Cortex Of Patients Research Articles

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

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

Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study

ObjectiveHepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. ResultsMEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. ConclusionsOur study revealed reduced synaptic plasticity of the primary motor cortex in HE. SignificanceReduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.

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

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

Changes of the Brain Causal Connectivity Networks in Patients With Long-Term Bilateral Hearing Loss.

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39–63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25–76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35–115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3–55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42–63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25–26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75–26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca’s area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson’s correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca’s area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.

New Horizons in Temporal Lobe Seizure Control.

In patients with mesial temporal lobe epilepsy, high-frequency, low-amplitude electrical stimulation (ES) was applied during 3 weeks through contacts of intracranial electrodes that defined the epileptogenic zone. This subacute ES induced cessation of spontaneous seizures, decreased the number of EEG interictal spikes, caused a 10-fold increase in threshold to induce postdischarges, and showed a profound decrease in regional blood flow of the stimulated area in SPECT studies. Autoradiography analysis of surgical specimens from these patients demonstrated increased expression of benzodiazepine receptors and in gamma-aminobutyric acid content, particularly in the parahippocampal cortex. These observations provided evidence of a gamma-aminobutyric acid-mediated antiepileptic effect induced by ES. Several reports of long-term hippocampal ES through internalized neurostimulators have confirmed the antiepileptic effect on mesial temporal lobe-initiated seizures, with preservation of neuropsychological performance, in particular memory functions. The experience of the authors is that the response is optimal in patients without hippocampal sclerosis evidenced by MRI, whereas it is less significant and delayed in patients with hippocampal sclerosis. Other studies reported the best result stimulating through the contacts in the subiculum, the transition between the hippocampus and parahippocampal cortex, that usually escapes to the hippocampal sclerosis. Currently, the effect of ES directed at the subiculum and the parahippocampal cortex in patients with hippocampal sclerosis is under investigation.

Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19.

The recent coronavirus disease of 2019 (COVID-19) pandemic has adversely affected people worldwide. A growing body of literature suggests the neurological complications and manifestations in response to COVID-19 infection. Herein, we explored the inflammatory and immune responses in the post-mortem cerebral cortex of patients with severe COVID-19. The participants comprised three patients diagnosed with severe COVID-19 from March 26, 2020, to April 17, 2020, and three control patients. Our findings demonstrated a surge in the number of reactive astrocytes and activated microglia, as well as low levels of glutathione along with the upregulation of inflammation- and immune-related genes IL1B, IL6, IFITM, MX1, and OAS2 in the COVID-19 group. Overall, the data imply that oxidative stress may invoke a glial-mediated neuroinflammation, which ultimately leads to neuronal cell death in the cerebral cortex of COVID-19 patients.

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

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

Motor Cortex Activation During Writing in Focal Upper-Limb Dystonia: An fNIRS Study

Background Functional imaging studies have associated dystonia with abnormal activation in motor and sensory brain regions. Commonly used techniques such as functional magnetic resonance imaging impose physical constraints, limiting the experimental paradigms. Functional near-infrared spectroscopy (fNIRS) offers a new noninvasive possibility for investigating cortical areas and the neural correlates of complex motor behaviors in unconstrained settings. Methods We compared the cortical brain activation of patients with focal upper-limb dystonia and controls during the writing task under naturalistic conditions using fNIRS. The primary motor cortex (M1), the primary somatosensory cortex (S1), and the supplementary motor area were chosen as regions of interest (ROIs) to assess differences in changes in both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) between groups. Results Group average activation maps revealed an expected pattern of contralateral recruitment of motor and somatosensory cortices in the control group and a more bilateral pattern of activation in the dystonia group. Between-group comparisons focused on specific ROIs revealed an increased activation of the contralateral M1 and S1 cortices and also of the ipsilateral M1 cortex in patients. Conclusions Overactivity of contralateral M1 and S1 in dystonia suggest a reduced specificity of the task-related cortical areas, whereas ipsilateral activation possibly indicates a primary disorder of the motor cortex or an endophenotypic pattern. To our knowledge, this is the first study using fNIRS to assess cortical activity in dystonia during the writing task under natural settings, outlining the potential of this technique for monitoring sensory and motor retraining in dystonia rehabilitation.

Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis.

BackgroundPatients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes.Methods and ResultsTen microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains in a blinded fashion. None of the subjects had a history of stroke or neurologic insults. In a similar manner, the following immunohistochemistry stains were performed: (1) glial fibrillary acidic protein (representing gliosis, reactive change of glial cells in response to damage); (2) CD3 (a T‐cell marker); (3) CD19 (a B‐cell marker); (4) CD68 (a macrophage marker); and (5) CD117 (a mast cell marker). Patients with RLS had significantly greater silent microvascular disease (P=0.015) and gliosis (P=0.003). T cells were increased in RLS compared with controls (P=0.009) and tended to colocalize with microvascular disease (P=0.003). Other markers did not differ. There was no correlation between microvascular lesion load and RLS severity or duration.ConclusionsPatients with RLS had statistically significantly more silent cerebral microvascular disease and gliosis than controls compatible with previous magnetic resonance imaging studies and with studies showing a link between RLS and hypertension, clinical stroke, and cardiovascular disease. T‐cell invasion may be a secondary phenomenon.

Altered Functional Connectivity of the Primary Visual Cortex in Patients With Iridocyclitis and Assessment of Its Predictive Value Using Machine Learning

PurposeTo explore the intrinsic functional connectivity (FC) alteration of the primary visual cortex (V1) between individuals with iridocyclitis and healthy controls (HCs) by the resting-state functional magnetic resonance imaging (fMRI) technique, and to investigate whether FC findings be used to differentiate patients with iridocyclitis from HCs.MethodsTwenty-six patients with iridocyclitis and twenty-eight well-matched HCs were recruited in our study and underwent resting-state fMRI examinations. The fMRI data were analyzed by Statistical Parametric Mapping (SPM12), Data Processing and Analysis for Brain Imaging (DPABI), and Resting State fMRI Data Analysis Toolkit (REST) software. Differences in FC signal values of the V1 between the individuals with iridocyclitis and HCs were compared using independent two-sample t-tests. Significant differences in FC between two groups were chosen as classification features for distinguishing individuals with iridocyclitis from HCs using a support vector machine (SVM) classifier that involved machine learning. Classifier performance was evaluated using permutation test analysis.ResultsCompared with HCs, patients with iridocyclitis displayed significantly increased FC between the left V1 and left cerebellum crus1, left cerebellum 10, bilateral inferior temporal gyrus, right hippocampus, and left superior occipital gyrus. Moreover, patients with iridocyclitis displayed significantly lower FC between the left V1 and both the bilateral calcarine and bilateral postcentral gyrus. Patients with iridocyclitis also exhibited significantly higher FC values between the right V1 and left cerebellum crus1, bilateral thalamus, and left middle temporal gyrus; while they displayed significantly lower FC between the right V1 and both the bilateral calcarine and bilateral postcentral gyrus (voxel-level P<0.01, Gaussian random field correction, cluster-level P<0.05). Our results showed that 63.46% of the participants were correctly classified using the leave-one-out cross-validation technique with an SVM classifier based on the FC of the left V1; and 67.31% of the participants were correctly classified based on the FC of the right V1 (P<0.001, non-parametric permutation test).ConclusionPatients with iridocyclitis displayed significantly disturbed FC between the V1 and various brain regions, including vision-related, somatosensory, and cognition-related regions. The FC variability could distinguish patients with iridocyclitis from HCs with substantial accuracy. These findings may aid in identifying the potential neurological mechanisms of impaired visual function in individuals with iridocyclitis.

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.

A Novel Smart Motor Imagery Intention Human-Computer Interaction Model Using Extreme Learning Machine and EEG Signals.

The brain is the central nervous system that governs human activities. However, in modern society, more and more diseases threaten the health of the brain and nerves and spinal cord, making the human brain unable to conduct normal information interaction with the outside world. The rehabilitation training of the brain-computer interface can promote the nerve repair of the sensorimotor cortex in patients with brain diseases. Therefore, the research of brain-computer interface for motor imaging is of great significance for patients with brain diseases to restore motor function. Due to the characteristics of non-stationary, nonlinear, and individual differences of EEG signals, there are still many difficulties in the analysis and classification of EEG signals at this stage. In this study, the Extreme Learning Machine (ELM) model was used to classify motor-imaging EEG signals, identify the user’s intention, and control external devices. Considering that single-modal features cannot represent the core information, this study uses a fusion feature that combines temporal and spatial features as the final feature data. The fusion features are input to the trained ELM classifier, and the final classification result is obtained. Two sets of BCI competition data in the BCI competition public database are used to verify the validity of the model. The experimental results show that the ELM model has achieved a classification accuracy of 0.7832 in the classification task of Data Sets IIb, which is higher than other comparison algorithms, and shows universal applicability among different subjects. In addition, the average recognition rate of this model in the Data Sets IIIa classification task reaches 0.8347, which has obvious advantages compared with the comparative classification algorithm. The classification effect is smaller than the classification effect obtained by the champion algorithm of the same project, which has certain reference value.

Morphological alterations of the pyramidal and stellate cells of the visual cortex in schizophrenia.

Schizophrenia is a severe brain disorder characterized by certain types of delusion, hallucination and thought disorder. Studies have revealed impaired synaptic plasticity and reduced gamma-aminobutyric acid levels of the visual cortex in patients with schizophrenia. While previous work established a critical role for interneurons and cortical connectivity in the generation of hallucinations, the present study set out to examine the morphology of pyramidal cells and interneurons from layers 3 and 4 in the primary visual cortex from schizophrenic brains and to identify any dendritic and spinal alterations in comparison to normal control brains. The morphological and morphometric changes of the pyramidal cells and the interneurons of the visual cortices of 10 brains obtained from patients with schizophrenia, in comparison to 10 age-matched controls, were studied using the Golgi method and 3D neuronal reconstruction techniques. Analysis using the Golgi impregnation technique revealed a significant loss of distal dendritic segments, tortuous branches and varicosities and an overall restriction of the dendritic field in the brains of schizophrenic patients in both pyramidal cells and in aspiny interneurons. The present results may explain certain clinical phenomena associated with the visual cortex usually encountered in schizophrenia.

Impaired cerebral microcirculation in isolated REM sleep behaviour disorder.

During the prodromal period of Parkinson's disease and other α-synucleinopathy-related parkinsonisms, neurodegeneration is thought to progressively affect deep brain nuclei, such as the locus coeruleus, caudal raphe nucleus, substantia nigra, and the forebrain nucleus basalis of Meynert. Besides their involvement in the regulation of mood, sleep, behaviour, and memory functions, these nuclei also innervate parenchymal arterioles and capillaries throughout the cortex, possibly to ensure that oxygen supplies are adjusted according to the needs of neural activity. The aim of this study was to examine whether patients with isolated REM sleep behaviour disorder, a parasomnia considered to be a prodromal phenotype of α-synucleinopathies, reveal microvascular flow disturbances consistent with disrupted central blood flow control. We applied dynamic susceptibility contrast MRI to characterize the microscopic distribution of cerebral blood flow in the cortex of 20 polysomnographic-confirmed patients with isolated REM sleep behaviour disorder (17 males, age range: 54-77 years) and 25 healthy matched controls (25 males, age range: 58-76 years). Patients and controls were cognitively tested by Montreal Cognitive Assessment and Mini Mental State Examination. Results revealed profound hypoperfusion and microvascular flow disturbances throughout the cortex in patients compared to controls. In patients, the microvascular flow disturbances were seen in cortical areas associated with language comprehension, visual processing and recognition and were associated with impaired cognitive performance. We conclude that cortical blood flow abnormalities, possibly related to impaired neurogenic control, are present in patients with isolated REM sleep behaviour disorder and associated with cognitive dysfunction. We hypothesize that pharmacological restoration of perivascular neurotransmitter levels could help maintain cognitive function in patients with this prodromal phenotype of parkinsonism.

RETRACTED ARTICLE: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4

BackgroundApolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer’s disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A2 (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known.MethodsMouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress.ResultsGreater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of patients with AD carrying APOE3/E4 compared to APOE3/E3. Greater cPLA2 phosphorylation was also observed in human postmortem frontal cortical synaptosomes and primary astrocytes after treatment with recombinant ApoE4 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition.ConclusionsOur findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.

Microstructural changes in the cingulate gyrus of patients with mild cognitive impairment induced by cerebral small vessel disease

ABSTRACT Objective: The purpose of our study was to distinguish the changes in the microstructure of the cingulate cortex in patients with mild cognitive impairment (MCI) induced by cerebral small vessel disease (CSVD). Method: 80 patients were diagnosed with CSVD in this study, including 55 patients with MCI and 25 patients without MCI. Diffusion kurtosis imaging (DKI) and Montreal cognitive assessment (MoCA) were performed in all patients. The anterior cingulate gyrus, posterior cingulate gyrus and middle cingulate gyrus were selected as the regions of interest, and some parameters were recorded. Results: Compared with the non-MCI group, the MCI group mainly showed obviously higher mean diffusion (MD) and radial diffusion (RD) values (P = 0.022 and P = 0.029) but lower fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK) and radial kurtosis (RK) values (P = 0.047, P = 0.001, P < 0.01, and P = 0.001, respectively) in the right anterior cingulate gyrus. Meanwhile, in the right posterior cingulate gyrus, the MCI group also showed higher axial diffusion (AD) and MD (P = 0.027 and P = 0.030) and lower AK (P = 0.014). Additionally, negative correlations of AD, MD, and RD with MoCA scores and positive correlations of FA, AK, MK and RK with MoCA scores were observed in some regions of the cingulate gyrus. Conclusions: DKI is a good method to examine microstructural damage in the cingulate cortex, and some parameters of DKI may be used as imaging biomarkers to detect early MCI in patients with CSVD.

Evaluation of plasma levels of BDNF in patients with disorder depressive

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

Functional connectivity alterations between default mode network and occipital cortex in patients with obsessive-compulsive disorder (OCD)

IntroductionA meta-analysis by Gürsel et al. (2018) found altered functional connectivity in OCD patients within and between default mode (DMN), salience (SN), and frontoparietal networks (FPN), as well as evidence for aberrant fronto-striatal circuitry.ObjectivesTesting the replicability of meta-analysis rsfMRI findings in OCD patients.MethodsWe measured functional connectivity during resting-state fMRI in a sample of OCD patients (n=24) and controls matched for age and sex (n=33). The CONN toolbox implemented in SPM was used to perform seed-to-voxel analysis using 30 seed regions based on the previous meta-analytic findings.ResultsOCD patients showed reduced functional connectivity between SN and DMN compared to controls, replicating previous findings. We did not observe significant group differences of functional connectivity within the DMN, SN, or FPN. The strongest finding consisted of altered connectivity between DMN and SN to the visual network. OCD patients showed reduced functional connectivity between the left lateral parietal seed (LPl) and the inferior lateral occipital pole left (iLOCl) compared to controls. Furthermore, the LPl was found to be hyperconnected with the right superior lateral occipital cortex (sLOCr) and the right precuneus. This finding was positively correlated to OCD symptom severity, especially compulsions.ConclusionsOur findings replicated partly the meta-analysis findings, specifically reduced connectivity between SN and DMN. Using seeds based on the meta-analysis, we identified aberrations between the SN and, in particular, the DMN to the visual network. This raises the question about the visual system’s involvement in OCD symptoms and the abnormal connectivity of a unimodal region to the multimodal DMN.DisclosureNo significant relationships.

Reduction of WDR81 impairs autophagic clearance of aggregated proteins and cell viability in neurodegenerative phenotypes.

Neurodegenerative diseases are characterized by neuron loss and accumulation of undegraded protein aggregates. These phenotypes are partially due to defective protein degradation in neuronal cells. Autophagic clearance of aggregated proteins is critical to protein quality control, but the underlying mechanisms are still poorly understood. Here we report the essential role of WDR81 in autophagic clearance of protein aggregates in models of Huntington’s disease (HD), Parkinson’s disease (PD) and Alzheimer’s disease (AD). In hippocampus and cortex of patients with HD, PD and AD, protein level of endogenous WDR81 is decreased but autophagic receptor p62 accumulates significantly. WDR81 facilitates the recruitment of autophagic proteins onto Htt polyQ aggregates and promotes autophagic clearance of Htt polyQ subsequently. The BEACH and MFS domains of WDR81 are sufficient for its recruitment onto Htt polyQ aggregates, and its WD40 repeats are essential for WDR81 interaction with covalent bound ATG5-ATG12. Reduction of WDR81 impairs the viability of mouse primary neurons, while overexpression of WDR81 restores the viability of fibroblasts from HD patients. Notably, in Caenorhabditis elegans, deletion of the WDR81 homolog (SORF-2) causes accumulation of p62 bodies and exacerbates neuron loss induced by overexpressed α-synuclein. As expected, overexpression of SORF-2 or human WDR81 restores neuron viability in worms. These results demonstrate that WDR81 has crucial evolutionarily conserved roles in autophagic clearance of protein aggregates and maintenance of cell viability under pathological conditions, and its reduction provides mechanistic insights into the pathogenesis of HD, PD, AD and brain disorders related to WDR81 mutations.

Susceptibility-Weighted Imaging in Neurodegenerative Disorders: A Review.

As human life expectancy increases, there is an increased prevalence of neurodegenerative disorders and dementia. There are many ongoing research trials for early diagnosis and management of dementia, and neuroimaging is a critical part of such studies. However, conventional neuroimaging often fails to provide enough diagnostic findings in patients with neurodegenerative disorders. In this context, different MRI sequences are currently under investigation to facilitate the accurate diagnosis of such disorders. Susceptibility-weighted imaging (SWI) is an innovative MRI technique that utilizes "magnitude" and "phase" images to produce an image contrast that is sensitive for the detection of susceptibility differences of the tissues. As many neurodegenerative disorders are associated with accelerated iron deposition and/or microhemorrhages in different parts of the brain, SWI can be applied to detect these diagnostic clues. For instance, in cerebral amyloid angiopathy, SWI can demonstrate cortical microhemorrhages, which are predominantly in the frontal and parietal regions. Or in Parkinson disease, abnormal swallow-tail sign on high-resolution SWI is highly diagnostic. Also, SWI is a useful sequence to detect the low signal intensity of precentral cortices in patients with amyotrophic lateral sclerosis. Being familiar with SWI findings in neurodegenerative disorders is critical for an accurate diagnosis. In this paper, the authors review the technical parameters of SWI, physiologic, and pathologic iron deposition in the brain, and the role of SWI in the evaluation of neurodegenerative disorders in daily practice.