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.

Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study.

OBJECTIVE: Diffuse axonal injury (DAI) is prevalent in traumatic brain injury (TBI), and is often associated with poor outcomes and cognitive impairment, including memory deficits. Few studies have explored visual memory after TBI and its relationship to executive functioning. Executive functioning is crucial for remembering an object's location, operating devices, driving, and route finding. We compared visual memory performance via the Rey-Osterrieth Complex Figure (ROCF) test 6 and 12 months after DAI. METHOD: In total, 40 patients (mean age 28.7 years; 87.5% male) with moderate-to-severe DAI following a road traffic accident completed the 1-year follow-up. There was a three-phase prospective assessment. In phase 1 (1-3 months after trauma), patients completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). In phases 2 (6 months) and 3 (12 months), they completed the BDI, STAI, and a neuropsychological battery [ROCF copy and recall, digit span forward/backward, Grooved Pegboard test, intelligence quotient (IQ) by Wechsler Adult Intelligence Scale-III (WAIS-III)]. RESULTS: There was an improvement in ROCF recall over time (p=0.013), but not ROCF copy (p=0.657).There was no change in executive function (Savage scores) copy (p=0.230) or recall (p=0.155). Age, years of education, severity of the trauma, and IQ did not influence ROCF recall improvement. CONCLUSION: There are time-dependent improvements in visual memory in patients with DAI. Neuroplasticity in the 1st months after trauma provides an opportunity for visuospatial memory learning. The present findings may be useful to formulate management plans for long-term TBI rehabilitation.

CRF type 1 receptors of the medial amygdala modulate inhibitory avoidance responses in the elevated T-maze.

Corticotropin-releasing factor (CRF) plays a critical role in the mediation of physiological and behavioral responses to stressors. In the present study, we investigated the role played by the CRF system within the medial amygdala (MeA) in the modulation of anxiety and fear-related responses. Male Wistar rats were bilaterally administered into the MeA with CRF (125 and 250 ng/0.2µl, experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 µl, experiment 2) and 10 min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. In clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. To further verify if the anxiogenic effects of CRF were mediated by CRFR1 activation, we also investigated the effects of the combined treatment with CRF (250 ng/0.2 µl) and antalarmin (25 ng/0.2 µl) (experiment 3). All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that CRF, in the two doses administered, facilitated ETM avoidance, an anxiogenic response. Antalarmin significantly decreased avoidance latencies, an anxiolytic effect, and was able to counteract the anxiogenic effects of CRF. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRF in the MeA exerts anxiogenic effects by activating type 1 receptors, which might be of relevance to the physiopathology of generalized anxiety disorder.

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.

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.

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.

Brain Connectivity and Functional Recovery in Patients With Ischemic Stroke.

BACKGROUND: Brain mapping studies have demonstrated that functional poststroke brain reorganization is associated with recovery of motor function. Nonetheless, the specific mechanisms associated with functional reorganization leading to motor recovery are still partly unknown. In this study, we performed a cross-sectional evaluation of poststroke subjects with the following goals: (1) To assess intra- and interhemispheric functional brain activation patterns associated with motor function in poststroke patients with variable degrees of recovery; (2) to investigate the involvement of other nonmotor functional networks in relationship with recovery. METHODS: We studied 59 individuals: 13 patients with function Rankin > 1 and Barthel < 100; 19 patients with preserved function with Rankin 0-1 and Barthel = 100; and 27 healthy controls. All subjects underwent structural and functional magnetic resonance imaging (3T Philips Achieva, Holland) using the same protocol (TR = 2 seconds, TE = 30 ms, FOV = 240 × 240 × 117, slice = 39). Resting state functional connectivity was used by in-house software, based on SPM12. Among patients with and without preserved function, the functional connectivity between the primary motor region (M1) and the contralateral hemisphere was increased compared with controls. Nonetheless, only patients with decreased function exhibited decreased functional connectivity between executive control, sensorimotor and visuospatial networks. CONCLUSION: Functional recovery after stroke is associated with preserved functional connectivity of motor to nonmotor networks.

Updates and Current Perspectives of Psychiatric Assessments after Traumatic Brain Injury: A Systematic Review.

Neuropsychological and psychiatric disorders represent a major concern and cause of disabilities after the trauma, contributing to worse recovery after traumatic brain injury (TBI). However, the lack of well-defined parameters to evaluate patient's psychiatric disorders leads to a wide range of diagnoses and symptoms. The aim of this study was to perform a review of literature in order to gather data of the most common scales and inventories used to assess and diagnose depression, anxiety, and posttraumatic stress disorder (PTSD) after TBI. We conducted a literature search via MEDLINE, PubMed, and Web of Science. We included reviews, systematic reviews, and meta-analysis studies, and we used the following keywords: "traumatic brain injury OR TBI," "depression OR depressive disorder," "anxiety," and "posttraumatic stress disorder OR PTSD." From 610 titles, a total of 68 systematic reviews or meta-analysis were included in the section "Results" of this review: depression (n = 32), anxiety (n = 9), and PTSD (n = 27). Depression after TBI is a more established condition, with more homogeneous studies. Anxiety and PTSD disorders have been studied in a heterogeneous way, usually as comorbidity with other psychiatric disorders. Some scales and inventories designed for the general community may not be appropriate for patients with TBI.

Relation between aerobic fitness and brain structures in amnestic mild cognitive impairment elderly.

Mild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer's disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD. Therefore, we aimed to investigate a possible relation between aerobic fitness (AF) and gray matter (GM) volume and AF and white matter (WM) integrity in aMCI with a CSF biomarker. Twenty-two participants with aMCI acquired the images on a 3.0-T MRI. AF was assessed by a graded exercise test on a treadmill. Voxel-based morphometry and tract-based spatial statistic methods were used to analyze the GM volume and WM microstructural integrity, respectively. We correlated AF and GM volume and WM integrity in aMCI (p < 0.05, FWE corrected, cluster with at least five voxels). There was a positive relation between AF and GM volume mostly in frontal superior cortex. In WM integrity, AF was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity and radial diffusivity, all in the same tracts that interconnect frontal, temporal, parietal, and occipital areas (longitudinal fasciculus, fronto-occipital fasciculus, and corpus callosum). These results suggest that aerobic fitness may have a positive influence on protection of brain even in aMCI CSF biomarker, a high-risk population to convert to AD.

A Semana Nacional e Latino Americana pela Conscientização sobre a Epilepsia em Campinas - Brasil / The 2014 National and Latino American Week for Epilepsy Awareness in Campinas - Brazil

Introdução: Com o objetivo de aumentar a conscientização sobre a Epilepsia na sociedade, a ASPE, o Instituto BRAINN (Instituto Brasileiro de Neurociência e Neurotecnologia - CEPID - Unicamp) e o Programa ABCérebro TV (http://www. abcerebro.tv/) promoveram a Semana Nacional e Latino-Americana para a Conscientização sobre a Epilepsia, entre os dias 9 a 13 de setembro. As atividades contaram com a participação de pacientes, alunos e professores da rede básica, profissionais da saúde e público em geral, assim como com a parceria da Prefeitura Municipal de Campinas. Objetivo: Relatar as principais atividades da Semana Nacional e Latino- Americana pela Conscientização sobre a Epilepsia, realizada entre os dias 9 a 13 de setembro de 2014. Métodos: Registro descritivo e fotográfico dos eventos para compor o presente relato. Resultados: A divulgação do evento e o estabelecimento da parceria com a rede pública de ensino básico permitiu a difusão de conhecimentos sobre Epilepsia tanto no meio acadêmico, quanto na sociedade. As atividades, com um caráter diversificado, foram capazes de promover a integração entre esses públicos, abrindo espaço para discussões, trocas e, principalmente, para quebrar o preconceito sobre a Epilepsia. Conclusão: A parceria entre a ASPE, uma organização não-governamental, o Instituto BRAINN, da pesquisa, e o canal de difusão e divulgação científica ABCérebro TV continuará a promover a divulgação sobre a Epilepsia para os mais diversos públicos,através das mídias sociais e dos eventos à comunidade, a partir de propostas de transformação social construídas em conjunto...

Introduction: Aiming to increase awareness about epilepsy in society, the non-governmental organization called Assistência à Saúde do Paciente com Epilepsia (ASPE), the Brazilian Institute for Neuroscience and Neurotechnology (BRAINN - Unicamp) and the ABCérebro TV (http://www.abcerebro.tv/) promoted the National and Latin American week for Epilepsy awareness, from 9 to 13 September. Activities were attended by patients, students and teachers from the Public Education System, health professionals and the general public, with the support of the Campinas City Council and the University of Campinas. Objective: To describe the activities during the Latin American and National Week for Epilepsy Awareness, held from 9 to 13 September, 2014. Methods: Descriptive records and qualitative analysis. Results and Discussion: This event and the establishment of partnerships with the public basic education allowed knowledge dissemination about epilepsy in the academic environment as well as in the society. Activities with different approaches promoted an integration between these groups, opening paths for discussions and exchanges, contributing to decrease prejudice about Epilepsy. Conclusion: The partnership between ASPE, a non-governmental organization, the BRAINN and ABCérebro TV will continue to promote disclosure on Epilepsy for all audiences, through social media and community events, according to social transformationprojects proposed by this group...