Search Results (1,213)

Understanding the developmental trajectories for recognizing facial expressions is important for a better understanding of development of psychiatric disorders. In this study, we examined the recognition of emotional and neutral facial expressions in 93 typically developing adolescents and adults. The Emotion Intensity Rating task required participants to rate the intensity of emotional expression in happy, neutral, and sad faces on a scale from 1 to 9. A score of ‘5’ had to be assigned to neutral faces, scores between ‘6’ (slightly happy) and ‘9’ (very happy) to happy faces, and scores between ‘4’ (slightly sad) and ‘1’ (very sad) to sad faces. Mixed effects models were used to examine the effects of age and emotion on recognition accuracy, reaction time (RT), and emotional intensity. Participants tended to misjudge neutral faces as sad. Adolescents were less accurate than adults for neutral face recognition. There were significant quadratic effects of age on accuracy (negative quadratic effect) and RT (positive quadratic effect). The most accurate and fastest performance was observed in 25- to 35-year-old subjects. This trajectory may be associated with prefrontal cortex maturation, which provides top–down control over the heightened amygdala response to ambiguity that may be misinterpreted as emotional content. Full article

Background: Repetitive transcranial magnetic stimulation (rTMS) has shown therapeutic effects in neurological patients by inducing neural plasticity. In this pilot study, we analyzed the modifying effects of high-frequency (HF-)rTMS applied to the dorsolateral prefrontal cortex (DLPFC) of patients with mild cognitive impairment (MCI) using an advanced approach of functional connectome analysis based on network control theory (NCT). Methods: Using local-to-global functional parcellation, average and modal controllability (AC/MC) were estimated for DLPFC nodes of prefrontal-lateral control networks (R/LH_Cont_PFCl_3/4) from a resting-state fMRI series acquired at three time points (T0 = baseline, T1 = T0 + 4 weeks, T2 = T1 + 20 weeks) in MCI patients receiving regular daily sessions of 10 Hz HF-rTMS (n = 10, 68.00 ± 8.16 y, 4 males) or sham (n = 10, 63.80 ± 9.95 y, 5 males) stimulation, between T0 and T1. Longitudinal (group) effects on AC/MC were assessed with non-parametric statistics. Spearman correlations (ρ) of AC/MC vs. neuropsychological (RBANS) score %change (at T1, T2 vs. T0) were calculated. Results: AC median was reduced in MCI-rTMS, compared to the control group, for RH_Cont_PFCl_3/4 at T1 and T2 (vs. T0). In MCI-rTMS patients, for RH_Cont_PFCl_3, AC % change at T1 (vs. T0) was negatively correlated with semantic fluency (ρ = −0.7939, p = 0.045) and MC % change at T2 (vs. T0) was positively correlated with story memory (ρ = 0.7416, p = 0.045). Conclusions: HF-rTMS stimulation of DLFC nodes significantly affects the controllability of the functional connectome in MCI patients. Emerging correlations between AC/MC controllability and cognitive performance changes, immediately (T1 vs. T0) and six months (T2 vs. T0) after treatment, suggest NCT could help explain the HF-rTMS impact on prefrontal-lateral control network, monitoring induced neural plasticity effects in MCI patients. Full article

Background: Repetitive transcranial magnetic stimulation (rTMS) has recently demonstrated significant potential in treating obsessive-compulsive disorder (OCD). However, its effectiveness depends on various parameters, including stimulation parameters, OCD subtypes and electrical fields (EFs) induced by rTMS in targeted brain regions that are less studied. Methods: Using the PRISMA approach, we examined 27 randomized control trials (RCTs) conducted from 1985 to 2024 using rTMS for the treatment of OCD and conducted several meta-analyses to investigate the role of rTMS parameters, including the EFs induced by each rTMS protocol, and OCD subtypes on treatment efficacy. Results: A significant, medium effect size was found, favoring active rTMS (g_PPC = 0.59, p < 0.0001), which was larger for the obsession subscale. Both supplementary motor area (SMA) rTMS (g_PPC = 0.82, p = 0.048) and bilateral dorsolateral prefrontal cortex (DLPFC) rTMS (gPPC = 1.14, p = 0.04) demonstrated large effect sizes, while the right DLPFC showed a significant moderate effect size for reducing OCD severity (g_PPC = 0.63, p = 0.012). These protocols induced the largest EFs in dorsal cognitive, ventral cognitive and sensorimotor circuits. rTMS protocols targeting DLPFC produced the strongest electrical fields in cognitive circuits, while pre-supplementary motor area (pre-SMA) and orbitofrontal cortex (OFC) rTMS protocols induced larger fields in regions linked to emotional and affective processing in addition to cognitive circuits. The pre-SMA rTMS modulated more circuits involved in OCD pathophysiology—sensorimotor, cognitive, affective, and frontolimbic—with larger electrical fields than the other protocols. Conclusions: While rTMS shows moderate overall clinical efficacy, protocols targeting ventral and dorsal cognitive and sensorimotor circuits demonstrate the highest potential. The pre-SMA rTMS appears to induce electrical fields in more circuits relevant to OCD pathophysiology. Full article

Mu opioid receptors (MORs) represent a vital mechanism related to the modulation of stress-induced analgesia (SIA). Previous studies have reported on the gamma-aminobutyric acid (GABA)ergic “disinhibition” mechanisms of MORs on the descending pain modulatory pathway of SIA induced in the midbrain. However, the role of the MORs expressed in the medial prefrontal cortex (mPFC), one of the main cortical areas participating in pain modulation, in SIA remains completely unknown. In this study, we investigated the contributions of MORs expressed on glutamatergic (MORGlut) and GABAergic (MORGABA) neurons of the medial prefrontal cortex (mPFC), as well as the functional role and activity of neurons projecting from the mPFC to the periaqueductal gray (PAG) region, in male mice. We achieved this through a combination of hot-plate tests, c-fos staining, and 1 h acute restraint stress exposure tests. The results showed that our acute restraint stress protocol produced mPFC MOR-dependent SIA effects. In particular, MORGABA was found to play a major role in modulating the effects of SIA, whereas MORGlut seemed to be unconnected to the process. We also found that mPFC–PAG projections were efficiently activated and played key roles in the effects of SIA, and their activation was mediated by MORGABA to a large extent. These results indicated that the activation of mPFC MORGABA due to restraint stress was able to activate mPFC–PAG projections in a potential “disinhibition” pathway that produced analgesic effects. These findings provide a potential theoretical basis for pain treatment or drug screening targeting the mPFC. Full article

Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation. Full article

Depression is a prevalent and debilitating mental disorder that affects millions worldwide. Current treatments, such as antidepressants targeting the serotonergic system, have limitations, including delayed onset of action and high rates of treatment resistance, necessitating novel therapeutic strategies. Ginsenoside Rc (G-Rc) has shown potential anti-inflammatory and neuroprotective effects, but its antidepressant properties remain unexplored. This study investigated the antidepressant effects of G-Rc in an L-alpha-aminoadipic acid (L-AAA)-induced mouse model of depression, which mimics the astrocytic pathology and neuroinflammation observed in major depressive disorder. Mice were administered G-Rc, vehicle, or imipramine orally after L-AAA injection into the prefrontal cortex. G-Rc significantly reduced the immobility time in forced swimming and tail suspension tests compared to vehicle treatment, with more pronounced effects than imipramine. It also attenuated the expression of pro-inflammatory cytokines (TNF-α, IL-6, TGF-β, lipocalin-2) and alleviated astrocytic degeneration, as indicated by increased GFAP and decreased IBA-1 levels. Additionally, G-Rc modulated apoptosis-related proteins, decreasing caspase-3 and increasing Bcl-2 levels compared to the L-AAA-treated group. These findings suggest that G-Rc exerts antidepressant effects by regulating neuroinflammation, astrocyte–microglia crosstalk, and apoptotic pathways in the prefrontal cortex, highlighting its potential as a novel therapeutic agent for depression. Full article

Extensive research has shed light on the cellular and functional underpinnings of higher cognition as influenced by the prefrontal cortex. Neurotransmitters act as key regulatory molecules within the PFC to assist with synchronizing cognitive state and arousal levels. The monoamine family of neurotransmitters, including dopamine, serotonin, and norepinephrine, play multifaceted roles in the cognitive processes behind learning and memory. The present review explores the organization and signaling patterns of monoamines within the PFC, as well as elucidates the numerous roles played by monoamines in learning and higher cognitive function. Full article

Despite the recommendation to treat depression using transcranial direct current stimulation (tDCS), novel findings raise doubts over the tDCS’s efficacy in managing depressive episodes. Neurophysiologic approaches to understanding the specificities of brain responses to tDCS in patients with depression remain to be explored. Objective: Our aim was to compare immediate hemodynamic responses to tDCS on the left dorsolateral prefrontal cortex (DLPFC; F3-Fp2 montage) in patients with depressive disorder and in controls (no additional stimuli). Methods: Sixteen participants were allocated to the depression group and sixteen to the control group. Both groups received 2 mA tDCS for 20 min, using the F3-Fp2 montage. The hemodynamic effect over the DLPFC was assessed using functional near-infrared intracranial spectroscopy (fNIRS) positioned on the left supraorbital region (Fp1). Mean, minimal, and maximal values of baseline and post-stimulation rates of oxygen saturation (SatO₂) were recorded. The oxygenated hemoglobin rates (HbO) were extracted. Results: Between-group differences were detected for minimal baseline rates of SatO₂ and HbO levels. The depression group showed lower results compared to the control group at baseline. After the protocol, only the depression group showed increased minimal rates of SatO₂ and HbO. The post-tDCS minimal rates were equal for both groups. Conclusions: The findings showed immediate anodal tDCS effects over DLPFC hemodynamics. The effects were exclusive to the lowest baseline rate group and did not affect the normal oxygen rate group. The minimal increase in SatO₂ and HbO rates after the protocol in the depression group suggests that those with reduced cerebral perfusion may be more affected by tDCS. Full article

Frontotemporal dementia (FTD) causes progressive neurodegeneration in the frontal and temporal lobes, leading to behavioral, cognitive, and language impairments. With no effective treatment available, exploring new therapeutic approaches is critical. Recent research highlights the transcription factor Nuclear Factor erythroid-derived 2-like 2 (NRF2) as vital in limiting neurodegeneration, with its activation shown to mitigate FTD-related processes like inflammation. Dimethyl fumarate (DMF), an NRF2 activator, has demonstrated neuroprotective effects in a TAU-dependent FTD mouse model, reducing neurodegeneration and inflammation. This suggests DMF repositioning potential for FTD treatment. Until now, no trial had been conducted to analyze the effect of DMF on TDP-43-dependent FTD. In this study, we aimed to determine the potential therapeutic efficacy of DMF in a TDP-43-related FTD mouse model that exhibits early cognitive impairment. Mice received oral DMF treatment every other day from presymptomatic to symptomatic stages. By post-natal day (PND) 60, an improvement in cognitive function is already evident, becoming even more pronounced by PND90. This cognitive enhancement correlates with the neuroprotection observed in the dentate gyrus and a reduction in astrogliosis in the stratum lacunosum-moleculare zone. At the prefrontal cortex (PFC) level, a neuroprotective effect of DMF is also observed, accompanied by a reduction in astrogliosis. Collectively, our results suggest a potential therapeutic application of DMF for patients with TDP-43-dependent FTD. Full article

Electroconvulsive therapy (ECT) is an effective treatment for severe and drug-resistant depression, yet its mode of action remains poorly understood. This study aimed to evaluate the effects of ECT on neurometabolism using ex vivo ¹H-[¹³C]-NMR spectroscopy in conjunction with intravenous infusion of [1,6-¹³C₂]glucose in a chronic variable mild stress (CVMS) model of depression. Both CVMS and control mice were subjected to seven sessions of electroconvulsive shock under mild isoflurane anesthesia. The CVMS mice exhibited a reduction in sucrose preference (CVMS 67.1 ± 14.9%, n = 5; CON 86.5 ± 0.6%, n = 5; p = 0.007), and an increase in immobility duration (175.9 ± 22.6 vs. 92.0 ± 23.0 s, p < 0.001) in the forced-swim test. The cerebral metabolic rates of glucose oxidation in glutamatergic (CMR_Glc(Glu)) (CVMS 0.134 ± 0.015 µmol/g/min, n = 5; CON 0.201 ± 0.045 µmol/g/min, n = 5; p_adj = 0.04) and GABAergic neurons (CMR_Glc(GABA)) (0.030 ± 0.002 vs. 0.046 ± 0.011 µmol/g/min, p_adj = 0.04) were reduced in the prefrontal cortex (PFC) of CVMS mice. ECT treatment in CVMS mice normalized sucrose preference [F(1,27) = 0.0024, p = 0.961] and immobility duration [F(1,28) = 0.434, p = 0.515], but not the time spent in the center zone (CVMS + ECT 10.4 ± 5.5 s, CON + sham 22.3 ± 11.4 s, p_adj = 0.0006) in the open field test. The ECT-treated CVMS mice exhibited reduced (p_adj = 0.021) CMR_Glc(Glu) in PFC (0.169 ± 0.026 µmol/g/min, n = 8) when compared with CVMS mice, which underwent the sham procedure (0.226 ± 0.030 µmol/g/min, n = 8). These observations are consistent with ECT’s anticonvulsant hypothesis for its anti-depressive action. Full article

Alzheimer’s disease (AD), the leading cause of dementia, is a multifactorial disease influenced by aging, genetics, and environmental factors. miRNAs are crucial regulators of gene expression and play significant roles in AD onset and progression. This exploratory study analyzed the expression levels of 28 genes and 5 miRNAs (miR-124-3p, miR-125b-5p, miR-21-5p, miR-146a-5p, and miR-155-5p) related to AD pathology and neuroimmune responses using RT-qPCR. Analyses were conducted in the prefrontal cortex (PFC) and the hippocampus (HPC) of the 5xFAD mouse AD model at 6 and 9 months old. Data highlighted upregulated genes encoding for glial fibrillary acidic protein (Gfap), triggering receptor expressed on myeloid cells (Trem2) and cystatin F (Cst7), in the 5xFAD mice at both regions and ages highlighting their roles as critical disease players and potential biomarkers. Overexpression of genes encoding for CCAAT enhancer-binding protein alpha (Cebpa) and myelin proteolipid protein (Plp) in the PFC, as well as for BCL2 apoptosis regulator (Bcl2) and purinergic receptor P2Y12 (P2yr12) in the HPC, together with upregulated microRNA(miR)-146a-5p in the PFC, prevailed in 9-month-old animals. miR-155 positively correlated with miR-146a and miR-21 in the PFC, and miR-125b positively correlated with miR-155, miR-21, while miR-146a in the HPC. Correlations between genes and miRNAs were dynamic, varying by genotype, region, and age, suggesting an intricate, disease-modulated interaction between miRNAs and target pathways. These findings contribute to our understanding of miRNAs as therapeutic targets for AD, given their multifaceted effects on neurons and glial cells. Full article

Background: Road safety improvement is a governmental priority due to driver-caused accidents. Driving style variation affects safety, with emotional regulation being pivotal. However, functional near-infrared spectroscopy (fNIRS) studies show inconsistent prefrontal cortex activity during emotion processing. This study examines prefrontal cortex response to negative emotional stimuli, particularly traffic accident images, across drivers diverse in age and gender. Method: The study involved 118 healthy males (44.38 ± 12.98 years) and 84 females (38.89 ± 10.60 years). The Multidimensional Driving Style Inventory (MDSI) was used to assess driving behavior alongside fNIRS recordings. Participants viewed traffic accident and neutral images while prefrontal oxygenation was monitored. Results: Women rated traffic accidents (t-test = 2.43; p < 0.016) and neutral images (t-test = 2.19; p < 0.030) lower in valence than men. Arousal differences were significant for traffic accident images (t-test = −3.06; p < 0.002). correlational analysis found an inverse relationship between Dissociative scale scores and oxygenation (all p-values ≤ 0.013). Greater prefrontal oxygenation occurred with neutral images compared to traffic accidents. Left hemisphere differences (t-test = 3.23; p < 0.001) exceeded right hemisphere differences (t-test = 2.46; p < 0.015). Subgroup analysis showed male participants to be driving these disparities. Among adaptive drivers, significant oxygenation differences between neutral and accident images were evident in both hemispheres (left: t-test = 2.72, p < 0.009; right: t-test = 2.22, p < 0.030). Conclusions: Male drivers with maladaptive driving styles, particularly dissociative ones, exhibit reduced prefrontal oxygenation when exposed to neutral and traffic accident images. This response was absent in female drivers, with no notable age-related differences. Full article

A two-factor account has been proposed as an explanatory model for the formation and maintenance of delusions. The first factor refers to a neurocognitive process leading to a significant change in subjective experience; the second factor has been regarded as a failure in hypothesis evaluation characterized by an impairment in metacognitive ability. This study was focused on the assessment of metacognition in patients with schizophrenia. The aims of the study were to measure the overconfidence in metacognitive judgments through the prediction of word list recall and to analyze the correlation between basic neurocognition (memory and executive function) and metacognition through a metamemory test and the severity of psychotic symptoms. Method: Fifty-one participants with a diagnosis of schizophrenia were evaluated. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychiatric symptoms, and the subtest of metamemory included in the Executive Functions and Frontal Lobe-2 battery (BANFE-2) was used to evaluate overconfidence and underestimation errors, intrusion and perseverative response, total volume of recall, and Brief Functioning Assessment Scale (FAST) for social functioning. Results: The strongest correlation is observed between overconfidence errors and the positive factor of the PANSS (r = 0.774, p < 0.001). For the enter model in the multiple linear regression (r = 0.78, r² = 0.61; F = 24.57, p < 0.001), the only significant predictor was overconfidence errors. Conclusion: Our results highlight the relevance of a metacognitive bias of overconfidence, strongly correlated with psychotic symptoms, and support the hypothesis that metacognitive defects contribute to the failure to reject contradictory evidence. From our perspective, these findings align with current mechanistic models of schizophrenia that focus on the role of the prefrontal cortex. Full article

Since game mechanics and their visual aspects have become more and more addictive, there is concern about the growing prevalence of Internet gaming disorder (IGD). In the current narrative review, we searched PubMed and Google Scholar databases for the keywords “igd biomarker gaming” and terms related to biomarker modalities. The biomarkers we found are grouped into several categories based on a measurement method and are discussed in the light of theoretical addiction models (tripartite neurocognitive model, I-PACE). Both theories point to gaming-related problems with salience and inhibition. The first dysfunction makes an individual more susceptible to game stimuli (raised reward seeking), and the second negatively impacts resistance to these stimuli (decreased cognitive control). The IGD patients’ hypersensitivity to reward manifests mostly in ventral striatum (VS) measurements. However, there is also empirical support for a ventral-to-dorsal striatal shift and transition from goal-directed to habitual behaviors. The deficits in executive control are demonstrated in parameters related to the prefrontal cortex (PFC), especially the dorsolateral prefrontal cortex (DLPFC). In general, the connection of PFC with reward under cortex nuclei seems to be dysregulated. Other biomarkers include reduced P3 amplitudes, high-frequency heart rate variability (HRV), and the number of eye blinks and saccadic eye movements during the non-resting state. A few studies propose a diagnostic (multimodal) model of IGD. The current review also comments on inconsistencies in findings in the nucleus accumbens (NAcc), anterior cingulate cortex (ACC), and precuneus and makes suggestions for future IGD studies. Full article

Background/Objectives: Electroencephalography (EEG) is considered a standard but powerful tool for the diagnosis of neurological and psychiatric diseases. With modern imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and magnetoencephalography (MEG), source localization can be improved, especially with low-resolution brain electromagnetic tomography (LORETA). The aim of this review is to explore the variety of modern techniques with emphasis on the efficacy of LORETA in detecting brain activity patterns in schizophrenia. The study’s novelty lies in the comprehensive survey of EEG methods and detailed exploration of LORETA in schizophrenia research. This evaluation aligns with clinical objectives and has been performed for the first time. Methods: The study is split into two sections. Part I examines different EEG methodologies and adjuncts to detail brain activity in deep layers in articles published between 2018 and 2023 in PubMed. Part II focuses on the role of LORETA in investigating structural and functional changes in schizophrenia in studies published between 1999 and 2024 in PubMed. Results: Combining imaging techniques and EEG provides opportunities for mapping brain activity. Using LORETA, studies of schizophrenia have identified hemispheric asymmetry, especially increased activity in the left hemisphere. Cognitive deficits were associated with decreased activity in the dorsolateral prefrontal cortex and other areas. Comparison of the first episode of schizophrenia and a chronic one may help to classify structural change as a cause or as a consequence of the disorder. Antipsychotic drugs such as olanzapine or clozapine showed a change in P300 source density and increased activity in the delta and theta bands. Conclusions: Given the relatively low spatial resolution of LORETA, the method offers benefits such as accessibility, high temporal resolution, and the ability to map depth layers, emphasizing the potential of LORETA in monitoring the progression and treatment response in schizophrenia. Full article