Brain Responses Research Articles

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines invitro. However, despite its genetic association with several neurological disorders, the invivo impact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that the loss of MARK2 invivo results in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, the loss of MARK2 produces substantial impairments in learning and memory, reduced anxiety, and defective social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, electrophysiological analysis of hippocampal slices indicates underlying neuronal hyperexcitability in MARK2-deficient neurons. Finally, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These results underscore the invivo role of MARK2 in governing synaptic connectivity, neuronal excitability, and cognitive functions.

Mapping common and distinct brain correlates among cognitive flexibility tasks: concordant evidence from meta-analyses.

Cognitive flexibility allows individuals to switch between different tasks, strategies, or ideas; an ability that is important for everyday life. The Wisconsin card sorting test (WCST) and task switching paradigm (TSP) are popular measures of cognitive flexibility. Although both tasks require switching, the TSP requires participants to memorize switching rules and retrieve them when they view a cue (rule-retrieval), whereas the classic WCST requires participants to discover the switching rule via trial-and-error (rule-discovery). Many functional magnetic resonance imaging studies have examined brain responses to these tasks. Extant meta-analyses show concordance in activation in a widespread set of areas including frontal, parietal, and cingulate cortices. Critically, past meta-analyses have not specifically examined brain correlates associated with rule derivation (i.e., rule-discovery vs. rule-retrieval) in cognitive flexibility tasks. We examine for the first time common and distinct concordance in brain responses to rule-discovery (i.e., WCST) and rule-retrieval (i.e., TSP), as well as TSP subtypes using quantitative meta-analyses. We analyzed data from 69 eligible articles with a total of 1617 young-adult participants. Conjunction results show concordance in common fronto-parietal areas predominantly in the left hemisphere. Contrast analyses show that rule-discovery required increased involvement in multiple cortical and subcortical regions such as frontopolar (Brodmann Area 10), parietal, insular cortex, thalamus and caudate nucleus predominantly in the right hemisphere. No significant differences in concordance were observed among the three, task switching paradigm sub-types. We propose a neuroanatomical model of cognitive flexibility and discuss theoretical and practical applications.

Differential modulations of theta and beta oscillations by audiovisual congruency in letter-speech sound integration.

The integration of visual letters and speech sounds is a crucial part of learning to read. Previous studies investigating this integration have revealed a modulation by audiovisual (AV) congruency, commonly known as the congruency effect. To investigate the cortical oscillations of the congruency effects across different oscillatory frequency bands, we conducted a Japanese priming task in which a visual letter was followed by a speech sound. We analyzed the power and phase properties of oscillatory activities in the theta and beta bands between congruent and incongruent letter-speech sound (L-SS) pairs. Our results revealed stronger theta-band (5-7Hz) power in the congruent condition and cross-modal phase resetting within the auditory cortex, accompanied by enhanced inter-trial phase coherence (ITPC) in the auditory-related areas in response to the congruent condition. The observed congruency effect of theta-band power may reflect increased neural activities in the left auditory region during L-SS integration. Additionally, theta ITPC findings suggest that visual letters amplify neuronal responses to the following corresponding auditory stimulus, which may reflect the differential cross-modal influences in the primary auditory cortex. In contrast, decreased beta-band (20-35 Hz) oscillatory power was observed in the right centroparietal regions for the congruent condition. The reduced beta power seems to be unrelated to the processing of AV integration, but may be interpreted as the brain response to predicting auditory sounds during language processing. Our data provide valuable insights by indicating that oscillations in different frequency bands contribute to the disparate aspects of L-SS integration.

Pharmacological manipulation of neurotransmitter activity induces disparate effects on cerebral blood flow and resting-state fluctuations

Abstract Functional MRI methods can assess aspects of drug-induced brain response. Resting blood oxygenation level dependent (BOLD) fMRI and arterial spin labeling (ASL) perfusion MRI indirectly measure brain function through the coupling of activity to cerebral blood flow (CBF) and oxygenation but their relative sensitivity has not been directly compared. We assessed changes in resting measures of BOLD and ASL MRI in response to two neurotransmitter modulators: citalopram, a selective serotonin reuptake inhibitor, and alprazolam, a positive allosteric modulator of GABA type A receptor. Thirty healthy subjects were imaged in a placebo-controlled study, with N=20 subjects receiving each treatment as part of an incomplete block design. Time-averaged CBF images from ASL and measures of resting-state fluctuations of BOLD and ASL images were assessed for significant effects. Following acute citalopram administration, analysis of the ASL data showed a reduction in time-averaged regional CBF in regions associated with high levels of 5-HT1A receptor density. In contrast, following alprazolam administration, BOLD amplitude of low frequency fluctuations showed a highly significant and cortically widespread increase, consistent with the distribution of GABA-A receptors. Only a marginal decrease in ASL CBF was detected after alprazolam intake. BOLD and ASL are each sensitive to drugs targeting neurotransmitter systems, but appear to reflect different aspects of neural metabolism and the balance between excitatory and inhibitory activity. Accordingly, their combination may best capture the effects of neurotransmitter modulations, and thus be advantageous for pharmacological MRI studies.

Autonomic nervous system responses to hypo- and hyperglycemia in type 2 diabetes and prediabetes.

Previous research points to a role of the brain in the regulation of glucose and pathogenesis of type 2 diabetes (T2D) via modulation of counter-regulatory hormone secretion and activity in the autonomic nervous system (ANS). The aim of this study was to investigate glucose-dependent responses of catecholamines and ANS activity in individuals with T2D, prediabetes (PD) and normoglycemia (NG). Cross-sectional. Individuals with T2D (n=19, 7 men, HbA1c 49 mmol/mol), prediabetes (PD, n=18, 8 men) and normoglycemia (NG, n=17, 3 men) underwent one stepwise hyperinsulinemic-euglycemic-hypoglycemic and one hyperglycemic clamp with repeated measurements of catecholamines, symptoms, heart rate variability (HRV) and hemodynamics. The hypoglycemic response of adrenaline was augmented in T2D and PD vs NG (both p<0.05) and there was a strong association with insulin resistance (p<0.05 for M-value). In relation to achieved glucose levels in both clamps, noradrenaline exhibited a steeper rise during hypoglycemia in T2D vs NG and PD (both p<0.05). There were trends toward more marked autonomic hypoglycemic symptoms in T2D vs PD and NG. By contrast, insulin resistance was associated with attenuated responses of heart rate and HRV-indices PLF and PHF at the target glucose plateau of 2.7 mmol/l (p<0.05), independent of BMI and HbA1c. Alterations in glucose-dependent responses of counter-regulatory hormones and the autonomic nervous system appear before, and probably contribute to, the onset of T2D. Together with other reported alterations in neuroendocrine pathways, the findings suggest that a maladaptation of the brain's responses to glucose fluctuations is important in T2D progression.

Investigating Brain Responses to Transcutaneous Electroacupuncture Stimulation: A Deep Learning Approach

This study investigates the neurophysiological effects of transcutaneous electroacupuncture stimulation (TEAS) on brain activity, using advanced machine learning techniques. This work analyzed the electroencephalograms (EEG) of 48 study participants, in order to analyze the brain’s response to different TEAS frequencies (2.5, 10, 80, and sham at 160 pulses per second (pps)) across 48 participants through pre-stimulation, during-stimulation, and post-stimulation phases. Our approach introduced several novel aspects. EEGNet, a convolutional neural network specifically designed for EEG signal processing, was utilized in this work, achieving over 95% classification accuracy in detecting brain responses to various TEAS frequencies. Additionally, the classification accuracies across the pre-stimulation, during-stimulation, and post-stimulation phases remained consistently high (above 92%), indicating that EEGNet effectively captured the different time-based brain responses across different stimulation phases. Saliency maps were applied to identify the most critical EEG electrodes, potentially reducing the number needed without sacrificing accuracy. A phase-based analysis was conducted to capture time-based brain responses throughout different stimulation phases. The robustness of EEGNet was assessed across demographic and clinical factors, including sex, age, and psychological states. Additionally, the responsiveness of different EEG frequency bands to TEAS was investigated. The results demonstrated that EEGNet excels in classifying EEG signals with high accuracy, underscoring its effectiveness in reliably classifying EEG responses to TEAS and enhancing its applicability in clinical and therapeutic settings. Notably, gamma band activity showed the highest sensitivity to TEAS, suggesting significant effects on higher cognitive functions. Saliency mapping revealed that a subset of electrodes (Fp1, Fp2, Fz, F7, F8, T3, T4) could achieve accurate classification, indicating potential for more efficient EEG setups.

NOise Reduction with DIstribution Corrected (NORDIC) principal component analysis improves brain activity detection across rodent and human functional MRI contexts.

NOise Reduction with DIstribution Corrected (NORDIC) principal component analysis (PCA) has been shown to selectively suppress thermal noise and improve the temporal signal-to-noise ratio (tSNR) in human functional magnetic resonance imaging (fMRI). However, the feasibility to improve data quality for rodent fMRI using NORDIC PCA remains uncertain. NORDIC PCA may also be particularly beneficial for improving topological brain mapping, as conventional mapping requires precise spatiotemporal signals from large datasets (ideally ~1 hour acquisition) for individual representations. In this study, we evaluated the effects of NORDIC PCA compared with "Standard" processing in various rodent fMRI contexts that range from task-evoked optogenetic fMRI to resting-state fMRI. We also evaluated the effects of NORDIC PCA on human resting-state and retinotopic mapping fMRI via population receptive field (pRF) modeling. In rodent optogenetic fMRI, apart from doubling the tSNR, NORDIC PCA resulted in a larger number of activated voxels and a significant decrease in the variance of evoked brain responses without altering brain morphology. In rodent resting-state fMRI, we found that NORDIC PCA induced a nearly threefold increase in tSNR and preserved task-free relative cerebrovascular reactivity (rCVR) across cortical depth. NORDIC PCA further improved the detection of TGN020-induced aquaporin-4 inhibition on rCVR compared with Standard processing without NORDIC PCA. NORDIC PCA also increased the tSNR for both human resting-state and pRF fMRI, and for the latter also increased activation cluster sizes while retaining retinotopic organization. This suggests that NORDIC PCA preserves the spatiotemporal precision of fMRI signals needed for pRF analysis, and effectively captures small activity changes with high sensitivity. Taken together, these results broadly demonstrate the value of NORDIC PCA for the enhanced detection of neural dynamics across various rodent and human fMRI contexts. This can in turn play an important role in improving fMRI image quality and sensitivity for translational and preclinical neuroimaging research.

Regulation of craving for real-time fMRI neurofeedback based on individual classification.

In previous real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) studies on smoking craving, the focus has been on within-region activity or between-region connectivity, neglecting the potential predictive utility of broader network activity. Moreover, there is debate over the use and relative predictive power of individual-specific and group-level classifiers. This study aims to further advance rtfMRI-NF for substance use disorders by using whole-brain rtfMRI-NF to assess smoking craving-related brain patterns, evaluate the performance of group-level or individual-level classification (n = 31) and evaluate the performance of an optimized classifier across repeated NF runs. Using real-time individual-level classifiers derived from whole-brain support vector machines, we found that classification accuracy between crave and no-crave conditions and between repeated NF runs increased across repeated runs at both individual and group levels. In addition, individual-level accuracy was significantly greater than group-level accuracy, highlighting the potential increased utility of an individually trained whole-brain classifier for volitional control over brain patterns to regulate smoking craving. This study provides evidence supporting the feasibility of using whole-brain rtfMRI-NF to modulate smoking craving-related brain responses and the potential for learning individual strategies through optimization across repeated feedback runs. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Pattern separation during encoding and Subsequent Memory Effect

Memory retrieval has been extensively studied in relation to the encoding processes that precede access to stored information. Event related potentials (ERP) research has compared brain potentials elicited during the study phase of successful and unsuccessful retrieval, finding greater activation for the subsequent retrieval information. In this work we were interested in exploring the neural markers associated to subsequent recognition when similar memories are subsequently encoded. We used a Subsequent Memory paradigm in which we manipulated the number of similar items within a category (2 or 6) that participants encoded. Manipulating the number of similar encoded items within a category allowed us to test whether encoding markers of subsequent recognition depend solely on memory trace strength or, on the contrary, successful recognition is influenced by subsequently presented similar memories, and consequently may not be reflected in higher activation in such cases. After a 20-minute period, participants performed a recognition task providing one of a three-option judgement: “old”, “similar” and “new”, which allowed us to test if the amplitude of ERP waveforms varied based on the similarity judgement of the unrecognized encoded item. We did not observe a significant parietal subsequent memory effect, however, old hits and similar false alarms were both significantly different from similar correct rejections and old false alarms in ERP retrieval. These findings suggest that differences in brain responses between conditions are specifically related to the retrieval process and not the encoding process, indicating potential differential effects on memory during retrieval. Moreover, it is also possible that differences in brain responses develop or change over the rest time between phases, influencing how these conditions manifest across different stages of information processing.

Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people.

Processing of Emotional Words in Children and Adolescents with Autism Spectrum Disorders.

Individuals with autism spectrum disorder (ASD) have difficulties in understanding emotional language, but little research has discussed the developmental course of the processing of emotional words in the clinical population. Previous studies have revealed distinct processing for emotion-label (e.g., happiness) and emotion-laden (e.g., birthday) words in typically developing (TD) children and adolescents. Extending these findings, the study used event-related potentials (ERPs) to explore the processing of these two types of emotional words in children and adolescents with ASD. The stimuli included two-character Chinese words with factors of word type (emotion-label versus emotion-laden) and valence (positive versus negative). The participants were 11 to 14-year-old children and adolescents with ASD (N = 23) and age-matched TD peers (N = 23). They categorized emotion valence for words while their brain responses were recorded. Both the TD and the ASD groups exhibited emotional processing for all emotional words across the N400 and late positivity component (LPC). The emotional processing was modulated by word type but varied with group and valence. A trend for group differences was observed in processing positive words at 500-600ms. In particular, the emotion effects of positive emotion-label words were positively correlated with social dysfunction across all participants. These findings suggested that children and adolescents with ASD have a selective impairment in understanding emotional concepts from language. The ERP measurements may reflect atypical emotional word processing for individuals with higher autistic severity in positive valence contexts.

The Effect of Memory Training on Cognitive Function: A Systematic Review

Memory is related to the processes that allow us to record, store and then retrieve experiences and information. Memory as an information processor is analogized by psychologists and neurologists as a computer. The recording process, called encoding, is the process of obtaining information conveyed to the system by translating it into neural code which is processed in the brain.The goal of the research titled is to systematically evaluate and synthesize existing studies to determine the impact of memory training interventions on various aspects of cognitive function. This includes assessing how memory training may enhance skills such as attention, processing speed, working memory, and overall cognitive performance. By identifying patterns, strengths, and limitations in the current literature, the study aims to provide insights into the effectiveness of memory training programs and guide future research and practical applications in cognitive enhancement.Method: Articles used in systematic reviews are typically sourced from various academic databases such as PubMed, PsycINFO, Scopus, and Google Scholar. These include studies published in peer-reviewed journals. The keywords used for searching may include phrases like "memory training," "cognitive function," "cognitive enhancement," "working memory," and other related terms. This combination of keywords helps filter relevant articles. For instance, in this review, there might be 150 articles identified through the initial search. After a selection process based on inclusion and exclusion criteria, approximately 30 articles are chosen for further analysis. The articles included in the systematic review are examined systematically, following the PRISMA 2020 guidelines: Study Identification,Study Selection,Data Extraction,Analysis and Synthesis Analyzing the results from the selected studies and compiling conclusions based on the available evidence.Results: The findings from these five literature studies cumulatively imply that activities involving the Al-Quran, such as listening, reading, or memorizing, have a positive impact on various aspects of physical and mental health, cognitive function, and brain responses. The implications of these results may stimulate further research in the field of cognitive interventions, as well as provide a more in-depth look at the role of memorization in the development of cognitive abilities at critical developmental stages.Conclusion: From the five studies reviewed, it can be concluded that memory training interventions, especially in the context of memorizing the Qur'an, contribute positively to the improvement of cognitive function in various age groups, including children, adolescents, adults, and the elderly. The implications of these findings give impetus to further research in the field of cognitive intervention, focusing on memorization strategies, as well as providing deeper insight into the role of memorization in the development of cognitive abilities at critical stages of life.

Methodological Choices Matter: A Systematic Comparison of TMS-EEG Studies Targeting the Primary Motor Cortex.

Transcranial magnetic stimulation (TMS) triggers time-locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. Here, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices. We scrutinized prevalent methodological choices and assessed how consistently they were reported in published papers. We extracted amplitudes and latencies from reported TEPs and compared specific TEP peaks and components between studies using distinct methods. Reporting of methodological details was overall sufficient, but some relevant information regarding the TMS settings and the recording and preprocessing of EEG data were missing in more than 25% of the included experiments. The published TEP latencies and amplitudes confirm the "prototypical" TEP waveform following stimulation of M1, comprising distinct N15, P30, N45, P60, N100, and P180 peaks. However, variations in amplitude were evident across studies. Higher stimulation intensities were associated with overall larger TEP amplitudes. Active noise masking during TMS generally resulted in lower TEP amplitudes compared to no or passive masking but did not specifically impact those TEP peaks linked to long-latency sensory processing. Studies implementing independent component analysis (ICA) for artifact removal generally reported lower TEP magnitudes. In summary, some aspects of reporting practices could be improved in future TEP studies to enable replication. Methodological choices, including TMS intensity and the use of noise masking or ICA, introduce systematic differences in reported TEP amplitudes. Further investigation into the significance of these and other methodological factors and their interactions is warranted.

Assessing the Influence of Visual Stimulus Properties on Steady-State Visually Evoked Potentials and Pupil Diameter.

Steady-State Visual Evoked Potentials (SSVEPs) are brain responses measurable via electroencephalography (EEG) in response to continuous visual stimulation at a constant frequency. SSVEPs have been instrumental in advancing our understanding of human vision and attention, as well as in the development of brain-computer interfaces (BCIs). Ongoing questions remain about which type of visual stimulus causes the most potent SSVEP response. The current study investigated the effects of color, size, and flicker frequency on the signal-to-noise ratio of SSVEPs, complemented by pupillary light reflex measurements obtained through an eye-tracker. Six participants were presented with visual stimuli that differed in terms of color (white, red, green), shape (circles, squares, triangles), size (10,000 to 30,000 pixels), flicker frequency (8 to 25 Hz), and grouping (one stimulus at a time vs. four stimuli presented in a 2×2 matrix to simulate a BCI). The results indicated that larger stimuli elicited stronger SSVEP responses and more pronounced pupil constriction. Additionally, the results revealed an interaction between stimulus color and flicker frequency, with red being more effective at lower frequencies and white at higher frequencies. Future SSVEP research could focus on the recommended waveform, interactions between SSVEP and power grid frequency, a wider range of flicker frequencies, a larger sample of participants, and a systematic comparison of the information transfer obtained through SSVEPs, pupil diameter, and eye movements.

Reduced auditory perception and brain response with quiet TMS coil

BackgroundElectromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC). ObjectiveTo compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil. MethodsNine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120 % RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal while stimulating the primary motor cortex. ResultsRMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100 % coil-specific RMT sounded like Cool-B65 at 34 % RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS- DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation. ConclusionsThe stimulation efficiency of qTMS-DCC matched Cool-B65 while having substantially lower perceived loudness and auditory-evoked potentials.

Idiosyncratic pupil regulation in autistic children.

Recent neuroimaging and eye-tracking studies have suggested that children with autism exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here, we extended this research to pupillometry recordings. We successfully acquired pupillometry recordings from 111 children (74 with autism), 4.5-years-old on average, who viewed three 90 s movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group as well as between each autistic child and all children in the TD group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group or the comparison group. Children with autism exhibited significantly weaker inter-subject correlations than TD children in all comparisons. These differences were independent of previously reported differences in gaze inter-subject correlations and were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. The results demonstrate the utility of measuring the idiosyncrasy of pupil regulation, which can be performed with passive viewing of movies even by young children with co-occurring intellectual disability. These findings reveal that a considerable number of children with autism have significantly less stable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

Pre-Stimulus Activity of Left and Right TPJ in Linguistic Predictive Processing: A MEG Study.

The left and right temporoparietal junctions (TPJs) are two brain areas involved in several brain networks, largely studied for their diverse roles, from attentional orientation to theory of mind and, recently, predictive processing. In predictive processing, one crucial concept is prior precision, that is, the reliability of the predictions of incoming stimuli. This has been linked with modulations of alpha power as measured with electrophysiological techniques, but TPJs have seldom been studied in this framework. The present article investigates, using magnetoencephalography, whether spontaneous oscillations in pre-stimulus alpha power in the left and right TPJs can modulate brain responses during a linguistic task that requires predictive processing in literal and non-literal sentences. Overall, results show that pre-stimulus alpha power in the rTPJ was associated with post-stimulus responses only in the left superior temporal gyrus, while lTPJ pre-stimulus alpha power was associated with post-stimulus activity in Broca's area, left middle temporal gyrus, and left superior temporal gyrus. We conclude that both the right and left TPJs have a role in linguistic prediction, involving a network of core language regions, with differences across brain areas and linguistic conditions that can be parsimoniously explained in the context of predictive processing.

Emotional dysregulation following prenatal stress is associated with altered prefrontal cortex responsiveness to an acute challenge in adolescence

Exposure to prenatal stress (PNS) has the potential to elicit multiple neurobiological alterations and increase the susceptibility to psychiatric disorders. Moreover, gestational stress may sensitize the brain toward an altered response to subsequent challenges. Here, we investigated the effects of PNS in rats and assessed whether these animals exhibit an altered brain responsiveness to an acute stress (AS) during adolescence. From gestational day 14 until delivery, Sprague Dawley dams were exposed to PNS or left undisturbed. During adolescence (PND38 to PND41), offspring were tested in the social interaction and splash test. At PND44 half of the animals were exposed to 5 min of forced swim stress. Males and Females exposed to PNS showed reduced sociability and increased anhedonic-like behavior. At the molecular level, exposure of adolescent rats to AS produced increased activation of the amygdala and ventral and dorsal hippocampus. Regarding the prefrontal cortex (PFC), we observed a pronounced activation in PNS males exposed to AS. Cell-type specific transcriptional analyses revealed a significant imbalance in the activation of PFC excitatory and inhibitory neurons in PNS males and females exposed to AS. Furthermore, stressed males exhibited disrupted HPA-axis function, while females showed impairments in the modulation of antioxidant genes. Our study shows that PNS induces emotional dysregulation and alters the responsiveness of the PFC to an acute stressor. Moreover, the disruption of excitatory and inhibitory balance during adolescence could influence the ability to respond to challenging events that may contribute to precipitate a full-blown pathologic condition.

An fMRI study of phrase structure and subject island violations.

In principle, functional neuroimaging provides uniquely informative data in addressing linguistic questions, because it can indicate distinct processes that are not apparent from behavioral data alone. This could involve adjudicating the source of unacceptability via the different patterns of elicited brain responses to different ungrammatical sentence types. However, it is difficult to interpret brain activations to syntactic violations. Such responses could reflect processes that have nothing intrinsically related to linguistic representations, such as domain-general executive function abilities. In order to facilitate the potential use of functional neuroimaging methods to identify the source of different syntactic violations, we conducted an fMRI experiment to identify the brain activation maps associated with two distinct syntactic violation types: phrase structure (created by inverting the order of two adjacent words within a sentence) and subject islands (created by extracting a wh-phrase out of an embedded subject). The comparison of these violations to control sentences surprisingly showed no indication of a generalized violation response, with almost completely divergent activation patterns. Phrase structure violations seemingly activated regions previously implicated in verbal working memory and structural complexity in sentence processing, whereas the subject islands appeared to activate regions previously implicated in conceptual-semantic processing, broadly defined. We review our findings in the context of previous research on syntactic and semantic violations using event-related potentials. Although our results suggest potentially distinct underlying mechanisms underlying phrase structure and subject island violations, our results are tentative and suggest important methodological considerations for future research in this area.

6468 Once-Weekly Semaglutide and Taste Perception in Women with Obesity

Abstract Disclosure: M. Jensterle Sever: None. J. Kovac: None. A. Vovk: None. S. Battelino: None. T. Battelino: None. A. Janez: None. Objective: Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that causes weight loss by reducing appetite and lowering the desire for energy-dense, salty, and spicy foods, thereby reducing energy intake. We hypothesized that semaglutide would improve the taste sensitivity and modulate the tongue transcriptomic profile associated with gustatory coding in women with obesity.Design: We conducted a 16-week, single-blinded, randomized, placebo-controlled clinical trial involving 30 women aged 33.7 ± 6.1 years with a body mass index of 36.4 ± 4.4 kg/m2, randomized in a 1:1 ratio to once-weekly semaglutide 1.0 mg or a placebo (ClinicalTrials.gov number, NCT04263415). Methods: Taste sensitivity was assessed by strips impregnated with different concentrations of four basic tastes. Biopsies of the tongue were performed for the gene expression analysis. The brain responses were evaluated by functional MRI with the sweet solution dripping onto the tongue before and after a standardized meal intake. Results: Semaglutide improved the taste sensitivity expressed as a mean (± SD) from 11.9 ± 1.9 points to 14.4 ± 1.0 points, with an estimated treatment difference (ETD) of 2.5 points [95% CI, 1.7 to 3.3]. Genes EYA, PRMT8, CRLF1, and CYP1B1, associated with taste signaling transduction pathways, neural plasticity, and renewal of taste buds in the tongue, exhibited differential RNA expression across all tests performed by a multi-tiered analytical pipeline. Semaglutide increased functional activity in the angular gyrus of the parietal cortex in response to tasting the sweet solution compared to the distilled water 30 minutes after a standardized meal intake (semaglutide vs. placebo, p&amp;lt;0.001). Angular gyrus functions as a cross-modal hub where converging multisensory information is combined and integrated to comprehend and give sense to events and stimuli, manipulate mental representations, and solve familiar problems. It expresses GLP-1 receptor and is a part of the default mode network associated with shifting attention between rewarding and neutral stimuli, which has reduced connectivity in people with obesity. Conclusion: The present study provided evidence that semaglutide improved taste sensitivity, altered gene expression in the tongue linked to taste perception, and altered functional brain activity in an integrative hub beyond hypothalamic and midbrain reward circuitry in response to the sweet taste stimulus. Future studies will clarify whether the efficacy of semaglutide in treating obesity is also a »matter of taste«. Presentation: 6/1/2024