in particular regarding the ventral larynx area in subcentral cortex. A surface registration based on sulcal labels indicated that such anatomical information can improve the alignment of functional data for group studies.

neuroscience↗

bioRxiv2019

Cognitive control of orofacial and vocal responses in the human frontal cortex

The frontal cortical areas critical for human speech production, i.e. the ventrolateral frontal cortex (cytoarchitectonic areas 44 and 45; VLF) and the dorsomedial frontal cortex (DMF) comprising the mid-cingulate cortex (MCC) and the pre-supplementary motor area (preSMA), exist in non-human primates and are implicated in cognitive vocal control functions. The present functional neuroimaging study seeks to define the basic roles of these VLF-DMF network regions in primate vocal production and how they might have been adapted for human speech. We demonstrate that area 44 and the MCC are respectively involved in the cognitive selection of orofacial, non-speech vocal and verbal responses, and the feedback-driven adaptation of these responses - roles that are likely preserved across primates. In contrast, area 45 and preSMA have roles that are specific to human speech: area 45 contributes to active verbal retrieval during learning, while preSMA is involved in processing verbal feedback during orofacial/vocal adaptations.

neuroscience↗

bioRxiv2019

Sulcal organization in the medial frontal cortex reveals insights into primate brain evolution

Although the relative expansion of the frontal cortex in primate evolution is generally accepted, the nature of the human uniqueness, if any, and between-species anatomo-functional comparisons of the frontal areas remain controversial. To provide a novel interpretation of the evolution of primate brains, sulcal morphological variability of the medial frontal cortex was assessed in old-world monkeys (macaque, baboon) and Hominoidea (chimpanzee, human). We discovered that both Hominoidea do possess a paracingulate sulcus, which was previously thought to be uniquely human and linked to higher cognitive functions like mentalizing. Also, we revealed systematic sulcal morphological organisations of the medial frontal cortex that can be traced from multiple old-world monkey to Hominoidea species, demonstrating an evolutionary conserved organizational principle. Our data provide a new framework to compare sulcal morphology, cytoarchitectonic areal distribution, connectivity, and function across the primate order, leading to clear predictions on how other primate brains might be anatomo-functionally organized.

neuroscience↗

bioRxiv2018

The human ventromedial prefrontal cortex sulcal morphology and its influence on its functional organization.

The ventromedial prefrontal cortex (vmPFC), which comprises several distinct cytoarchitectonic areas, is a key brain region supporting decision-making processes and it has been shown to be one of the main hubs of the Default Mode Network, a network classically activated during resting state. We here examined the inter-individual variability in the vmPFC sulcal morphology in 57 humans (37 females) and demonstrated that the presence/absence of the inferior rostral sulcus and the subgenual intralimbic sulcus influences significantly the sulcal organization of this region. Furthermore, the sulcal organization influences the location of the vmPFC peak of the Default Mode Network, demonstrating that the location of functional activity can be affected by local sulcal patterns. These results are critical for the investigation of the function of the vmPFC and show that taking into account the sulcal variability might be essential to guide the interpretation of neuroimaging studies.\n\nSIGNIFICANCE STATEMENTThe ventromedial prefrontal cortex (vmPFC) is one of the main hubs of the Default Mode Network and plays a central role in value coding and decision-making. The present study provides a complete description of the inter-individual variability of anatomical morphology of this large portion of prefrontal cortex and its relation to functional organization. We have shown that two supplementary medial sulci predominantly determine the organization of the vmPFC, which in turn affect the location of the functional peak of activity in this region. Those results show that taking into account the variability in sulcal patterns might be essential to guide the interpretation of neuroimaging studies of the human brain and of the vmPFC in particular.

neuroscience↗