When moving faces activate the house area: an fMRI study of object-file retrieval

<p>Abstract</p> <p>Background</p> <p>The visual cortex of the human brain contains specialized modules for processing different visual features of an object. Confronted with multiple objects, the system needs to attribute the correct features to each object (often referred to as 'the binding problem'). The brain is assumed to integrate the features of perceived objects into object files – pointers to the neural representations of these features, which outlive the event they represent in order to maintain stable percepts of objects over time. It has been hypothesized that a new encounter with one of the previously bound features will reactivate the other features in the associated object file according to a kind of pattern-completion process.</p> <p>Methods</p> <p>Fourteen healthy volunteers participated in an fMRI experiment and performed a task designed to measure the aftereffects of binding visual features (houses, faces, motion direction). On each trial, participants viewed a particular combination of features (S1) before carrying out a speeded choice response to a second combination of features (S2). Repetition and alternation of all three features was varied orthogonally.</p> <p>Results</p> <p>The behavioral results showed the standard partial repetition costs: a reaction time increase when one feature was repeated and the other feature alternated between S1 and S2, as compared to complete repetitions or alternations of these features. Importantly, the fMRI results provided evidence that repeating motion direction reactivated the object that previously moved in the same direction. More specifically, perceiving a face moving in the same direction as a just-perceived house increased activation in the parahippocampal place area (PPA). A similar reactivation effect was not observed for faces in the fusiform face area (FFA). Individual differences in the size of the reactivation effects in the PPA and FFA showed a positive correlation with the corresponding partial repetition costs.</p> <p>Conclusion</p> <p>Our study provides the first neural evidence that features are bound together on a single presentation and that reviewing one feature automatically reactivates the features that previously accompanied it.</p

Pseudocontinuous arterial spin labeling reveals dissociable effects of morphine and alcohol on regional cerebral blood flow

We have examined sensitivity and specificity of pseudocontinuous arterial spin labeling (PCASL) to detect global and regional changes in cerebral blood flow (CBF) in response to two different psychoactive drugs. We tested alcohol and morphine in a placebo-controlled, double-blind randomized study in 12 healthy young men. Drugs were administered intravenously. Validated pharmacokinetic protocols achieved minimal intersubject and intrasubject variance in plasma drug concentration. Permutation-based statistical testing of a mixed effect repeated measures model revealed a widespread increase in absolute CBF because of both morphine and alcohol. Conjunction analysis revealed overlapping effects of morphine and alcohol on absolute CBF in the left anterior cingulate, right hippocampus, right insula, and left primary sensorimotor areas. Effects of morphine and alcohol on relative CBF (obtained from z-normalization of absolute CBF maps) were significantly different in the left putamen, left frontoparietal network, cerebellum, and the brainstem. Corroborating previous PET results, our findings suggest that PCASL is a promising tool for central nervous system drug research

The functional and neural mechanisms of action preparation: roles of EBA and FFA in voluntary action control

Ideomotor theory claims that actions are cognitively represented and accessed via representations of the sensory effects they evoke. Previous studies provide support for this claim by showing that the presentation of action effects primes activation in corresponding motor structures. However, whether people actually use action-effect representations to control their motor behavior is not yet clear. In our fMRI study, we had participants prepare for manual or facial actions on a trial-by-trial basis, and hypothesized that preparation would be mediated by the cortical areas that code for the perceptual effects of these actions. Preparing for manual action induced higher activation of hand-related areas of motor cortex (demonstrating actual preparation) and of the extrastriate body area, which is known to mediate the perception of body parts. In contrast, preparing for facial action induced higher activation of face-related motor areas and of the fusiform face area, known to mediate face perception. These observations provide further support for the ideomotor theory and suggest that visual imagery might play a role in voluntary action control

Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia

ObjectiveWe aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of microtubule-associated protein tau and progranulin mutations.MethodsIn this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk for frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, and structural and functional MRI. We used voxel-based morphometry and tract-based spatial statistics for voxelwise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsula, anterior midcingulate cortex (aMCC), and posterior cingulate cortex.ResultsAlthough carriers (n = 37) and noncarriers (n = 38) had similar neuropsychological performance, worse performance on Stroop III, Ekman faces, and Happé cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy and increased radial diffusivity throughout frontotemporal white matter tracts were found in carriers and correlated with higher age. Reductions in functional aMCC connectivity were found in carriers compared with controls, and connectivity between frontoinsula and aMCC seeds and several brain regions significantly decreased with higher age in carriers but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found.ConclusionsThis study convincingly demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials

Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia

ObjectiveWe aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of microtubule-associated protein tau and progranulin mutations.MethodsIn this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk for frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, and structural and functional MRI. We used voxel-based morphometry and tract-based spatial statistics for voxelwise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsula, anterior midcingulate cortex (aMCC), and posterior cingulate cortex.ResultsAlthough carriers (n = 37) and noncarriers (n = 38) had similar neuropsychological performance, worse performance on Stroop III, Ekman faces, and Happé cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy and increased radial diffusivity throughout frontotemporal white matter tracts were found in carriers and correlated with higher age. Reductions in functional aMCC connectivity were found in carriers compared with controls, and connectivity between frontoinsula and aMCC seeds and several brain regions significantly decreased with higher age in carriers but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found.ConclusionsThis study convincingly demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials

Presymptomatic white matter integrity loss in familial frontotemporal dementia in the GENFI cohort: A cross-sectional diffusion tensor imaging study.

Objective: We aimed to investigate mutation-specific white matter (WM) integrity changes in presymptomatic and symptomatic mutation carriers of the C9orf72,MAPT, and GRN mutations by use of diffusion-weighted imaging within the Genetic Frontotemporal dementia Initiative (GENFI) study. Methods: One hundred and forty mutation carriers (54 C9orf72, 30 MAPT, 56 GRN), 104 presymptomatic and 36 symptomatic, and 115 noncarriers underwent 3T diffusion tensor imaging. Linear mixed effects models were used to examine the association between diffusion parameters and years from estimated symptom onset in C9orf72,MAPT, and GRN mutation carriers versus noncarriers. Post hoc analyses were performed on presymptomatic mutation carriers only, as well as left-right asymmetry analyses on GRN mutation carriers versus noncarriers. Results: Diffusion changes in C9orf72 mutation carriers are present significantly earlier than both MAPT and GRN mutation carriers - characteristically in the posterior thalamic radiation and more posteriorly located tracts (e.g., splenium of the corpus callosum, posterior corona radiata), as early as 30 years before estimated symptom onset. MAPT mutation carriers showed early involvement of the uncinate fasciculus and cingulum, sparing the internal capsule, whereas involvement of the anterior and posterior internal capsule was found in GRN. Restricting analyses to presymptomatic mutation carriers only, similar - albeit less extensive - patterns were found: posteriorly located WM tracts (e.g., posterior thalamic radiation, splenium of the corpus callosum, posterior corona radiata) in presymptomatic C9orf72, the uncinate fasciculus in presymptomatic MAPT, and the internal capsule (anterior and posterior limbs) in presymptomatic GRN mutation carriers. In GRN, most tracts showed significant left-right differences in one or more diffusion parameter, with the most consistent results being found in the UF, EC, RPIC, and ALIC. Interpretation: This study demonstrates the presence of early and widespread WM integrity loss in presymptomatic FTD, and suggests a clear genotypic "fingerprint." Our findings corroborate the notion of FTD as a network-based disease, where changes in connectivity are some of the earliest detectable features, and identify diffusion tensor imaging as a potential neuroimaging biomarker for disease-tracking and -staging in presymptomatic to early-stage familial FTD

Presymptomatic white matter integrity loss in familial frontotemporal dementia in the GENFI cohort: A cross-sectional diffusion tensor imaging study.

OBJECTIVE: We aimed to investigate mutation-specific white matter (WM) integrity changes in presymptomatic and symptomatic mutation carriers of the C9orf72,MAPT, and GRN mutations by use of diffusion-weighted imaging within the Genetic Frontotemporal dementia Initiative (GENFI) study. METHODS: One hundred and forty mutation carriers (54 C9orf72, 30 MAPT, 56 GRN), 104 presymptomatic and 36 symptomatic, and 115 noncarriers underwent 3T diffusion tensor imaging. Linear mixed effects models were used to examine the association between diffusion parameters and years from estimated symptom onset in C9orf72,MAPT, and GRN mutation carriers versus noncarriers. Post hoc analyses were performed on presymptomatic mutation carriers only, as well as left-right asymmetry analyses on GRN mutation carriers versus noncarriers. RESULTS: Diffusion changes in C9orf72 mutation carriers are present significantly earlier than both MAPT and GRN mutation carriers - characteristically in the posterior thalamic radiation and more posteriorly located tracts (e.g., splenium of the corpus callosum, posterior corona radiata), as early as 30 years before estimated symptom onset. MAPT mutation carriers showed early involvement of the uncinate fasciculus and cingulum, sparing the internal capsule, whereas involvement of the anterior and posterior internal capsule was found in GRN. Restricting analyses to presymptomatic mutation carriers only, similar - albeit less extensive - patterns were found: posteriorly located WM tracts (e.g., posterior thalamic radiation, splenium of the corpus callosum, posterior corona radiata) in presymptomatic C9orf72, the uncinate fasciculus in presymptomatic MAPT, and the internal capsule (anterior and posterior limbs) in presymptomatic GRN mutation carriers. In GRN, most tracts showed significant left-right differences in one or more diffusion parameter, with the most consistent results being found in the UF, EC, RPIC, and ALIC. INTERPRETATION: This study demonstrates the presence of early and widespread WM integrity loss in presymptomatic FTD, and suggests a clear genotypic "fingerprint." Our findings corroborate the notion of FTD as a network-based disease, where changes in connectivity are some of the earliest detectable features, and identify diffusion tensor imaging as a potential neuroimaging biomarker for disease-tracking and -staging in presymptomatic to early-stage familial FTD