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.

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.

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.

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.

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.

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.

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.

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.

Noninvasive brain stimulation of addiction:one target for all?

Noninvasive brain stimulation includes repetitive transcranial magnetic stimulation(rTMS)and transcranial direct current stimulation(tDCS),and emerges as a prospective approach for addiction treatment in clinical practices.The dorsolateral prefrontal cortex(DLPFC)is regarded as the most effective stimulation target,giving its important position in controlling cue-elicited drug craving and initiating drug abuse.In this paper,through literature searches(e.g.Pubmed,Google Scholar),34 studies(2003–2021)were identified examining the effect of rTMS,tDCS on cravings,and consumption of substance use disorders,including tobacco,alcohol,opioids,and stimulants.We summarize the main methods,designs,and effects of rTMS or tDCS that are delivered to the DLPFC on different types of addiction.We conclude that targeting DLPFC might be effective for all types of drug addiction.