Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged -〉 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions： anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only （partial coefficient = 0.453, P = 0.045）, after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.661, P = 0.001） and between the left prefrontal cortex volume and Verbal Fluency Test （partial coefficient = 0.573, P = 0.004） in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.

Neuronal degeneration in the hippocampus and dorsolateral prefrontal cortex in depressive disorder Correlation between ~1H-MRS and Minnesota Multiphasic Personality Inventory

Previous studies using magnetic resonance imaging（MRI）and functional MRI to study depression have primarily focused on proton magnetic resonance spectroscopy（1H-MRS）appearance in various areas of the brain and volume measurements in the limbic system.However,results have not been consistent.To the best of our knowledge,very little is known about the relationship between 1H-MRS appearance and depression inventory.In the present study,the relationship between 1H-MRS appearance in depressive patients and Minnesota Multiphasic Personality Inventory-2 scale was analyzed.MRI and 1H-MRS exhibited widened sulci and cisterns,as well as an absence of abnormal signals in depressive patients.In addition,N-acetyl aspartate/total creatine ratios in bilateral hippocampi and dorsolateral prefrontal cortex were significantly less in depressive patients than in control subjects（P 〈 0.01）.In contrast,choline-containing compounds/total creatine ratios in the dorsolateral prefrontal cortex were significantly greater in depressive patients than in control subjects（P 〈 0.01）.These ratios significantly and positively correlated with patient total depression scores as assessed using the Minnesota Multiphasic Personality Inventory-2 scale（r=0.934 7,0.878 7,P 〈 0.01）.These results suggested that 1H-MRS could be used to reveal a reduced number of neurons in the hippocampus and dorsolateral prefrontal cortex,as well as altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex,in patients with depressive disorder.Abnormal mechanisms partially reflected severity of depressive disorder.

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

Positive Effect of Transcranial Direct Current Stimulation on Visual Verbal Working Memory in Patients with Attention-Deficit/Hyperactivity Disorder

Background: Working memory is an executive function that plays an important role in many aspects of daily life, and its impairment in patients with attention-deficit/hyperactivity disorder (ADHD) affects quality of life. The dorsolateral prefrontal cortex (DLPFC) has been a good target site for transcranial direct current stimulation (tDCS) due to its intense involvement in working memory. In our 2018 study, tDCS improved visual-verbal working memory in healthy subjects. Objective: This study examines the effects of tDCS on ADHD patients, particularly on verbal working memory. Methods: We conducted an experiment involving verbal working memory of two modalities, visual and auditory, and a sustained attention task that could affect working memory in 9 ADHD patients. Active or sham tDCS was applied to the left DLPFC in a single-blind crossover design. Results: tDCS significantly improved the accuracy of visual-verbal working memory. In contrast, tDCS did not affect auditory-verbal working memory and sustained attention. Conclusion: tDCS to the left DLPFC improved visual-verbal working memory in ADHD patients, with important implications for potential ADHD treatments.

Dorsolateral prefrontal cortex, working memory and episodic memory processes: insight through transcranial magnetic stimulation techniques

The ability to recall and recognize facts we experienced in the past is based on a complex mechanism in which several cerebral regions are implicated. Neuroimaging and lesion studies agree in identifying the frontal lobe as a crucial structure for memory processes, and in particular for working memory and episodic memory and their relationships. Furthermore, with the introduction of transcranial magnetic stimulation （TMS） a new way was proposed to investigate the relationships between brain correlates, memory functions and behavior. The aim of this review is to present the main findings that have emerged from experiments which used the TMS technique for memory analysis. They mainly focused on the role of the dorsolateral prefrontal cortex in memory process. Furthermore, we present state-of-the-art evidence supporting a possible use of TMS in the clinic. Specifically we focus on the treatment of memory deficits in depression and anxiety disorders.

Structural Asymmetry of Dorsolateral Prefrontal Cortex Correlates with Depressive Symptoms： Evidence from Healthy Individuals and Patients with Major Depressive Disorder

In this study,we investigated the role of structural asymmetry of the dorsolateral prefrontal cortex（DLPFC） in the continuum of depression from healthy individuals to patients.Structural magnetic resonance imaging was performed in 70 patients with major depressive disorder（MDD）,49 matched controls,and 349 healthy university students to calculate structural asymmetry indexes of the DLPFC.First-episode,treatment-naive MDD patients showed a relatively lower asymmetry index than healthy controls,and their asymmetry index was negatively correlated with the depressive symptoms.This abnormality was normalized by antidepressants in medicated MDD patients.Furthermore,the asymmetry index was negatively correlated with the depressive symptoms in university students;this was replicated at two time points in a subgroup of students,suggesting good test-retest reliability.Our findings are consistent with previous studiesthat support the imbalance hypothesis of MDD and suggest a potential structural basis underlying the functional asymmetry of the DLPFC in depression.In future,the structural index of the DLPFC may become a potential biomarker to evaluate individuals＇ risk for the onset of MDD.

Schizophrenia-associated MicroRNA–Gene Interactions in the Dorsolateral Prefrontal Cortex

Schizophrenia-associated anomalies in gene expression in postmortem brain can be attributed to a combination of genetic and environmental influences. Given the small effect size of common variants, it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. At the gene level, however, there may be more impact from common environmental exposures mediated by influential epigenomic modifiers, such as microRNA(miRNA). We hypothesise that dysregulation of miRNAs and their alteration of gene expression have significant implications in the pathophysiology of schizophrenia. In this study, we integrate changes in cortical gene and miRNA expression to identify regulatory interactions and networks associated with the disorder. Gene expression analysis in post-mortem prefrontal dorsolateral cortex(BA 46)(n = 74 matched pairs of schizophrenia, schizoaffective, and control samples)was integrated with miRNA expression in the same cohort to identify gene–miRNA regulatory networks. A significant gene–miRNA interaction network was identified, including miR-92 a, miR-495,and miR-134, which converged with differentially expressed genes in pathways involved in neurodevelopment and oligodendrocyte function. The capacity for miRNA to directly regulate gene expression through respective binding sites in BCL11 A, PLP1, and SYT11 was also confirmed to support the biological relevance of this integrated network model. The observations in this study support the hypothesis that mi RNA dysregulation is an important factor in the complex pathophysiology of schizophrenia.

The dorsolateral pre-frontal cortex bi-polar error-related potential in a locked-in patient implanted with a daily use brain–computer interface

While brain computer interfaces(BCIs)ofer the potential of allowing those sufering from loss of muscle control to once again fully engage with their environment by bypassing the afected motor system and decoding user intentions directly from brain activity,they are prone to errors.One possible avenue for BCI performance improvement is to detect when the BCI user perceives the BCI to have made an unintended action and thus take corrective actions.Error-related potentials(ErrPs)are neural correlates of error awareness and as such can provide an indication of when a BCI system is not performing according to the user’s intentions.Here,we investigate the brain signals of an implanted BCI user sufering from locked-in syndrome(LIS)due to late-stage ALS that prevents her from being able to speak or move but not from using her BCI at home on a daily basis to communicate,for the presence of error-related signals.We frst establish the presence of an ErrP originating from the dorsolateral pre-frontal cortex(dLPFC)in response to errors made during a discrete feedback task that mimics the click-based spelling software she uses to communicate.Then,we show that this ErrP can also be elicited by cursor movement errors in a continuous BCI cursor control task.This work represents a frst step toward detecting ErrPs during the daily home use of a communications BCI.

Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials

Transcranial direct current stimulation(tDCS)has been reportedly beneficial for different neurodegenerative disorders.tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH).This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs).The databases of PsycINFO(2000–2019),PubMed(2000–2019),EMBASE(2000–2019),CINAHL(2000–2019),Web of Science(2000–2019),and Scopus(2000–2019)were systematically searched.The clinical trials with RCT design were selected for final analysis.A total of nine RCTs were eligible and included in the review.Nine RCTs were included in the final analysis.Among them,six RCTs reported a significant reduction of AVH after repeated sessions of tDCS,whereas three RCTs did not show any advantage of active tDCS over sham tDCS.The current studies showed an overall decrease of approximately 28%of AVH after active tDCS and 10%after sham tDCS.The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions.In this regard,cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs.The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA,20-minute duration)over 5 consecutive days(10 sessions)with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area.Some patient-specific and diseasespecific factors such as young age,nonsmoking status,and higher frequencies of AVHs seemed to be the predictors of treatment response.Taken together,the results of tDCS as an alternative treatment option for AVH show controversy among current literatures,since not all studies were positive.However,the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH.Further RCTs,with larger sample sizes,should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting.

Takeda G protein-coupled receptor 5 modu⁃lates depression-like behaviors via hippocam⁃pal CA3 pyramidal neurons afferent to dorso⁃lateral septum

OBJECTIVE Takeda G protein-coupled receptor 5(TGR5)is recognized as a promising target for type 2 diabetes and metabolic syndrome;its expression has been demonstrat⁃ed in the brain and is thought to be neuroprotec⁃tive.Here,we hypothesize that dysfunction of central TGR5 may contribute to the pathogene⁃sis of depression.METHODS In well-established chronic social defeat stress(CSDS)and chronic restraint stress(CRS)models of depression,we investigated the functional roles of TGR5 in CA3 pyramidal neurons(PyNs)and underlying mech⁃anisms of the neuronal circuit in depression(for in vivo studies,n=10;for in vitro studies,n=5-10)using fiber photometry;optogenetic,chemoge⁃netic,pharmacological,and molecular profiling techniques;and behavioral tests.RESULTS Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs.Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777,a specific agonist,protected against CSDS and CRS,exerting sig⁃nificant antidepressant-like effects that were mediated via CA3 PyN activation.Conversely,genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behav⁃iors.Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS.Silencing and stimula⁃tion of CA3 PyNs→somatostatin-GABAergic(gamma-aminobutyric acidergic)neurons of the dorsolateral septum circuit bidirectionally regulat⁃ed depression-like behaviors,and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs.CON⁃CLUSION TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission,suggesting that TGR5 could be a novel target for developing antidepressants.

Transcriptomic analyses of humans and mice provide insights into depression

Accumulating studies have been conducted to identify risk genes and relevant biological mechanisms underlying major depressive disorder(MDD).In particular,transcriptomic analyses in brain regions engaged in cognitive and emotional processes,e.g.,the dorsolateral prefrontal cortex(DLPFC),have provided essential insights.Based on three independent DLPFC RNA-seq datasets of 79 MDD patients and 75 healthy controls,we performed differential expression analyses using two alternative approaches for cross-validation.We also conducted transcriptomic analyses in mice undergoing chronic variable stress(CVS)and chronic social defeat stress(CSDS).We identified 12 differentially expressed genes(DEGs)through both analytical methods in MDD patients,the majority of which were also dysregulated in stressed mice.Notably,the mRNA level of the immediate early gene FOS(Fos proto-oncogene)was significantly decreased in both MDD patients and CVS-exposed mice,and CSDSsusceptible mice exhibited a greater reduction in Fos expression compared to resilient mice.These findings suggest the potential key roles of this gene in the pathogenesis of MDD related to stress exposure.Altered transcriptomes in the DLPFC of MDD patients might be,at least partially,the result of stress exposure,supporting that stress is a primary risk factor for MDD.

Assessment of Stress Cognitive Control and Executive Function with Stress Control Rating Scale (ECOSTRESS) and Low Resolution Brain Electromagnetic Tomography (LORETA) (In Portuguese People in Situations of Unemployment and Economic Insufficiency)

This article reviews the constructs of stress, appraisal, coping, according to a transactional perspective, and executive function, and presents a stress control rating scale (ECOSTRESS), which design is founded in these constructs. This psychometric tool is useful in the assessment of cognitive control of stress, correlated with the function of dorsolateral prefrontal cortex. It has been validated for its use in the assessment of Portuguese people in situations of stress related to unemployment and economic insufficiency. Also, within the context of the cognitive control of stress, it is highlighted the usefulness of low resolution brain electromagnetic tomography (LORETA).

Neural and Cognitive Markers and Regulation of Emotion in Depression: A Mini-Review and a Short Case Report

In the presented short clinical case of depression, the constructs of Research Domain Criteria (RDoC) of loss (negative valence systems) and cognitive control (cognitive systems) have been operationalized. It has been concluded that a normal cognitive control of emotion, requiring the functional and structural integrity of prefrontal cortex (PFC) and orbitofrontal cortex (OFC), is lacking in depression, but its amelioration can be achieved through the implementation of cognitive remediation/rehabilitation programs. A mini-review on neural and cognitive markers and regulation of emotion in depression is previously presented.

Longitudinal rCBF Changes Measured with SPECT in Patients with Depression Undergoing Treatment

Regional cerebral blood flow (rCBF) studies of major depression have yielded variable results. The present study employed a longitudinal observation method to measure rCBF every 3 months during treatment. Thirteen patients with major depressive disorder underwent single-photon emission computed tomography (SPECT) with 99mTc-HMPAO three times over a 6-month period. rCBF was analyzed with the Statistical Parametric Mapping. The findings were compared to scans from 14 normal control subjects. Depression symptoms were rated using the Hamilton Rating Scale for Depression. At baseline, the main regions with lower rCBF compared to controls were the middle and inferior frontal gyri, superior temporal gyrus, and cingulate cortex. Three months later, despite significant improvement of depressive symptoms, decreased rCBF was observed in the same regions, but to lesser extent. At 6 months, depressive symptoms showed continued improvement, and rCBF in the superior temporal gyrus increased up to control levels, but rCBF in the temporal pole, cingulate, and inferior frontal gyrus remained low. The results of the present study suggest that there might be time- and state-dependent differences in rCBF recovery in patients with major depression.

Sufficiently Elevated Core Body Temperature May Be Necessary to Maintain Cerebral Blood Flow Response throughout the Morning

In comparison to a carbohydrate-rich breakfast, a nutritionally balanced breakfast reportedly leads to a higher core body temperature because of diet-induced thermogenesis (DIT) and also results in higher task performance. This study aimed to examine the relationships among the core body temperature, blood glucose level, cerebral blood flow, and cognitive performance when the core body temperature is raised to a similar extent as in DIT in the morning. This crossover study included 18 male participants who performed four sets of cognitive tests in the morning with four different foot baths and glucose intake conditions. In elevated body temperature (EBT) conditions, the core body temperature was increased by a foot bath at 42˚C or 39˚C, while in low body temperature (LBT) conditions, it was maintained at 35˚C by a foot bath;the participants received no glucose or two intakes of 20-g glucose for each thermal condition. In addition to the core body temperature measurement, the cerebral blood flow in the dorsolateral prefrontal cortex (DLPFC) was measured using near-infrared spectroscopy. Three blood collections were performed to measure the changes in blood glucose levels. The results revealed that in the EBT conditions, the core body temperature remained 0.3˚C - 0.5˚C higher than that at wake-up time, while the glucose intake conditions increased blood glucose levels which remained higher than those during fasting. No significant between-treatment difference was observed in the results of cognitive tests. However, the blood flow in the DLPFC increased during the second test period in the EBT/glucose and LBT/glucose conditions, whereas during the fourth test period, it increased solely in the EBT/glucose condition. Thus, in addition to the blood glucose level, an elevated core body temperature within the physiological range may be needed for long-term maintenance of the cerebral blood flow response.

Stress prevention by modulation of autonomic nervous system (heart rate variability): A preliminary study using transcranial direct current stimulation

Introduction: Transcranial Direct Current Stimulation (tDCS) is a non-invasive, technique for brain stimulation. Anodal stimulation causes neuronal depolarisation and long-term potentiation, while cathodal stimulation causes hyperpolarisation and long-term depression. Stressors are associated with an increase in sympathetic cardiac control, a decrease in parasympathetic control, or both. Associated with these reactions is a frequently reported increase in Low Frequency (LF) Heart Rate Variability (HRV), a decrease in High Frequency (HF) power, and/or an increase in the LF/HF ratio. Objectives and aims: The present work aims to explore the tDCS potential in the modulation of the Autonomic Nervous System (ANS), through indirect stimulation of Anterior Cingulate Cortex (ACC). Methods: Two subjects, a 39 year old female and a 49 year old male, gave informed consent. Saline soaked synthetic sponges involving two, thick, metalic (stainless steel) rectangles, with an area of 25 cm2 each have been used as electrodes, connected to Iomed Phoresor II Auto device. It has been delivered a 2 mA current, for 20 minutes, over the left Dorsolateral Prefrontal Cortex (DLPFC) (Anode). Spectrum analysis (cStress software) of HRV has been performed before and after tDCS administration. Results: The female/male subject results of LF power, HF power and LF/HF ratio, before tDCS administration, were, respectively: 50.1 nu/60 nu, 46.1 nu/21.7 nu and 1.087/2.771;and, after tDCS administration, respectively: 33.5 nu/52.7 nu, 47.6 nu/ 22.8 nu and 0.704/2.312. Conclusions: tDCS over the left DLPFC (left ACC) increased parasympathetic activity and decreased sympathetic activity, suggesting the importance of tDCS in the management of stress-related disorders.

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation.This stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal cortex(DLPFC)interacts with the hippocampus in the online processing of sequential information.Twenty patients with epilepsy(eight women,age 27.6±8.2 years)completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus.Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise(random trials)than to maintain ordered lines(ordered trials)before recalling the orientation of a particular line.First,the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC(3–10 Hz).In particular,the hippocampal theta power increase correlated with the memory precision of line orientation.Second,theta phase coherences between the DLPFC and hippocampus were enhanced for ordering,especially for more precisely memorized lines.Third,the theta band DLPFC→hippocampus influence was selectively enhanced for ordering,especially for more precisely memorized lines.This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation

The rostral agranular insular cortex(RAIC)has been associated with pain modulation.Although the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive under the neuropathic pain state.Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve(CPN)ligation.The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice,glutamatergic,or GABAergic neuron cannabinoid receptor 1(CB1R)knockdown mice with the whole-cell patch-clamp and pain behavioral methods.The E/I ratio(amplitude ratio between mEPSCs and mIPSCs)was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice.Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice.The analgesic effect of ACEA(a CB1R agonist)was alleviated along with bilateral dorsolateral funiculus lesions,with the administration of AM251(a CB1R antagonist),and in CB1R knockdown mice in GABAergic neurons,but not glutamatergic neurons of the RAIC.Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.

Transcranial Direct Current Stimulation in ADHD:A Systematic Review of Efficacy,Safety,and Protocol-induced Electrical Field Modeling Results

Transcranial direct current stimulation(tDCS)is a promising method for altering cortical excitability with clinical implications.It has been increasingly used in neurodevelopmental disorders,especially attention-deficit hyperactivity disorder(ADHD),but its efficacy(based on effect size calculations),safety,and stimulation parameters have not been systematically examined.In this systematic review,we aimed to(1)explore the effectiveness of tDCS on the clinical symptoms and neuropsychological deficits of ADHD patients,(2)evaluate the safety of tDCS application,especially in children with ADHD,(3)model the electrical field intensity in the target regions based on the commonly-applied and effective versus less-effective protocols,and(4)discuss and propose advanced tDCS parameters.Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach,a literature search identified 14 empirical experiments investigating tDCS effects in ADHD.Partial improving effects of tDCS on cognitive deficits(response inhibition,working memory,attention,and cognitive flexibility)or clinical symptoms(e.g.,impulsivity and inattention)are reported in10 studies.No serious adverse effects are reported in 747 sessions of tDCS.The left and right dorsolateral prefrontal cortex are the regions most often targeted,and anodal tDCS the protocol most often applied.An intensity of 2 mA induced stronger electrical fields than 1 mA in adults with ADHD and was associated with significant behavioral changes.In ADHD children,however,the electrical field induced by 1 mA,which is likely larger than the electrical field induced by 1 mA in adults due to the smaller head size of children,was sufficient to result in significant behavioral change.Overall,tDCS seems to be a promising method for improving ADHD deficits.However,the clinical utility of tDCS in ADHD cannot yet be concluded and requires further systematic investigation in larger sample sizes.Cortical regions involved in ADHD pathophysiology,stimulation parameters(e.g.intensity,duration,polarity,and electrode size),and types of symptom/deficit are potential determinants of tDCS efficacy in ADHD.Developmental aspects of tDCS in childhood ADHD should be considered as well.

ZNF804A Variation May Affect Hippocampal-Prefrontal Resting-State Functional Connectivity in Schizophrenic and Healthy Individuals

The ZNF804 A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804 A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity（RSFC） between the hippocampus and the dorsolateral prefrontal cortex（DLPFC） in both schizophrenic patients and healthy controls. The homozygous ZNF804 A rs1344706 genotype（AA） conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC（F（2,165） = 13.43,P ／ 0.001）. The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804 A rs1344706 on hippocampalprefrontal RSFC associated with schizophrenia.