Dorsolateral Prefrontal Cortex Of Patients Research Articles

280. Acute Temporal Interference Stimulation of the Left Dorsolateral Prefrontal Cortex in Patients With Depression: First Results of a Double-Blind Controlled Study

280. Acute Temporal Interference Stimulation of the Left Dorsolateral Prefrontal Cortex in Patients With Depression: First Results of a Double-Blind Controlled Study

Safety and efficacy of repetitive stimulation of the left dorsolateral prefrontal cortex using transcranial focused ultrasound in treatment-resistant depressed patients: A non-inferiority randomized controlled trial protocol

BackgroundAbout 30% of patients diagnosed with major depressive disorder fail with the mainstream pharmacological treatment. Patients who do not achieve clinical remission of symptoms, even with two different antidepressants, are classified with treatment-resistant depression (TDR). This condition imposes an additional burden with increased Disability Adjusted Life Years. Therefore, complementary treatments, such as neuromodulation, are necessary. The transcranial focused ultrasound (tFUS) has emerged in the past few years as a reliable method for non-invasive neuromodulation in humans and may help treat TRD. This study aims to propose a research protocol for a non-inferiority randomized clinical trial of TDR with tFUS. MethodsPatients with documented TRD will be screened upon entering the TRD outpatient clinic at UFMG (Brazil). One hundred patients without a clinical history of other psychiatric illness, anatomical abnormalities on magnetic resonance imaging (MRI), or treatment with electroconvulsive therapy will be invited to participate. Patients will be randomized (1:1) into two groups: 1) treatment with a previously established protocol of transcranial magnetic stimulation; and 2) treatment with a similar protocol using the stimulation. Besides regular consultations in the outpatient clinic, both groups will attend 7 protocolled spaced days of brain stimulation targeted at the left dorsolateral prefrontal cortex. They will also be submitted to 4 sessions of image studies (2 MRIs, 2 positron-emission tomography), 3 of neuropsychological assessments (at baseline, 1 week and 2 months after treatment), the Montgomery-Åsberg Depression Rating Scale to analyze the severity of depressive symptoms. DiscussionThis clinical trial intends to verify the safety and clinical efficacy of tFUS stimulation of the dorsolateral prefrontal cortex of patients with TRD, compared with a previously established neuromodulation method.

Neuroplasticity of the left dorsolateral prefrontal cortex in patients with treatment-resistant depression as indexed with paired associative stimulation: a TMS-EEG study.

Major depressive disorder affects over 300 million people globally, with approximately 30% experiencing treatment-resistant depression (TRD). Given that impaired neuroplasticity underlies depression, the present study focused on neuroplasticity in the dorsolateral prefrontal cortex (DLPFC). Here, we aimed to investigate the differences in neuroplasticity between 60 individuals with TRD and 30 age- and sex-matched healthy controls (HCs). To induce neuroplasticity, participants underwent a paired associative stimulation (PAS) paradigm involving peripheral median nerve stimulation and transcranial magnetic stimulation (TMS) targeting the left DLPFC. Neuroplasticity was assessed by using measurements combining TMS with EEG before and after PAS. Both groups exhibited significant increases in the early component of TMS-evoked potentials (TEP) after PAS (P < 0.05, paired t-tests with the bootstrapping method). However, the HC group demonstrated a greater increase in TEPs than the TRD group (P = 0.045, paired t-tests). Additionally, event-related spectral perturbation analysis highlighted that the gamma power significantly increased after PAS in the HC group, whereas it was decreased in the TRD group (P < 0.05, paired t-tests with the bootstrapping method). This gamma power modulation revealed a significant group difference (P = 0.006, paired t-tests), indicating an inverse relationship for gamma power modulation. Our findings underscore the impaired neuroplasticity of the DLPFC in individuals with TRD.

Identifying the neurostimulation target for treatment of cognitive impairment in aging and early cerebral small vessel disease

To develop individualized approaches to the use of neuromodulation as a non-pharmacological treatment of cognitive impairment (CI) based on the assessment of compensatory brain reserves in functional MRI (fMRI). Twenty-one adults over 45 years of age, representing a continuum from healthy norm to mild cognitive impairment due to aging and early cerebral small vessel disease, were studied. All participants underwent fMRI while performing two executive tasks - a modified Stroop task and selective counting. To assess the ability to compensate for CI in real life, functional activation and connectivity were analyzed using the BRIEF-MoCA score as a covariate, which is the difference in ratings between the Behavior Rating Inventory of Executive Function (BRIEF) and the Montreal Cognitive Assessment Scale (MoCA). Both fMRI tasks were associated with activation of areas of the frontoparietal control network, as well as supplementary motor area (SMA) and the pre-SMA, the lateral premotor cortex, and the cerebellum. An increase in pre- SMA connectivity was observed during the tasks. The BRIEF-MoCA score correlated firstly with connectivity of the left dorsolateral prefrontal cortex (DLPFC) and secondly with involvement of the occipital cortex during the counting task. The developed technique allows identification of the functionally relevant target within the left DLPFC in patients with CI in aging and early cerebral microangiopathy.

The Neurological Rehabilitation of Adults With Coma and Disorders of Consciousness.

Severe quantitative disorders of consciousness (DoC) due to acute brain injury affect up to 47% of patients upon admission to intensive care and early rehabilitation units. Nevertheless, the rehabilitation of this vulnerable group of patients has not yet been addressed in any German-language guidelines and has only been studied in a small number of randomized clinical trials. In an S3 clinical practice guideline project, a systematic literature search was carried out for interventions that could improve consciousness in patients with coma, unresponsive wakefulness syndrome, or minimally conscious state after acute brain injury, and an evidence-based evaluation of these interventions was performed. Recommendations concerning diagnostic methods and medical ethics were issued by consensus. Misdiagnoses are common in patients with DoC, with minimal consciousness often going unrecognized. Patients with DoC should, therefore, be repeatedly assessed with standardized instruments, particularly the Coma Recovery Scale-Revised. The literature search yielded 54 clinical trials, mostly of low quality; there were two randomized controlled clinical trials providing level 1 evidence. The best available evidence for the improvement of impaired consciousness is for the administration of amantadine (4 studies) and for anodal transcranial direct-current stimulation of the left dorsolateral prefrontal cortex in patients in the minimal conscious state (8 studies, 2 systematic reviews). Further important components of rehabilitation include positioning methods and sensory stimulation techniques such as music therapy. For the first time, evidence-based German-language clinical practice guidelines have now become available for the neurological rehabilitation of patients with DoC.

Effectiveness of adjunctive low-frequency repetitive transcranial magnetic stimulation therapy over the left dorsolateral prefrontal cortex in patients with obsessive-compulsive disorder refractory to medical treatment:A double-blind, randomized clinical trial

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. The Food and Drug Administration (FDA) approved repetitive transcranial magnetic stimulation (rTMS) to treat OCD in 2018. So far, various approaches to treat this disorder have been evaluated. We evaluated the effect of adjunctive low-frequency rtMS over the left dorsolateral prefrontal cortex in patients with OCD refractory to treatment. The present clinical trial was done on 37 patients with OCD referring from the psychiatry clinic, 22 Bahman Hospital, Qazvin province, between 2018 and 2020 and patients were randomly divided into two groups. The intervention group received rTMS treatment at 1Hz for 20min (1200 pulses/day) over the left DLPFC area as adjunctive to the medical treatment three times a week and for five weeks, whereas those in the control group were subjected to only the sham condition plus their medical treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOC.S) was completed by patients before the study, following sessions 5 and 10 during the intervention, at the end of the intervention, and three to six months after the intervention under the direct supervision of a psychiatrist. SPSS software version 26 was used to compare the results between the two groups. The intervention group showed significantly lower mean Y-BOCS scores after the intervention and at follow-up (P<0.05) and all patients of the intervention group showed significantly lower Y-BOCS scores than their own baseline scores (P<0.05). Also, using antipsychotic agents along with the serotonergic agents yielded significantly lower scores in the intervention group at the end of the intervention (P<0.05). All the patients were found with higher follow-up scores than their scores at the end of the intervention; however, this difference was not significant (p>0.05). Adjunctive low-frequency (1Hz) rTMS over the left DLPFC is able to effectively reduce Y-BOCS score in OCD patients refractory to treatment following 15 sessions, and the reduction was durable even after three to six months. Using antipsychotic agents as an adjuvant with serotonergic agents was identified as a possible predictor for response to adjunctive rTMS therapy.

Impaired neuroplasticity in the dorsolateral prefrontal cortex of patients with treatment-resistant depression indexed by paired associative stimulation paradigm and a combined TMS-EEG measurements

Impaired neuroplasticity in the dorsolateral prefrontal cortex of patients with treatment-resistant depression indexed by paired associative stimulation paradigm and a combined TMS-EEG measurements

Neurochemical correlates of cognitive functions in euthymic patients with bipolar disorder: 1H-MRS study.

We assessed and correlated neurochemical levels and cognitive functions in left dorsolateral prefrontal cortex (DLPFC) and left hippocampus in euthymic patients with bipolar disorder and compared these with healthy controls METHODOLOGY: Twenty-five right-handed euthymic patients (HAM-D score<7, and YMRS score<7) with bipolar disorder and 20 age and gender matched controls were compared for neurometabolites (n-acetylaspartate - tNAA, choline - Cho, creatinine - Cr, myoinositol - Ins, and glutamine/glutamate - Glu/Gln) measured in left DLPFC and left hippocampus using single voxel magnetic resonance spectroscopy (MRS) and cognitive functions assessed using trail making test (TMT - A and B), wisconsin card sorting test (WCST), and wechsler memory scale (WMS-III Indian adaptation). The two groups were comparable on socio-demographic variables. tNAA levels in DLPFC and hippocampus, and glutamate levels in hippocampus were found to be significantly lower and Inositol and glutamine levels in hippocampus were found to be significantly higher in patients as compared to controls. Patients performed significantly poorly as compared to controls on TMT A & B, all subscales of WMS - III, 5 subscales of WCST, including perseverative responses and errors. The tNAA and glutamate levels in left DLPFC in patients correlated with scores on TMT A & B, and several subscales of WCST and WMS-III. tNAA concentration in left hippocampus in patients correlated with scores on subscales of WMS-III. Neurochemical dysfunction in select brain areas directly correlates with impairment in cognitive functions seen in patients with bipolar disorder in euthymic phase.

Upper cortical layer-driven network impairment in schizophrenia.

Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.

Combined fractional anisotropy and subcortical volumetric deficits in patients with mild-to-moderate depression: Evidence from the treatment of antidepressant traditional Chinese medicine

Numerous neuroimaging studies have demonstrated that diverse brain structural plasticity could occur in a human brain during a depressive episode. However, there is a lack of knowledge regarding the underlying mechanisms of mild-to-moderate depression (MMD), especially the changes of brain structural characteristics after treatment with the Shuganjieyu capsule (SG), a kind of traditional Chinese medicine that has been recommended for the specialized treatment of MMD. In this study, we investigated the structural brain plasticity in MMD that have been undergoing 8 weeks of SG treatment compared with age- and sex-matched healthy controls (HCs) and assessed the relationship between these brain structural alternations and clinical symptoms in MMD. At the baseline, we found that: (1) fractional anisotropy (FA) values in patients with MMD were found to be significantly increased in the regions of anterior limb of internal capsule (ALIC) [MNI coordinates: Peak (x/y/z) = 102, 126, 77; MMD FApeak (Mean ± SD) = 0.621 ± 0.043; HCs FApeak (Mean ± SD) = 0.524 ± 0.052; MMD > HCs, t = 9.625, p < 0.001] and posterior limb of internal capsule (PLIC) [MNI coordinates: Peak (x/y/z) = 109, 117, 87; MMD FApeak (Mean ± SD) = 0.694 ± 0.042; HCs FApeak (Mean ± SD) = 0.581 ± 0.041; MMD > HCs, t = 12.90, p < 0.001], and FA values were significantly positively correlated with HAMD scores in patients with MMD. (2) Patients with MMD showed smaller gray matter volume (GMV) of the dorsolateral prefrontal cortex (DLPFC), frontal cortex, occipital cortex, and precuneus, and the GMV of DLPFC was negatively correlated with HAMD scores. After SG treatment, we found that (1) the HAMD scores decreased; (2) FA values were significantly decreased in the regions of the ALIC and PLIC compared to those at baseline and TBSS revealed no significant differences in FA values between patients with MMD and HCs. (3) The structural characteristics of DLPFC in patients with MMD obtained at the 8th week were improved, e.g., no significant differences in GMV of DLPFC between the two groups. Taken together, our results provided neuroimaging evidence suggesting that SG is an effective treatment for patients with MMD. Moreover, alterations of GMV after 8 weeks of SG treatment indicated a potential modulation mechanism in brain structural plasticity within the DLPFC in patients with MMD.

More Than Just Statics: Temporal Dynamic Changes in Inter- and Intrahemispheric Functional Connectivity in First-Episode, Drug-Naive Patients With Major Depressive Disorder.

Several functional magnetic resonance imaging (fMRI) studies have demonstrated abnormalities in static intra- and interhemispheric functional connectivity among diverse brain regions in patients with major depressive disorder (MDD). However, the dynamic changes in intra- and interhemispheric functional connectivity patterns in patients with MDD remain unclear. Fifty-eight first-episode, drug-naive patients with MDD and 48 age-, sex-, and education level-matched healthy controls (HCs) underwent resting-state fMRI. Whole-brain functional connectivity, analyzed using the functional connectivity density (FCD) approach, was decomposed into ipsilateral and contralateral functional connectivity. We computed the intra- and interhemispheric dynamic FCD (dFCD) using a sliding window analysis to capture the dynamic patterns of functional connectivity. The temporal variability in functional connectivity was quantified as the variance of the dFCD over time. In addition, intra- and interhemispheric static FCD (sFCD) patterns were calculated. Associations between the dFCD variance and sFCD in abnormal brain regions and the severity of depressive symptoms were analyzed. Compared to HCs, patients with MDD showed lower interhemispheric dFCD variability in the inferior/middle frontal gyrus and decreased sFCD in the medial prefrontal cortex/anterior cingulate cortex and posterior cingulate cortex/precuneus in both intra- and interhemispheric comparisons. No significant correlations were found between any abnormal dFCD variance or sFCD at the intra- and interhemispheric levels and the severity of depressive symptoms. Our results suggest intra- and interhemispheric functional connectivity alterations in the dorsolateral prefrontal cortex (DLPFC) and default mode network regions involved in cognition, execution and emotion. Furthermore, our study emphasizes the essential role of altered interhemispheric communication dynamics in the DLPFC in patients with MDD. These findings contribute to our understanding of the pathophysiology of MDD.

Accelerated Resting-State fMRI-Guided Theta Burst Stimulation to the Right DLPFC for Late-Life Depression: A Pilot Study

<h3>Introduction</h3> Repetitive transcranial magnetic stimulation (rTMS) is FDA-approved for treatment of major depressive disorder; however, its efficacy in late-life depression (LLD) may be reduced due to age-related changes (see Figure 1). rTMS of the dorsolateral prefrontal cortex (DLPFC) has been shown to affect mood control via modulation of the subgenual cingulate cortex (SgCC). The area within the DLPFC having maximum anticorrelated activity to the SgCC is currently believed the most efficacious target for rTMS for depression. While trials of accelerated neuronavigated rTMS to the left DLPFC for depression have shown large effects for depression,¹ there has not yet been a validation of this technique specifically for LLD. Additionally, no studies have tested accelerated intermittent theta burst stimulation (iTBS) to the right DLPFC for depression, although it may have benefit for both depression and anxiety.² We proposed a pilot study of accelerated resting-state functional MRI (rsfMRI)-guided iTBS for LLD and hypothesized that this intervention would result in a significant improvement in depressive and generalized anxiety disorder symptoms. <h3>Methods</h3> A total of 18 elderly patients (ages 50-79 years) with a clinical diagnosis of moderate to severe major depressive disorder of at least 6 months' duration were recruited from local clinics. Each patient underwent rsfMRI and behavioral assessment prior to treatment. Change in depressive symptoms was measured by the Inventory of Depressive Symptoms (IDS-30-C). Change in anxiety symptoms was measured by the Generalized Anxiety Disorder-7 (GAD-7). Each participant's unique stimulation target was found by preprocessing resting-state data within Analysis of Functional NeuroImages (AFNI). A connectivity map of the bilateral SgCC as defined by the Brainnetome atlas was computed and smoothed to 12mm. The maximally anti-correlated voxel within the DLPFC search region (Brodmann areas 9 and 46) was located. A 3mm sphere around the target voxel was warped to subject space and exported to a neuronavigation system. Each participant received 45 sessions of iTBS to their fMRI target with a Magventure MagPro X100 stimulator with Cool-B70 coil (see Figure 2). Stimulation parameters were: 5Hz burst frequency, 50Hz intraburst frequency, 2 second train duration, 8 second intertrain interval, 60 trains/session, 5 sessions/day, 50 minute intersession interval, for 9 days totaling 81,000 pulses. After the 15th and 45th treatments, participants repeated clinical and imaging assessments (see Figure 3). Depression scores were elicited by phone interview at one and three months after treatment. Means and standard deviations of depressive and anxious symptoms were calculated for each visit. Repeated measures analysis of variances (ANOVA) was used to assess change in symptoms over time. Changes in connectivity between nodes in the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) were analyzed with independent components analysis (ICA) in Statistical Parametric Mapping (SPM). <h3>Results</h3> Mean age of the 18 patients (2M, 16F) was 63 ± 7.4 years. Mean duration of depression was 166 ± 154.4 months. Nine patients had comorbid GAD and five patients had comorbid posttraumatic stress disorder. Four of the 18 patients had previously undergone ECT. Mean depression (IDS-30-C) scores decreased throughout the study protocol (Visit 1: 39.31 ± 9.24; Visit 2: 30.74 ± 10.44; Visit 3: 20.79 ± 8.13) and remained below pre-treatment values at one month (19.84 ± 15.63) and three months (20.34 ± 14.15) (F(4,28) = 7.15, p = .0004, ??_p² = 0.5) (see Figure 4). Mean GAD-7 scores (N=18) also decreased with treatment (Visit 1: 9.95 ± 5.89; Visit 2: 9.58 ± 5.28; Visit 3: 6.53 ± 5.00) (F(2,36) = 7, p < .006, ??_p² = 0.28) (see Figure 5). Preliminary analysis of changes in connectivity from Visit 1 to Visit 3 indicate significantly increased within-network connectivity in the DMN (p = .003), and decreased between-network connectivity between the DMN and FPC (p = .011). <h3>Conclusions</h3> In this single-arm, uncontrolled pilot study, accelerated rsfMRI-guided iTBS to the right DLPFC in patients with LLD was effective in reducing both symptoms of depression and generalized anxiety. Connectivity changes in DMN and FPN network components were also observed. Future work should confirm these effects in a larger sample size and controlled study design. <h3>Secondary Rationale</h3> Reason for Late-Breaking Status: Data collection was continued beyond the regular submission deadline to attain greater statistical power to inform study conclusions. <h3>This research was funded by</h3> UNM Successful Aging Pilot Grant, Mind Research Network Center of Biomedical Research Excellence (COBRE) Pilot Grant (NIH/NIGMS 5P30GM122734-03)

Genetics and Brain Transcriptomics of Completed Suicide.

The authors sought to study the transcriptomic and genomic features of completed suicide by parsing the method chosen, to capture molecular correlates of the distinctive frame of mind of individuals who die by suicide, while reducing heterogeneity. The authors analyzed gene expression (RNA sequencing) from postmortem dorsolateral prefrontal cortex of patients who died by suicide with violent compared with nonviolent means, nonsuicide patients with the same psychiatric disorders, and a neurotypical group (total N=329). They then examined genomic risk scores (GRSs) for each psychiatric disorder included, and GRSs for cognition (IQ) and for suicide attempt, testing how they predict diagnosis or traits (total N=888). Patients who died by suicide by violent means showed a transcriptomic pattern remarkably divergent from each of the other patient groups but less from the neurotypical group; consistently, their genomic profile of risk was relatively low for their diagnosed illness as well as for suicide attempt, and relatively high for IQ: they were more similar to the neurotypical group than to other patients. Differentially expressed genes (DEGs) associated with patients who died by suicide by violent means pointed to purinergic signaling in microglia, showing similarities to a genome-wide association study of Drosophila aggression. Weighted gene coexpression network analysis revealed that these DEGs were coexpressed in a context of mitochondrial metabolic activation unique to suicide by violent means. These findings suggest that patients who die by suicide by violent means are in part biologically separable from other patients with the same diagnoses, and their behavioral outcome may be less dependent on genetic risk for conventional psychiatric disorders and be associated with an alteration of purinergic signaling and mitochondrial metabolism.

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.

Repetitive Transcranial Magnetic Stimulation Modulates Frontal and Temporal Time-Varying EEG Network in Generalized Anxiety Disorder: A Pilot Study.

Generalized Anxiety Disorder (GAD) is a highly prevalent yet poorly understood chronic mental disorder. Previous studies have associated GAD with excessive activation of the right dorsolateral prefrontal cortex (DLPFC). This study aimed to investigate the effect of low-frequency repetitive transcranial magnetic stimulation (repetitive TMS, rTMS) targeting the right DLPFC on clinical symptoms and TMS-evoked time-varying brain network connectivity in patients with GAD. Eleven patients with GAD received 1 Hz rTMS treatment targeting the right DLPFC for 10 days. The severity of the clinical symptoms was evaluated using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) at baseline, right after treatment, and at the one-month follow-up. Co-registration of single-pulse TMS (targeting the right DLPFC) and electroencephalography (TMS-EEG) was performed pre- and post-treatment in these patients and 11 healthy controls. Time-varying brain network connectivity was analyzed using the adaptive directed transfer function. The scores of HAMA and HAMD significantly decreased after low-frequency rTMS treatment, and these improvements in ratings remained at the one-month follow-up. Analyses of the time-varying EEG network in the healthy controls showed a continuous weakened connection information outflow in the left frontal and mid-temporal regions. Compared with the healthy controls, the patients with GAD showed weakened connection information outflow in the left frontal pole and the posterior temporal pole at baseline. After 10-day rTMS treatment, the network patterns showed weakened connection information outflow in the left frontal and temporal regions. The time-varying EEG network changes induced by TMS perturbation targeting right DLPFC in patients with GAD were characterized by insufficient information outflow in the left frontal and temporal regions. Low-frequency rTMS targeting the right DLPFC reversed these abnormalities and improved the clinical symptoms of GAD.

MEG activity of the dorsolateral prefrontal cortex during optic flow stimulations detects mild cognitive impairment due to Alzheimer's disease.

Dorsal stream, which has a neuronal connection with dorsolateral prefrontal cortex (DLPFC), is known to be responsible for detection of motion including optic flow perception. Using magnetoencephalography (MEG), this study aimed to examine neural responses to optic flow stimuli with looming motion in the DLPFC in patients with mild cognitive impairment due to Alzheimer’s disease (AD-MCI) compared with cognitively unimpaired participants (CU). We analyzed the neural responses by evaluating maximum source-localized power for the AD-MCI group (n = 11) and CU (n = 20), focusing on six regions of interest (ROIs) that form the DLPFC: right and left dorsal Brodmann area 9/46 (A9/46d), Brodmann area 46 (A46) and ventral Brodmann area 9/46 (A9/46v). We found significant differences in the maximum power between the groups in the left A46 and A9/46v. Moreover, in the left A9/46v, the maximum power significantly correlated with the Wechsler Memory Scale-Revised general memory score and delayed recall score. The maximum power in the left A9/46v also revealed high performance in AD-MCI versus CU classification with the area under the ROC curve of 0.90. This study demonstrated that MEG during the optic flow task can be useful in discriminating AD-MCI from CU.

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.

Dorsolateral Prefrontal Cortex Single Nuclei Tensor Decomposition Identifies Shared Genetic Risk for Major Depressive Disorder and Schizophrenia in Suicidal Subjects

Previous reports on brain co-expression networks have assigned genes to unique co-expression gene sets using cluster-based strategies. This feature is incompatible with the diversity of cell populations involved. We investigated gene co-expression in single nuclei RNA-sequencing from the dorsolateral prefrontal cortex of patients with Major Depressive Disorder (MDD) and neurotypical controls (NC) using Tensor Models to identify components with overlapping gene memberships. We associated co-expression components with diagnosis and risk for psychiatric disorders.

Efficacy of High-Frequency Rhythmic Transcranial Magnetic Stimulation in Endogenous Depressive Disorders at Juvenile Age

Objectives. To seek neurophysiological predictors of the effi cacy of rhythmic transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex in patients with depressive disorders of different nosological categories. Materials and methods. A total of 34 juvenile patients (all male) with protracted treatment-refractory depressive states were studied. Investigation of patients used psychopathological and psychometric methods (Hamilton scale) and electroencephalography. The search for predictors of therapeutic efficacy was carried out using a wide range of neurophysiological indicators and different protocols for high-frequency rTMS (10 and 20 Hz). Results and conclusions. The most significant changes were identified on rTMS at 20 Hz. Favorable treatment effects on the EEG were found to correlate with higher spectral power in the α and β1 subranges.