Thickness in Entorhinal and Subicular Cortex Predicts Episodic Memory Decline in Mild Cognitive Impairment

Identifying subjects with mild cognitive impairment (MCI) most likely to decline in cognition over time is a major focus in Alzheimer's disease (AD) research. Neuroimaging biomarkers that predict decline would have great potential for increasing the efficacy of early intervention. In this study, we used high-resolution MRI, combined with a cortical unfolding technique to increase visibility of the convoluted medial temporal lobe (MTL), to assess whether gray matter thickness in subjects with MCI correlated to decline in cognition over two years. We found that thickness in the entorhinal (ERC) and subicular (Sub) cortices of MCI subjects at initial assessment correlated to change in memory encoding over two years (ERC: r = 0.34; P = .003) and Sub (r = 0.26; P = .011) but not delayed recall performance. Our findings suggest that aspects of memory performance may be differentially affected in the early stages of AD. Given the MTL's involvement in early stages of neurodegeneration in AD, clarifying the relationship of these brain regions and the link to resultant cognitive decline is critical in understanding disease progression

A Longitudinal Study of the Long-Term Consequences of Drinking during Pregnancy: Heavy In Utero Alcohol Exposure Disrupts the Normal Processes of Brain Development

Exposure to alcohol in utero can cause birth defects including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging (MRI) to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering “experience” over time may improve brain trajectories in individuals with heavy PAE, and possibly other neurodevelopmental disorders

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli

Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping

A novel map of Broca's language region is proposed based on transmitter receptor distributions as functionally relevant molecular markers. It sheds new light on the relation between anatomy and functional segregation

The Manipulative Complexity of Lower Paleolithic Stone Toolmaking

Early stone tools provide direct evidence of human cognitive and behavioral evolution that is otherwise unavailable. Proper interpretation of these data requires a robust interpretive framework linking archaeological evidence to specific behavioral and cognitive actions.Here we employ a data glove to record manual joint angles in a modern experimental toolmaker (the 4(th) author) replicating ancient tool forms in order to characterize and compare the manipulative complexity of two major Lower Paleolithic technologies (Oldowan and Acheulean). To this end we used a principled and general measure of behavioral complexity based on the statistics of joint movements.This allowed us to confirm that previously observed differences in brain activation associated with Oldowan versus Acheulean technologies reflect higher-level behavior organization rather than lower-level differences in manipulative complexity. This conclusion is consistent with a scenario in which the earliest stages of human technological evolution depended on novel perceptual-motor capacities (such as the control of joint stiffness) whereas later developments increasingly relied on enhanced mechanisms for cognitive control. This further suggests possible links between toolmaking and language evolution

Tracking Down Abstract Linguistic Meaning: Neural Correlates of Spatial Frame of Reference Ambiguities in Language

This functional magnetic resonance imaging (fMRI) study investigates a crucial parameter in spatial description, namely variants in the frame of reference chosen. Two frames of reference are available in European languages for the description of small-scale assemblages, namely the intrinsic (or object-oriented) frame and the relative (or egocentric) frame. We showed participants a sentence such as “the ball is in front of the man”, ambiguous between the two frames, and then a picture of a scene with a ball and a man – participants had to respond by indicating whether the picture did or did not match the sentence. There were two blocks, in which we induced each frame of reference by feedback. Thus for the crucial test items, participants saw exactly the same sentence and the same picture but now from one perspective, now the other. Using this method, we were able to precisely pinpoint the pattern of neural activation associated with each linguistic interpretation of the ambiguity, while holding the perceptual stimuli constant. Increased brain activity in bilateral parahippocampal gyrus was associated with the intrinsic frame of reference whereas increased activity in the right superior frontal gyrus and in the parietal lobe was observed for the relative frame of reference. The study is among the few to show a distinctive pattern of neural activation for an abstract yet specific semantic parameter in language. It shows with special clarity the nature of the neural substrate supporting each frame of spatial reference

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity

Neural Basis of Self and Other Representation in Autism: An fMRI Study of Self-Face Recognition

Autism is a developmental disorder characterized by decreased interest and engagement in social interactions and by enhanced self-focus. While previous theoretical approaches to understanding autism have emphasized social impairments and altered interpersonal interactions, there is a recent shift towards understanding the nature of the representation of the self in individuals with autism spectrum disorders (ASD). Still, the neural mechanisms subserving self-representations in ASD are relatively unexplored.We used event-related fMRI to investigate brain responsiveness to images of the subjects' own face and to faces of others. Children with ASD and typically developing (TD) children viewed randomly presented digital morphs between their own face and a gender-matched other face, and made "self/other" judgments. Both groups of children activated a right premotor/prefrontal system when identifying images containing a greater percentage of the self face. However, while TD children showed activation of this system during both self- and other-processing, children with ASD only recruited this system while viewing images containing mostly their own face.This functional dissociation between the representation of self versus others points to a potential neural substrate for the characteristic self-focus and decreased social understanding exhibited by these individuals, and suggests that individuals with ASD lack the shared neural representations for self and others that TD children and adults possess and may use to understand others