Decreased Brain Activity Research Articles

Hypersensitivity to low intensity fearful faces in autism when fixation is constrained to the eyes

Previous studies that showed decreased brain activation in people with autism spectrum disorder (ASD) viewing expressive faces did not control that participants looked in the eyes. This is problematic because ASD is characterized by abnormal attention to the eyes. Here, we collected fMRI data from 48 participants (27 ASD) viewing pictures of neutral faces and faces expressing anger, happiness, and fear at low and high intensity, with a fixation cross between the eyes. Group differences in whole brain activity were examined for expressive faces at high and low intensity versus neutral faces. Group differences in neural activity were also investigated in regions of interest within the social brain, including the amygdala and the ventromedial prefrontal cortex (vmPFC). In response to low intensity fearful faces, ASD participants showed increased activation in the social brain regions, and decreased functional coupling between the amygdala and the vmPFC. This oversensitivity to low intensity fear coupled with a lack of emotional regulation capacity could indicate an excitatory/inhibitory imbalance in their socio-affective processing system. This may result in social disengagement and avoidance of eye-contact to handle feelings of strong emotional reaction. Our results also demonstrate the importance of careful control of gaze when investigating emotional processing in ASD. Hum Brain Mapp 38:5943-5957, 2017. © 2017 Wiley Periodicals, Inc.

Functional subdivisions of the hypothalamus using areal parcellation and their signal changes related to glucose metabolism

The hypothalamus consists of numerous nuclei, and is regarded as the highest center for various autonomic functions. Although each hypothalamic nucleus implements a distinct function, it remains difficult to investigate the human hypothalamus at the nucleus level. In the present high-resolution functional MRI study, we utilized areal parcellation to discriminate individual nuclei in the human hypothalamus based on areal profiles of resting-state functional connectivity. The areal parcellation detected ten foci that were expected to represent hypothalamic nuclei, and the locations of the foci were consistent with those of the hypothalamic nuclei identified in previous histological studies. Regions of interest (ROI) analyses revealed contrasting brain activity changes following glucose ingestion: decrease in the ventromedial hypothalamic nucleus and increase in the lateral hypothalamic area in parallel with blood glucose increase. Moreover, decreased brain activity in the arcuate nucleus predicted future elevation of blood insulin during the first 10 min after glucose ingestion. These results suggest that the hypothalamic nuclei can putatively be determined using areal parcellation, and that the ROI analysis of the human hypothalamic nuclei is useful for future scientific and clinical investigations into the autonomic functions.

Emotional fMR auditory paradigm demonstrates normalization of limbic hyperactivity after cognitive behavior therapy for auditory hallucinations

To date, no study has evaluated the effects on brain function of cognitive behavior therapy (CBT) for persistent auditory hallucinations. This study explored the changes in brain activation associated with an emotional auditory paradigm when patients with schizophrenia and auditory hallucinations were treated with CBT. Functional magnetic resonance (fMR) imaging data were obtained from 55 subjects (17 patients with schizophrenia in the therapy group, 24 patients with schizophrenia in the control patient group, and 14 healthy control subjects). The patients in the experimental group were treated with 16–20 bi-weekly sessions of CBT, whereas the patients in the control group received treatment as usual. fMR images were obtained at baseline, 9 and 14months after enrollment. Patients who received CBT showed significant decrease in brain activation in right and left amygdalae, and the left middle temporal gyrus, compared to both control groups. Significantly reductions in the brain activation of therapy patients were found in both amygdalae, but also in the left superior temporal gyrus and the right superior frontal gyrus at 14-month follow-up. Significant and stable reductions in the abnormal activation of key limbic regions appear to be attributable to the CBT during an emotional auditory paradigm in patients with schizophrenia and persistent auditory hallucinations. These results point to the availability of a biological imaging biomarker for CBT effects in patients with persistent auditory hallucinations.

Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm

To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO2 (etCO2) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO2 fluctuations of ≥5 mm Hg. Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO2 increase and 70 episodes of etCO2 decrease. During etCO2 increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO2 returned to baseline. During etCO2 decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO2 to baseline. An acute increase in etCO2 is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO2 monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain.

Cerebral oxygenation during cortical activation: the differential influence of three exercise training modalities. A randomized controlled trial.

To determine if a cerebral oxygenation response during cortical activation is influenced by exercise training mode. Sixty-seven individuals (55-75years old) volunteered for this 16-week intervention study. Participants were randomized into a resistance training (RT) group (n=22), high-intensity interval training (HIIT) group (n=13), moderate continuous training (MCT) group (n=13) and a control (CON) group (n=19). Near-infrared spectroscopy was used to measure cerebral oxygenation during the Stroop task. A submaximal Bruce treadmill test was used to measure changes in walking endurance. The GROUP×TIME interaction for reaction time on the naming and executive Stroop conditions were not significant (P>0.05). At post-test, the CON group showed increased brain activation, with significantly higher relative oxy-haemoglobin (O2Hb) values during the naming Stroop condition compared to pre-test (P=0.03), while their increased relative O2Hb on the complex condition showed a distinct trend toward significance (P=0.09). MCT and HIIT participants exhibited decreased brain activation during the Stroop task, with MCT showing a significant increase in relative deoxy-haemoglobin (HHb) compared to pre-test during the naming and executive Stroop conditions (P<0.05). The HIIT group improved significantly in walking endurance (P=0.04). Sixteen weeks of exercise training resulted in more efficient cerebral oxygenation during cortical activation compared to a no-exercise control group. Furthermore, HIIT and MCT were superior to RT for task-efficient cerebral oxygenation and improved oxygen utilization during cortical activation in older individuals.

Distinct effects of reminding mortality and physical pain on the default-mode activity and activity underlying self-reflection

ABSTRACTBehavioral research suggests that reminding both mortality and negative affect influences self-related thoughts. Using functional magnetic resonance imaging (MRI), we tested the hypothesis that reminders of mortality and physical pain decrease brain activity underlying self-related thoughts. Three groups of adults underwent priming procedures during which they answered questions pertaining to mortality, physical pain, or leisure time, respectively. Before and after priming, participants performed personality trait judgments on oneself or a celebrity, identified the font of words, or passively viewed a fixation. The default-mode activity and neural activity underlying self-reflection were identified by contrasting viewing a fixation vs. font judgment and trait judgments on oneself vs. a celebrity, respectively. The analyses of the pre-priming functional MRI (fMRI) data identified the default-mode activity in the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (MPFC), and parahippocampal gyrus, and the activity underlying instructed self-reflection in both the ventral and dorsal regions of the MPFC. The analyses of the post-priming fMRI data revealed that, relative to leisure time priming, reminding mortality significantly reduced the default-mode PCC activity, and reminding physical pain significantly decreased the dorsal MPFC activity during instructed self-reflection. Our findings suggest distinct neural underpinnings of the effect of reminding morality and aversive emotion on default-mode and instructed self-reflection.

Longitudinal recovery of local neuronal activity and consciousness level in acquired brain injury.

Decreased brain activity in the default mode network, particularly in the precuneus (PCU), has been consistently shown in acquired brain injury (ABI) patients. However, it is unclear whether resting-state brain activity recovers longitudinally in ABI patients and whether functional activity restoration is associated with improvements in consciousness level. Here, resting-state fMRI data were acquired from 23 ABI patients and 30 age- and gender-matched controls with two longitudinal observations for each participant. The fMRI data were analyzed using amplitude of low-frequency fluctuation (ALFF) to measure the fluctuation strength of local spontaneous activity, and seed-based functional connectivity was used to measure functional relationship with the seed region in the whole brain. The level of consciousness was assessed using the Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) on both scanning days of the patients. Interaction effect between the two groups and two scans in ALFF was observed in the PCU, which was driven by restored ALFF in the ABI, while a stable ALFF in the control group. Moreover, restoration of ALFF in the PCU correlated with improvements in both the CRS-R and GCS. Specifically, recovery of ALFF in the PCU primarily reflected the signals of the slow-4 frequency band (0.027-0.073 Hz). Based on the functional connectivity maps of the PCU, we observed a nonsignificant interaction effect or correlation with consciousness level. These findings suggest local activity in the PCU but possibly not its functional connectivity, is related to the longitudinal changes in behavioral responsiveness in ABI. Hum Brain Mapp 38:3579-3591, 2017. © 2017 Wiley Periodicals, Inc.

Reduced brain activity in female patients with non-alcoholic fatty liver disease as measured by near-infrared spectroscopy.

Patients with non-alcoholic fatty liver disease (NAFLD) have impaired health-related quality of life including physical and mental state. Near-infrared spectroscopy (NIRS) is a useful tool for evaluation of brain activity and depressive state. This study aimed to determine the brain activity of female NAFLD patients using NIRS. Cerebral oxygenated hemoglobin (oxy-Hb) concentration during a verbal fluency task (VFT) was measured using NIRS in 24 female NAFLD patients and 15 female healthy controls. The Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire was administered to both groups before NIRS. There was no significant difference in CES-D score between groups. However, the oxy-Hb concentration and number of words during the VFT were less in NAFLD compared to healthy controls. The mean value of oxy-Hb concentration during 0–60 s VFT in the frontal lobe was also smaller in NAFLD patients compared to healthy controls (0.082 ± 0.126 vs. 0.183 ± 0.145, P < 0.001). Cerebral oxygen concentration is poorly reactive in response to VFT in female NAFLD patients. This may indicate an association between decreased brain activity and NAFLD regardless of depression.

Meta-analysis of aberrant brain activity in psychopathy

IntroductionPsychopathy is characterized by superficial charm, untruthfulness, lack of remorse, antisocial behavior, egocentricity as well as poverty in major affective reactions. This clinical profile has been empirically conceptualized and validated. Recent brain imaging studies suggest abnormal brain activity underlying psychopathic behavior. However, no reliable pattern of altered neural activity has been disclosed so far.ObjectiveTo identify consistent changes of brain activity in psychopaths and to investigate whether these could explain known psychopathology.MethodsFirst, we used activation likelihood estimation to meta-analyze brain activation changes in psychopaths across 28 functional magnetic resonance imaging studies reporting 753 foci from 155 analyses (P &lt; 0.05, corrected). Second, we functionally characterized the ensuing regions employing meta-data of a large-scale neuroimaging database (P &lt; 0.05, corrected).ResultsPsychopathy was consistently associated with decreased brain activity in the right amygdala, the dorsomedial prefrontal cortex (DMPFC), and bilaterally in the lateral prefrontal cortex (LPFC). Consistently increased activity was observed bilaterally in the fronto-insular cortex (FIC) (Fig. 1). Moreover, we found that the physiological functional role of the candidate regions related to social cognition (DMFPC), cognitive speech and semantic processing (left FIC/LPFC), emotional and cognitive reward processing (right amygdala/FIC) as well as somesthesis and executive functions (RLPFC).ConclusionPsychopathy is characterized by abnormal brain activity of bilateral prefrontal cortices and the right amygdala, which mediate psychological functions known to be impaired in psychopaths. Hence, aberrant neural activity can account for pertinent psychopathology in psychopathy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Brain activity underlying negative self- and other-perception in adolescents: The role of attachment-derived self-representations

One of teenagers’ key developmental tasks is to engage in new and meaningful relationships with peers and adults outside the family context. Attachment-derived expectations about the self and others in terms of internal attachment working models have the potential to shape such social reorientation processes critically and thereby influence adolescents’ social-emotional development and social integration. Because the neural underpinnings of this developmental task remain largely unknown, we sought to investigate them by functional magnetic resonance imaging. We asked n = 44 adolescents (ages 12.01–18.84 years) to evaluate positive and negative adjectives regarding either themselves or a close other during an adapted version of the well-established self-other trait-evaluation task. As measures of attachment, we obtained scores reflecting participants’ positive versus negative attachment-derived self- and other-models by means of the Relationship Questionnaire. We controlled for possible confounding factors by also obtaining scores reflecting internalizing/externalizing problems, schizotypy, and borderline symptomatology. Our results revealed that participants with a more negative attachment-derived self-model showed increased brain activity during positive and negative adjective evaluation regarding the self, but decreased brain activity during negative adjective evaluation regarding a close other, in bilateral amygdala/parahippocampus, bilateral anterior temporal pole/anterior superior temporal gyrus, and left dorsolateral prefrontal cortex. These findings suggest that a low positivity of the self-concept characteristic for the attachment anxiety dimension may influence neural information processing, but in opposite directions when it comes to self- versus (close) other-representations. We discuss our results in the framework of attachment theory and regarding their implications especially for adolescent social-emotional development and social integration.

Resting-State Brain Abnormalities in Chronic Subjective Tinnitus: A Meta-Analysis.

Purpose: The neural mechanisms that give rise to the phantom sound of tinnitus have not been fully elucidated. Neuroimaging studies have revealed abnormalities in resting-state activity that could represent the neural signature of tinnitus, but there is considerable heterogeneity in the data. To address this issue, we conducted a meta-analysis of published neuroimaging studies aimed at identifying a common core of resting-state brain abnormalities in tinnitus patients.Methods: A systematic search was conducted for whole-brain resting-state neuroimaging studies with SPECT, PET and functional MRI that compared chronic tinnitus patients with healthy controls. The authors searched PubMed, Science Direct, Web of Knowledge and Embase databases for neuroimaging studies on tinnitus published up to September 2016. From each study, coordinates were extracted from clusters with significant differences between tinnitus subjects and controls. Meta-analysis was performed using the activation likelihood estimation (ALE) method.Results: Data were included from nine resting-state neuroimaging studies that reported a total of 51 distinct foci. The meta-analysis identified consistent regions of increased resting-state brain activity in tinnitus patients relative to controls that included, bilaterally, the insula, middle temporal gyrus (MTG), inferior frontal gyrus (IFG), parahippocampal gyrus, cerebellum posterior lobe and right superior frontal gyrus. Moreover, decreased brain activity was only observed in the left cuneus and right thalamus.Conclusions: The current meta-analysis is, to our knowledge, the first to demonstrate a characteristic pattern of resting-state brain abnormalities that may serve as neuroimaging markers and contribute to the understanding of neuropathophysiological mechanisms for chronic tinnitus.

The influence of trait anxiety and illusory kinesthesia on pain threshold.

[Purpose] It has also been reported that decreased activity in the reward pathway causes a decrease in brain activity in the descending pain control system in people with high trait anxiety. Activation of this system is dependent on both the reward pathway and motor areas. Recently, studies have also shown that motor areas are activated by illusory kinesthesia. It was aimed to explore whether anxiety trait modulates the influence of illusory kinesthesia on pain threshold. [Subjects and Methods] The pain threshold and trait anxiety at rest before vibratory tendon stimulation (the task) were measured. After the task, the pain threshold, the illusory kinesthesia angle, and the intensity of illusory kinesthesia for patients with and without illusory kinesthesia were measured. A total of 35 healthy right-handed students participated, among whom 22 and 13 were included in the illusion and no-illusion groups, respectively. [Results] There was a significant increase in the pain threshold after task completion in both groups; however, there was no statistically significant difference between the two groups. Correlational analysis revealed that State-Trait Anxiety Inventory-trait score correlated negatively with the pain threshold in the no-illusion group, but there was no correlation in the illusion group. [Conclusion] The pain threshold improved regardless of the size of trait anxiety in the illusion group, but did not improve merely through sensory input by vibratory stimulation in the no-illusion group. Thus, illusory kinesthesia has effect of increasing the pain threshold.

Night duty and decreased brain activity of medical residents: a wearable optical topography study

ABSTRACTBackground: Overwork, fatigue, and sleep deprivation due to night duty are likely to be detrimental to the performance of medical residents and can consequently affect patient safety.Objective: The aim of this study was to determine the possibility of deterioration of cerebral function of sleep-deprived, fatigued residents using neuroimaging techniques.Design: Six medical residents were instructed to draw blood from artificial vessels installed on the arm of a normal cooperator. Blood was drawn at a similar time of the day, before and after night duty. To assess sleep conditions during night duty, the participants wore actigraphy units throughout the period of night duty. Changes in cerebral hemodynamics, during the course of drawing blood, were measured using a wearable optical topography system.Results: The visual analogue scale scores after night duty correlated negatively with sleep efficiency during the night duty (ρ = −0.812, p = 0.050). The right prefrontal cortex activity was significantly decreased in the second trial after night duty compared with the first (p = 0.028). The extent of [oxy-Hb] decrease, indicating decreased activity, in the right dorsolateral prefrontal cortex correlated negatively with the Epworth sleepiness score after night duty (ρ = −0.841, p = 0.036).Conclusions: Sleep deprivation and fatigue after night duty, caused a decrease in the activity of the right dorsolateral prefrontal cortex of the residents, even with a relatively easy routine. This result implies that the brain activity of medical residents exposed to stress on night duty, although not substantially sleep-deprived, was impaired after the night duty, even though they apparently performed a simple medical technique appropriately. Reconsideration of the shift assignments of medical residents is strongly advised.Abbreviations: DLPFC: Dorsolateral prefrontal cortex; ESS: Epworth sleepiness scale; PSQI: Pittsburgh sleep quality index; ROI: Regions of interest; VAS: Visual analogue scale; WOT: Wearable optical topography

Motor sequence learning-induced neural efficiency in functional brain connectivity

Previous studies have shown the functional neural circuitry differences before and after an explicitly learned motor sequence task, but have not assessed these changes during the process of motor skill learning. Functional magnetic resonance imaging activity was measured while participants (n=13) were asked to tap their fingers to visually presented sequences in blocks that were either the same sequence repeated (learning block) or random sequences (control block). Motor learning was associated with a decrease in brain activity during learning compared to control. Lower brain activation was noted in the posterior parietal association area and bilateral thalamus during the later periods of learning (not during the control). Compared to the control condition, we found the task-related motor learning was associated with decreased connectivity between the putamen and left inferior frontal gyrus and left middle cingulate brain regions. Motor learning was associated with changes in network activity, spatial extent, and connectivity.

Functional alterations of fronto-limbic circuit and default mode network systems in first-episode, drug-naïve patients with major depressive disorder: A meta-analysis of resting-state fMRI data

BackgroundThe neurobiological mechanisms of depression are increasingly being explored through resting-state brain imaging studies. However, resting-state fMRI findings have varied, perhaps because of differences between study populations, which included the disorder course and medication use. The aim of our study was to integrate studies of resting-state fMRI and explore the alterations of abnormal brain activity in first-episode, drug-naïve patients with major depressive disorder. MethodsRelevant imaging reports in English were searched, retrieved, selected and subjected to analysis by activation likelihood estimation, a coordinate-based meta-analysis technique (final sample, 31 studies). Coordinates extracted from the original reports were assigned to two categories based on effect directionality. ResultsCompared with healthy controls, the first-episode, medication-naïve major depressive disorder patients showed decreased brain activity in the dorsolateral prefrontal cortex, superior temporal gyrus, posterior precuneus, and posterior cingulate, as well as in visual areas within the occipital lobe, lingual gyrus, and fusiform gyrus, and increased activity in the putamen and anterior precuneus. LimitationsNot every study that has reported relevant data met the inclusion criteria. ConclusionResting-state functional alterations were located mainly in the fronto-limbic system, including the dorsolateral prefrontal cortex and putamen, and in the default mode network, namely the precuneus and superior/middle temporal gyrus. Abnormal functional alterations of the fronto-limbic circuit and default mode network may be characteristic of first-episode, drug-naïve major depressive disorder patients.

Abnormal interactions of verbal- and spatial-memory networks in young people at familial high-risk for schizophrenia

BackgroundWorking memory impairment (especially in verbal and spatial domains) is the core neurocognitive impairment in schizophrenia and the familial high-risk (FHR) population. Inconsistent results have been reported in clinical and neuroimaging studies examining the verbal- and spatial-memory deficits in the FHR subjects, due to sample differences and lack of understanding on interactions of the brain regions for processing verbal- and spatial-working memory. MethodsFunctional MRI data acquired during a verbal- vs. spatial-memory task were included from 51 young adults [26 FHR and 25 controls]. Group comparisons were conducted in brain activation patterns responding to 1) verbal-memory condition (A), 2) spatial-memory condition (B), 3) verbal higher than spatial (A–B), 4) spatial higher than verbal (B–A), 5) conjunction of brain regions that were activated during both A and B (A∧B). Group difference of the laterality index (LI) in inferior frontal lobe for condition A was also assessed. ResultsCompared to controls, the FHR group exhibited significantly decreased brain activity in left inferior frontal during A, and significantly stronger involvement of ACC, PCC, paracentral gyrus for the contrast of A–B. The LI showed a trend of reduced left-higher-than-right pattern for verbal-memory processing in the HR group. ConclusionsOur findings suggest that in the entire functional brain network for working-memory processing, verbal information processing associated brain pathways are significantly altered in people at familial high risk for developing schizophrenia. Future studies will need to examine whether these alterations may indicate vulnerability for predicting the onset of Schizophrenia.

Functional and structural connectivity of the visual system in infants with perinatal brain injury.

Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls. Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups. Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants. Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates.

Correlation Between Brain Activation Changes and Cognitive Improvement Following Cognitive Remediation Therapy in Schizophrenia: An Activation Likelihood Estimation Meta-analysis.

Background:Several studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have indicated that cognitive remediation therapy (CRT) might improve cognitive function by changing brain activations in patients with schizophrenia. However, the results were not consistent in these changed brain areas in different studies. The present activation likelihood estimation (ALE) meta-analysis was conducted to investigate whether cognitive function change was accompanied by the brain activation changes, and where the main areas most related to these changes were in schizophrenia patients after CRT. Analyses of whole-brain studies and whole-brain + region of interest (ROI) studies were compared to explore the effect of the different methodologies on the results.Methods:A computerized systematic search was conducted to collect fMRI and PET studies on brain activation changes in schizophrenia patients from pre- to post-CRT. Nine studies using fMRI techniques were included in the meta-analysis. Ginger ALE 2.3.1 was used to perform meta-analysis across these imaging studies.Results:The main areas with increased brain activation were in frontal and parietal lobe, including left medial frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and inferior parietal lobule in patients after CRT, yet no decreased brain activation was found. Although similar increased activation brain areas were identified in ALE with or without ROI studies, analysis including ROI studies had a higher ALE value.Conclusions:The current findings suggest that CRT might improve the cognition of schizophrenia patients by increasing activations of the frontal and parietal lobe. In addition, it might provide more evidence to confirm results by including ROI studies in ALE meta-analysis.

Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial.

BackgroundPotent combined antiretroviral therapy decreased the incidence and severity of HIV-associated neurocognitive disorders (HAND); however, no specific effective pharmacotherapy exists for HAND. Patients with HIV commonly have deficits in working memory and attention, which may negatively impact many other cognitive domains, leading to HAND. Since HAND may lead to loss of independence in activities of daily living and negative emotional well-being, and incur a high economic burden, effective treatments for HAND are urgently needed. This study aims to determine whether adaptive working memory training might improve cognitive functions and neural network efficiency and possibly decrease neuroinflammation. This study also aims to assess whether subjects with the LMX1A-rs4657412 TT(AA) genotype show greater training effects from working memory training than TC(AG) or CC(GG)-carriers.Methods/Design60 HIV-infected and 60 seronegative control participants will be randomized to a double-blind active-controlled study, using adaptive versus non-adaptive Cogmed Working Memory Training® (CWMT), 20–25 sessions over 5–8 weeks. Each subject will be assessed with near- and far-transfer cognitive tasks, self-reported mood and executive function questionnaires, and blood-oxygenation level-dependent functional MRI during working memory (n-back) and visual attention (ball tracking) tasks, at baseline, 1-month, and 6-months after CWMT. Furthermore, genotyping for LMX1A-rs4657412 will be performed to identify whether subjects with the TT(AA)-genotype show greater gain or neural efficiency after CWMT than those with other genotypes. Lastly, cerebrospinal fluid will be obtained before and after CWMT to explore changes in levels of inflammatory proteins (cytokines and chemokines) and monoamines.DiscussionImproving working memory in HIV patients, using CWMT, might slow the progression or delay the onset of HAND. Observation of decreased brain activation or normalized neural networks, using fMRI, after CWMT would lead to a better understanding of how neural networks are modulated by CWMT. Moreover, validating the greater training gain in subjects with the LMX1A-TT(AA) genotype could lead to a personalized approach for future working memory training studies. Demonstrating and understanding the neural correlates of the efficacy of CWMT in HIV patients could lead to a safe adjunctive therapy for HAND, and possibly other brain disorders.Trial registrationClinicalTrial.gov, NCT02602418.

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial.

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrolment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17days each (0.6mg for 7days, 1.2mg for 7days, and 1.8mg for 3days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (functional MRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide -0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3mg) recently approved for obesity. ClinicalTrials.gov NCT01562678 FUNDING : The study was funded by Novo Nordisk, NIH UL1 RR025758 and 5T32HD052961.