Region Of Interest Analysis Research Articles

Brain Resting-State Network Alterations Associated With Crohn's Disease.

Inflammatory bowel disease (IBD) is a chronic disease that is associated with aspects of brain anatomy and activity. In this preliminary MRI study, we investigated differences in brain structure and in functional connectivity (FC) of brain regions in 35 participants with Crohn's disease (CD) and 21 healthy controls (HC). Voxel-based morphometry (VBM) analysis was performed to contrast CD and HC structural images. Region of interest (ROI) analyses were run to assess FC for resting-state network nodes. Independent component analysis (ICA) identified whole brain differences in FC associated with resting-state networks. Though no structural differences were found, ROI analyses showed increased FC between the frontoparietal (FP) network and salience network (SN), and decreased FC between nodes of the default mode network (DMN). ICA results revealed changes involving cerebellar (CER), visual (VIS), and SN components. Differences in FC associated with sex were observed for both ROI analysis and ICA. Taken together, these changes are consistent with an influence of CD on the brain and serve to direct future research hypotheses.

Simultaneous voxel-based magnetic susceptibility and morphometry analysis using magnetization-prepared spoiled turbo multiple gradient echo.

This study aimed to develop and test a simultaneous acquisition and analysis pipeline for voxel-based magnetic susceptibility and morphometry (VBMSM) on a single dataset using young volunteers, elderly healthy volunteers, and an Alzheimer's disease (AD) group. 3D T1 -weighted and multi-echo phase images for VBM and quantitative susceptibility mapping (QSM) were simultaneously acquired using a magnetization-prepared spoiled turbo multiple gradient echo sequence with inversion pulse for QSM (MP-QSM). The magnitude image was split into gray matter (GM) and white matter (WM) and was spatially normalized. The susceptibility map was reconstructed from the phase images. The segmented image and susceptibility map were compared with those obtained from conventional multiple spoiled gradient echo (mGRE) and MP-spoiled gradient echo (MP-GRE) in healthy volunteers to validate the availability of MP-QSM by numerical measurements. To assess the feasibility of the VBMSM analysis pipeline, voxel-based comparisons of susceptibility and morphometry in MP-QSM were conducted in volunteers with a bimodal age distribution, and in elderly volunteers and the AD group, using spatially normalized GM and WM volume images and a susceptibility map. GM/WM contrasts in MP-QSM, MP-GRE, and mGRE were 0.14 ± 0.011, 0.17 ± 0.015, and 0.045 ± 0.010, respectively. Segmented GM and WM volumes in the MP-QSM closely coincided with those in the MP-GRE. Region of interest analyses indicated that the mean susceptibility values in MP-QSM were completely in agreement with those in mGRE. In an evaluation of the aging effect, a significant increase and decrease in susceptibility and volume were found by VBMSM in deep GM and WM, respectively. Between the elderly volunteers and the AD group, the characteristic susceptibility and volume changes in GM and WM were observed. The proposed MP-QSM sequence makes it possible to acquire acceptable-quality images for simultaneous analysis and determine brain atrophy and susceptibility distribution without image registration by using voxel-based analyses.

Abstract WP44: Less Infarct Volume Growth in Early Window Mechanical Thrombectomy Compared to Late Window in Emergent Large Vessel Occlusion

Background: While clearly beneficial based on outcome analysis, there has been limited data regarding prevention of further infarct growth in late (6-24 hour) compared to the early window (<6 hour) mechanical thrombectomy (MT). More expedient revascularization in the early group prevents further growth, but the presence of good collaterals in late window patients may prevent infarct progression over time. The aim of this study is to compare infarct growth between early and late window intervention. Methods: We reviewed consecutive patients presenting to a comprehensive stroke center from January 2016 to December 2018 with emergent large vessel occlusion (ELVO) undergoing MT. Standard protocol included pre-procedural MRI imaging and only those with post-procedural MRI were included. Patients were divided into early (<6 hour from onset to arterial puncture) and late (6-24 hour from onset to arterial puncture) groups. Infarct volume on MRI was measured using region of interest analysis by investigators blinded to group. MRI growth between pre- and post- MT MRI was compared using both absolute difference (post minus pre volume) and ratio (pre:post volume). Results: Among 117 patients meeting inclusion criteria, 40 (34.2%) patients had early and 77 (65.8%) late interventions. Those in the early group showed a trend toward lower infarct volume growth compared to those in the late group (16.0 +/- 42.9 vs 31.4 +/- 60.9 mL growth, p = 0.16). Ratios of pre to post MT infarct volume was significantly different in early and late intervention group (1.07 +/- 1.6 vs 0.63 +/- 0.33, p = 0.02), signifying less infarct growth in the early group. Conclusion: In patients with ELVO for whom MT was performed, there was less infarct growth in the early time window compared to the late window.

Plasma inflammatory biomarkers link to diffusion tensor imaging metrics in virally suppressed HIV-infected individuals.

Inflammation may contribute to brain white matter health in people living with HIV who report cognitive symptoms despite adherence to combination antiretroviral therapy and viral suppression. We explored relationships between diffusion tensor imaging (DTI) metrics of white matter, plasma biomarkers of immune activation, and cognitive function in the HIV-infected population. Retrospective study of older adults living with HIV who are combination antiretroviral therapy adherent, virally suppressed, and self-report cognitive symptoms. MRI, blood draws, and standardized neuropsychological test scores were collected from HIV-infected individuals. DTI metrics (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity) and plasma biomarkers (soluble CD163, soluble CD14, neopterin, IFN γ-induced protein 10, monocyte chemoattractant protein 1) were quantified. Statistical analysis explored associations between biomarker levels or neuropsychological test scores and DTI metrics using region of interest analyses and a voxelwise approach. A total of 43 participants with median (interquartile range) age of 64 (62-66 years), CD4 cell count of 600 (400-760 cell/μl) who were all virally suppressed (<100 copies/ml) were selected. Higher levels of monocyte chemoattractant protein 1 associated with lower fractional anisotropy and higher mean diffusivity (P < 0.05) across white matter tracts including corpus callosum, corona radiata, and superior longitudinal fasciculus. Higher neopterin associated with higher mean diffusivity in the genu of corpus callosum, and higher soluble CD14 associated with lower fractional anisotropy in the bilateral superior corona radiata (P < 0.05). Worse global performance and speed domain scores associated with higher mean diffusivity and lower fractional anisotropy, and worse executive domain scores associated with lower fractional anisotropy (P < 0.05). Elevated inflammatory plasma biomarkers link to white matter abnormalities among virally suppressed individuals. DTI abnormalities associate to cognitive performance. We conclude that inflammatory processes impact clinically relevant brain health indices despite viral suppression.

A preliminary attempt to visualize nigrosome 1 in the substantia nigra for Parkinson's disease at 3T: An efficient susceptibility map-weighted imaging (SMWI) with quantitative susceptibility mapping using deep neural network (QSMnet).

Visibility of nigrosome 1 in the substantia nigra (SN) is used as an MR imaging biomarker for Parkinson's disease. Because of lower susceptibility induced tissue contrast and SNR visualization of the SN pars compacta (SNPC) using conventional imaging technique in the clinical field strength (≤3T) has been limited. Susceptibility map-weighted imaging (SMWI) has been proposed to visualize SNPC at 3T. To better visualize nigrosome 1 and SN areas using SMWI, accurate estimation of the quantitative susceptibility mapping (QSM) map is essential. In SMWI processing, however, QSM processing time using conventional algorithms is the most time-consuming step and may limit clinical use. In this study, we introduce an efficient SMWI processing approach using the deep neural network (QSMnet). To improve the processing speed of SMWI while maintaining similar image quality to that obtained with the conventional method, QSMnet was applied to generate a susceptibility mask for SMWI processing. To conduct a deep learning-based image to image operation modified QSMnet was utilized. The network was trained with in vivo MR data from 57 healthy controls. To validate SMWI results from QSMnet, four datasets from healthy controls were used as the test datasets. As a preliminary attempt to explore the clinical applicability, Parkinson's disease patient data were additionally tested. The SWMI images generated by QSMnet and conventional model-based QSM outputs were compared. To validate SMWI results, region of interest (ROI) analysis was performed. The mean signal values at the nigrosome 1 and the surrounding regions were measured to calculate contrast-to-noise ratio (CNR). The experimental results confirmed that the proposed approach using QSMnet provided similar QSM and SMWI compared to that obtained with conventional iLSQR while the processing speed was much improved (5.4 times faster). The QSM results from QSMnet show similar tissue contrast with results from iLSQR. When compared, the absolute mean intensity difference between two methods near the nigrosome 1 was 0.015ppm. SMWI results using susceptibility masks from QSMnet demonstrated signal distribution and tissue contrast that was comparable with those results from the conventional iLSQR method. The absolute difference maps of SMWI were calculated to show the similarity between the two methods. The overall mean absolute difference value in the presented ROIs obtained from healthy controls (n=4) and a PD patient (n=1) were 2.31 and 1.81, respectively. Mean CNR values (10 ROIs; n=5; including both sides; 1.42 for QSMnet; 1.43 for iLSQR) between SN and nigrosome 1 in SMWI results obtained by ROI analysis were similar (P=0.724). In this study, we assessed an efficient approach for SMWI visualizing SN and nigrosome 1 on 3T. QSMnet provides a similar SMWI image to that obtained with the conventional iterative QSM algorithm and improves QSM processing speed by avoiding iterative computation. Since QSM is the most time-consuming step of SMWI processing, QSMnet can help to achieve a higher processing speed of SMWI. These results suggest that SMWI imaging with susceptibility masks using QSMnet is a more efficient approach.

Neuroinflammation and White Matter Alterations in Obesity Assessed by Diffusion Basis Spectrum Imaging.

Human obesity is associated with low-grade chronic systemic inflammation, alterations in brain structure and function, and cognitive impairment. Rodent models of obesity show that high-calorie diets cause brain inflammation (neuroinflammation) in multiple regions, including the hippocampus, and impairments in hippocampal-dependent memory tasks. To determine if similar effects exist in humans with obesity, we applied Diffusion Basis Spectrum Imaging (DBSI) to evaluate neuroinflammation and axonal integrity. We examined diffusion-weighted magnetic resonance imaging (MRI) data in two independent cohorts of obese and non-obese individuals (Cohort 1: 25 obese/21 non-obese; Cohort 2: 18 obese/41 non-obese). We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain white matter (WM) analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between the obese and non-obese groups. In both cohorts, the obese group had significantly greater DBSI-derived restricted fraction (DBSI-RF; an indicator of neuroinflammation-related cellularity), and significantly lower DBSI-derived fiber fraction (DBSI-FF; an indicator of apparent axonal density) in several WM tracts (all corrected p < 0.05). Moreover, using region of interest analyses, average DBSI-RF and DBSI-FF values in the hippocampus were significantly greater and lower, respectively, in obese relative to non-obese individuals (Cohort 1: p = 0.045; Cohort 2: p = 0.008). Hippocampal DBSI-FF and DBSI-RF and amygdalar DBSI-FF metrics related to cognitive performance in Cohort 2. In conclusion, these findings suggest that greater neuroinflammation-related cellularity and lower apparent axonal density are associated with human obesity and cognitive performance. Future studies are warranted to determine a potential role for neuroinflammation in obesity-related cognitive impairment.

Brain free water alterations in first-episode psychosis: a longitudinal analysis of diagnosis, course of illness, and medication effects.

Multiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features. The current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses. Patients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity. Our results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.

Putaminal diffusion tensor imaging measures predict disease severity across human prion diseases.

Therapeutic trials of disease-modifying agents in neurodegenerative disease typically require several hundred participants and long durations for clinical endpoints. Trials of this size are not feasible for prion diseases, rare dementia disorders associated with misfolding of prion protein. In this situation, biomarkers are particularly helpful. On diagnostic imaging, prion diseases demonstrate characteristic brain signal abnormalities on diffusion-weighted MRI. The aim of this study was to determine whether cerebral water diffusivity could be a quantitative imaging biomarker of disease severity. We hypothesized that the basal ganglia were most likely to demonstrate functionally relevant changes in diffusivity. Seventy-one subjects (37 patients and 34 controls) of whom 47 underwent serial scanning (23 patients and 24 controls) were recruited as part of the UK National Prion Monitoring Cohort. All patients underwent neurological assessment with the Medical Research Council Scale, a functionally orientated measure of prion disease severity, and diffusion tensor imaging. Voxel-based morphometry, voxel-based analysis of diffusion tensor imaging and regions of interest analyses were performed. A significant voxel-wise correlation of decreased Medical Research Council Scale score and decreased mean, radial and axial diffusivities in the putamen bilaterally was observed (P < 0.01). Significant decrease in putamen mean, radial and axial diffusivities over time was observed for patients compared with controls (P = 0.01), and there was a significant correlation between monthly decrease in putamen mean, radial and axial diffusivities and monthly decrease in Medical Research Council Scale (P < 0.001). Step-wise linear regression analysis, with dependent variable decline in Medical Research Council Scale, and covariates age and disease duration, showed the rate of decrease in putamen radial diffusivity to be the strongest predictor of rate of decrease in Medical Research Council Scale (P < 0.001). Sample size calculations estimated that, for an intervention study, 83 randomized patients would be required to provide 80% power to detect a 75% amelioration of decline in putamen radial diffusivity. Putamen radial diffusivity has potential as a secondary outcome measure biomarker in future therapeutic trials in human prion diseases.

Individual differences in anxiety and automatic amygdala response to fearful faces: A replication and extension of Etkin et al. (2004)

Trait anxiety refers to the stable tendency to attend to threats and experience fears and worries across many situations. According to the widely noticed, pioneering investigation by Etkin et al. (2004) trait anxiety is strongly associated with reactivity in the right basolateral amygdala to non-conscious threat. Although this observation was based on a sample of only 17 individuals, no replication effort has been reported yet. We reexamined automatic amygdala responsiveness as a function of anxiety in a large sample of 107 participants. Besides self-report instruments, we administered an indirect test to assess implicit anxiety. To assess early, automatic stages of emotion processing, we used a color-decision paradigm presenting brief (33 ms) and backward-masked fearful facial expressions. N = 56 participants were unaware of the presence of masked faces. In this subset of unaware participants, the relationship between trait anxiety and basolateral amygdala activation by fearful faces was successfully replicated in region of interest analyses. Additionally, a relation of implicit anxiety with masked fear processing in the amygdala and temporal gyrus was observed. We provide evidence that implicit measures of affect can be valuable predictors of automatic brain responsiveness and may represent useful additions to explicit measures. Our findings support a central role of amygdala reactivity to non-consciously perceived threat in understanding and predicting dispositional anxiety, i.e. the frequency of spontaneously occurring anxiety in everyday life.

Differential impact of interleukin-6 promoter gene polymorphism on hippocampal volume in antipsychotic-naïve schizophrenia patients.

Background:Differential susceptibility model hypothesizes that a genotype need not be unfavorable all the time as postulated in stress-diathesis model but can be beneficial in a supportive context. Single-nucleotide polymorphism (SNP) (rs18000795) within the promoter region of interleukin-6 (IL-6) gene was earlier noted to have a differential susceptibility on hippocampal volume in schizophrenia (SCZ).Materials and Methods:We examined antipsychotic-naïve/free SCZ patients (n = 35) in comparison with healthy controls (n = 68). Hippocampus volumes were assessed in 3 Tesla magnetic resonance imaging using voxel-based morphometry. Region of interest analysis was done using hippocampus mask. IL-6 SNP (rs1800795) was genotyped using TaqMan allelic discrimination assay.Results:A significantly deficient right (T = 3.03; KE= 392; PSVC-FWE= 0.04) and left (T = 3.03; KE= 47; Puncorr= 0.03) hippocampal gray matter volumes were noted in SCZ patients after controlling for the potential confounding effects of age, sex, and total brain volume. There was a significant diagnosis x rs1800795 genotype interaction involving both left (T = 2.17, KE= 95, Puncorr= 0.02) and right (T = 1.82, KE= 29, Puncorr= 0.04) hippocampal volumes. Patients with GG (left: F =5.78; P = 0.02; right: F =6.21; P = 0.01) but not GC/CC genotype (left: F =0.89; P = 0.34; right: F <0.01; P = 0.95) had volume depletion.Conclusion:A paradoxical smaller hippocampal volume with GG genotype was noted in SCZ. Further elucidation of its mechanistic basis might have translational implications.

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally.Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally).Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions.Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.

알코올 사용 장애자의 현출 네트워크의 기능적 연결성 증가

Objective: The aim of this study is to identify the altered functional connectivities of the salience network during resting state among individual with alcohol use disorder using functional magnetic resonance imaging.BRBRBackground: Individuals with Alcohol Use Disorder (AUD) has shown significant attention and attraction to alcohol-related stimuli. The previous studies demonstrated the neuropsychological, physiological responses elicited by alcohol-related cue. These researches suggested the altered functional connectivities between brain areas related to incentive salience among AUD patients, but not yet fully explored the functional connectivities in salience network during resting-state among AUD patients in the literatures.BRBRMethod: In this study, functional magnetic resonance imaging data were acquired for 22 AUD patients and 22 healthy controls with similar demographic characteristics. The functional connectivities between the regions in salience network was chosen as the region of interest (ROI), and the ROI to ROI analysis with time series signals was conducted. After that two-sample t test was performed.BRBRResults: In the results, AUD patients exhibited increased functional connectivities in the right anterior insula - left supramarginal gyrus, the right supramarginal gyrus - left rostral prefrontal cortex, right supramarginal gyrus - right rostral prefrontal cortex, and right supramarginal gyrus - left supramarginal gyrus compared to healthy controls. The strengths of functional connectivity in these areas were linked to the severity of AUD measured by Alcohol Use Disorder Identification Test (AUDIT).BRBRConclusion: The results of the study suggest that abnormal incentive salience toward alcohol-related stimuli might be associated with the aberrant functional connectivities in salience network.BRBRApplication: The aberrant functional connectivities in salience network might apply for discrimination of AUD, and determination the severity of AUD as neuroimaging markers.

Renal BOLD MRI in patients with chronic kidney disease: comparison of the semi-automated twelve layer concentric objects (TLCO) and manual ROI methods

Blood oxygenation level dependent (BOLD) MRI technique is used to evaluate changes in intra-renal oxygenation in chronic kidney disease (CKD). The purpose of this study was to evaluate if the novel twelve layer concentric objects (TLCO) method has advantages over the manually defined regions of interest (ROI) analysis. Existing renal BOLD MRI data acquired before and after furosemide on a 3T scanner from 41 CKD patients and 13 age matched healthy controls were analyzed using TLCO method and compared with previously reported ROI analysis. Regional R2* measurements were strongly correlated between the two methods, while ΔR2* was moderately correlated. Medullary R2* by ROI analysis showed higher values compared to R2*_Inner by TLCO, probably due to the contributions from the cortex to R2*_Inner. R2*_Slope and Δ(R2*_Slope), unique parameters based on the TLCO method provided the most significant differences between stage 3a CKD patients and controls and were correlated with eGFR. There was a high degree of agreement between the two methods in terms of regional R2* measurements and both methods did not show differences between moderate CKD patients and controls. However, R2*_Slope and Δ(R2*_Slope) showed the largest sensitivity in distinguishing CKD from controls.

Arithmetic in the adult deaf signing brain.

We have previously shown that deaf signers recruit partially different brain regions during simple arithmetic compared to a group of hearing non-signers, despite similar performance. Specifically, hearing individuals show more widespread activation in brain areas that have been related to the verbal system of numerical processing, i.e., the left angular and inferior frontal gyrus, whereas deaf individuals engaged brain areas that have been related to the quantity system of numerical processing, i.e., the right horizontal intraparietal sulcus. This indicates that compared to hearing non-signers, deaf signers can successfully make use of processes located in partially different brain areas during simple arithmetic. In this study, which is a conceptual replication and extension of the above-presented study, the main aim is to understand similarities and differences in neural correlates supporting arithmetic in deaf compared to hearing individuals. The primary objective is to investigate the role of the right horizontal intraparietal gyrus, the left inferior frontal gyrus, the hippocampus, and the left angular gyrus during simple and difficult arithmetic and how these regions are connected to each other. A second objective is to explore what other brain regions support arithmetic in deaf signers. Up to 34 adult deaf signers and the same amount of hearing non-signers will be enrolled in an functional magnetic resonance imaging study that will include simple and difficult subtraction and multiplication. Brain imaging data will be analyzed using whole-brain analysis, region of interest analysis and connectivity analysis. This is the first study to investigate neural underpinnings of arithmetic of different difficulties in deaf individuals.

Verbal suggestions of nicotine content modulate ventral tegmental neural activity during the presentation of a nicotine-free odor in cigarette smokers

Expectancies of nicotine content have been shown to impact smokers’ subjective responses and smoking behaviors. However, little is known about the neural substrates modulated by verbally induced expectancies in smokers. In this study we used functional magnetic resonance imaging (fMRI) to investigate how verbally induced expectations, regarding the presence or absence of nicotine, modulated smokers’ neural response to a nicotine-free odor. While laying in the scanner, all participants (N = 24) were given a nicotine-free odor, but whereas one group was correctly informed about the absence of nicotine (control group n = 12), the other group was led to believe that the presented odor contained nicotine (expectancy group n = 12). Smokers in the expectancy group had significantly increased blood-oxygen-level-dependent (BOLD) responses during the presentation of the nicotine-free odor in the left ventral tegmental area (VTA), and in the right insula, as compared to smokers in the control group (Regions of interest analysis with pFWE-corrected p ≤ 0.05). At a more liberal uncorrected statistical level (p-unc ≤ 0.001), increased bilateral reactivity in the dorsolateral prefrontal cortex (dlPFC) was also observed in the expectancy group as compared with the control group. Our findings suggest that nicotine-expectancies induced through verbal instructions can modulate nicotine relevant brain regions, without nicotine administration, and provide further neural support for the key role that cognitive expectancies play in the cause and treatment of nicotine dependence.

The neural and molecular basis of working memory function in psychosis: a multimodal PET-fMRI study

Working memory (WM) deficits predict clinical and functional outcomes in schizophrenia but are poorly understood and unaddressed by existing treatments. WM encoding and WM retrieval have not been investigated in schizophrenia without the confounds of illness chronicity or the use of antipsychotics and illicit substances. Moreover, it is unclear if WM deficits may be linked to cannabinoid 1 receptor dysfunction in schizophrenia. Sixty-six volunteers (35 controls, 31 drug-free patients with diagnoses of schizophrenia or schizoaffective disorder) completed the Sternberg Item-Recognition paradigm during an fMRI scan. Neural activation during WM encoding and WM retrieval was indexed using the blood-oxygen-level-dependent hemodynamic response. A subset of volunteers (20 controls, 20 drug-free patients) underwent a dynamic PET scan to measure [11C] MePPEP distribution volume (ml/cm3) to index CB1R availability. In a whole-brain analysis, there was a significant main effect of group on task-related BOLD responses in the superior parietal lobule during WM encoding, and the bilateral hippocampus during WM retrieval. Region of interest analyses in volunteers who had PET/fMRI indicated that there was a significant main effect of group on task-related BOLD responses in the right hippocampus, left DLPFC, left ACC during encoding; and in the bilateral hippocampus, striatum, ACC and right DLPFC during retrieval. Striatal CB1R availability was positively associated with mean striatal activation during WM retrieval in male patients (R = 0.5, p = 0.02) but not male controls (R = −0.20, p = 0.53), and this was significantly different between groups, Z = −2.20, p = 0.02. Striatal CB1R may contribute to the pathophysiology of WM deficits in male patients and have implications for drug development in schizophrenia.

Using principal component analysis to characterize eye movement fixation patterns during face viewing.

Human faces contain dozens of visual features, but viewers preferentially fixate just two of them: the eyes and the mouth. Face-viewing behavior is usually studied by manually drawing regions of interest (ROIs) on the eyes, mouth, and other facial features. ROI analyses are problematic as they require arbitrary experimenter decisions about the location and number of ROIs, and they discard data because all fixations within each ROI are treated identically and fixations outside of any ROI are ignored. We introduce a data-driven method that uses principal component analysis (PCA) to characterize human face-viewing behavior. All fixations are entered into a PCA, and the resulting eigenimages provide a quantitative measure of variability in face-viewing behavior. In fixation data from 41 participants viewing four face exemplars under three stimulus and task conditions, the first principal component (PC1) separated the eye and mouth regions of the face. PC1 scores varied widely across participants, revealing large individual differences in preference for eye or mouth fixation, and PC1 scores varied by condition, revealing the importance of behavioral task in determining fixation location. Linear mixed effects modeling of the PC1 scores demonstrated that task condition accounted for 41% of the variance, individual differences accounted for 28% of the variance, and stimulus exemplar for less than 1% of the variance. Fixation eigenimages provide a useful tool for investigating the relative importance of the different factors that drive human face-viewing behavior.

Improvement Of Frontal Lobe Dysfunction And White Matter Integrity By rTMS In Treatment-Resistant Depression.

AimThe impairment experienced by many individuals with depression is closely related to the cognitive symptoms of the disorder. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method providing a promising technique for improving cognitive symptoms in treatment-resistant depression (TRD). In the present study, we investigated whether a relationship exists between improvements in frontal lobe dysfunction induced by rTMS and improvement of white matter integrity revealed by diffusion tensor imaging (DTI) in TRD patients receiving rTMS treatment.MethodsA total of 12 patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study (August 2013–January 2019). Frontal lobe function and depressive symptoms were assessed at baseline and at the endpoint of rTMS treatment. Fractional anisotropy (FA), as a measure of white matter integrity obtained from DTI, was investigated using a region-of-interest (ROI) approach.ResultsrTMS treatment significantly improved depressive symptom scores and some subscales of frontal lobe dysfunction. Category scores in the Word Fluency Test and scores on part 3 of the Color Stroop Test were improved independently of the improvement of depressive symptoms. In the ROI analysis, none of the FA increases in any region were correlated with improvement of any frontal lobe function (n = 12).ConclusionAlthough rTMS resulted in partial improvement of frontal lobe dysfunction as well as white matter integrity, we found no correlation between improved frontal lobe dysfunction and improved white matter integrity in TRD patients.

Artificial neural network for myelin water imaging.

To demonstrate the application of artificial neural network (ANN) for real-time processing of myelin water imaging (MWI). Three neural networks, ANN-IMWF , ANN-IGMT2 , and ANN-II, were developed to generate MWI. ANN-IMWF and ANN-IGMT2 were designed to output myelin water fraction (MWF) and geometric mean T2 of intra- and extra-cellular water signal(GMT2,IEW ), respectively, whereas ANN-II generates a T2 distribution. For the networks, gradient and spin echo data from 18 healthy controls (HC) and 26 multiple sclerosis patients (MS) were utilized. Among them, 10 HC and 12 MS had the same scan parameters and were used for training (6 HC and 6 MS), validation (1 HC and 1 MS), and test sets (3 HC and 5 MS). The remaining data had different scan parameters and were applied to exam effects of the scan parameters. The network results were compared with those of conventional MWI in the white matter mask and regions of interest. The networks produced highly accurate results, showing averaged normalized root-mean-squared error under 3% for MWF and 0.4% for GMT2,IEW in the white matter mask of the test set. In the region of interest analysis, the differences between ANNs and conventional MWI were less than 0.1% in MWF and 0.1 ms in GMT2,IEW (no statistical difference and R2 > 0.97). Datasets with different scan parameters showed increased errors. The average processing time was 0.68 s in ANNs, gaining 11,702 times acceleration in the computational speed (conventional MWI: 7,958 s). The proposed neural networks demonstrate the feasibility of real-time processing for MWI with high accuracy.

Altered resting-state functional connectivity within the developing social brain after pediatric traumatic brain injury.

Traumatic brain injury (TBI) in childhood and adolescence can interrupt expected development, compromise the integrity of the social brain network (SBN) and impact social skills. Yet, no study has investigated functional alterations of the SBN following pediatric TBI. This study explored functional connectivity within the SBN following TBI in two independent adolescent samples. First, 14 adolescents with mild complex, moderate or severe TBI and 16 typically developing controls (TDC) underwent resting‐state functional magnetic resonance imaging 12–24 months post‐injury. Region of interest analyses were conducted to compare the groups' functional connectivity using selected SBN seeds. Then, replicative analysis was performed in an independent sample of adolescents with similar characteristics (9 TBI, 9 TDC). Results were adjusted for age, sex, socioeconomic status and total gray matter volume, and corrected for multiple comparisons. Significant between‐group differences were detected for functional connectivity in the dorsomedial prefrontal cortex and left fusiform gyrus, and between the left fusiform gyrus and left superior frontal gyrus, indicating positive functional connectivity for the TBI group (negative for TDC). The replication study revealed group differences in the same direction between the left superior frontal gyrus and right fusiform gyrus. This study indicates that pediatric TBI may alter functional connectivity of the social brain. Frontal‐fusiform connectivity has previously been shown to support affect recognition and changes in the function of this network could relate to more effortful processing and broad social impairments.