Responses In Prefrontal Cortex Research Articles

Prefrontal Cortex Responses to Social Video Stimuli in Young Children with and without Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting individuals worldwide and characterized by deficits in social interaction along with the presence of restricted interest and repetitive behaviors. Despite decades of behavioral research, little is known about the brain mechanisms that influence social behaviors among children with ASD. This, in part, is due to limitations of traditional imaging techniques specifically targeting pediatric populations. As a portable and scalable optical brain monitoring technology, functional near infrared spectroscopy (fNIRS) provides a measure of cerebral hemodynamics related to sensory, motor, or cognitive function. Here, we utilized fNIRS to investigate the prefrontal cortex (PFC) activity of young children with ASD and with typical development while they watched social and nonsocial video clips. The PFC activity of ASD children was significantly higher for social stimuli at medial PFC, which is implicated in social cognition/processing. Moreover, this activity was also consistently correlated with clinical measures, and higher activation of the same brain area only during social video viewing was associated with more ASD symptoms. This is the first study to implement a neuroergonomics approach to investigate cognitive load in response to realistic, complex, and dynamic audiovisual social stimuli for young children with and without autism. Our results further confirm that new generation of portable fNIRS neuroimaging can be used for ecologically valid measurements of the brain function of toddlers and preschool children with ASD.

Sporoderm-removed Ganoderma lucidum spores ameliorated early depression-like behavior in a rat model of sporadic Alzheimer's disease.

Introduction: Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer's disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer's disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear. Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test. Results: Behavioral tests demonstrated that RGLS (360 and 720mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC. Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

Dorso-medial prefrontal cortex responses to social smiles predict sociability in early human development

Abstract Dorso-medial prefrontal cortex (dmPFC) plays a vital role in social cognition and behavior among humans. Enhanced responses in dmPFC when viewing social scenes predict increased levels of sociability in adults. The current longitudinal study examined the association between dmPFC response and sociability in early development. Brain responses were measured in response to social smiles and frowns using functional near-infrared spectroscopy (fNIRS) at 11 months. Individual differences in sociability were measured using the Early Childhood Behavior Questionnaire (ECBQ) at 18 months. Our longitudinal results show that greater engagement of the dmPFC when processing social smiles, but not frowns, at 11 months predicts higher levels of sociability at 18 months. This demonstrates that early variability in dmPFC response during positive social interactions is linked to individual differences in overtly displayed social behavior. This supports the view that dmPFC plays an important role in social cognition and behavior from early in human ontogeny.

Aerobic fitness as a moderator of acute aerobic exercise effects on executive function.

This study aimed to investigate the moderating role of aerobic fitness on the effect of acute exercise on improving executive function from both behavioral and cerebral aspects. Thirty-four young individuals with motor skills were divided into high- and low-fitness groups based on their maximal oxygen uptake. Both groups completed 30min of moderate-intensity aerobic exercise on a power bike. Executive function tests (Flanker, N-back, More-odd-shifting) were performed before and after exercise and functional near-infrared spectroscopy was used to monitor prefrontal cerebral blood flow changes during the tasks. The results indicated significant differences between the two groups regarding executive function. Participants with lower aerobic fitness performed better than their higher fitness counterparts in inhibitory control and working memory, but not in cognitive flexibility. This finding suggests that the aerobic fitness may moderate the extent of cognitive benefits gained from acute aerobic exercise. Furthermore, the neuroimaging data indicated negative activation in the frontopolar area and dorsolateral prefrontal cortex in response to three complex tasks. These findings underscore the importance of considering individual aerobic fitness when assessing the cognitive benefits of exercise and could have significant implications for tailoring fitness programs to enhance cognitive performance.

The ventromedial prefrontal cortex in response to threat omission is associated with subsequent explicit safety memory

In order to memorize and discriminate threatening and safe stimuli, the processing of the actual absence of threat seems crucial. Here, we measured brain activity with fMRI in response to both threat conditioned stimuli and their outcomes by combining threat learning with a subsequent memory paradigm. Participants (N = 38) repeatedly saw a variety of faces, half of which (CS+) were associated with an aversive unconditioned stimulus (US) and half of which were not (CS-). When an association was later remembered, the hippocampus had been more active (than when forgotten). However, the ventromedial prefrontal cortex predicted subsequent memory specifically during safe associations (CS- and US omission responses) and the left dorsolateral prefrontal cortex during outcomes in general (US and US omissions). In exploratory analyses of the theoretically important US omission, we found extended involvement of the medial prefrontal cortex and an enhanced functional connectivity to visual and somatosensory cortices, suggesting a possible function in sustaining sensory information for an integration with semantic memory. Activity in visual and somatosensory cortices together with the inferior frontal gyrus also predicted memory performance one week after learning. The findings imply the importance of a close interplay between prefrontal and sensory areas during the processing of safe outcomes—or ‘nothing’—to establish declarative safety memory.

The effects of 17β-trenbolone and bisphenol A on sexual behavior and social dominance via the hypothalamic-pituitary-gonadal axis in male mice

17β-Trenbolone (17-TB) is well documented as an environmental endocrine disruptor in aquatic biological studies, but its effects on mammals remain poorly understood. Furthermore, 17-TB acts as a hormone with properties similar to testosterone, and the consequences of juvenile exposure on adult social behavior remain uncertain. Bisphenol A (BPA) acts as an estrogen-like hormone, compared to 17-TB. Three-week-old male Balb/c mice were exposed orally to 17-TB (100 µg/(kg·day)) and BPA (4 mg/(kg·day)) for 28 days. Assessments of social interactions and a three-chamber test showed that 17-TB increased virility in male mice, intensified both male and female sexual behavior, and attracted and accepted female mice. It also increased social dominance through tube tests in male mice and markedly activated the c-Fos+ immune response in the medial prefrontal cortex (mPFC) and basal amygdala (BLA). ELISA data showed that 17-TB and BPA exposure significantly affected serum gonadotropin-releasing hormone (GnRH), growth hormone (GH), estradiol (E2), and luteinizing hormone (LH) levels, as well as testicular lesions and androgen receptor (ARβ) and estrogen receptor (ERα) synthesis. Testicular transcriptomic analysis further confirmed that could disrupt steroid synthesis and linoleic acid-related biometabolic processes. These findings suggest the influence of 17-TB and BPA exposure on sexual behavior and fertility in male mice, possibly through modulation of the hypothalamic-pituitary-gonadal axis. This study provides insights relevant to human reproductive health and neuro-social behavioral research, and the potential risk of environmental disturbances should not be overlooked.

Corticostriatal activity related to performance during continuous de novo motor learning

Corticostriatal regions play a pivotal role in visuomotor learning. However, less research has been done on how fMRI activity in their subregions is related to task performance, which is provided as visual feedback during motor learning. To address this, we conducted an fMRI experiment in which participants acquired a complex de novo motor skill using continuous or binary visual feedback related to performance. We found a highly selective response related to performance in the entire striatum in both conditions and a relatively higher response in the caudate nucleus for the binary feedback condition. However, the ventromedial prefrontal cortex (vmPFC) response was significant only for the continuous feedback condition. Furthermore, we also found functional distinction of the striatal subregions in random versus goal-directed motor control. These findings underscore the substantial effects of the visual feedback indicating performance on distinct corticostriatal responses, thereby elucidating its significance in reinforcement-based motor learning.

A developmental increase of inhibition promotes the emergence of hippocampal ripples

Sharp wave-ripples (SPW-Rs) are a hippocampal network phenomenon critical for memory consolidation and planning. SPW-Rs have been extensively studied in the adult brain, yet their developmental trajectory is poorly understood. While SPWs have been recorded in rodents shortly after birth, the time point and mechanisms of ripple emergence are still unclear. Here, we combine in vivo electrophysiology with optogenetics and chemogenetics in 4 to 12-day-old mice to address this knowledge gap. We show that ripples are robustly detected and induced by light stimulation of channelrhodopsin-2-transfected CA1 pyramidal neurons only from postnatal day 10 onwards. Leveraging a spiking neural network model, we mechanistically link the maturation of inhibition and ripple emergence. We corroborate these findings by reducing ripple rate upon chemogenetic silencing of CA1 interneurons. Finally, we show that early SPW-Rs elicit a more robust prefrontal cortex response than SPWs lacking ripples. Thus, development of inhibition promotes ripples emergence.

Mapping expectancy-based appetitive placebo effects onto the brain in women

Suggestions about hunger can generate placebo effects on hunger experiences. But, the underlying neurocognitive mechanisms are unknown. Here, we show in 255 women that hunger expectancies, induced by suggestion-based placebo interventions, determine hunger sensations and economic food choices. Functional magnetic resonance imaging in a subgroup (n = 57/255) provides evidence that the strength of expecting the placebo to decrease hunger moderates medial prefrontal cortex activation at the time of food choice and attenuates ventromedial prefrontal cortex (vmPFC) responses to food value. Dorsolateral prefrontal cortex activation linked to interference resolution formally mediates the suggestion-based placebo effects on hunger. A drift-diffusion model characterizes this effect by showing that the hunger suggestions bias participants’ food choices and how much they weigh tastiness against the healthiness of food, which further moderates vmPFC–dlPFC psychophysiological interactions when participants expect decreased hunger. Thus, suggestion-induced beliefs about hunger shape hunger addressing economic choices through cognitive regulation of value computation within the prefrontal cortex.

Modulation of prefrontal couplings by prior belief-related responses in ventromedial prefrontal cortex.

Humans and other animals can maintain constant payoffs in an uncertain environment by steadily re-evaluating and flexibly adjusting current strategy, which largely depends on the interactions between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). While the ventromedial PFC (vmPFC) represents the level of uncertainty (i.e., prior belief about external states), it remains unclear how the brain recruits the PFC-MD network to re-evaluate decision strategy based on the uncertainty. Here, we leverage non-linear dynamic causal modeling on fMRI data to test how prior belief-dependent activity in vmPFC gates the information flow in the PFC-MD network when individuals switch their decision strategy. We show that the prior belief-related responses in vmPFC had a modulatory influence on the connections from dorsolateral PFC (dlPFC) to both, lateral orbitofrontal (lOFC) and MD. Bayesian parameter averaging revealed that only the connection from the dlPFC to lOFC surpassed the significant threshold, which indicates that the weaker the prior belief, the less was the inhibitory influence of the vmPFC on the strength of effective connections from dlPFC to lOFC. These findings suggest that the vmPFC acts as a gatekeeper for the recruitment of processing resources to re-evaluate the decision strategy in situations of high uncertainty.

Early top-down control of internal selection induced by retrospective cues in visual working memory: advantage of peripheral over central cues.

Attention can be deployed among external sensory stimuli or internal working memory (WM) representations, and recent primate studies have revealed that these external and internal selections share a common neural basis in the prefrontal cortex (PFC). However, it remains to be elucidated how PFC implements these selections, especially in humans. The present study aimed to further investigate whether PFC responded differentially to the peripheral and central retrospective cues (retro-cues) that induced attention selection among WM representations. To achieve this, we combined magnetoencephalography (MEG, Experiment 1) and transcranial magnetic stimulation (TMS, Experiment 2) with an orientation-recall paradigm. Experiment 1 found that a peripheral retro-cue with 100% reliability had a greater benefit on WM performance than a central retro-cue, while this advantage of peripheral over central cues vanished when the cue reliability dropped to 50% (non-informative). MEG source analysis indicated that the 100% peripheral retro-cue elicited earlier (~125 ms) PFC responses than the central retro-cue (~275 ms). Meanwhile, Granger causality analysis showed that PFC had earlier (0-200 ms) top-down signals projecting to the superior parietal lobule (SPL) and the lateral occipital cortex (LOC) after the onset of peripheral retro-cues, while these top-down signals appeared later (300-500 ms) after the onset of central retro-cues. Importantly, PFC activity within this period of 300-500 ms correlated with the peripheral advantage in behavior. Moreover, Experiment 2 applied TMS at different time points to test the causal influence of brain activity on behavior and found that stimulating PFC at 100 ms abolished the behavioral benefit of the peripheral retro-cue, as well as its advantage over the central retro-cue. Taken together, our results suggested that the advantage of peripheral over central retro-cues in the mnemonic domain is realized through faster top-down control from PFC, which challenged traditional opinions that the top-down control of attention on WM required at least 300 ms to appear. The present study highlighted that in addition to the causal role of PFC in attention selection of WM representations, timing was critical as well and faster was better.

GABAA receptor availability relates to emotion-induced BOLD responses in the medial prefrontal cortex: simultaneous fMRI/PET with [11C]flumazenil.

The fMRI BOLD response to emotional stimuli highlighting the role of the medial prefrontal cortex (MPFC) has been thoroughly investigated. Recently, the relationship between emotion processing and GABA levels has been studied using MPFC proton magnetic resonance spectroscopy (1H-MRS). However, the role of GABAA receptors in the MPFC during emotion processing remains unexplored. Using [11C]flumazenil PET, we investigated the relationship between the binding potential of GABAA receptors and emotion processing as measured using simultaneous fMRI BOLD. We hypothesized a correlation between the percent signal change in the BOLD signal and the binding potential of GABAA receptors in the MPFC. In a combined simultaneous fMRI and [11C]flumazenil-PET study, we analyzed the data from 15 healthy subjects using visual emotional stimuli. Our task comprised two types of emotional processing: passive viewing and appraisal. Following the administration of a bolus plus infusion protocol, PET and fMRI data were simultaneously acquired in a hybrid 3 T MR-BrainPET. We found a differential correlation of BOLD percent signal change with [11C]flumazenil binding potential in the MPFC. Specifically, [11C]flumazenil binding potential in the ventromedial prefrontal cortex (vMPFC) correlated with passive viewing of emotionally valenced pictures. In contrast, the [11C]flumazenil binding potential and the BOLD signal induced by picture appraisal did show a correlation in the paracingulate gyrus. Our data deliver first evidence for a relationship between MPFC GABAA receptors and emotion processing in the same region. Moreover, we observed that GABAA receptors appear to play different roles in emotion processing in the vMPFC (passive viewing) and paracingulate gyrus (appraisal).

Cannabis use during pregnancy and hemodynamic responses to infant cues in pregnancy: an exploratory study.

Cannabis is one of the most commonly used substances during pregnancy and has the potential to negatively impact parent-infant relationships. The prefrontal cortex (PFC) response to infant cues during pregnancy has been associated with subsequent positive parenting behaviors. However, PFC activation is altered in individuals who use cannabis. As the potency of cannabis has changed over the years, little is known about the specific role of cannabis use on gestational parent brain responses to infant cues. Using functional Near-Infrared Spectroscopy (fNIRS) in the second trimester of pregnancy, we measured hemodynamic responses to an infant cry task and an infant faces task among individuals who were using cannabis (N = 14) and compared them with those who were not using cannabis (N = 45). For the infant cry task, pregnant individuals listened to cry sounds and matched white noise. For the infant faces task, they viewed happy, sad, and neutral faces. There was no significant difference between the two groups after adjusting for multiple comparisons. Without adjusting for multiple comparisons, we found preliminary evidence for the differences in the dorsomedial PFC associated with heightened response to infant cry among individuals who use cannabis. The groups were also different in the dorsolateral PFC associated with decreased response to infant sad faces among individuals who use cannabis. Our preliminary data suggests that cannabis use during pregnancy was associated with brain activation in the regions involved in the emotional regulation and information processes. However, the results did not survive after adjustment for multiple comparisons, thus future research with larger sample sizes is needed to confirm potential differences in brain function among cannabis-using pregnant individuals.

Binge Eating (BE) and Obesity: Brain Activity and Psychological Measures before and after Roux-En-Y Gastric Bypass (RYGB).

Brain activity in response to food cues following Roux-En-Y Gastric Bypass (RYGB) in binge eating (BE) or non-binge eating (NB) individuals is understudied. Here, 15 RYGB (8 BE; 7 NB) and 13 no treatment (NT) (7 BE; 6 NB) women with obesity underwent fMRI imaging while viewing high and low energy density food (HEF and LEF, respectively) and non-food (NF) visual cues. A region of interest (ROI) analysis compared BE participants to NB participants in those undergoing RYGB surgery pre-surgery and 4 months post. Results were corrected for multiple comparisons using liberal (p < 0.006 uncorrected) and stringent (p < 0.05 FDR corrected) thresholds. Four months following RYGB (vs. no treatment (NT) control), both BE and NB participants showed greater reductions in blood oxygen level-dependent (BOLD) signals (a proxy of local brain activity) in the dorsomedial prefrontal cortex in response to HEF (vs. LEF) cues (p < 0.006). BE (vs. NB) participants showed greater increases in the precuneus (p < 0.006) and thalamic regions (p < 0.05 corrected) to food (vs. NF). For RYGB (vs. NT) participants, BE participants, but not NB participants, showed lower BOLD signal in the middle occipital gyrus (p < 0.006), whilst NB participants, but not BE participants, showed lower signal in inferior frontal gyrus (p < 0.006) in response to HEF (vs. LEF). Results suggest distinct neural mechanisms of RGYB in BE and may help lead to improved clinical treatments.

Sialic Acid Enhanced the Antistress Capability under Challenging Situations by Increasing Synaptic Transmission

BackgroundIn early life, sialic acid (SA) plays a crucial role in neurodevelopment and neuronal function. However, it remains unclear whether and how SA supplementation in early life promotes behavioral response to stress in adolescence. ObjectivesThis study aimed to examine the effects and mechanisms of SA on the antistress capability under challenging situations. MethodsIn this study, C57BL/6 mice were daily supplemented with 1 μL SA solution/g body weight at the dose of 10 mg/kg/d from postnatal day (PND) 5–45. The antistress behaviors, including open field, elevated plus maze, forced swimming test, and tail suspension test, were performed at PND 46, PND 48, PND 50, and PND 52 to detect the antistress ability of SA, respectively. ResultsOur results showed that SA-treated mice were more active in facing challenging situations. The fiber photometry experiment showed that SA promoted the excitatory neuronal response in the medial prefrontal cortex (mPFC), which was extensively interconnected to stress. Besides, electrophysiological results revealed SA enhanced synaptic transmission rather than neuronal excitability of mPFC excitatory neurons. It was also supported by the increasing spine density of mPFC excitatory neurons. At the molecular amount, the SA elevated the transmitter release-related proteins of mPFC, including Synapsin 1 and vesicular glutamate transporter 1 (VGlut 1). Furthermore, SA supplementation enhanced synaptic transmission mainly by altering the kinetics of synaptic transmission. ConclusionsThe SA supplementation enhanced the response capability to stress under challenging situations, and the enhanced synaptic transmission of mPFC excitatory neurons may be the neurological basis of active response under challenging situations. In general, our findings suggested that SA supplementation in early life can promote stress resistance in adolescence.

Relation of Overweight/Obesity to Reward Region Response to Food Reward and the Moderating Effects of Parental History of Eating Pathology in Adolescent Females.

To test whether overweight/obesity is associated with an elevated reward region response to milkshake cues and a low reward region response to milkshake receipt. To test whether the risk for eating pathology moderates the effects of weight status on the neural response to milkshake cues and milkshake receipt. The current study used functional magnetic resonance imaging (fMRI) to examine the neuronal responses of female adolescents (n = 80; M age = 14.6 ± 0.9; M BMI = 21.9 ± 3.6; 41% with a biological parental history of eating pathology) during a food receipt paradigm. Females with overweight/obesity showed a greater ventromedial prefrontal cortex (vmPFC), and ventral anterior cingulate (ACC) response to milkshake cues and a greater ventral striatum, subgenual ACC, and dorsomedial prefrontal cortex response to milkshake receipt than those with a healthy weight. Females with overweight/obesity plus a parental history of eating pathology showed a greater vmPFC/medial orbitofrontal cortex response to milkshake cues than those without a parental history of eating pathology and those with a healthy weight. Females with overweight/obesity and without a parental history of eating pathology showed a greater thalamus and striatum response to milkshake receipt. Overweight/obesity is associated with an elevated reward region response to palatable food cues and food receipt. A risk for eating pathology enhances the reward region response to food cues in those with excess weight.

Sex differences in emotion- and reward-related neural responses predicting increases in substance use in adolescence

Adolescent substance use is a significant public health problem and there is a need for effective substance use preventions. To develop effective preventions, it is important to identify neurobiological risk factors that predict increases in substance use in adolescence and to understand potential sex differences in risk mechanisms. The present study used functional magnetic resonance imaging and hierarchical linear modeling to examine negative emotion- and reward-related neural responses in early adolescence predicting growth in substance use to middle adolescence in 81 youth, by sex. Adolescent neural responses to negative emotional stimuli and monetary reward receipt were assessed at age 12–14. Adolescents reported on substance use at age 12–14 and at 6 month, and 1, 2, and 3 year follow-ups. Adolescent neural responses did not predict initiation of substance use (yes/no), but, among users, neural responses predicted growth in substance use frequency. For girls, heightened right amygdala responses to negative emotional stimuli in early adolescence predicted growth in substance use frequency through middle adolescence. For boys, blunted left nucleus accumbens and bilateral ventromedial prefrontal cortex responses to monetary reward predicted growth in substance use frequency. Findings suggest different emotion and reward-related predictors of the development of substance use for adolescent girls versus boys.

The regulations on cortical activation and functional connectivity of the dorsolateral prefrontal cortex-primary somatosensory cortex elicited by acupuncture with reinforcing-reducing manipulation.

Traditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations. Functional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted. In comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC). These findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation's effect. ClinicalTrials.gov, identifier, ChiCTR2100051893.

The fNIRS evaluation of frontal and temporal lobe cortical activation in Chinese first-episode medication-naïve and recurrent depression during a verbal fluency task.

Functional near-infrared spectroscopy (fNIRS) identifies neurophysiological differences between psychiatric disorders by assessing cortical hemodynamic function. Few trials have studied differences in brain functional activity between first-episode medication-naïve depression patients (FMD) and recurrent major depression (RMD). We aimed to determine the differences between FMD and RMD in oxygenated hemoglobin concentration ([oxy-Hb]), and to investigate the correlation between frontotemporal cortex activation and clinical symptoms. We recruited 40 patients with FMD, 53 with RMD, and 38 healthy controls (HCs) from May 2021 to April 2022. Symptom severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). A 52-channel fNIRS measured changes in [oxy-Hb] during VFT performance. Both patient groups performed poorly during the VFT task compared with HC (FDR p < 0.05), but there was no significant difference between the two patient groups. Analysis of variance showed that mean [oxy-Hb] activation was lower in both the frontal and temporal lobes in the MDD group compared with HCs (FDR p < 0.05). Additionally, patients with RMD had a significantly lower hemodynamic response in the right dorsolateral prefrontal cortex (DLPFC) and dorsal frontal pole cortex (DFPC) than patients with FMD (FDR p < 0.05). No significant correlation was found between changes in mean [oxy-Hb] and either medical history or clinical symptoms (FDR p < 0.05). The presence of different neurofunctional activity in some of the same brain regions in FMD and RMD patients implied a link between the level of complexity activation in frontal regions and the stage of MDD. Cognitive impairment may already be present at the beginning of an MDD episode. www.chictr.org.cn, identifier ChiCTR2100043432.

Oxytocin promotes prefrontal population activity via the PVN-PFC pathway to regulate pain

Neurons in the prefrontal cortex (PFC) can provide top-down regulation of sensory-affective experiences such as pain. Bottom-up modulation of sensory coding in the PFC, however, remains poorly understood. Here, we examined how oxytocin (OT) signaling from the hypothalamus regulates nociceptive coding in the PFC. Invivo time-lapse endoscopic calcium imaging in freely behaving rats showed that OT selectively enhanced population activity in the prelimbic PFC in response to nociceptive inputs. This population response resulted from the reduction of evoked GABAergic inhibition and manifested as elevated functional connectivity involving pain-responsive neurons. Direct inputs from OT-releasing neurons in the paraventricular nucleus (PVN) of the hypothalamus are crucial to maintaining this prefrontal nociceptive response. Activation of the prelimbic PFC by OT or direct optogenetic stimulation of oxytocinergic PVN projections reduced acute and chronic pain. These results suggest that oxytocinergic signaling in the PVN-PFC circuit constitutes a key mechanism to regulate cortical sensory processing.