The role of task on the human brain's responses to, and representation of, visual regularity defined by reflection and rotation.

Identifying and segmenting objects in an image is generally achieved effortlessly and is facilitated by the presence of symmetry: a principle of perceptual organisation used to interpret sensory inputs from the retina into meaningful representations. However, while imaging studies show evidence of symmetry selective responses across extrastriate visual areas in the human brain, whether symmetry is processed automatically is still under debate. We used functional Magnetic Resonance Imaging (fMRI) to study the response to and representation of two types of symmetry: reflection and rotation. Dot pattern stimuli were presented to 15 human participants (10 female) under stimulus-relevant (symmetry) and stimulus-irrelevant (luminance) task conditions. Our results show that symmetry-selective responses emerge from area V3 and extend throughout extrastriate visual areas. This response is largely maintained when participants engage in the stimulus irrelevant task, suggesting an automaticity to processing visual symmetry. Our multi-voxel pattern analysis (MVPA) results extend these findings by suggesting that not only spatial organisation of responses to symmetrical patterns can be distinguished from that of non-symmetrical (random) patterns, but also that representation of reflection and rotation symmetry can be differentiated in extrastriate and object-selective visual areas. Moreover, task demands did not affect the neural representation of the symmetry information. Intriguingly, our MVPA results show an interesting dissociation: representation of luminance (stimulus irrelevant feature) is maintained in visual cortex only when task relevant, while information of the spatial configuration of the stimuli is available across task conditions. This speaks in favour of the automaticity for processing perceptual organisation: extrastriate visual areas compute and represent global, spatial properties irrespective of the task at hand.

Object recognition in primates: what can early visual areas contribute?

Introduction: If neuroscientists were asked which brain area is responsible for object recognition in primates, most would probably answer infero-temporal (IT) cortex. While IT is likely responsible for fine discriminations, and it is accordingly dominated by foveal visual inputs, there is more to object recognition than fine discrimination. Importantly, foveation of an object of interest usually requires recognizing, with reasonable confidence, its presence in the periphery. Arguably, IT plays a secondary role in such peripheral recognition, and other visual areas might instead be more critical. Methods: To investigate how signals carried by early visual processing areas (such as LGN and V1) could be used for object recognition in the periphery, we focused here on the task of distinguishing faces from non-faces. We tested how sensitive various models were to nuisance parameters, such as changes in scale and orientation of the image, and the type of image background. Results: We found that a model of V1 simple or complex cells could provide quite reliable information, resulting in performance better than 80% in realistic scenarios. An LGN model performed considerably worse. Discussion: Because peripheral recognition is both crucial to enable fine recognition (by bringing an object of interest on the fovea), and probably sufficient to account for a considerable fraction of our daily recognition-guided behavior, we think that the current focus on area IT and foveal processing is too narrow. We propose that rather than a hierarchical system with IT-like properties as its primary aim, object recognition should be seen as a parallel process, with high-accuracy foveal modules operating in parallel with lower-accuracy and faster modules that can operate across the visual field.

The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.

BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Sex-based differences have been described in schizophrenia epidemiology, symptomatology and outcomes. Different studies explored the impact of schizophrenia in the brain transcriptome, however we lack a consensus transcriptomic profile that considers sex and differentiates specific cerebral regions. METHODS: We performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. RESULTS: We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in females and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. CONCLUSIONS: Our results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females.

Schizophrenia is a serious illness characterised by changes in perception, mood and behaviour that profoundly affect patients and society. The frequency, symptoms and progression of schizophrenia are different in women and men, but the biological reason for this is not understood. The identification of disease mechanisms specific in men and women, is relevant because it would allow a better understanding of this pathology, as well as improving the personalisation of diagnoses and treatments for patients. To achieve this goal, in this work we reviewed all available RNA sequencing studies of post-mortem brain samples from women and men affected by schizophrenia. Then, we compared gene expression in each study by sex, and integrated all study results in different brain regions: prefrontal cortex, hippocampus and all-studies. We discovered significant changes between men and women: 265 genes differentially expressed in the prefrontal cortex, 1414 genes in the hippocampus and 66 genes in meta-analyses of all-studies. The study of these genes revealed increased immune response functions in the prefrontal cortex of men and in the hippocampus of women with schizophrenia, as well as increased neurotransmission and synapses in the prefrontal cortex of women with schizophrenia. Our results report multiple gene expression changes in specific brain regions of patients with schizophrenia, providing new insights into the role of sex in schizophrenia.

Expression of WNT Signaling Genes in the Dorsolateral Prefrontal Cortex in Schizophrenia.

Gene expression alterations in postmortem schizophrenia tissue are well-documented and are influenced by genetic, medication, and epigenetic factors. The Wingless/Integrated (WNT) signaling pathway, critical for cell growth and development, is involved in various cellular processes including neurodevelopment and synaptic plasticity. Despite its importance, WNT signaling remains understudied in schizophrenia, a disorder characterized by metabolic and bioenergetic defects in cortical regions. In this study, we examined the gene expression of 10 key WNT signaling pathway transcripts: IQGAP1, CTNNß1, GSK3ß, FOXO1, LRP6, MGEA5, TCF4, ßTRC, PPP1Cß, and DVL2 in the dorsolateral prefrontal cortex (DLPFC) using postmortem tissue from schizophrenia subjects (n = 20, 10 males, 10 females) compared to age, pH, and postmortem interval (PMI)-matched controls (n = 20, 10 males, 10 females). Employing the R-shiny application Kaleidoscope, we conducted in silico "lookup" studies from published transcriptomic datasets to examine cell- and region-level expression of these WNT genes. In addition, we investigated the impact of antipsychotics on the mRNA expression of the WNT genes of interest in rodent brain transcriptomic datasets. Our findings revealed no significant changes in region-level WNT transcript expression; however, analyses of previously published cell-level datasets indicated alterations in WNT transcript expression and antipsychotic-specific modulation of certain genes. These results suggest that WNT signaling transcripts may be variably expressed at the cellular level and influenced by antipsychotic treatment, providing novel insights into the role of WNT signaling in the pathophysiology of schizophrenia.

Evaluation of Mild Cognitive Impairment through Perientorhinal/Hippocampal Imaging and Comprehensive Neuropsychological and Psychophysical Assessment.

Mild cognitive impairment (MCI) is a significant concern as it is a risk factor for AD progression, and early detection is vital in order to delay dementia onset and enable potential therapeutic interventions. Olfactory impairment is recognized as a predictive biomarker in neurodegenerative processes. The aims of this study were to explore the degree of entorhinal cortical atrophy (ERICA) and the severity of MCI symptoms; to analyze magnetic resonance imaging (MRI) results for the entorhinal cortex, parahippocampal gyrus, peri entorhinal cortex, and the cerebellar tentorium; and to perform a comprehensive neuropsychological and psychophysical assessment. The main results highlighted that in our sample-multidomain amnesic MCI patients with hyposmic symptomatology-we found that ERICA scores were associated with the severity of anxiety symptomatology. One possible hypothesis to explain this observation is that anxiety may contribute to neurodegenerative processes by inducing chronic stress and inflammation. Future research should consider the longitudinal development of neuropsychological scores, anxiety disorders, and brain atrophy to determine their potential predictive value for MCI progression. These findings suggest the importance of psychological factors in MCI progression and the utility of neuropsychological assessment alongside neuroimaging techniques for early detection and follow-up in MCI patients.

Identifying the Shared and Dissociable Neural Bases between Self-Worth and Moral Ambivalence.

Self-ambivalence, a prevalent phenomenon in daily life, has been increasingly substantiated by research. It refers to conflicting self-views and evaluations, primarily concerning self-worth and morality. Previous behavioral research has distinguished self-worth and moral ambivalence, but it remains unclear whether they have separable neural bases. The present study addressed this question by examining resting-state brain activity (i.e., the fractional amplitude of low-frequency fluctuations, fALFF) and connectivity (i.e., resting-state functional connectivity, RSFC) in 112 college students. The results found that self-worth ambivalence was positively related to the fALFF in the orbitofrontal cortex (OFC) and left superior parietal lobule (SPL). The RSFC strength between the SPL and precuneus/posterior cingulate cortex (PCC) was positively related to self-worth ambivalence. Moral ambivalence was positively associated with the fALFF in the left SPL (extending into the temporoparietal junction) and right SPL. The RSFC strengths between the left SPL/TPJ and OFC, as well as the RSFC strengths between the right SPL as a seed and the bilateral middle and inferior temporal gyrus, were associated with moral ambivalence. Overall, the neural bases of self-worth and moral ambivalence are associated with the SPL and OFC, involved in attentional alertness and value representation, respectively. Additionally, the neural basis of moral ambivalence is associated with the TPJ, responsible for mentalizing.

Dysfunction of motor cortices in Parkinson's disease.

The cerebral cortex has long been thought to be involved in the pathophysiology of motor symptoms of Parkinson's disease. The impaired cortical function is believed to be a direct and immediate effect of pathologically patterned basal ganglia output, mediated to the cerebral cortex by way of the ventral motor thalamus. However, recent studies in humans with Parkinson's disease and in animal models of the disease have provided strong evidence suggesting that the involvement of the cerebral cortex is much broader than merely serving as a passive conduit for subcortical disturbances. In the present review, we discuss Parkinson's disease-related changes in frontal cortical motor regions, focusing on neuropathology, plasticity, changes in neurotransmission, and altered network interactions. We will also examine recent studies exploring the cortical circuits as potential targets for neuromodulation to treat Parkinson's disease.

Investigating the Effects of Repetitive Paired-Pulse Transcranial Magnetic Stimulation on Visuomotor Training Using TMS-EEG.

I-wave periodicity repetitive paired-pulse transcranial magnetic stimulation (iTMS) can modify acquisition of a novel motor skill, but the associated neurophysiological effects remain unclear. The current study therefore used combined TMS-electroencephalography (TMS-EEG) to investigate the neurophysiological effects of iTMS on subsequent visuomotor training (VT). Sixteen young adults (26.1 ± 5.1 years) participated in three sessions including real iTMS and VT (iTMS + VT), control iTMS and VT (iTMSControl + VT), or iTMS alone. Motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) were measured before and after iTMS, and again after VT, to assess neuroplastic changes. Irrespective of the intervention, MEP amplitude was not changed after iTMS or VT. Motor skill was improved compared with baseline, but no differences were found between stimulus conditions. In contrast, the P30 peak was altered by VT when preceded by control iTMS (P < 0.05), but this effect was not apparent when VT was preceded by iTMS or following iTMS alone (all P > 0.15). In contrast to expectations, iTMS was unable to modulate MEP amplitude or influence motor learning. Despite this, changes in P30 amplitude suggested that motor learning was associated with altered cortical reactivity. Furthermore, this effect was abolished by priming with iTMS, suggesting an influence of priming that failed to impact learning.

Developmentally stable representations of naturalistic image structure in macaque visual cortex.

To determine whether post-natal improvements in form vision result from changes in mid-level visual cortex, we studied neuronal and behavioral responses to texture stimuli that were matched in local spectral content but varied in "naturalistic" structure. We made longitudinal measurements of visual behavior from 16 to 95 weeks of age, and of neural responses from 20 to 56 weeks. We also measured behavioral and neural responses in near-adult animals more than 3 years old. Behavioral sensitivity reached half-maximum around 25 weeks of age, but neural sensitivities remained stable through all ages tested. Neural sensitivity to naturalistic structure was highest in V4, lower in V2 and inferotemporal cortex (IT), and barely discernible in V1. Our results show a dissociation between stable neural performance and improving behavioral performance, which may reflect improved processing capacity in circuits downstream of visual cortex.

Neurotensin-specific corticothalamic circuit regulates innate response conflict.

Animals must simultaneously select and balance multiple action contingencies in ambiguous situations: for instance, evading danger during feeding. This has rarely been examined in the context of information selection; despite corticothalamic pathways that mediate sensory attention being relatively well characterized, neural mechanisms filtering conflicting actions remain unclear. Here, we develop a new loom/feed test to observe conflict between naturally induced fear and feeding and identify a novel anterior cingulate cortex (ACC) output to the ventral anterior and ventral lateral thalamus (VA/VL) that adjusts selectivity between these innate actions. Using micro-endoscopy and fiber photometry, we reveal that activity in corticofugal outputs was lowered during unbalanced/singularly occupied periods, as were the resulting decreased thalamic initiation-related signals for less-favored actions, suggesting that the integration of ACC-thalamic firing may directly regulate the output of behavior choices. Accordingly, the optoinhibition of ACC-VA/VL circuits induced high bias toward feeding at the expense of defense. To identify upstream "commander" cortical cells gating this output, we established dual-order tracing (DOT)-translating ribosome affinity purification (TRAP)-a scheme to label upstream neurons with transcriptome analysis-and found a novel population of neurotensin-positive interneurons (ACCNts). The photoexcitation of ACCNts cells indeed caused similarly hyper-selective behaviors. Collectively, this new "corticofugal action filter" scheme suggests that communication in multi-step cingulate circuits may critically influence the summation of motor signals in thalamic outputs, regulating bias between innate action types.

Effects of adolescent intermittent ethanol exposure on cortical perineuronal net and parvalbumin expression in adulthood mediate behavioral inflexibility.

BACKGROUND: Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads to increased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown. METHODS: We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning. RESULTS: We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part through changes in PV and PNN fluorescent measures in the AIC. CONCLUSIONS: This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium-Pilocarpine Model of Epilepsy.

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unaltered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex terminates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant contributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

Developing Effective Radio Frequency Vacuum Drying Processes for Moutan Cortex: Effect on Moisture Migration, Drying Kinetics, Physicochemical Quality, and Microstructure.

This study aims to maximize the post-harvest quality of Moutan Cortex and reduce energy consumption. Radio frequency vacuum (RFV) technology was used to dehydrate Moutan Cortex in this study to investigate the effects of different drying temperatures, plate spacing, and vacuum degree on the drying kinetics, physicochemical quality, and microstructure of Moutan Cortex. The results showed that RFV drying shortened the dehydration time of the Moutan Cortex by 10.71-28.57% and increased the drying rate by 15.79-54.39% compared to hot-air drying. The best color (∆E = 6.08 ± 0.28, BI = 26.97 ± 0.98) and relatively high retention of polysaccharides, total phenolics, total flavonoids, antioxidant properties, paeonol, gallic acid, paeoniflorin, and benzoylpaeoniflorin contents were observed in the dried products of Moutan Cortex at a drying temperature of 50 °C, spacing of 90 mm, and vacuum of 0.025 MPa. Analyzing the microstructure, it was found that RFV drying could effectively inhibit the shrinkage and collapse of the cellular structure, and a regular and loose honeycomb pore structure appeared inside the samples, which contributed to the rapid migration of the internal moisture. This study can provide a theoretical reference basis for the selection and application of industrialized processing methods of high-quality Moutan Cortex.

Modification of Keratin Integrations and the Associated Morphogenesis in Frizzling Chicken Feathers.

The morphological and compositional complexities of keratinized components make feathers ingenious skin appendages adapted to diverse ecological needs. Frizzling feathers, characterized by their distinct curling phenotypes, offer a unique model to explore the intricate morphogenesis in developing a keratin-based bioarchitecture over a wide range of morphospace. Here, we investigated the heterogeneous allocation of α- and ß-keratins in flight feather shafts of homozygous and heterozygous frizzle chickens by analyzing the medulla-cortex integrations using quantitative morphology characterizations across scales. Our results reveal the intriguing construction of the frizzling feather shaft through the modified medulla development, leading to a perturbed balance of the internal biomechanics and, therefore, introducing the inherent natural frizzling compared to those from wild-type chickens. We elucidate how the localized developmental suppression of the α-keratin in the medulla interferes with the growth of the hierarchical keratin organization by changing the internal stress in the frizzling feather shaft. This research not only offers insights into the morphogenetic origin of the inherent bending of frizzling feathers but also facilitates our in-depth understanding of the developmental strategies toward the diverse integuments adapted for ecological needs.

Noises on-How the Brain Deals with Acoustic Noise.

What is noise? When does a sound form part of the acoustic background and when might it come to our attention as part of the foreground? Our brain seems to filter out irrelevant sounds in a seemingly effortless process, but how this is achieved remains opaque and, to date, unparalleled by any algorithm. In this review, we discuss how noise can be both background and foreground, depending on what a listener/brain is trying to achieve. We do so by addressing questions concerning the brain's potential bias to interpret certain sounds as part of the background, the extent to which the interpretation of sounds depends on the context in which they are heard, as well as their ethological relevance, task-dependence, and a listener's overall mental state. We explore these questions with specific regard to the implicit, or statistical, learning of sounds and the role of feedback loops between cortical and subcortical auditory structures.

Association of Overweight and Obesity with Impaired Executive Functioning in Mexican Adolescents: The Importance of Inhibitory Control.

Overweight and obesity are major public health issues worldwide, including in Mexico, particularly among adolescents. This study aimed to analyze the associations between nutritional status and impaired executive function (EF) in Mexican adolescents. A case-control study was conducted with 98 male and female adolescents, categorized into normal weight and overweight/obese groups based on body mass index. EF was assessed using the BANFE-2 test. The prevalence of overweight and obesity was 54.3%. The EF assessment revealed that 82.45% of the overweight/obese group exhibited mild-to-severe impairment, compared to only 36.58% in the normal weight group (X2 = 21.69, p < 0.0001). In the inhibitory control assessment, adolescents with overweight and obesity performed worse than their normal-weight counterparts. Specifically, females with overweight/obesity scored lower than females with normal weight on the risk-benefit processing test. The risk of severe EF impairment significantly increased with the presence of overweight/obesity (OR = 7.8, p < 0.0001). These findings indicate that EF, particularly inhibitory control and risk-benefit processing, is impaired in adolescents with overweight or obesity.

Cholinergic input to mouse visual cortex signals a movement state and acutely enhances layer 5 responsiveness.

Acetylcholine is released in visual cortex by axonal projections from the basal forebrain. The signals conveyed by these projections and their computational significance are still unclear. Using two-photon calcium imaging in behaving mice, we show that basal forebrain cholinergic axons in the mouse visual cortex provide a binary locomotion state signal. In these axons, we found no evidence of responses to visual stimuli or visuomotor prediction errors. While optogenetic activation of cholinergic axons in visual cortex in isolation did not drive local neuronal activity, when paired with visuomotor stimuli, it resulted in layer-specific increases of neuronal activity. Responses in layer 5 neurons to both top-down and bottom-up inputs were increased in amplitude and decreased in latency, whereas those in layer 2/3 neurons remained unchanged. Using opto- and chemogenetic manipulations of cholinergic activity, we found acetylcholine to underlie the locomotion-associated decorrelation of activity between neurons in both layer 2/3 and layer 5. Our results suggest that acetylcholine augments the responsiveness of layer 5 neurons to inputs from outside of the local network, possibly enabling faster switching between internal representations during locomotion.

Reduction of Glyoxalase 1 Expression Links Fetal Methylmercury Exposure to Autism Spectrum Disorder Pathogenesis.

Glyoxalase 1 (Glo1) is an essential enzyme to detoxify methylglyoxal (MGO), a cytotoxic byproduct of glycolysis. Accumulating studies have shown an important role of Glo1 in regulating cortical development and neurogenesis, potentially contributing to the pathogenesis of autism spectrum disorder (ASD) when impaired. We have previously shown that prenatal exposure to non-apoptotic low-dose methylmercury (MeHg), an environmental pollutant, induces premature cortical neurogenesis and ASD-like behaviors in a rodent model. In this study, we aimed to determine the underlying molecular mechanisms that mediate prenatal MeHg-induced premature neuronal differentiation and abnormal neurodevelopment. Using single-cell RNA sequencing (scRNA-seq) and real-time quantitative PCR (RT-qPCR), we found that prenatal MeHg exposure at a non-apoptotic dose significantly reduced Glo1 gene expression in embryonic cultured radial glia precursors (RGPs). In cultured RGPs, the knockdown of Glo1 expression increased neuronal production at the expense of the cultured RGPs population, while overexpression of Glo1 restored MeHg-induced neuronal differentiation back to normal levels. Furthermore, we found that co-treatment with both MeHg and multiple MGO scavengers or a CREB inhibitor (iCREB) mitigated MeHg-induced premature neuronal differentiation, reinforcing the role of Glo1 and CREB in mediating MeHg-induced neuronal differentiation. Our findings demonstrate a direct link between MeHg exposure and expression of an ASD risk gene Glo1 in cortical development, supporting the important role of gene-environment interaction in contributing to the etiology of neural developmental disorders, such as ASD.

Semantic structures facilitate threat memory integration throughout the medial temporal lobe and medial prefrontal cortex.

Emotional experiences can profoundly impact our conceptual model of the world, modifying how we represent and remember a host of information even indirectly associated with that experienced in the past. Yet, how a new emotional experience infiltrates and spreads across pre-existing semantic knowledge structures (e.g., categories) is unknown. We used a modified aversive sensory preconditioning paradigm in fMRI (n = 35) to investigate whether threat memories integrate with a pre-established category to alter the representation of the entire category. We observed selective but transient changes in the representation of conceptually related items in the amygdala, medial prefrontal cortex, and occipitotemporal cortex following threat conditioning to a simple cue (geometric shape) pre-associated with a different, but related, set of category exemplars. These representational changes persisted beyond 24 h in the hippocampus and perirhinal cortex. Reactivation of the semantic category during threat conditioning, combined with activation of the hippocampus or medial prefrontal cortex, was predictive of subsequent amygdala reactivity toward novel category members at test. This provides evidence for online integration of emotional experiences into semantic categories, which then promotes threat generalization. Behaviorally, threat conditioning by proxy selectively and retroactively enhanced recognition memory and increased the perceived typicality of the semantic category indirectly associated with threat. These findings detail a complex route through which new emotional learning generalizes by modifying semantic structures built up over time and stored in memory as conceptual knowledge.

Motor cortex activation mediates associations between striatal dopamine depletion and manual dexterity in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) presents with a progressive decline in manual dexterity, attributed to dysfunction in the basal ganglia-thalamus-cortex loop, influenced by dopaminergic deficits in the striatum. Recent research suggests that the motor cortex may play a pivotal role in mediating the relationship between striatal dopamine depletion and motor function in PD. Understanding this connection is crucial for comprehending the origins of manual dexterity impairments in PD. Therefore, our study aimed to explore how motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD. MATERIALS AND METHODS: We enrolled 26 mildly affected PD patients in their off-medication phase to undergo [18F]FDOPA PET/CT scans for evaluating striatal dopaminergic function. EEG recordings were conducted during bimanual anti-phase finger tapping tasks to evaluate motor cortex activity, specifically focusing on Event-Related Desynchronization in the beta band. Manual dexterity was assessed using the Purdue Pegboard Test. Regression-based mediation analysis was conducted to examine whether motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD. RESULTS: Mediation analysis revealed a significant direct effect of putamen dopamine depletion on manual dexterity for the affected hand and assembly tasks (performed with two hands), with motor cortex activity mediating this association. In contrast, while caudate nucleus dopamine depletion showed a significant direct effect on manual dexterity, motor cortex mediation on this association was not observed. CONCLUSION: Our study confirms the association between striatum dopamine depletion and impaired manual dexterity in PD, with motor cortex activity mediating this relationship.