Dorsolateral Prefrontal Areas Research Articles

Association between intra-individual variability and prefrontal cortex activity measured by functional Near Infrared Spectroscopy (fNIRS) in children with ADHD

ABSTRACT This study uses fNIRS to determine whether there is a difference in the relationship between intra-individual variability and frontal lobe activity between ADHD patients and typically developing children. A total of 28 subjects (14 in ADHD patient group and 14 in control group) participated in this study. The subjects were tested for K-SADS and intelligence, and then the frontal lobe activity of the subjects was measured by continuous performance test, using functional near-infrared spectroscopy (NIRSIT). Processing speed index was significantly lower in the ADHD patient group than in the control group (p = .04). The CPT test results showed a positive correlation in the activity of the right dorsolateral prefrontal region in the patient group, but not at a statistically significant level. In the control group, activity showed a significant level of negative correlation with commission and hit reaction time standard deviation (p = .023; p = .063 respectively). In contrary to ADHD patient group, activation of the right dorsolateral prefrontal area was significantly correlated with reduction of intra-individual variability. This result showing that the relationship between activation of the right dorsolateral prefrontal area of the ADHD patient group and intra-individual variability shows a different pattern from typically developing children.

Verbal learning in frontal patients: area 9 is critical for employing semantic strategies.

Learning is a long-term memory process heavily influenced by the control processes implemented by working memory, including recognition of semantic properties of items by which subjects generate a semantic structure of engrams. The aim of this study is to investigate the verbal learning strategies of patients affected by a tumor in the left frontal lobe to highlight the role of area 9. Ten patients with frontal low-grade gliomas and ten healthy control subjects, matched for age, sex and education, were recruited and then evaluated with a two-part verbal learning test: multi-trial word list learning in free recall, and multi-trial word list learning preceded by an explicit semantic strategy cue. Frontal patients were divided into two groups: those either with frontal lesions involving or sparing area 9. In comparison to healthy control subjects, frontal patients with lesions involving area 9 memorized fewer words and displayed difficulty in using semantic strategies. When the strategy was suggested by the examiner, their performance improved, but to a lesser extent than the healthy control. Conversely, frontal patients with lesions sparing area 9 showed similar results to healthy control subjects. The results suggested that, while the identification of the categorical criterion requires the integrity of the entire dorsolateral prefrontal area, only area 9, and not the surrounding areas, could be responsible for the effective use of semantic strategies in learning tasks.

Impact of Repetitive Transcranial Magnetic Stimulation on Cognitive and Psychiatric Dysfunction in Patients with Fibromyalgia: A Double-Blinded, Randomized Clinical Trial.

Few randomized controlled trials have reported that repetitive transcranial magnetic stimulation (rTMS) has controversial results for managing multiple domains of fibromyalgia-related symptoms. This work aimed to evaluate the effect of low-frequency rTMS over the right dorsolateral prefrontal area (DLPFC) on the Fibromyalgia Impact Questionnaire (FIQ) concerning psychiatric and cognitive disorders. Forty-two eligible patients with fibromyalgia (FM) were randomized to have 20 sessions of active or sham rTMS (1 Hz, 120% of resting motor threshold with a total of 1200 pules/session) over the right DLPFC. All participants were evaluated at baseline, post sessions, and 3 months after sessions with the FIQ, Hamilton depression, and anxiety rating scales (HDRS and HARS), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Tower of London test (TOL), the Trail Making, and Digit Span Tests. Both groups showed improvement in most rating scales at 1 and 3 months follow-up, with greater improvement in the active group, with significant correlation between FIQ cognitive rating scales, including RAVLT and TOL. Twenty sessions of low-frequency rTMS over the right DLPFC can improve FIQ scores regarding the psychiatric and cognitive symptoms of medicated patients with FM to a greater extent than sham. Changes in RAVLT and TOL correlated with changes in FIQ results.

Anxiety symptoms without depression are associated with cognitive control network (CNN) dysfunction: An fNIRS study.

Anxiety is a common psychological disorder associated with other mental disorders, with depression being the most common comorbidity. Few studies have examined the neural mechanisms underlying anxiety after controlling for depression. This study aimed to explore whether there are differences in cortical activation in anxiety patients with different severities whose depression are normal. In the current study, depression levels were normal for 366 subjects-139 healthy subjects, 117 with mild anxiety, and 110 with major anxiety. Using the Hospital Anxiety and Depression Scale (HADS) and a verbal fluency task (VFT) to test subjects' anxiety and depression and cognitive function, respectively. A 53-channel guided near-infrared spectroscopic imaging technology (fNIRS) detected the concentration of oxyhemoglobin (oxy-Hb). Correlation analysis between anxiety severity and oxy-Hb concentration in the brain cortex was performed, as well as ANOVA analysis of oxy-Hb concentration among the three anxiety severity groups. The results showed that anxiety severity was significantly and negatively correlated with oxy-Hb concentrations in the left frontal eye field (lFEF) and in the right dorsolateral prefrontal area (rDLPFC). The oxy-Hb concentration in the lFEF and the rDLPFC were significantly lower in the major anxiety disorder group than that in the control group. This suggests that decreased cortical activity of the lFEF and rDLPFC may be neural markers of anxiety symptoms after controlling for depression. Anxiety symptoms without depression may be result from the dysfunction of the cognitive control network (CCN) which includes the lFEF and rDLPFC.

Meta-modeling the effects of anodal left prefrontal transcranial direct current stimulation on working memory performance

Abstract Numerous studies have demonstrated the beneficial effects of anodal prefrontal transcranial direct current stimulation (tDCS) on working memory. However, a large variability exists in the applied tDCS parameters and working memory outcome measures. Using a meta-modeling approach, we investigated the relationship between tDCS electric fields in the left prefrontal cortex and improvements in working memory performance. Using this approach, a vector of outcome measures is correlated with the tDCS-related electric fields across several studies. These performance-electric field correlations (PEC) are calculated for each spatial location of the grey matter. Extracting 354 data points from 67 studies, we compared the spatial maps of tDCS effects on I) working memory accuracy and speed (regardless of working memory type and time of assessment), II) verbal and visuospatial working memory (regardless of performance measurement and time of assessment), and III) performance during and after stimulation (regardless of performance measurement and working memory type). We found that accuracy improves when anodal tDCS is applied to inferior frontal regions (Brodmann area 47) while working memory speed benefits from stimulation to dorsolateral and anterior prefrontal areas (Brodmann areas 9/10). Furthermore, the beneficial effects of left prefrontal tDCS are exclusive to verbal working memory, with no improvements in visuospatial working memory. We also observed region-specific effects only for task performance during, but not after, stimulation. The results of this study elucidate the causal involvement of prefrontal regions in working memory and can help guide tDCS placement for therapeutic application in disorders that involve working memory deficits.

Strong but Fragmented Memory of a Stressful Episode.

While it is commonly assumed that stressful events are vividly remembered, it remains largely unknown whether all aspects of memory for a stressful episode are enhanced. In this preregistered study, we tested whether stress enhances later remembering of individual elements of a stressful episode at the cost of impaired processing of the association between these elements. Therefore, male and female participants (N = 122) underwent a stressful (or control) episode during which they encoded a series of stimuli. To investigate stress effects on the memory for individual events and the links between these, we used temporal sequence effects in recognition memory tested 24 h after encoding. Specifically, we tested whether stress would affect the memory enhancement for a target item if this is preceded by another item that also preceded the target during encoding (recognition priming). Our results showed that participants recalled single events encoded under stress better than those encoded under nonstressful conditions, but were less able to leverage the temporal sequence of events encoded under stress to cue memory at delayed recall, reflected in reduced memory for items preceded by the item that preceded them also during encoding. Functional near-infrared spectroscopy further revealed that encoding under stress was accompanied by opposite changes in inferotemporal and dorsolateral prefrontal areas. Together, our data suggest that acute stress induces a mode of memory formation that results in strong but less integrated memories.

Anxious individuals shift emotion control from lateral frontal pole to dorsolateral prefrontal cortex

Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPl) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPl-based emotional action control fails in highly-anxious individuals. Their FPl is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPl during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPl excitability and amygdalofugal projections strength. The findings characterize circuit-level vulnerabilities in anxious individuals, showing that even mild emotional challenges can saturate FPl neural range, leading to a neural bottleneck in the control of emotional action tendencies.

Influence of Transcranial Direct Current Stimulation and Exercise on Physical Capacity and Gait in Multiple Sclerosis: A Cross-Over Pilot Study.

Physical capacity provides a link between disease or impairment and limitations in activity; in multiple sclerosis (MS), it is limited and decreased. The aim of this study was to study the effects of exercise and transcranial direct current stimulation (tDCS) on the left dorsolateral prefrontal cortex area in MS patients with fatigue and an impaired gait ability. A cross-over design was carried out on fifteen patients with two disability associations, but three were excluded. Before and after each intervention, the 6 min walk test (6MWT) and the 2 min walk test (2MWT) were used to assess walking ability and the Modified Fatigue Impact Scale (MFIS) was used to assess fatigue. A total of twelve patients were enrolled (48.0 median age, Kurtzke Disability Scale (EDSS) 3.66 ± 1.3): five females and seven males. After the application of the exercise program, significant improvements were observed in the 6MWT (p < 0.001, g = 0.159) and 2MWT (p < 0.001, g = 0.182). Furthermore, fatigue was significantly reduced after the application of the exercise program (p < 0.05, g = 0.742) and after tDCS (p < 0.05, g = 0.525). We could consider therapeutic exercise in the future to improve the walking ability and fatigue in MS patients. Furthermore, tDCS did not exert a significant improvement in walking ability, but it appeared to influence fatigue. Clinical trial registration code: ACTRN12622000264785.

Interaction of Person-Affect-Cognition-Execution (I-PACE) Model on Addictive Behavior

AbstractsIntroductions: Adiction is a pattern of substance abuse behavior characterized by overuse of the substance (compulsive use), the safety of its availability, and a high likelihood of relapse after discontinuation. There are 3 (three) stages of addiction, those are a stage of internal change, lifestyle change, and life breakdown. Objectives: This study aims to explore the I-PACE concepts about its components and their relation with the emergence of addictive usage of certain internet services including gaming, online gambling, pornography addiction, online shopping, and social networking. Methods: This study is a literature review that collects from various source of scientific journals related to the psychiatric management of the disorder. Several studies from the international database Pubmed Central including textbooks review papers, comments, and editorials are reviewed to evaluate I-PACE concepts concerning the components and their interaction with addictive behavior. Results: The findings show that the I-PACE model which includes the P component (person), the A component (affective), the C component (cognitive), and the E component (executive function) explains the disruption in a person’s decision-making. The anatomy of the frontostriatal circuit, notably between the ventral striatum, amygdala, and dorsolateral prefrontal area, is particularly significant for the early stages of the addictive process and the dorsal striatum for the latter stages. Conclusions: Interactions between components that occur in certain situations will result in addictive behavior due to the formation of satisfaction and compensation related to that behavior .

FMRI neurofeedback leads to long-term symptomatic reduction in treatment-resistant patients with obsessive-compulsive disorder

Introduction Obsessive‐compulsive disorder (OCD) is a severe condition with a profound impact on the health, social and professional functioning of the patients. More than one third of the patients do not achieve remission of the symptoms after first‐line treatment with cognitive‐behavioral therapy and selective serotonin reuptake inhibitor medication. Neurofeedback is a promising technique that allows the non‐invasive self‐regulation of neural activity associated with symptomatic manifestation. Previous literature reported preliminary evidence of positive effects of functional magnetic resonance imaging (fMRI) neurofeedback on OCD symptoms. However, these studies have small samples and/or were not controlled. Additionally, these studies did not involve treatment‐resistant patients. Objectives We aim at developing a fMRI neurofeedback task to treatment-resistant OCD patients and to explore the underlying brain changes. Methods We implemented a sham‐controlled double‐blinded fMRI neurofeedback protocol to target hyperactivity in orbitofrontal regions in treatment‐resistant OCD patients with contamination/cleaning symptoms. The protocol had two sessions of neurofeedback (72 min of total training). The patients included were under treatment‐as‐usual. Results Our preliminary results with the experimental group (n = 10 patients) demonstrated decreased OCD and stress symptoms three months after the neurofeedback sessions. Moreover, immediately after the neurofeedback sessions, we observed reduced functional connectivity between orbitofrontal and temporoparietal regions, and increased brain activity in dorsolateral prefrontal and premotor areas during symptomatic provocation. The brain functional changes might be associated with a better control over obsessions. Conclusions fMRI neurofeedback led to long-term symptomatic reduction in treatment-resistant patients with OCD. Our results need further validation with the sham‐control group but highlight the efficacy of fMRI neurofeedback for refractory OCD and the necessity of prolonged neurofeedback protocols. Disclosure of Interest None Declared

Effectiveness of Transcranial Direct Current Stimulation in Behavioral and Cognitive Aspects of Executive Function in Children with Autism Spectrum Disorder

Background: Despite their high effectiveness, rehabilitation therapies can reduce the number of families with children with autism spectrum disorder (ASD) visiting clinics due to the number of treatment sessions and the long duration of treatment. The use of technological methods, such as transcranial direct current stimulation (tDCS) as one of the therapeutic interventions to improve cognitive function in rehabilitation clinics, can help reduce the duration of treatment for these children. Objectives: The present study was carried out to examine the effectiveness of tDCS in behavioral and cognitive aspects of executive functions in children with ASD. Methods: A pretest and posttest design with follow-up were used in this study. The subjects were children with high-functioning ASD aged 8 - 11 years who were selected by the convenience sampling method from occupational therapy clinics in Tehran, Iran. A total of 20 eligible candidates were included in the study according to inclusion and exclusion criteria. The subjects were randomly divided into two groups (10 subjects in each group). The intervention group received tDCS during 12 sessions of 20 minutes in the dorsolateral prefrontal cortex area, with an electrode size of 35 cm2 for 3 weeks (four sessions per week). The control group received common cognitive interventions used in occupational therapy clinics in 12 sessions of 60 minutes (one hour) for 6 weeks (two sessions per week). Follow-up was performed one month after the end of the interventions. The research instruments included the Behavior Rating Inventory of Executive Function and computer-based tests, such as the Tower of London, Wisconsin Card Sorting Test, and Stroop test. Results: The results demonstrated that tDCS, similar to cognitive rehabilitation, could affect the cognitive functions of the brain, such as executive functions, and several basic cognitive processes, such as inhibitory control, cognitive flexibility, and mental planning. Conclusions: The findings recommended using tDCS as a new intervention method to improve the cognitive function of individuals with ASD. This is due to the lasting effect of the results of this intervention as a technological instrument with faster results than other clinical interventions.

Increased cortical activation and enhanced functional connectivity in the prefrontal cortex ensure dynamic postural balance during dual-task obstacle negotiation in the older adults: A fNIRS study

ObjectiveBy analyzing the cortical activation and functional connectivity of the prefrontal cortex (PFC) during dual-task obstacle negotiation in the older adults, cognitive resources allocation and neural regulatory mechanisms of aging brain were shed light on in complex walking conditions. MethodsTwenty-eight healthy right-handed subjects participated in the study, including 15 men and 13 women (age: 68.6 ± 4.1 years, height: 162.96 ± 6.05 cm, weight: 63.63 ± 9.64 kg). There were four tasks: Normal Walk (NW), Obstacle Negotiation during Normal Walk (NW + ON), Walk while performing Cognitive Task (WCT), and Obstacle Negotiation during Walk while performing Cognitive Task (WCT + ON). Participants wore functional near-infrared spectroscopy (fNIRS) to collect hemodynamic signals from various regions of interest (ROIs) in the PFC, while the three-dimensional motion capture system was used to test the gait velocity. Cognitive task data was recorded. ResultsIn WCT + ON, the HbO2 concentration change value (△HbO2) of the left dorsolateral prefrontal cortex was significantly greater than that in the other three tasks (p < 0.05), and the△HbO2 of the right dorsolateral prefrontal cortex was significantly greater than that in NW + ON (p < 0.05). The gait velocities in the four tasks were significantly different (p < 0.05) (NW > WCT > NW + ON > WCT + ON). There was no significant difference in cognitive performance between in the WCT and WCT + ON (p > 0.05). In WCT + ON, the left and right dorsolateral prefrontal areas had strong functional connectivity and the left frontal pole was most widely connected to the other ROIs. Compared to that in NW, the functional connectivity of the left prefrontal lobe was significantly enhanced in WCT + ON (p < 0.05). ConclusionsAs walking difficulty increased, the PFC activation in the older adults changed from right-sided to bilateral activation, indicating that the left PFC cognitive resources compensated for the right PFC in dual-task obstacle negotiation. The cognitive resources recruitment in dual-task obstacle negotiation might be achieved by synchronization and coordination of associated brain areas in the PFC, primarily to maintain dynamic postural balance when walking.

Improving Attention through Individualized fNIRS Neurofeedback Training: A Pilot Study.

Attention is a particularly important indicator in life, as inattention can lead to many negative consequences. As a non-invasive intervention, real-time neurofeedback training can effectively enhance individuals’ attention adjustment abilities. However, previous studies have neglected to consider differences among individuals. In this study, an individualized neurofeedback training (INT) method based on functional near-infrared spectroscopy (fNIRS) was proposed for attention improvement and compared with non-individualized neurofeedback training (NINT). The neurofeedback channels and thresholds were determined individually for each subject. Then, participants conducted four runs of neurofeedback training. Two attention tests (i.e., AX version of continuous performance task (AX-CPT) and attention network test (ANT)) were used to assess the performance of the neurofeedback training. The length of time that the two groups of participants continuously kept their oxygenated hemoglobin concentration above a threshold showed an increasing trend, and the improvement rate of the INT group was higher than that of the NINT group. The reaction times for both groups showed a downward trend, but the INT group declined more significantly. In the fNIRS data, it was observed that the activation degree of the INT group in the middle and dorsolateral prefrontal areas was higher than that of the NINT group. It is preliminarily proved that the proposed INT method can effectively improve the attention level, and its overall performance is better than that of the NINT method.

An evolutionary gap in primate default mode network organization

SUMMARYThe human default mode network (DMN) is engaged at rest and in cognitive states such as self-directed thoughts. Interconnected homologous cortical areas in primates constitute a network considered as the equivalent. Here, based on a cross-species comparison of the DMN between humans and non-hominoid primates (macaques, marmosets, and mouse lemurs), we report major dissimilarities in connectivity profiles. Most importantly, the medial prefrontal cortex (mPFC) of non-hominoid primates is poorly engaged with the posterior cingulate cortex (PCC), though strong correlated activity between the human PCC and the mPFC is a key feature of the human DMN. Instead, a fronto-temporal resting-state network involving the mPFC was detected consistently across non-hominoid primate species. These common functional features shared between non-hominoid primates but not with humans suggest a substantial gap in the organization of the primate’s DMN and its associated cognitive functions.

Systems-Level Analysis of Genetic Variants Reveals Functional and Spatiotemporal Context in Treatment-resistant Schizophrenia.

Treatment-resistant schizophrenia (TRS) occurs in one-third of the patients, but the molecular determinants of poor antipsychotic response remain unclear. We compared genetic data of patients with TRS (n = 63) with non-TRS (n = 111) by polygenic risk scores (PRS) calculated by PRSice software using PGC2_SCZ (Psychiatric Genomics Consortium - Schizophrenia) data. TRS criteria followed the International Psychopharmacology Algorithm Project SCZ algorithm. Statistical clustering and functional enrichment analyses of genes harboring TRS-linked variants were performed. Individuals on the top three deciles of schizophrenia PRS distribution exhibited higher odds of being refractory to antipsychotics than those on the bottom three deciles. Clusters of interacting variant-harboring genes were identified among the association signals. They are upregulated in the dorsolateral prefrontal, orbitofrontal, temporal, and inferior parietal areas during adolescence and early adulthood. Similar gene modules were found using transcriptional data from the same brain regions in individuals with schizophrenia. Genes were enriched among markers of cortical interneurons and somatosensory pyramidal cells. Finally, the enrichment of the clustered genes in drug-response expression signatures revealed compounds that could be employed to identify novel antipsychotic targets. In conclusion, we identified variant-harboring genes that may predispose SCZ patients to poor antipsychotic response and found statistically enriched clusters which provided functional and spatiotemporal context for TRS, suggesting that genotypic variation may converge to biological alterations at the interplay between actin dynamics and synaptic organization.

Effect of Transcranial Direct Current Stimulation on the Mismatch Negativity Features of Deviated Stimuli in Children With Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a devastating mental disorder in children. Currently, there is no effective treatment for ASD. Transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation neuromodulation technology, is a promising method for the treatment of ASD. However, the manner in which tDCS changes the electrophysiological process in the brain is still unclear. In this study, we used tDCS to stimulate the dorsolateral prefrontal cortex area of children with ASD (one group received anode tDCS, and the other received sham tDCS) and investigated the changes in evoked EEG signals and behavioral abilities before and after anode and sham stimulations. In addition to tDCS, all patients received conventional rehabilitation treatment. Results show that although conventional treatment can effectively improve the behavioral ability of children with ASD, the use of anode tDCS with conventional rehabilitation can boost this improvement, thus leading to increased treatment efficacy. By analyzing the electroencephalography pre- and post-treatment, we noticed a decrease in the mismatch negativity (MMN) latency and an increase in the MMN amplitude in both groups, these features are considered similar to MMN features from healthy children. However, no statistical difference between the two groups was observed after 4 weeks of treatment. In addition, the MMN features correlate well with the aberrant behavior checklist (ABC) scale, particularly the amplitude of MMN, thus suggesting the feasibility of using MMN features to assess the behavioral ability of children with ASD.

Neural Correlates of Letter and Semantic Fluency in Primary Progressive Aphasia.

Verbal fluency (VF) is an informative cognitive task. Lesion and functional imaging studies implicate distinct cerebral areas that support letter versus semantic fluency and the understanding of neural and cognitive mechanisms underlying task performance. Most lesion studies include chronic stroke patients. People with primary progressive aphasia (PPA) provide complementary evidence for lesion-deficit associations, as different brain areas are affected in stroke versus PPA. In the present study we sought to determine imaging, clinical and demographic correlates of VF in PPA. Thirty-five patients with PPA underwent an assessment with letter and category VF tasks, evaluation of clinical features and an MRI scan for volumetric analysis. We used stepwise regression models to determine which brain areas are associated with VF performance while acknowledging the independent contribution of clinical and demographic factors. Letter fluency was predominantly associated with language severity (R2 = 38%), and correlated with the volume of the left superior temporal regions (R2 = 12%) and the right dorsolateral prefrontal area (R2 = 5%). Semantic fluency was predominantly associated with dementia severity (R2 = 47%) and correlated with the volume of the left inferior temporal gyrus (R2 = 7%). No other variables were significantly associated with performance in the two VF tasks. We concluded that, independently of disease severity, letter fluency is significantly associated with the volume of frontal and temporal areas whereas semantic fluency is associated mainly with the volume of temporal areas. Furthermore, our findings indicated that clinical severity plays a critical role in explaining VF performance in PPA, compared to the other clinical and demographic factors.

Clinical subtypes of frontotemporal dementia show different patterns of cortical atrophy

AbstractBackgroundFrontotemporal dementia (FTD) is a progressive neurodegenerative disorder associated with atrophy of the frontal and/or anterior temporal lobes, it is highly heterogeneous and represents about 5% of all cases of dementia and it is one of the most common causes of early‐onset dementia (Onyike and Diehl‐Schmid, 2013). FTD syndromes can be divided into three major groups: the behavioral variant (bvFTD) characterised by prominent early behavioral and personality changes, and the two language variants: the semantic variant (svFTD) and the non‐fluent primary progressive aphasia (pnfaFTD).MethodIn our study we used MRI scans from a frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) database: 133 age and sex matched controls, 70 bvFTD, 36 svFTD and 30 pnfaFTD. Each scan was pre‐processed (Intensity normalization, N3, linear registration, brain masking); tissue classification was performed using BISON (Dadar 2020). All scans were then processed using FALCON (Fonov 2020) to extract its cortical surface anc calculate thickness. Statistical analysis was performed on vertex level.ResultFigure 1 shows relative cortical difference between groups relative to controls, Figure 2 shows areas of significant differences (FDR 1%): the decrease of cortical thickness in the bvFTD group was located in frontal lobes, bilaterally as well as the temporal poles (specially in medial frontal and dorsolateral prefrontal areas). In svFTD, however, cortical thinning is limited to the anterior and lateral temporal lobe, predominantly on the left side. Finally, pnfaFTD shows left sided cortical thinning in prefrontal and Broca’s areas.ConclusionThe identification of predicted patterns of atrophy in each FTD subtype supports the validity of FALCON as an accurate tool to measure cortical changes in neurodegenerative disease. FALCON could be a useful tool for the development of the biomarkers associated with disease and improve understanding of disease progression.

Electroencephalographic connectivity predicts clinical response to repetitive transcranial magnetic stimulation in patients with insomnia disorder

BackgroundAccumulating evidence suggests that low frequency repetitive transcranial magnetic stimulation (rTMS), which generally decreases cortical excitability and remodels plastic connectivity, improves sleep quality in patients with insomnia disorder. However, the effects of rTMS vary substantially across individuals and treatment is sometimes unsatisfactory, calling for biomarkers for predicting clinical outcomes. ObjectiveThis study aimed to investigate whether functional connectivity of the target network in electroencephalography is associated with the clinical response to low frequency rTMS in patients with insomnia disorder. MethodsTwenty-five patients with insomnia disorder were subjected to 10 sessions of treatment with 1 Hz rTMS over the right dorsolateral prefrontal cortex. Resting-state electroencephalography was collected before rTMS. Pittsburgh Sleep Quality Index, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Mini-Mental State Exam were performed before and after rTMS treatment, with a follow-up after one month. Electroencephalographic connectivity was measured by the power envelope connectivity at the source level. Partial least squares regression identified models of connectivity that maximally accounted for the rTMS response. ResultsScores of Pittsburgh Sleep Quality Index, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale were decreased after rTMS and one-month later. Baseline weaker connectivity of a network in the beta and alpha bands between a brain region approximating the stimulated right dorsolateral prefrontal cortex and areas located in the frontal, insular, and limbic cortices was associated with a greater change in Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale following rTMS. ConclusionsLow frequency rTMS could improve sleep quality and depressive moods in patients with insomnia disorder. Moreover, electroencephalographic functional connectivity would potentially be a robust biomarker for predicting the therapeutic effects.

Cortical Serotonergic and Catecholaminergic Denervation in MPTP-Treated Parkinsonian Monkeys.

Decreased cortical serotonergic and catecholaminergic innervation of the frontal cortex has been reported at early stages of Parkinson's disease (PD). However, the limited availability of animal models that exhibit these pathological features has hampered our understanding of the functional significance of these changes during the course of the disease. In the present study, we assessed longitudinal changes in cortical serotonin and catecholamine innervation in motor-symptomatic and asymptomatic monkeys chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Densitometry and unbiased stereological techniques were used to quantify changes in serotonin and tyrosine hydroxylase (TH) immunoreactivity in frontal cortices of 3 control monkeys and 3 groups of MPTP-treated monkeys (motor-asymptomatic [N = 2], mild parkinsonian [N = 3], and moderate parkinsonian [N = 3]). Our findings revealed a significant decrease (P<0.001) in serotonin innervation of motor (Areas 4 and 6), dorsolateral prefrontal (Areas 9 and 46), and limbic (Areas 24 and 25) cortical areas in motor-asymptomatic MPTP-treated monkeys. Both groups of symptomatic MPTP-treated animals displayed further serotonin denervation in these cortical regions (P<0.0001). A significant loss of serotonin-positive dorsal raphe neurons was found in the moderate parkinsonian group. On the other hand, the intensity of cortical TH immunostaining was not significantly affected in motor asymptomatic MPTP-treated monkeys, but underwent a significant reduction in the moderate symptomatic group (P<0.05). Our results indicate that chronic intoxication with MPTP induces early pathology in the corticopetal serotonergic system, which may contribute to early non-motor symptoms in PD.