Sensory Regions Research Articles

A comparative machine learning study of schizophrenia biomarkers derived from functional connectivity

Functional connectivity holds promise as a biomarker of schizophrenia. Yet, the high dimensionality of predictive models trained on functional connectomes, combined with small sample sizes in clinical research, increases the risk of overfitting. Recently, low-dimensional representations of the connectome such as macroscale cortical gradients and gradient dispersion have been proposed, with studies noting consistent gradient and dispersion differences in psychiatric conditions. However, it is unknown which of these derived measures has the highest predictive capacity and how they compare to raw functional connectivity specifically in the case of schizophrenia. Our study evaluates which connectome features derived from resting state functional MRI — functional connectivity, gradients, or gradient dispersion — best identify schizophrenia. To this end, we leveraged data of 936 individuals from three large open-access datasets: COBRE, LA5c, and SRPBS-1600. We developed a pipeline which allows us to aggregate over a million different features and assess their predictive potential in a single, computationally efficient experiment. We selected top 1% of features with the largest permutation feature importance and trained 13 classifiers on them using 10-fold cross-validation. Our findings indicate that functional connectivity outperforms its low-dimensional derivatives such as cortical gradients and gradient dispersion in identifying schizophrenia (Mann–Whitney test conducted on test accuracy: connectivity vs. 1st gradient: U = 142, p < 0.003; connectivity vs. neighborhood dispersion: U = 141, p = 0.004). Additionally, we demonstrated that the edges which contribute the most to classification performance are the ones connecting primary sensory regions. Functional connectivity within the primary sensory regions showed the highest discrimination capabilities between subjects with schizophrenia and neurotypical controls. These findings along with the feature selection pipeline proposed here will facilitate future inquiries into the prediction of schizophrenia subtypes and transdiagnostic phenomena.

Developmental Trajectories and Differences in Functional Brain Network Properties of Preterm and At-Term Neonates.

Premature infants, born before 37 weeks of gestation can have alterations in neurodevelopment and cognition, even when no anatomical lesions are evident. Resting-state functional neuroimaging of naturally sleeping babies has shown altered connectivity patterns, but there is limited evidence on the developmental trajectories of functional organization in preterm neonates. By using a large dataset from the developing Human Connectome Project, we explored the differences in graph theory properties between at-term (n = 332) and preterm (n = 115) neonates at term-equivalent age, considering the age subgroups proposed by the World Health Organization for premature birth. Leveraging the longitudinal follow-up for some preterm participants, we characterized the developmental trajectories for preterm and at-term neonates, for this purpose linear, quadratic, and log-linear mixed models were constructed with gestational age at scan as an independent fixed-effect variable and random effects were added for the intercept and subject ID. Significance was defined at p < 0.05, and the model with the lowest Akaike Information Criterion (AIC) was selected as the best model. We found significant differences between groups in connectivity strength, clustering coefficient, characteristic path length and global efficiency. Specifically, at term-equivalent ages, higher connectivity, clustering coefficient and efficiency are identified for neonates born at later postmenstrual ages. Similarly, the characteristic path length showed the inverse pattern. These results were consistent for a variety of connectivity thresholds at both the global (whole brain) and local level (brain regions). The brain regions with the greatest differences between groups include primary sensory and motor regions and the precuneus which may relate to the risk factors for sensorimotor and behavioral deficits associated with premature birth. Our results also show non-linear developmental trajectories for premature neonates, but decreased integration and segregation even at term-equivalent age. Overall, our results confirm altered functional connectivity, integration and segregation properties of the premature brain despite showing rapid maturation after birth.

A core set of neural states underlying memory reactivation of naturalistic events in the posterior medial cortex.

In sensory and mid-level regions of the brain, stimulus information is often topographically organized; functional responses are arranged in maps according to features such as retinal coordinates, auditory pitch, and object animacy or size. However, such organization is typically measured during stimulus input, e.g., when subjects are viewing gratings or images. Much less is known about the possible spatial organization of function during episodic recall of real-world events, which seems to drive higher-order cortical regions in the default mode network, particularly in posterior midline areas. Prior studies have shown that when multiple people remember a common experience, event-specific activity patterns in the posterior medial cortex are similar across individuals. This indicates that spatially organized functional responses underlying episodic recall do exist. In this paper we leverage fMRI data collected during recall of naturalistic movies to identify a core set of neural states in the posterior medial cortex. These states are stimulus-locked, reactivated during recall, and have a shared spatial organization across brains. We show that a surprisingly small number of these states (16 states across hemispheres) is sufficient to achieve the same levels of reactivation in the posterior medial cortex as when using the standard methods of the field. Furthermore, these states are significantly related to actions and social-affective features of events in the movies. Together, these findings elucidate the properties of a spatially organized code within the posterior default mode network which appears during natural recollection of memories.

Pain is what you think: functional magnetic resonance imaging evidence toward a cognitive and affective approach for pain research

The sensory/discriminative domain of pain is often given more consideration than the cognitive and affective influences that ultimately make pain what it is: a highly subjective experience that is based on an individual's life history and experiences. While many investigations of the underlying mechanisms of pain have focused on solely noxious stimuli, few have compared somatosensory stimuli that cross the boundary from innocuous to noxious. Of those that have, there is little consensus on the similarities and differences in neural signaling across these sensory domains. The purpose of this study was to apply our established network connectivity analyses toward the goal of understanding the neural mechanisms behind sensory, cognitive, and affective responses to noxious and innocuous stimuli. Functional MRI data were collected from 19 healthy women and men that experienced warm and hot thermal stimuli across multiple trials. This is a within-subjects cross-sectional experimental study with repeated measures. Ratings of stimulus intensity and unpleasantness that were collected during each run confirmed significant perceptual differences between the two types of stimuli. Despite this finding, no group differences in network connectivity were found across conditions. When individual differences related to pain ratings were investigated, subtle differences were found in connectivity that could be attributed to sensory and association regions in the innocuous condition, and cognitive, affective, and autonomic regions in the pain condition. These results were reflected in the time-course data for each condition. Overall, signaling mechanisms for innocuous and noxious somatosensation are intricately linked, but pain-specific perception appears to be driven by our psychological and autonomic states.

Synaptic Structure and Transcriptomic Profiling of Reward and Sensory Brain Areas in Male Mice of Fentanyl Addiction.

Opioid-based medications are powerful analgesics commonly prescribed for pain management, but they are also highly addictive. The over-prescription of opioids analgesics has triggered current opioid crisis, which now has expanded to heroin and illicit synthetic opioids like fentanyl and its analogues. The side effects of fentanyl abuse have been well recognized, yet the underlying molecular adaptations across brain regions upon fentanyl exposure remain elusive. The transmission electron microscopy (TEM) and next-generation RNA-sequencing (RNA-seq) were used to investigate the ultrastructure synaptic alterations and transcriptional profiling changes of reward and sensory brain regions in mice after fentanyl exposure. The naloxone-precipitated acute withdrawal symptoms were observed in mice exposed to fentanyl. Results of TEM showed an increase in the number of synapses, widening of synaptic gaps, and thickening of postsynaptic density in the NAc of the fentanyl addiction mice, accompanied by obvious mitochondrial swelling. RNA-seq identified differentially expressed genes (DEGs) in prefrontal cortex of mice brains after fentanyl exposure, and the expression of some addiction-related genes such as Calm4, Cdh1, Drd1/2/3/4, F2rl2, Gabra6, Ht2cr, Oprk1 and Rxfp3 showed the most striking changes among experimental groups. KEGG enrichment analysis indicated that these DEGs were related to the development of addiction behavior, dopaminergic/GABAergic/serotonergic synapse, synapse assembly/synaptic plasticity/synaptic vesicle cycle, cAMP/MAPK signaling pathway, neuroactive ligand-receptor interactions. These transcriptomic changes may be correlated with the structural and behavioral changes observed in fentanyl-exposed mice. The findings of this study contribute to a better understanding of the molecular mechanism of addiction behavior, which is essential for the development of optimized therapy strategies for addicts.

Extent of genetic and epigenetic factor reprogramming via a single viral vector construct in deaf adult mice.

In the adult mammalian cochlea, hair cell loss is irreversible and causes deafness. The basic helix-loop transcription factor Atoh1 is essential for normal hair cell development in the embryonic ear. Over-expression of Atoh1 in the adult cochlea by gene therapy can convert supporting cells (cells that underlie hair cells) into a hair cell lineage. However, the regeneration outcomes can be inconsistent. Given that hair cell development is regulated by multiple signalling and transcriptional factors in a temporal and spatial manner, a more complex combinatorial approach targeting additional transcription factors may be required for efficient hair cell regeneration. There is evidence that epigenetic factors are responsible for the lack in regenerative capacity of the deaf adult cochlea. This study aimed to develop a combined gene therapy approach to reprogram both the genome and epigenome of supporting cells to improve the efficiency of hair cell regeneration. Adult Pou4f3-DTR mice were used in which the administration of diphtheria toxin was used to ablate hair cells whilst leaving supporting cells relatively intact. A single adeno-associated viral construct was used to express human Atoh1, Pou4f3 and short hairpin RNA against Kdm1a (regeneration gene therapy) at two weeks following partial or severe hair cell ablation. The average transduction of the inner supporting cells, as measured by the control AAV2.7m8-GFP vector in the deaf cochlea, was only 8 % while transduction in the outer sensory region was <1 %. At 4- and 6-weeks post-treatment the number of Myo+ hair cells in the control and regeneration gene therapy-treated mice were not significantly different. Of note, although both control and regeneration gene therapy treated cochleae contained supporting cells that co-expressed the hair cell marker Myo7a and the supporting cell marker Sox2, the regeneration gene therapy treated cochleae had significantly higher numbers of these cells (p < 0.05). Furthermore, among these treated cochleae, those that had more hair cell loss had a higher number of Myo7a positive supporting cells (R2=0.33, Pearson correlation analysis, p < 0.001). Overall, our results indicate that the adult cochlea possesses limited intrinsic spontaneous regenerative capacity, that can be further enhanced by genetic and epigenetic reprogramming.

Impact of rTMS and iTBS on Cerebral Hemodynamics and Swallowing in Unilateral Stroke: Insights from fNIRS.

BACKGROUND Swallowing is a complex behavior involving the musculoskeletal system and higher-order brain functions. We investigated the effects of different modalities of repetitive transcranial magnetic stimulation (rTMS) on the unaffected hemisphere and observed correlation between suprahyoid muscle activity and cortical activation in unilateral stroke patients when swallowing saliva, based on functional near-infrared spectroscopy (fNIRS). MATERIAL AND METHODS From November 2022 to March 2023, twenty-five patients with unilateral stroke were screened using computed tomography or magnetic resonance imaging and identified via a video fluoroscopic swallow study. Finally, patients were divided into rTMS (n=10) and iTBS (n=10) groups. Both groups received 2 weeks of stimulation on unaffected suprahyoid motor cortex. Surface electromyographic measured peak amplitude and swallowing time of bilateral suprahyoid muscles, and penetration-aspiration scale was assessed at baseline and after treatment. fNIRS monitored oxyhemoglobin beta values (OBV) in the primary motor, sensory, and bilateral prefrontal cortex (PFC). RESULTS Both groups showed significant improvements in penetration-aspiration scale, peak amplitude, and swallowing time, compared with baseline (P<0.001), and increased OBV in unaffected regions (P<0.05), especially PFC (P<0.001). No significant OBV increases were seen in affected regions (P>0.05). After treatment, OBV in the unaffected PFC was significantly higher than in the unaffected primary sensory and motor cortex regions for both groups (P<0.05). No significant differences were observed between groups in outcome measures (P>0.05). CONCLUSIONS rTMS and iTBS significantly improved swallowing function in unilateral stroke, relying on compensation by the unaffected cortex, particularly the PFC. iTBS may outperform rTMS by shortening treatment sessions and improving efficiency.

The Lifespan Evolution of Individualized Neurophysiological Traits.

This study examines how brain activity reflects the development of individuality across a person's life. Using magnetoencephalography to capture brief recordings of spontaneous brain activity, the researchers distinguished between over 1,000 individuals, spanning ages 4 to 89. They found that the brain regions most associated with individuality change with age: sensory and motor regions become increasingly distinctive in early adulthood, highlighting their role in shaping a person's unique characteristics of brain activity. The study also revealed that changes in brain activity across different ages correspond to specific patterns of gene expression, shedding light on how genetics influence brain individuality. These findings deepen our understanding of the biological foundations of inter-individual differences and how it evolves over the lifespan.

A domain-general process for theta-rhythmic sampling of either environmental information or internally stored information.

Many everyday tasks, such as shopping for groceries, require the sampling of both environmental information and internally stored information. Selective attention involves the preferential processing and sampling of behaviorally important information from the external environment, while working memory involves the preferential processing and sampling of behaviorally important, internally stored information. These essential cognitive processes share neural resources within a large-scale network that includes frontal, parietal, and sensory cortices, and these shared neural resources can lead to between-domain interactions. Previous research has linked external sampling during selective attention and internal sampling during working memory to theta-rhythmic (3-8 Hz) neural activity in higher-order (e.g., frontal cortices) and sensory regions (e.g., visual cortices). Such theta-rhythmic neural activity might help to resolve the competition for shared neural resources by isolating neural activity associated with different functions over time. Here, we used EEG and a dual-task design (i.e., a task that required both external and internal sampling) to directly compare (i) theta-dependent fluctuations in behavioral performance during external sampling with (ii) theta-dependent fluctuations in behavioral performance during internal sampling. Our findings are consistent with a domain-general, theta-rhythmic process for sampling either external information or internal information. We further demonstrate that interactions between external and internal information-specifically, when to-be-detected information matches to-be-remembered information-are not dependent on theta-band activity (i.e., theta phase). Given that these theta-independent 'match effects' occur during early processing stages (peaking at 75 ms), we propose that theta-rhythmic sampling modulates external and internal information during later processing stages.

Environmental Enrichment Attenuates Repetitive Behavior and Alters the Functional Connectivity of Pain and Sensory Pathways in C58 Mice.

Restricted repetitive behaviors (RRB) encompass a variety of inflexible behaviors, which are diagnostic for autism spectrum disorder (ASD). Despite being requisite diagnostic criteria, the neurocircuitry of these behaviors remains poorly understood, limiting treatment development. Studies in translational animal models show environmental enrichment (EE) reduces the expression of RRB, although the underlying mechanisms are largely unknown. This study used functional magnetic resonance imaging to identify functional connectivity alterations associated with RRB and its attenuation by EE in C58 mice, an animal model of RRB. Extensive differences were observed between C58 mice and C57BL/6 control mice. Higher RRB was associated with altered connectivity between the somatosensory network and reticular thalamic nucleus and between striatal and sensory processing regions. Animals housed in EE displayed increased connectivity between the somatosensory network and the anterior pretectal nucleus and hippocampus, as well as reduced connectivity between the visual network and area prostriata. These results suggest aberrant sensory perception is associated with RRB in C58 mice. EE may reduce RRB by altering functional connectivity in pain and visual networks. This study raises questions about the role of sensory processing and pain in RRB development and identifies new potential intervention targets.

Changes in the sensory regions of the brain in patients with multiple sclerosis after complex neurorehabilitation according to resting functional magnetic resonance imaging

BACKGROUND: Multiple sclerosis is the one of leading causes of non-traumatic disability in young adult patients. An in-depth understanding of the processes of neuroplasticity underlying rehabilitation measures will ensure full and effective recovery of patients with this disease. AIM: To evaluate changes in the brain connectome in patients with multiple sclerosis in response to complex rehabilitation. MATERIALS AND METHODS: A prospective cohort study included 20 patients with relapsing-remitting multiple sclerosis (EDSS 1.5–6.5) in remission. All patients underwent comprehensive inpatient neurorehabilitation in a volume corresponding to individual rehabilitation needs for 5 weeks. To assess changes in the connectome, resting-state functional magnetic resonance imaging (rs-fMRI) was performed at three points: before the start of rehabilitation, immediately after its completion, and one month after discharge from the hospital. Statistical analysis is carried out using the CONN 7 (based on MathLab). Clinical neurological examination included examination using functional tests, passing questionnaires, and determining scores on the EDSS scale before and after rehabilitation. RESULTS: A total of 20 patients were examined, 13 of them at three control points. According to rs-fMRI data, clusters of decreased connectivity were identified between the left parahippocampal gyrus and the lateral cortex of the right occipital lobe, and between the right parahippocampal gyrus and the precuneus (p-FWE, p-FDR of cluster size and mass 0.05). Clusters of increased connectivity were determined between the left inferior temporal gyrus and the lateral occipital cortex of the left hemisphere, between the left middle temporal gyrus and the right frontal field, between the pole of the left temporal lobe and the lateral cortex of the left hemisphere (p-FWE, p-FDR of cluster size and mass 0.05). Other clusters of sufficient size demonstrated borderline statistical significance (individual adjusted p values for cluster size and mass exceeded 0.05). CONCLUSION: The identified changes indicate a functional reorganization of brain structures responsible for the perception of complex visual information, the functioning of executive control systems, as well as the implementation of memory and sequential action planning.

Multitasking practice eliminates modality-based interference by separating task representations in sensory brain regions.

The debate on the neural basis of multitasking costs evolves around neural overlap between concurrently performed tasks. Recent evidence suggests that training-related reductions in representational overlap in fronto-parietal brain regions predict multitasking improvements. Cognitive theories assume that overlap of task representations may lead to unintended information exchange between tasks (i.e., crosstalk). Modality-based crosstalk was suggested as a source for multitasking costs in multisensory settings. Robust findings of increased costs for certain modality mappings may be explained by crosstalk between the stimulus modality in one task and sensory action consequences in the concurrently performed task. Whether modality-based crosstalk emerges from representational overlap in general fronto-parietal multitasking regions or modality-specific regions is not known yet. In this functional neuroimaging study, we investigate neural overlap during multitasking performance in humans, focusing on modality compatibility by employing multivariate pattern analysis and modality-specific practice interventions in three groups (total N = 54, 24 females). We observed significant differences between modality compatible and modality incompatible single-task representations, specifically in the auditory cortex but not in fronto-parietal regions. Notably, improved auditory decoding accuracy related to modality incompatible tasks was predictive of performance gains in the corresponding dual task along with complete elimination of modality-specific dual-task costs. This predictive relationship was evident only in the group practicing modality incompatible mappings, suggesting that specific practice on task sets with modality overlap influenced both neural representations and subsequent multitasking performance. This study contributes to the integration of cognitive theory and neuroscience and the role of task representations in dual-task interference.Significance Statement In a society dominated by multitasking, understanding its neurocognitive basis and plasticity is crucial for key aspects of everyday tasks. We investigate the neural mechanisms behind multitasking limitations, offering insights for targeted cognitive interventions. The study builds upon established theories of cognitive multitasking and imaging research, addressing the concept of modality-based crosstalk - the unintended exchange of modality-based information between tasks. Through functional brain imaging and pattern analysis, we examined how neural task representations contribute to performance costs in dual tasks with varying degrees of modality overlap. Notably, our findings demonstrate a practice-related decrease in neural overlap which is associated with substantial multitasking improvements, specifically in the auditory cortex, emphasizing the contribution of sensory regions to flexible multidimensional task representations.

Neuroanatomical correlates of subjective tinnitus: insights from advanced cortical morphology analysis.

Subjective tinnitus, characterized by the perception of phantom sounds in the absence of external stimuli, presents significant challenges in both audiology and neurology. Once thought to primarily involve aberrant neural activity within auditory pathways, it is now understood to engage a broader array of neuroanatomical structures. This study investigated the connections between auditory, cognitive, and sensory processing regions, which are crucial for unraveling the complex neurobiological basis of tinnitus. Using high-resolution T1-weighted magnetic resonance imaging, we compared 52 individuals with subjective tinnitus with 52 age-matched healthy controls, focusing on cerebral cortex features, including fractal dimensionality, gyrification, and sulcal depth. Covariate analyses were conducted to explore the relationships between tinnitus duration, Tinnitus Handicap Inventory scores, anxiety score, and neuroanatomical changes. We found significant alterations in key brain regions involved in sensory processing, cognition, and emotional regulation, including the insula, lateral occipital cortex, middle frontal gyrus, and superior parietal lobule. These neuroanatomical changes were strongly correlated with the severity and chronicity of tinnitus symptoms. Our findings reveal profound structural changes in the brain associated with subjective tinnitus, offering valuable insights into the condition's underlying mechanisms and providing a potential framework for guiding future research and therapeutic interventions.

Hearing Function Moderates Age-Related Differences in Brain Morphometry in the HCP Aging Cohort.

There are well-established relationships between aging and neurodegenerative changes, and between aging and hearing loss. The goal of this study was to determine how structural brain aging is influenced by hearing loss. Human Connectome Project Aging data were analyzed, including T1-weighted Magnetic Resonance Imaging (MRI) and Words in noise (WIN) thresholds (n = 623). Freesurfer extracted gray and white matter volume, and cortical thickness, area, and curvature. Linear regression models targeted (1) interactions between age and WIN threshold and (2) correlations with WIN threshold adjusted for age, both corrected for false discovery rate (pFDR < 0.05). WIN threshold moderated age-related increase in volume in bilateral inferior lateral ventricles, with a higher threshold associated with increased age-related ventricle expansion. Age-related differences in the occipital cortex also increased with higher WIN thresholds. When controlling for age, high WIN threshold was correlated with reduced cortical thickness in Heschl's gyrus, calcarine sulcus, and other sensory regions, and reduced temporal lobe white matter. Older volunteers with poorer hearing and cognitive scores had the lowest volume in left parahippocampal white matter. These results suggest that better hearing is associated with reduced age-related differences in medial temporal lobe, while better hearing at any age is associated with greater cortical tissue in auditory and other sensory regions. Future longitudinal studies are needed to assess the causal nature of these relationships, but these results indicate interventions that preserve or protect hearing function may combat some neurodegenerative changes in aging.

The DLPFC is centrally involved in resolving Stroop conflicts, suppressing distracting sensory input within the auditory and visual system.

Cognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear. To further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based event-related potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory theta-burst stimulation-a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)-over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices. The results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials ("Gratton effect") that was only accomplished with an intact DLPFC (i.e., following placebo stimulation). Because non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities.

Development of Sensory Regions vs the Rest of the Cortex in Autism

Development of Sensory Regions vs the Rest of the Cortex in Autism

Challenges and Approaches in the Study of Neural Entrainment.

When exposed to rhythmic stimulation, the human brain displays rhythmic activity across sensory modalities and regions. Given the ubiquity of this phenomenon, how sensory rhythms are transformed into neural rhythms remains surprisingly inconclusive. An influential model posits that endogenous oscillations entrain to external rhythms, thereby encoding environmental dynamics and shaping perception. However, research on neural entrainment faces multiple challenges, from ambiguous definitions to methodological difficulties when endogenous oscillations need to be identified and disentangled from other stimulus-related mechanisms that can lead to similar phase-locked responses. Yet, recent years have seen novel approaches to overcome these challenges, including computational modeling, insights from dynamical systems theory, sophisticated stimulus designs, and study of neuropsychological impairments. This review outlines key challenges in neural entrainment research, delineates state-of-the-art approaches, and integrates findings from human and animal neurophysiology to provide a broad perspective on the usefulness, validity, and constraints of oscillatory models in brain-environment interaction.

Structural and functional neural correlates of sensorimotor deficits in progression of hepatic encephalopathy

Hepatic encephalopathy (HE) is a neurological condition that occurs as a complication of liver dysfunction that involves sensorimotor symptoms in addition to cognitive and behavioral changes, particularly in cases of severe liver disease or cirrhosis. Previous studies have reported spatially distributed structural and functional abnormalities related to HE, but the exact relationship between the structural and functional alterations with respect to disease progression remains unclear. In this study, we performed surface-based cortical thickness comparisons and functional connectivity (FC) analyses between three cross-sectional groups: healthy controls (HC, N = 51), patients with minimal hepatic encephalopathy (MHE, N = 50), patients with overt hepatic encephalopathy (OHE, N = 51). In addition to the distributed cortical thinning that is extensively thought to be associated with cognitive decline in HE, we found significant cortical thickening in the left parahippocampal gyrus cortex in the OHE group (p < 0.001, p = 0.009) as compared to the HC and MHE group respectively, which is further corroborated by the significant correlation between the cortical thickness and digit symbol test (DST) scores. Furthermore, the decreased FC between the right postcentral gyrus and several sensory regions (bilateral somatosensory and visual cortices) was found to be significant in MHE patients as compared to the HC group. Our results revealed cross-sectional structural and functional variations concerning disease progression across different subsystems (e.g., visual, motor and sensory), providing evidence that can potentially explain the mechanisms underlying the sensorimotor and cognitive deficits related to HE.

Brain network fingerprints of Alzheimer's disease risk factors in mouse models with humanized APOE alleles

Alzheimer's disease (AD) presents complex challenges due to its multifactorial nature, poorly understood etiology, and late detection. The mechanisms through which genetic and modifiable risk factors influence disease susceptibility are under intense investigation, with APOE being the major genetic risk factor for late onset AD. Yet the impact of unique risk factors on brain networks is difficult to disentangle, and their interactions remain unclear.To model multiple risk factors, including APOE genotype, age, sex, diet, and immunity we used a cross sectional design, leveraging mice expressing human APOE and NOS2 genes, conferring a reduced immune response compared to mouse Nos2. We used network topological and GraphClass analyses of brain connectomes derived from accelerated diffusion-weighted MRI to assess the global and local impact of risk factors, in the absence of AD pathology.Aging and a high-fat diet impacted extensive networks comprising AD-vulnerable regions, including the temporal association cortex, amygdala, and the periaqueductal gray, involved in stress responses. Sex impacted networks including sexually dimorphic regions (thalamus, insula, hypothalamus) and key memory-processing areas (fimbria, septum). APOE genotypes modulated connectivity in memory, sensory, and motor regions, while diet and immunity both impacted the insula and hypothalamus. Notably, these risk factors converged on a circuit comprising 63 of 54,946 total connections (0.11% of the connectome), highlighting shared vulnerability amongst multiple AD risk factors in regions essential for sensory integration, emotional regulation, decision making, motor coordination, memory, homeostasis, and interoception. APOE genotype specific immune signatures support the design of interventions tailored to risk profiles. Sparse Canonical Correlation Analysis (CCA) including spatial memory as a risk factor resulted in a network comprising 80 edges, showing significant overlap with risk-associated networks from GraphClass. The largest overlaps were observed with networks impacted by diet (47 edges), immunity (39 edges), APOE3 vs 4 (26 edges), sex (23 edges), and age (19 edges), the resulting networks supporting the use of sensory cues in spatial memory retrieval.These network-based biomarkers hold translational value for distinguishing high-risk versus low-risk participants at preclinical AD stages, suggest circuits as potential therapeutic targets, and advance our understanding of network fingerprints associated with AD risk.

Involvement of a lateral entorhinal cortex engram in episodic-like memory recall

Episodic memory relies on the entorhinal cortex (EC), a crucial hub connecting the hippocampus and sensory processing regions. This study investigates the role of the lateral EC (LEC) in episodic-like memory in mice. Here, we employ the object-place-context-recognition task (OPCRT), a behavioral test used to study episodic-like memory in rodents. Electrophysiology in brain slices reveals that OPCRT specifically induces a shift in the threshold for the induction of synaptic plasticity in LEC superficial layer II. Additionally, a dual viral system is used to express chemogenetic receptors coupled to the c-Fos promoter in neurons recruited during the learning. We demonstrate that the inhibition of LEC neurons impairs the performance of the mice in the memory task, while their stimulation significantly facilitates memory recall. Our findings provide evidence for an episodic-like memory engram in the LEC and emphasize its role in memory processing within the broader network of episodic memory.