Prefrontal Cortex Of Patients Research Articles

Computational modeling of electric fields for prefrontal tDCS across patients with schizophrenia and mood disorders

This cross-diagnostic study aims to computationally model electric field (efield) for prefrontal transcranial direct current stimulation in mood disorders and schizophrenia. Enrolled were patients with major depressive disorder (n = 23), bipolar disorder (n = 24), schizophrenia (n = 23), and healthy controls (n = 23). The efield was simulated using SimNIBS software (ver.2.1.1). Electrodes were placed at the left and right prefrontal areas and the current intensity was set to 2 mA intensity. Schizophrenia and major depressive disorder groups showed significantly lower 99.5th percentile efield strength than healthy controls. In voxel-wise analysis, patients with schizophrenia showed a significant reduction of simulated efield strength in the bilateral frontal lobe, cerebellum and brain stem compared with healthy controls. Among the patients with schizophrenia, reduction of simulated efield strength was not significantly correlated with psychiatric symptoms or global functioning. The patients with bipolar disorder showed no significant difference in simulated efield strength compared with healthy controls, and there was no significant difference between the clinical groups. Our results suggest attenuated electrophysiological response to transcranial direct current stimulation to the prefrontal cortex in patients with schizophrenia, and to some extent in patients with major depressive disorder.

RTMS Therapy Reduces Hypofrontality in Patients With Depression as Measured by fNIRS.

Multichannel functional near-infrared spectroscopy (fNIRS) is a tool used to capture changes in cerebral blood flow. A consistent result for depression is a decrease in blood flow in the frontal cortex leading to hypofrontality, which indicates multidomain functional impairment. Repetitive transcranial magnetic stimulation (rTMS) and elective convulsive therapy (ECT) are alternatives to antidepressant drugs for the treatment of depression but the underlying mechanism is yet to be elucidated. The aim of the current study was to evaluate cerebral blood flow using fNIRS following rTMS treatment in patients with depression. The cerebral blood flow of 15 patients with moderate depression after rTMS treatment was measured using fNIRS. While there was clear hypofrontality during pre-treatment (5 ± 2.5), a notable increase in oxygenated hemoglobin was observed after 30 sessions with rTMS (50 ± 15). This increased blood flow was observed in a wide range of channels in the frontal cortex; however, the centroid values were similar between the treatments. Increased blood flow leads to the activation of neuronal synapses, as noted with other neuromodulation treatments such as electroconvulsive therapy. This study describes the rTMS-induced modulation of blood oxygenation response over the prefrontal cortex in patients with depression, as captured by fNIRS. Future longitudinal studies are needed to assess cerebral blood flow dynamics during rTMS treatment for depression.

Glutamatergic dysfunction is associated with phenotypes of VGF-overexpressing mice.

VGF nerve growth factor inducible (VGF) is a neuropeptide precursor, which is induced by several neurotrophic factors, including nerve growth factor and brain-derived neurotrophic factor. Clinically, an upregulation of VGF levels has been reported in the cerebrospinal fluid and prefrontal cortex of patients with schizophrenia. In our previous study, mice overexpressing VGF exhibited schizophrenia-related behaviors. In the current study, we characterized the biochemical changes in the brains of VGF-overexpressing mice. Metabolomics analysis of neurotransmitters revealed that glutamic acid and N-acetyl-L-aspartic acid were increased in the striatum of VGF-overexpressing mice. Additionally, the present study revealed that MK-801, which causes the disturbance in glutamic acid metabolism, increased the expression level of VGF-derived peptide (NAPP129, named VGF20), and VGF-overexpressing mice had higher sensitivity to MK-801. These results suggest that VGF may modulate the regulation of glutamic acid levels and the degree of glutamic acid signaling.

Downregulation of connexin 43 potentiates amitriptyline-induced brain-derived neurotrophic factor expression in primary astrocytes through lysophosphatidic acid receptor1/3, Src, and extracellular signal-regulated kinase

Connexin 43 (Cx43) expression is decreased in the prefrontal cortex of patients with depression, but its significance is still unknown. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are involved in the effects of antidepressant. However, the relationship between Cx43 expression and induction of brain-derived neurotrophic factor production by antidepressants is unknown. On the basis of our previous study, which showed that adrenergic receptors stimulation results in potentiation of BDNF expression in astrocytes with downregulated Cx43 expression, we investigated the induction of BDNF expression by amitriptyline, a tricyclic antidepressant, in Cx43-knockdown astrocytes. Amitriptyline treatment potentiated BDNF expression in Cx43-knockdown astrocytes compared with those treated with non-targeting small interfering RNA (siRNA). Using a pharmacological approach, we revealed that the potentiating effect of amitriptyline on BDNF expression was mediated by lysophosphatidic acid (LPA) receptor1/3 (LPA1/3) stimulation and subsequent activation of Src-extracellular signal-regulated kinase (ERK) signaling. These findings suggest that downregulation of Cx43 in patients with depression might contribute to the therapeutic efficacy of antidepressants rather than the pathogenesis of depression.

Increased Prefrontal Activation During Verbal Fluency Task After Repetitive Transcranial Magnetic Stimulation Treatment in Depression: A Functional Near-Infrared Spectroscopy Study.

BackgroundPrevious studies have shown the clinical effect of 2 Hz repetitive transcranial magnetic stimulation (rTMS) for depression; however, its underlying neural mechanisms are poorly understood. The aim of this study was to examine the effects of rTMS on the activity of the prefrontal cortex in patients with depression, using functional near-infrared spectroscopy (fNIRS).MethodsForty patients with major depressive disorder (MDD) and 40 healthy controls were enrolled in this study. Patients underwent 4 weeks of 2 Hz TMS delivered to the right dorsolateral prefrontal cortex (DLPFC). fNIRS was used to measure the changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex during a verbal fluency task (VFT) in depressed patients before and after rTMS treatment. The severity of depression was assessed using the Hamilton Rating Scale for Depression-24 item (HAMD-24).ResultsPrior to rTMS, depressed patients exhibited significantly smaller [oxy-Hb] values in the bilateral prefrontal cortex during the VFT compared with the healthy controls. After 4 weeks of 2 Hz right DLPFC rTMS treatment, increased [oxy-Hb] values in the bilateral frontopolar prefrontal cortex (FPPFC), ventrolateral prefrontal cortex (VLPFC) and left DLPFC during the VFT were observed in depressed patients. The increased [oxy-Hb] values from baseline to post-treatment in the right VLPFC in depressed patients were positively related to the reduction of HAMD score following rTMS.ConclusionThese findings suggest that the function of the prefrontal cortex in depressed patients was impaired and could be recovered by 2 Hz rTMS. The fNIRS-measured prefrontal activation during a cognitive task is a potential biomarker for monitoring depressed patients’ treatment response to rTMS.

Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session

ObjectivesTranscutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear.MethodsTotal twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes.ResultsThe scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment.ConclusionsIt manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

Efficacy of Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex in Patients With Minimally Conscious State

BackgroundThe treatment of patients in a minimally conscious state (MCS) remains challenging. Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method in treating neurologic diseases by regulating the cortical excitability. The aim is to investigate the effect of tDCS in patients with MCS in this study.MethodsEleven patients in MCS were enrolled in the study. All the patients received 5 daily sessions of 20-min sham tDCS, followed by 10 sessions of 20-min real tDCS. The anodal electrode and cathodal electrodes were placed over the left dorsolateral prefrontal cortex (DLPFC) and the right eyebrow, respectively. Assessment of Coma Recovery Scale-Revised (CRS-R) scores and resting-state functional MRI (rs-fMRI) scans was conducted three times in each patient: before tDCS (baseline, T0), post-sham tDCS at week 1 (T1), and post-real tDCS at week 2 (T2). The whole-brain functional connectivity (FC) was obtained by bilaterally computing FC from six seed regions: precuneus, middle frontal gyrus, supplemental motor area, angular gyrus, superior temporal gyrus, and occipital lobe. One-way repeated measure ANOVA was used to compare the differences of CRS-R scores and FC at T0, T1, and T2. The false discovery rate correction of p < 0.001 was adopted for controlling multiple comparisons in FC analysis.ResultsFive patients with MCS showed obvious clinical improvement represented by increased CRS-R scores post- 2-week real tDCS. The CRS-R scores did not change post- 1-week sham treatment. No side effects were reported during the study. The FC of the bilateral supplementary motor area, right angular gyrus, and right superior temporal gyrus were significantly enhanced after 2-week real tDCS compared with that after 1-week sham-tDCS. In addition, FC of bilateral occipital lobe and right precuneus were significantly enhanced post- 2-week real tDCS compared with the baseline.ConclusionOur findings indicated that tDCS over DLPFC could serve as a potentially effective therapy for improving the consciousness state in patients with MCS. The FC in rs-fMRI can be modulated by tDCS at both the stimulation site (left DLPFC) and the distant regions.

The effect of low-frequency repetitive transcranial magnetic stimulation on left dorsolateral prefrontal cortex in patients with the obsessive-compulsive disorder: a double-blinded, sham-controlled clinical trial

BackgroundObsessive-compulsive disorder (OCD) is a complicated neuropsychiatric disorder, which its prevalence ranges from 2 to 4%. In 30–60% of patients due to intolerance of side effects or partial response to treat symptoms of the disease remain or relapse. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive therapeutic option to treat this condition. Transcranial magnetic stimulation can be applied for treating with no anesthesia. The current study intended to evaluate the effectiveness of low-frequency rTMS on the left dorsolateral prefrontal cortex as an adjunct treatment in combination with standard medication in patients with OCD.ResultsIn both groups of intervention and sham, the Y-BOCS scale was decreased. There was no significant difference between the two groups (P=0.82). Also after 15 sessions, the symptoms of OCD patients were improved. Although the treatment process was the same in the control group, none of the patients showed any serious complications, such as seizures, severe headache, neurological complication, or cognitive impairment during treatment.ConclusionsIt seems that treatment with 1 Hz rTMS on the left dorsolateral prefrontal cortex does not play an effective role in the recovery of OCD patients.Trial registrationName of the registry: Therapeutic effect comparison of the Repetitive Transcranial MagneticMagnetic Stimulation (RTMS) combination therapy with drug versus medication monotherapy in obsessive-compulsive disorder (OCD). Trial registration number: IRCT ID: IRCT20200728048240N1. Date of registration: 2020/8/8.

Anxiety in Parkinson's disease: A resting-state high density EEG study

ObjectiveTo identify markers of Parkinson's disease (PD) related anxiety, using high density electroencephalography (hd-EEG). Methods108 patients participated in the study. They were divided into two groups: with and without clinically relevant anxiety, according to their score on the Parkinson Anxiety Scale. Resting-state hd-EEG was recorded. Spectral and functional connectivity characteristics were compared between the two groups. ResultsThirty-three patients (31%) had significant anxiety symptoms. In the spectral analysis, relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without. Functional connectivity analysis showed a stronger connectivity between the left insula and several regions of the right prefrontal cortex in patients with anxiety than in those without. ConclusionThis study shows the pivotal role of the insula and frontal cortex in the pathophysiology of anxiety in PD and extends the results of previous studies using magnetic resonance imaging or positron emission tomography imaging.

Link between structural connectivity of the medial forebrain bundle, functional connectivity of the ventral tegmental area, and anhedonia in unipolar depression

The ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) are essential for experiencing pleasure and initiating motivated behaviour. The VTA, NAcc, and PFC are connected through the medial forebrain bundle (MFB). In humans, two branches have been described: an infero-medial branch (imMFB) and a supero-lateral branch (slMFB). This study aimed to explore the associations between structural connectivity of the MFB, functional connectivity (FC) of the VTA, anhedonia, and depression severity in patients with depression. Fifty-six patients with unipolar depression and 22 healthy controls matched for age, sex, and handedness were recruited at the University Hospital of Psychiatry and Psychotherapy in Bern, Switzerland. Diffusion-weighted imaging and resting-state functional magnetic resonance imaging scans were acquired. Using manual tractography, the imMFB and slMFB were reconstructed bilaterally for each participant. Seed-based resting-state FC was computed from the VTA to the PFC. Hedonic tone was assessed using the Fawcett-Clark Pleasure Scale. We identified reduced tract volume and reduced number of tracts in the left slMFB. There was an increase in FC between the VTA and right medial PFC in patients with depression. Depression severity was associated with reduced tract volume and fewer tracts in the left slMFB. Reduced hedonic tone was associated with reduced tract volume. Conversely, reduced hedonic tone was associated with increased FC between the VTA and the PFC. In conclusion, our results suggest reduced structural connectivity of the slMFB in patients with depression. Increases in FC between the VTA and PFC may be associated with anhedonia or compensatory hyperactivity.

Neural Activation via Acupuncture in Patients With Major Depressive Disorder: A Functional Near-Infrared Spectroscopy Study

Background and Objective: Acupuncture is used as an alternative treatment for patients with major depressive disorder (MDD). The associated therapeutic effect of acupuncture is often attributed to its modulatory effect on the activity of the pre-frontal cortex (PFC), although the mechanism is not well-studied. We employed a repeated measures design to investigate the brain modulatory effect of acupuncture on the PFC in a group of patients with MDD and investigated whether the modulatory effect is influenced by the severity of the disease.Methods: A total of 47 patients diagnosed with MDD were enrolled in this functional near-infrared spectroscopy experiment. The severity of depressive symptoms was measured at baseline using the Hamilton Depression Rating Scale-24 (HAMD). The cortical activation in the bilateral PFC areas during a verbal fluency task (VFT) was measured before and after a single session of acupuncture in the Baihui acupoint. We further explored the potential correlation between the severity of MDD and task-related activation before and after acupuncture.Results: A single session of acupuncture significantly tended to enhance the activation level of the left frontopolar cortex in patients with severe depression during VFT, but a null effect was found in those with mild to moderate depression. Among patients with severe depression, a strong correlation was observed between HAMD scores and the change in VFT-related activation after acupuncture in the left dorsolateral PFC (DLPFC).Conclusion: A single session of acupuncture did not significantly modulate the activation of the left PFC in patients with mild to moderate depression; however, it demonstrated a tendency to enhance the activation of the frontopolar area in patients with severe depression. Among patients with severe depression, there is a correlation between the activation by acupuncture of left DLPFC during executive functioning and the severity of depressive symptoms, suggesting that the brain activity induced by acupuncture is likely to be influenced by the baseline disease severity in patients with MDD.

Effects of transcutaneous auricular vagus nerve stimulation on brain functional connectivity of medial prefrontal cortex in patients with primary insomnia.

As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI.

Application of Near-Infrared Spectroscopy for Understanding Spontaneous Brain Activity During Resting State in Schizophrenia: A Mini Review.

Spontaneous brain activity occurs at rest, as represented by the default mode network. A resting paradigm is suitable for investigating brain function of patients with psychiatric diseases who may have difficulties adhering to goal-oriented tasks. Evidence accumulated in neuroimaging studies using functional magnetic resonance imaging has shown that the resting cerebral blood flow is impaired in psychiatric diseases. Near-infrared spectroscopy (NIRS), a simple neuroimaging modality, is an optimal tool for the resting paradigm, because it can offer a comfortable environment for measurement. Recent NIRS studies have demonstrated some promising data of altered resting activity in the prefrontal cortex of patients with schizophrenia, which may be exploited to develop further applications of NIRS in clinical psychiatry. Based on these findings, we emphasize the benefits of NIRS for assessing the prefrontal pathophysiology during the resting state and some methodological issues to be noted while analyzing cerebral blood flow using NIRS; moreover, we focus on interpreting these changes based on the complex nature of the spontaneous brain activity during resting state.

Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex.

BackgroundNeuromorphological changes are consistently reported in the prefrontal cortex of patients with stress-related disorders and in rodent stress models, but the effects of stress on astrocyte morphology and the potential link to behavioral deficits are relatively unknown.MethodsTo answer these questions, transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promotor were subjected to 7, 21, or 35 days of chronic restraint stress (CRS). CRS-induced behavioral effects on anhedonia- and anxiety-like behaviors were measured using the sucrose intake and the PhenoTyper tests, respectively. Prefrontal cortex GFP+ or GFAP+ cell morphology was assessed using Sholl analysis, and associations with behavior were determined using correlation analysis.ResultsCRS-exposed male and female mice displayed anxiety-like behavior at 7, 21, and 35 days and anhedonia-like behavior at 35 days. Analysis of GFAP+ cell morphology revealed significant atrophy of distal processes following 21 and 35 days of CRS. CRS induced similar decreases in intersections at distal radii for GFP+ cells accompanied by increased proximal processes. In males, the number of intersections at the most distal radius step significantly correlated with anhedonia-like behavior (r = 0.622, P < .05) for GFP+ cells and with behavioral emotionality calculated by z-scoring all behavioral measured deficits (r = −0.667, P < .05). Similar but not significant correlations were observed in females. No correlation between GFP+ cell atrophy with anxiety-like behavior was found.ConclusionChronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic and behavioral changes associated with stress-related disorders.

Resting-state functional magnetic resonance imaging analysis of abnormal directional functional connectivity of the nucleus accumbens in patients with chronic tinnitus

Objective: To investigate abnormal directional functional connectivity of the nucleus accumbens (NAc) in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI), and to determine the relationship between the degree of this connectivity and tinnitus characteristics. Methods: The resting-state fMRI data of 40 patients with bilateral chronic tinnitus (12 males and 28 females, aged from 26 to 63(50.6±11.6) years) and 40 healthy controls with normal hearing (16 males and 24 females, aged from 26 to 70(45.9±12.4)years) were retrospectively enrolled from the Department of Otolaryngology, Nanjing First Hospital from January 2017 to January 2020. The bilateral NAc were selected as seeds to detect the directional functional connectivity with the whole brain, then the effective connectivity values between the two groups were compared using Granger Causality Analysis (GCA), and the correlation between the effective connectivity and the characteristics of tinnitus was calculated. Results: Compared with healthy controls, the effective connectivity from the left NAc to left middle frontal gyrus in patients with bilateral chronic tinnitus was increased [(1.0±0.2)vs(0.6±0.3)], the effective connectivity from the right NAc to left inferior frontal gyrus was enhanced [(0.9±0.3)vs(0.6±0.4)], the effective connectivity from the right middle temporal gyrus to left NAc was enhanced [(1.0±0.2)vs(0.5±0.3)], the effective connectivity from the right middle frontal gyrus to right NAc was also enhanced[(1.0±0.2)vs(0.5±0.3)](all P<0.05). After adjusting for age, gender, education level, and gray matter volume, positive correlations was observed between the Tinnitus Handicap Questionnaire (THQ) scores and increased effective connectivity values from the left NAc to the left middle frontal gyrus (r=0.386, P=0.020). Additionally, enhanced effective connectivity values from the right middle frontal gyrus to the right NAc was also positively associated with tinnitus duration (r=0.390, P=0.019). Conclusion: The directional functional connectivity between the NAc and prefrontal cortex in patients with chronic tinnitus is enhanced.

Changes in prefrontal cortex activation with exercise in knee osteoarthritis patients with chronic pain: An fNIRS study

The role of exercise on pain modulatory mechanism of the prefrontal areas is not clear. We aimed to determine the effects of exercise on functional activity of the prefrontal cortex in patients with knee osteoarthritis (OA) with chronic pain and to assess the relationships between changes in clinical variables and cortical hemodynamics with exercise via functional near-infrared spectroscopy (fNIRS). Fifteen patients with knee OA with chronic pain were included. All participants attended an exercise program 3 times a week for 6 weeks. Pain during activity was assessed by visual analogue scale (VAS). Pain catastrophization, kinesiophobia and functionality were also measured. Brain hemodynamic activity was assessed with a 47-channel fNIRS system before and after the exercise. Pain, pain catastrophization, kinesiophobia and functionality scores significantly improved (p < 0.05) while functional activity of the dorsolateral prefrontal cortex (DLPFC) during painful stimuli was significantly reduced after exercise program (p < 0.05). Change in cortical hemodynamic activity within the DLPFC was significantly correlated with change in pain perception (R = 0.54, p < 0.05) and pain catastrophization scores (R = 0.44, p < 0.05). Exercise resulted in improvements in clinical assessments of pain severity and pain catastrophization which was accompanied by alterations in prefrontal cortex activation. We provided evidence about the pain modulatory effects of exercise at cortical level which is correlated with clinical improvements in patients with chronic pain. We demonstrate the feasibility and potential of fNIRS methodology for i) elucidating the neural mechanisms underlying chronic and stimulus evoked pain, and ii) exploring the effect of treatment methods on brain functionality.

Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study.

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.

Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

Bipolar disorder (BD) is a severe mental disorder characterized by repeated mood swings. Although genetic factors are collectively associated with the etiology of BD, the underlying molecular mechanisms, particularly how environmental factors affect the brain, remain largely unknown. We performed promoter-wide DNA methylation analysis of neuronal and nonneuronal nuclei in the prefrontal cortex of patients with BD (N = 34) and controls (N = 35). We found decreased DNA methylation at promoters in both cell types in the BD patients. Gene Ontology (GO) analysis of differentially methylated region (DMR)-associated genes revealed enrichment of molecular motor-related genes in neurons, chemokines in both cell types, and ion channel- and transporter-related genes in nonneurons. Detailed GO analysis further revealed that growth cone- and dendrite-related genes, including NTRK2 and GRIN1, were hypermethylated in neurons of BD patients. To assess the effect of medication, neuroblastoma cells were cultured under therapeutic concentrations of three mood stabilizers. We observed that up to 37.9% of DMRs detected in BD overlapped with mood stabilizer-induced DMRs. Interestingly, mood stabilizer-induced DMRs showed the opposite direction of changes in DMRs, suggesting the therapeutic effects of mood stabilizers. Among the DMRs, 12 overlapped with loci identified in a genome-wide association study (GWAS) of BD. We also found significant enrichment of neuronal DMRs in the loci reported in another GWAS of BD. Finally, we performed qPCR of DNA methylation-related genes and found that DNMT3B was overexpressed in BD. The cell-type-specific DMRs identified in this study will be useful for understanding the pathophysiology of BD.

Evaluation of plasma levels of BDNF in patients with disorder depressive

IntroductionAccording to the World Health Organization (WHO, 2017) depressive disorder continues to be the most widespread and growing mental illness in the world, also assumes that in 2020 depression will have a prevalence equal to one in six individuals. Studies of neuroanatomy have highlighted structural alterations in the hippocampus, striatal nuclei and prefrontal cortex in patients with mood disorders. This alteration in depressed patients is closely related to the secretion of neurotrophic factors, in particular there is a reduction in BDNF (Brain Derived Neurotrophic Factor).ObjectivesThe objective of this study is to demonstrate which treatments are effective in reducing depressive symptoms that allow the increase of BDNF and consequently the structural homostaticity of the brain.MethodsWe have selected data from the literature of the last decade, collected on major search engines such as: Google Scholar, Research Gate, PubMed, Ebsco. Articles collected by selecting the following Keyword: depression, BDNF (Brain Derived Neurotrophic Factor), neuroimaging cognitive behavior therapy.ResultsThe results show that in patients treated with a single drug treatment or vagus nerve stimulation, repetitive transcranial magnetic stimulation (Lang et al., 2008) or electroconvulsive therapy had improvements in BDNF levels, although compared to drug treatment there are problems of no responders, no compliance and lack of effectiveness in reducing vulnerability to relapse. In addition, the study has shown that patients treated with cognitive behavioral therapy have reported greater changes in the frontal and temporal cortex reducing both depressive symptoms and the risk of relapse.ConclusionsUnderlines the importance of an integrated approach

The rostro-caudal gradient in the prefrontal cortex and its modulation by subthalamic deep brain stimulation in Parkinson\u2019s disease

Deep brain stimulation of the subthalamic nucleus (STN-DBS) alleviates motor symptoms in Parkinson’s disease (PD) but also affects the prefrontal cortex (PFC), potentially leading to cognitive side effects. The present study tested alterations within the rostro-caudal hierarchy of neural processing in the PFC induced by STN-DBS in PD. Granger-causality analyses of fast functional near-infrared spectroscopy (fNIRS) measurements were used to infer directed functional connectivity from intrinsic PFC activity in 24 PD patients treated with STN-DBS. Functional connectivity was assessed ON stimulation, in steady-state OFF stimulation and immediately after the stimulator was switched ON again. Results revealed that STN-DBS significantly enhanced the rostro-caudal hierarchical organization of the PFC in patients who had undergone implantation early in the course of the disease, whereas it attenuated the rostro-caudal hierarchy in late-implanted patients. Most crucially, this systematic network effect of STN-DBS was reproducible in the second ON stimulation measurement. Supplemental analyses demonstrated the significance of prefrontal networks for cognitive functions in patients and matched healthy controls. These findings show that the modulation of prefrontal functional networks by STN-DBS is dependent on the disease duration before DBS implantation and suggest a neurophysiological mechanism underlying the side effects on prefrontally-guided cognitive functions observed under STN-DBS.