Disruption of Resting-State Functional Connectivity in Acute Ischemic Stroke: Comparisons Between Right and Left Hemispheric Insults.

Few resting-state functional magnetic resonance imaging (RS-fMRI) studies evaluated the impact of acute ischemic changes on cerebral functional connectivity (FC) and its relationship with functional outcomes after acute ischemic stroke (AIS), considering the side of lesions. To characterize alterations of FC of patients with AIS by analyzing 12 large-scale brain networks (NWs) with RS-fMRI. Additionally, we evaluated the impact of the side (right (RH) or left (LH) hemisphere) of insult on the disruption of brain NWs. 38 patients diagnosed with AIS (17 RH and 21 LH) who performed 3T MRI scans up to 72 h after stroke were compared to 44 healthy controls. Images were processed and analyzed with the software toolbox UF2C with SPM12. For the first level, we generated individual matrices based on the time series extraction from 70 regions of interest (ROIs) from 12 functional NWs, constructing Pearson's cross-correlation; the second-level analysis included an analysis of covariance (ANCOVA) to investigate differences between groups. The statistical significance was determined with p < 0.05, after correction for multiple comparisons with false discovery rate (FDR) correction. Overall, individuals with LH insults developed poorer clinical outcomes after six months. A widespread pattern of lower FC was observed in the presence of LH insults, while a contralateral pattern of increased FC was identified in the group with RH insults. Our findings suggest that LH stroke causes a severe and widespread pattern of reduction of brain networks' FC, presumably related to the impairment in their long-term recovery.

Impairment of daily occupations in multiple sclerosis: analysis of neuroimaging, general and social cognition, and reserve.

BACKGROUND: Multiple Sclerosis (MS) can impact performance of daily occupations in both relapsing-remitting (RRMS) and secondary-progressive (SPMS) clinical courses. Work force participation decreases with advancing physical disability but the influence of non-motor factors, neuroimaging, and reserve have been scarcely investigated. We aimed to evaluate MRI, clinical, and cognitive (social and general) factors associated with impairment in different daily occupations and address whether cognitive and brain reserve have a positive impact on the ability to maintain these activities. METHODS: We prospectively enrolled persons with MS (PwMS) who underwent clinical examination (Expanded Disability Status Scale - EDSS; Timed 25-Foot Walk Test - T25FW; and the Nine Hole Peg Test - 9HPT), general neuropsychological assessment (Brief Repeatable Battery of Neuropsychological Tests - BRBN, including the Symbol Digit Modalities Test - SDMT), social cognition evaluation (Reading the Mind in the Eyes Test), cognitive reserve questionnaire, and MRI (FreeSurfer). We also enrolled healthy subjects for comparison as a control group. Daily occupations (employment, money management, and driving abilities) were assessed in all individuals with questionnaires. RESULTS: We included 62 PwMS (32 RRMS and 30 SPMS; mean age 42.8 years; median educational time 12.75 years) and 67 controls (mean age 39.7; median educational time 12.0 years) which were similar regarding demographics, education, and socioeconomic status (p > 0.1). Most PwMS (67.7%) had work-restrictions. They also reported fewer money management and driving abilities than controls (p < 0.001). Work-restriction was associated with physical disability (p = 0.006), SDMT and BRBN performance (p = 0.035 and p = 0.031, respectively), and T2-lesion volume (p = 0.022), with large effect sizes (d > 0.75). After hierarchical linear regression, money management was associated with hand dexterity, general and social cognition, and cognitive reserve (p < 0.03). Variables associated with driving abilities included fatigue, verbal fluency, striatum volume, and brain reserve (p < 0.05). CONCLUSIONS: PwMS have more frequent work-restrictions and impairment in money management and driving abilities compared to controls. Cognitive function, physical disability, and MS-lesion burden are strongly associated with work-restriction. Social cognition can also influence financial capacity. Cognitive and brain reserve can help retain some of these daily occupations.

Fully automatic segmentation of brain lacunas resulting from resective surgery using a 3D deep learning model.

The rapid and constant development of deep learning (DL) strategies is pushing forward the quality of object segmentation in images from diverse fields of interest. In particular, these algorithms can be very helpful in delineating brain abnormalities (lesions, tumors, lacunas, etc), enabling the extraction of information such as volume and location, that can inform doctors or feed predictive models. In this study, we describe ResectVol DL, a fully automatic tool developed to segment resective lacunas in brain images of patients with epilepsy. ResectVol DL relies on the nnU-Net framework that leverages the 3D U-Net deep learning architecture. T1-weighted MRI datasets from 120 patients (57 women; 31.5 ± 15.9 years old at surgery) were used to train (n=78) and test (n=48) our tool. Manual segmentations were carried out by five different raters and were considered as ground truth for performance assessment. We compared ResectVol DL with two other fully automatic methods: ResectVol 1.1.2 and DeepResection, using the Dice similarity coefficient (DSC), Pearson's correlation coefficient, and relative difference to manual segmentation. ResectVol DL presented the highest median DSC (0.92 vs. 0.78 and 0.90), the highest correlation coefficient (0.99 vs. 0.63 and 0.94) and the lowest median relative difference (9 vs. 44 and 12 %). Overall, we demonstrate that ResectVol DL accurately segments brain lacunas, which has the potential to assist in the development of predictive models for postoperative cognitive and seizure outcomes.

Differences in structural and functional default mode network connectivity in amyloid positive mild cognitive impairment: a longitudinal study.

PURPOSE: Default mode network (DMN) has emerged as a potential biomarker of Alzheimer's disease (AD); however, it is not clear whether it can differentiate amnestic mild cognitive impairment with altered amyloid (aMCI-Aß +) who will evolve to AD. We evaluated if structural and functional connectivity (FC), hippocampal volumes (HV), and cerebrospinal fluid biomarkers (CSF-Aß42, p-Tau, and t-Tau) can differentiate aMCI-Aß + converters from non-converters. METHODS: Forty-eight individuals (18 normal controls and 30 aMCI subjects in the AD continuum - with altered Aß42 in the CSF) were followed up for an average of 13 months. We used MultiAtlas, UF2C, and Freesurfer software to evaluate diffusion tensor imaging, FC, and HV, respectively, INNOTEST® kits to measure CSF proteins, and neuropsychological tests. Besides, we performed different MANOVAs with further univariate analyses to differentiate groups. RESULTS: During follow-up, 8/30 aMCI-Aß + converted (26.6%) to AD dementia. There were no differences in multivariate analysis between groups in CSF biomarkers (p = 0.092) or at DMN functional connectivity (p = 0.814). aMCI-Aß + converters had smaller right HV than controls (p = 0.013), and greater right cingulum parahippocampal bundle radial diffusivity than controls (p < 0.001) and non-converters (p = 0.036). CONCLUSION: In this exploratory study, structural, but not functional, DMN connectivity alterations may differentiate aMCI-Aß + subjects who converted to AD dementia.

Incorporation of quantitative MRI in a model to predict temporal lobe epilepsy surgery outcome.

Quantitative volumetric brain MRI measurement is important in research applications, but translating it into patient care is challenging. We explore the incorporation of clinical automated quantitative MRI measurements in statistical models predicting outcomes of surgery for temporal lobe epilepsy. Four hundred and thirty-five patients with drug-resistant epilepsy who underwent temporal lobe surgery at Cleveland Clinic, Mayo Clinic and University of Campinas were studied. We obtained volumetric measurements from the pre-operative T1-weighted MRI using NeuroQuant, a Food and Drug Administration approved software package. We created sets of statistical models to predict the probability of complete seizure-freedom or an Engel score of I at the last follow-up. The cohort was randomly split into training and testing sets, with a ratio of 7:3. Model discrimination was assessed using the concordance statistic (C-statistic). We compared four sets of models and selected the one with the highest concordance index. Volumetric differences in pre-surgical MRI located predominantly in the frontocentral and temporal regions were associated with poorer outcomes. The addition of volumetric measurements to the model with clinical variables alone increased the model's C-statistic from 0.58 to 0.70 (right-sided surgery) and from 0.61 to 0.66 (left-sided surgery) for complete seizure freedom and from 0.62 to 0.67 (right-sided surgery) and from 0.68 to 0.73 (left-sided surgery) for an Engel I outcome score. 57% of patients with extra-temporal abnormalities were seizure-free at last follow-up, compared to 68% of those with no such abnormalities (P-value = 0.02). Adding quantitative MRI data increases the performance of a model developed to predict post-operative seizure outcomes. The distribution of the regions of interest included in the final model supports the notion that focal epilepsies are network disorders and that subtle cortical volume loss outside the surgical site influences seizure outcome.

Subacute functional connectivity correlates with cognitive recovery six months after stroke.

BACKGROUND AND PURPOSE: Cognitive impairment is a common consequence of stroke, and the rewiring of the surviving brain circuits might contribute to cognitive recovery. Studies investigating how the functional connectivity of networks change across time and whether their remapping relates to cognitive recovery in stroke patients are scarce. We aimed to investigate whether resting-state functional connectivity was associated with cognitive performance in stroke patients and if any alterations in these networks were correlated with cognitive recovery. METHODS: Using an fMRI ROI-ROI approach, we compared the ipsilesional, contralesional and interhemispheric functional connectivity of three resting-state networks involved in cognition - the Default Mode (DMN), Salience (SN) and Central Executive Networks (CEN), in subacute ischemic stroke patients (time 1, n = 37, stroke onset: 24.32 ± 7.44 days, NIHSS: 2.66 ± 3.45) with cognitively healthy controls (n = 20). Patients were reassessed six months after the stroke event (time 2, n = 20, stroke onset: 182.05 ± 8.17 days) to verify the subsequent reorganization of functional connections and whether such reorganization was associated with cognitive recovery. RESULTS: At time 1, patients had weaker interhemispheric connectivity in the DMN than controls; better cognitive performance at time 1 was associated with stronger interhemispheric and ipsilesional DMN connectivity, and weaker contralesional SN connectivity. At time 2, there were no changes in functional connectivity in stroke patients, compared to time 1. Better cognitive recovery measured at time 2 (time 2 - time 1) was associated with stronger functional connectivity in the DMN, and weaker interhemispheric subacute connectivity in the SN, both from time 1. CONCLUSIONS: Stroke disrupts the functional connectivity of the DMN, not only at the lesioned hemisphere but also between hemispheres. Six months after the stroke event, we could not detect the remapping of networks. Cognitive recovery was associated with the connectivity of both the DMN and SN of time 1. Our findings may be helpful for facilitating further understanding of the potential mechanisms underlying post-stroke cognitive performance.

Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis.

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE-HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.

Patterns of default mode network in temporal lobe epilepsy with and without hippocampal sclerosis.

The default mode network (DMN) consists of the deactivation of specific regions during the performance of cognitive tasks and activation during resting or mind wandering. Several pieces of evidence indicate the impairment of DMN in patients with mesial temporal lobe epilepsy (MTLE). However, most of these studies combined different underlying etiologies, failing to disentangle the influence of seizures and presence and side of hippocampal sclerosis (HS). We included 119 patients with MTLE divided into right-HS (n = 42), left-HS (n = 46), and magnetic resonance imaging (MRI)-negative MTLE (n = 31) and controls (n = 59). All underwent resting-state seed-based functional connectivity (FC), with a seed placed at the posterior cingulate cortex (PCC), an essential node for the DMN. To access group inferences, we used an SPM (Statistical Parametric Mapping) full-factorial model to compare patterns of activation using pairwise comparisons among all groups. Our results indicate a different pattern of DMN FC when controlling for side and presence of HS. The group with right-HS had increased FC in the left angular gyrus and the left middle occipital gyrus, when compared to controls, and increased FC of the left hippocampus when compared to the group with left-HS. The MRI-negative group had increased FC of the left hippocampus, left ventral diencephalon, and left fusiform gyrus as compared to left-HS, but did not show any areas of reduced FC compared to controls. By contrast, the group with left-HS did not show areas of increased FC compared to controls or the right-HS and had reduced FC in the left hippocampus compared to controls. Hence, the right-HS presented increased FC in areas related to the DMN in the left hemisphere; the MRI-negative group also showed increased FC in left-sided structures close to temporal lobe when compared to left-HS, probably indicating engagement in a compensatory system. In a subanalysis considering only the MRI-negative with left-sided EEG (electroencephalogram) subgroup, we found differences against controls, with left angular gyrus more connected in the first group, but no significant differences when compared to the group with left-HS. We conclude that the origin of seizures on the left hemisphere seems to engender a less prominent capacity of recruiting other neighbor areas related to DMN as compared to right-HS and controls. Considering recent studies that have revealed the importance of DMN for cognitive skills and memory, our findings may indicate that deficiencies exhibited by patients with left-HS temporal lobe epilepsy (TLE) in connecting to the DMN could be a surrogate marker of their known worse neuropsychological performance. Further studies with direct comparisons between cognitive tests and FC within the DMN are needed to validate these findings, especially for MRI-negative patients. This article is part of the Special Issue "NEWroscience 2018".

Temporal lobe structural evaluation after transsylvian selective amygdalohippocampectomy.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adolescents and adults, and in 65% of cases, it is related to hippocampal sclerosis (HS). Selective surgical approaches to the treatment of MTLE have as their main goal resection of the amygdala and hippocampus with minimal damage to the neocortex, temporal stem, and optic radiations (ORs). The object of this study was to evaluate late postoperative imaging findings on the temporal lobe from a structural point of view. METHODS: The authors conducted a retrospective evaluation of all patients with refractory MTLE who had undergone transsylvian selective amygdalohippocampectomy (SAH) in the period from 2002 to 2015. A surgical group was compared to a control group (i.e., adults with refractory MTLE with an indication for surgical treatment of epilepsy but who did not undergo the surgical procedure). The inferior frontooccipital fasciculus (IFOF), uncinate fasciculus (UF), and ORs were evaluated on diffusion tensor imaging analysis. The temporal pole neocortex was evaluated using T2 relaxometry. RESULTS: For the IFOF and UF, there was a decrease in anisotropy, voxels, and fibers in the surgical group compared with those in the control group (p < 0.001). An increase in relaxometry time in the surgical group compared to that in the control group (p < 0.001) was documented, suggesting gliosis and neuronal loss in the temporal pole. CONCLUSIONS: SAH techniques do not seem to totally preserve the temporal stem or even spare the neocortex of the temporal pole. Therefore, although the transsylvian approaches have been considered to be anatomically selective, there is evidence that the temporal pole neocortex suffers structural damage and potentially functional damage with these approaches.

Hippocampal atrophy disrupts the language network but not hemispheric language lateralization.

OBJECTIVE: It is still unclear how temporal lobe epilepsy (TLE) with and without hippocampal atrophy (HA) affects cortical language distribution. We aimed to investigate the role of the hippocampus on language lateralization, activation pattern, and functional connectivity (FC) in patients with TLE. METHODS: We investigated 93 patients with TLE-divided into right HA (RHA), left HA (LHA), and negative magnetic resonance imaging (MRI) (non-HA)-and 101 controls using a semantic-language functional MRI (fMRI) task and the Boston Naming Test (BNT). RESULTS: Groups did not differ in the frequency of atypical language lateralization (LL), which correlated differently with handedness in each brain region and group. Blood-oxygen-level dependend (BOLD) activation patterns and region of interest (ROI)-to-ROI FC differed between LHA and controls, as well as between LHA and non-HA patients. In the task activation pattern analysis, there was a decrease in the activation of patients with LHA relative to controls, exactly in the left hippocampus. However, non-HA patients had increased FC relative to controls in the left superior temporal gyrus region. Seed-to-voxel FC demonstrated greater differences between patients and controls and smaller differences among patient groups. The non-HA group was similar to controls, except for increased BOLD activation and increase FC in the superior temporal gyri. RHA and LHA differed from controls in BNT. BNT correlated with fMRI activation in RHA and non-HA groups. SIGNIFICANCE: LHA affected naming performance, fMRI semantic task activation pattern, and FC more than RHA and non-HA. Contrary to our expectations, LHA did not increase the frequency of atypical LL. Regardless of the side, HA impacts negatively on the language network but not on hemispheric language lateralization.

Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies.

OBJECTIVE: To analyze the lifetime trajectories in genetic generalized epilepsies (GGEs) and investigate the impact of symptoms of anxiety and depression on resting state functional connectivity (FC). METHODS: Seventy-four GGE patients were classified according to the pharmacological response as seizure-free (12 patients), pharmacoresistant (PhR; 14 patients), and fluctuating (FL; 48 patients). Fifty-four subjects completed both the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), and 38 also underwent 3-T resting state functional magnetic resonance imaging. These 38 patients were subdivided into a positive group (13 patients with concurrent symptoms of depression and anxiety) and a negative group (21 asymptomatic patients and four with mild anxiety or depression symptoms). For FC analysis of resting state networks, we matched 38 healthy asymptomatic volunteers and used the UF2C toolbox running on MATLAB2017/SPM12. RESULTS: The PhR group presented shorter duration of epilepsy (P = 0.016) and follow-up (P < 0.001) compared to the FL group. The PhR group showed higher levels (median = 20) on the BAI and BDI. Myoclonic seizures were the most difficult to control, as 50% of subjects persisted with them at last appointment, compared to generalized tonic-clonic seizures and absence seizures (<40%). Patients with concurrent anxiety and depression symptoms were 7.7 times more likely to exhibit pharmacoresistant seizures, although an increase of 1 year of epilepsy duration was associated with a decrease in the odds of presenting pharmacoresistance by a factor of 0.9. Overall, FC was altered between default mode network (DMN) and visuospatial/dorsal attention. However, only the positive group displayed abnormal FC between DMN and left executive control network, and between salience and visuospatial/dorsal attention. SIGNIFICANCE: Our findings may help clinicians to have a better understanding of GGE clinical course and increase attention to the potential relationship of psychopathologies and brain connectivity.

Major Depressive Disorder Associated With Reduced Cortical Thickness in Women With Temporal Lobe Epilepsy.

Background: Major Depressive Disorder (MDD) is highly prevalent in patients with mesial temporal lobe epilepsy (MTLE), especially in women, carrying significant morbidity. This study aimed to investigate the cortical thickness (CT) abnormalities associated with MDD in women with MTLE and hippocampal atrophy (HA). Also, we investigated the impact of MDD upon the volumes of the hippocampus and amygdala in these patients. Methods: We included 50 women with MTLE and HA (20 left, LMTLE; 30 right, RMTLE), 41 healthy women in the control group, and 15 women with MDD without epilepsy. MTLE patients were subdivided into three groups: MTLE-without-MDD (23 MTLE patients without MDD), MTLE-mild-MDD (nine MTLE patients with mild symptoms of MDD), and MTLE-severe-MDD (18 MTLE patients with moderate to severe symptoms of MDD). The five groups were balanced for age (p = 0.56). All participants had high-resolution 3D T1-weighted images in a 3T scanner. We used FreeSurfer 6.0 for volumetry and CT parcellation. All participants were submitted to a clinical psychological evaluation through the Structured Clinical Interview for DSM-IV (SCID-IV) and completed the Beck Depression Inventory (BDI-II). Results: We identified a smaller ipsilateral amygdala volume (p = 0.04) in the MTLE-severe-MDD group when compared to the control group. Our results presented a reduced ipsilateral lateral orbitofrontal cortex (p = 0.02) in the MTLE-severe-MDD in comparison to the MTLE-mild-MDD group. We also identified a thinner ipsilateral fusiform gyrus (p < 0.01) in the MTLE-severe-MDD compared to both MTLE-without-MDD and control groups. A reduced CT of the contralateral superior frontal gyrus (p = 0.02) was observed in the MTLE-severe-MDD in comparison to the MTLE-mild-MDD group. Conclusions: The identification of areas with reduced CT and atrophy of the ipsilateral amygdala in women with MTLE and MDD suggest that the cortical thinning in the network of the paralimbic system is related to the co-occurrence and intensity of depressive symptoms in this group.

Cognitive Reserve Relates to Functional Network Efficiency in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.

BACKGROUND: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). METHODS: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. RESULTS: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. LIMITATIONS: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. CONCLUSION: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Depression and anxiety symptoms are associated to disruption of default mode network in subacute ischemic stroke.

Depression and anxiety symptoms are common after stroke and associated to reduction in quality of life and poor physical and social outcomes. The Default Mode Network (DMN) plays an important role in the emotional processing. We investigated whether these symptoms are associated to a disruption of DMN functional connectivity in the first month after stroke. Thirty-four subacute ischemic stroke patients were submitted to: 1) behavioral assessment through Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Structured Clinical Interview for DSM Disorders; 2) neuropsychological assessment using Mini Mental State Examination and Montreal Cognitive Assessment; 3) resting state functional magnetic resonance imaging acquisition using a 3 T scanner (Philips Achieva). Patients with depression and/or anxiety symptoms showed an increased DMN functional connectivity in left inferior parietal gyrus and left basal nuclei, when compared to stroke controls. Specific correlation between BDI/BAI scores and DMN functional connectivity indicated that depression symptoms are correlated with increased functional connectivity in left inferior parietal gyrus, while anxiety symptoms are correlated with increased functional connectivity in cerebellum, brainstem and right middle frontal gyrus. Our study provides new insights into the underlying mechanisms of post stroke depression and anxiety, suggesting an alternate explanation other than regional structural damage following ischemic event, that these psychiatric symptoms are related to brain network dysfunction.

Clinical and Imaging Evaluation of Transuncus Selective Amygdalohippocampectomy.

BACKGROUND: Various reports have described the transuncus (TU) approach as a selective route to the amygdala and hippocampus, but this approach has not yet been submitted to solid postoperative imaging analysis. The objective of this study was to evaluate the anatomy, surgical technique, postoperative imaging analysis, and outcome in a series of patients with temporal lobe epilepsy who underwent selective amigdalohippocampectomy via a TU approach. METHODS: This was a prospective study of 25 consecutive patients who underwent selective amigdalohippocampectomy through a TU approach. The temporal stem and temporal pole were evaluated through different modalities of 3-Tesla magnetic resonance imaging, including tractography of optic radiation (OR), uncinate fascicle, and inferior fronto-occipital fascicle. Visual field analysis was performed with automated perimetry. RESULTS: The mean age was 40 ± 8.21 years, and mean follow-up was 26.44 + 12.58 months. Postoperatively, 21 patients (84%) were classified as Engel I (good seizure control). Diffusion tensor imaging (DTI) data showed that 78.2% of patients had some structural damage to the temporal stem and fibers of the uncinate fascicle were identified postoperatively in only 3 patients (13.04%). The inferior fronto-occipital fascicle was identified in 18 patients (78.3%); however, subsequent DTI analysis of the remaining fibers showed them to be damaged. Integrity of the OR did not differ between these 2 groups. CONCLUSIONS: A TU approach is a feasible and efficient approach to selective amigdalohippocampectomy for surgical treatment of temporal lobe epilepsy. Postoperative DTI analysis suggests that a TU approach results in more injury to the temporal stem and its associated white matter fiber tracts than expected by previous anatomic studies; however, it was efficient in preserving OR.

Does Side of Onset Influence the Pattern of Cerebral Atrophy in Parkinson's Disease?

BACKGROUND: Imaging studies have revealed widespread neurodegeneration in Parkinson's disease (PD), but only a few considered the issue of asymmetrical clinical presentations. OBJECTIVE: To investigate if the side of onset influences the pattern of gray matter (GM) atrophy in PD. METHODS: Sixty patients (57.87 ± 10.27 years) diagnosed with idiopathic PD according to the U.K. Brain Bank criteria, 26 with right-sided disease onset (RDO) and 34 with left-sided disease onset (LDO), were compared to 80 healthy controls (HC) (57.1 ± 9.47 years). We acquired T1-weighted images on a 3 T scanner. Images were processed and analyzed with VBM8 (SPM8/Dartel) on Matlab R2012b platform. Statistic assessments included a two-sample test (family-wise error p < 0.05) with extent threshold of 20 voxels. RESULTS: Compared to HC, LDO patients had GM atrophy in the insula, putamen, anterior cingulate, frontotemporal cortex, and right caudate, while the RDO group showed atrophy at the anterior cingulate, insula, frontotemporal, and occipital cortex. CONCLUSION: This study revealed widespread GM atrophy in PD, predominantly in the left hemisphere, regardless of the side of onset. Future investigations should also consider handedness and side of onset to better characterize cerebral involvement and its progression in PD.

Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Pattern of Reduced Functional Connectivity and Structural Abnormalities in Parkinson's Disease: An Exploratory Study.

BACKGROUND: MRI brain changes in Parkinson's disease (PD) are controversial. OBJECTIVES: We aimed to describe structural and functional changes in PD. METHODS: Sixty-six patients with PD (57.94 ± 10.25 years) diagnosed according to the UK Brain Bank criteria were included. We performed a whole brain analysis using voxel-based morphometry (VBM-SPM 8 software), cortical thickness (CT) using CIVET, and resting-state fMRI using the Neuroimaging Analysis Kit software to compare patients and controls. For VBM and CT we classified subjects into three groups according to disease severity: mild PD [Hoehn and Yahr scale (HY) 1-1.5], moderate PD (HY 2-2.5), and severe PD (HY 3-5). RESULTS: We observed gray matter atrophy in the insula and inferior frontal gyrus in the moderate PD and in the insula, frontal gyrus, putamen, cingulated, and paracingulate gyri in the severe groups. In the CT analysis, in mild PD, cortical thinning was restricted to the superior temporal gyrus, gyrus rectus, and olfactory cortex; in the moderate group, the postcentral gyrus, supplementary motor area, and inferior frontal gyrus were also affected; in the severe PD, areas such as the precentral and postentral gyrus, temporal pole, fusiform, and occipital gyrus had reduced cortical thinning. We observed altered connectivity at the default mode, visual, sensorimotor, and cerebellar networks. CONCLUSION: Subjects with mild symptoms already have cortical involvement; however, further cerebral involvement seems to follow Braak's proposed mechanism. Similar regions are affected both structurally and functionally. We believe the combination of different MRI techniques may be useful in evaluating progressive brain involvement and they may eventually be used as surrogate markers of disease progression.