Disease burden affects aging brain function

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear. METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years. RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated with lower relative activity in orbitofrontal, superior frontal, temporal pole and parahippocampal regions, and greater activity in lateral temporal, occipital, and cerebellar regions. Examination of the individual health conditions comprising the index score showed hypertension and chronic kidney disease individually contributed to the overall multimorbidity pattern of altered activity. Longitudinally, both increases and decreases in activity were seen in relation to increasing multimorbidity over time. These associations were identified in orbitofrontal, lateral temporal, brainstem, and cerebellar areas. CONCLUSION: Together, these results show that greater multimorbidity is associated with widespread areas of altered brain activity, supporting a link between health and changes in aging brain function

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network

Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury.

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on functional connectivity patterns. Networks were calculated from resting-state magnetoencephalographic recordings from 15 brain injured patients and 14 healthy controls by means of wavelet coherence in standard frequency bands. We compared the parameters defining the network, such as number and strength of interactions as well as their topology, in controls and patients for two conditions: following a traumatic brain injury and after a rehabilitation treatment. A loss of delta- and theta-based connectivity and conversely an increase in alpha- and beta-band-based connectivity were found. Furthermore, connectivity parameters approached controls in all frequency bands, especially in slow-wave bands. A correlation between network reorganization and cognitive recovery was found: the reduction of delta-band-based connections and the increment of those based on alpha band correlated with Verbal Fluency scores, as well as Perceptual Organization and Working Memory Indexes, respectively. Additionally, changes in connectivity values based on theta and beta bands correlated with the Patient Competency Rating Scale. The current study provides new evidence of the neurophysiological mechanisms underlying neuronal plasticity processes after brain injury, and suggests that these changes are related with observed changes at the behavioural leve

On the Functional Significance of the P1 and N1 Effects to Illusory Figures in the Notch Mode of Presentation

The processing of Kanizsa figures have classically been studied by flashing the full “pacmen” inducers at stimulus onset. A recent study, however, has shown that it is advantageous to present illusory figures in the “notch” mode of presentation, that is by leaving the round inducers on screen at all times and by removing the inward-oriented notches delineating the illusory figure at stimulus onset. Indeed, using the notch mode of presentation, novel P1and N1 effects have been found when comparing visual potentials (VEPs) evoked by an illusory figure and the VEPs to a control figure whose onset corresponds to the removal of outward-oriented notches, which prevents their integration into one delineated form. In Experiment 1, we replicated these findings, the illusory figure was found to evoke a larger P1 and a smaller N1 than its control. In Experiment 2, real grey squares were placed over the notches so that one condition, that with inward-oriented notches, shows a large central grey square and the other condition, that with outward-oriented notches, shows four unconnected smaller grey squares. In response to these “real” figures, no P1 effect was found but a N1 effect comparable to the one obtained with illusory figures was observed. Taken together, these results suggest that the P1 effect observed with illusory figures is likely specific to the processing of the illusory features of the figures. Conversely, the fact that the N1 effect was also obtained with real figures indicates that this effect may be due to more global processes related to depth segmentation or surface/object perception

Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA)

Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/ behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = − 2.12, p = .055), GABA/Glx ratio (t(12) = − 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met ‘clinical responder’ criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network

Contributions of the hippocampus and related ventromedial temporal cortices to memory in the rhesus monkey

Thesis (Ph.D.)--Boston UniversityPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.While memory function in primates depends on the integrity of the medial temporal lobe, the contribution of the hippocampal formation (HF) independent of the overlying ventromedial temporal cortices, particularly the entorhinal (ENT) and parahippocampal (PHG) cortices, remains unclear. To address this issue we have prepared groups of rhesus monkeys with ibotenic acid lesions of the HF or aspiration lesions of the ENT or PHG cortices. We then administered behavioral tasks to assess the effects of these lesions relative to normal controls. To test recognition memory, the Delayed Non-Matching to Sample (DNMS) task and the Delayed Recognition Span Task (DRST) were administered. On DNMS, all groups were impaired on both acquisition and 2 and 10 minute delays. The DRST, administered in Spatial, Color and Object conditions, yielded slightly different results. On the Spatial condition, all groups were impaired on both unique and repeated trials of the task. On the Color condition, all groups were impaired on unique trials while only the HF group was impaired on repeated trials. On the Object condition, ENT and PHG groups were only impaired on unique trials, while the HF group was unimpaired. To assess associative memory, two choice reversals were administered in Spatial (SR) and Object (OR) modalities. On the SR task, The HF group was impaired on acquisition and the first of three reversal phases. The ENT group was impaired on all three reversals, and the PHG group was impaired on only the last. On the OR task, HF animals were impaired on all reversals, while ENT animals were impaired on the initial reversal and PHG animals on the last two. These results indicate that damage to the HF alone causes impairments in recognition, spatial processing and object reversal learning. They also indicate that ENT and PHG regions make unique contributions to memory processes as seen in additional impairments on DRST and the inability to perform spatial reversals. Thus impairments previously attributed to hippocampal damage in studies where the ENT and PHG cortices were removed in conjunction with the HF need to be reevaluated in view of additional contributions provided by these cortical regions.2031-01-0