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.

Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex.

The human posteromedial cortex (PMC), which includes the precuneus (PC), represents a multimodal brain area implicated in emotion, conscious awareness, spatial cognition, and social behavior. Here, we describe the presence of Nissl-stained elongated spindle-shaped neurons (suggestive of von Economo neurons, VENs) in the cortical layer V of the anterior and central PC of adult humans. The adapted "single-section" Golgi method for postmortem tissue was used to study these neurons close to pyramidal ones in layer V until merging with layer VI polymorphic cells. From three-dimensional (3D) reconstructed images, we describe the cell body, two main longitudinally oriented ascending and descending dendrites as well as the occurrence of spines from proximal to distal segments. The primary dendritic shafts give rise to thin collateral branches with a radial orientation, and pleomorphic spines were observed with a sparse to moderate density along the dendritic length. Other spindle-shaped cells were observed with straight dendritic shafts and rare branches or with an axon emerging from the soma. We discuss the morphology of these cells and those considered VENs in cortical areas forming integrated brain networks for higher-order activities. The presence of spindle-shaped neurons and the current discussion on the morphology of putative VENs address the need for an in-depth neurochemical and transcriptomic characterization of the PC cytoarchitecture. These findings would include these spindle-shaped cells in the synaptic and information processing by the default mode network and for general intelligence in healthy individuals and in neuropsychiatric disorders involving the PC in the context of the PMC functioning.

Differences in Cortical Structure and Functional MRI Connectivity in High Functioning Autism.

Autism spectrum disorders (ASD) represent a complex group of neurodevelopmental conditions characterized by deficits in communication and social behaviors. We examined the functional connectivity (FC) of the default mode network (DMN) and its relation to multimodal morphometry to investigate superregional, system-level alterations in a group of 22 adolescents and young adults with high-functioning autism compared to age-, and intelligence quotient-matched 29 healthy controls. The main findings were that ASD patients had gray matter (GM) reduction, decreased cortical thickness and larger cortical surface areas in several brain regions, including the cingulate, temporal lobes, and amygdala, as well as increased gyrification in regions associated with encoding visual memories and areas of the sensorimotor component of the DMN, more pronounced in the left hemisphere. Moreover, patients with ASD had decreased connectivity between the posterior cingulate cortex, and areas of the executive control component of the DMN and increased FC between the anteromedial prefrontal cortex and areas of the sensorimotor component of the DMN. Reduced cortical thickness in the right inferior frontal lobe correlated with higher social impairment according to the scores of the Autism Diagnostic Interview-Revised (ADI-R). Reduced cortical thickness in left frontal regions, as well as an increased cortical thickness in the right temporal pole and posterior cingulate, were associated with worse scores on the communication domain of the ADI-R. We found no association between scores on the restrictive and repetitive behaviors domain of ADI-R with structural measures or FC. The combination of these structural and connectivity abnormalities may help to explain some of the core behaviors in high-functioning ASD and need to be investigated further.