The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity

This work was supported by a grant of the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (DFG, Grant Number EXC 1086).Peer reviewedPostprintPostprin

Hippocampus-Avoidance Whole-Brain Radiation Therapy Is Efficient in the Long-Term Preservation of Hippocampal Volume

Background and Purpose: With improved life expectancy, preventing neurocognitive decline after cerebral radiotherapy is gaining more importance. Hippocampal damage has been considered the main culprit for cognitive deficits following conventional whole-brain radiation therapy (WBRT). Here, we aimed to determine to which extent hippocampus-avoidance WBRT (HA-WBRT) can prevent hippocampal atrophy compared to conventional WBRT. Methods and Materials: Thirty-five HA-WBRT and 48 WBRT patients were retrospectively selected, comprising a total of 544 contrast-enhanced T1-weighted magnetic resonance imaging studies, longitudinally acquired within 24 months before and 48 months after radiotherapy. HA-WBRT patients were treated analogously to the ongoing HIPPORAD-trial (DRKS00004598) protocol with 30 Gy in 12 fractions and dose to 98% of the hippocampus ≤ 9 Gy and to 2% ≤ 17 Gy. WBRT was mainly performed with 35 Gy in 14 fractions or 30 Gy in 10 fractions. Anatomical images were segmented and the hippocampal volume was quantified using the Computational Anatomy Toolbox (CAT), including neuroradiological expert review of the segmentations. Results: After statistically controlling for confounding variables such as age, gender, and total intracranial volume, hippocampal atrophy was found after both WBRT and HA-WBRT (p Conclusion: HA-WBRT is a therapeutic option for patients with multiple brain metastases, which can effectively and durably minimize hippocampal atrophy compared to conventional WBRT

Inferior Frontal Gyrus Volume Loss Distinguishes Between Autism and (Comorbid) Attention-Deficit/Hyperactivity Disorder—A FreeSurfer Analysis in Children

Objective: Autism spectrum (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with a high rate of comorbidity. To date, diagnosis is based on clinical presentation and distinct reliable biomarkers have been identified neither for ASD nor ADHD. Most previous neuroimaging studies investigated ASD and ADHD separately.Method: To address the question of structural brain differences between ASD and ADHD, we performed FreeSurfer analysis in a sample of children with ADHD (n = 30), with high-functioning ASD (n = 14), with comorbid high-functioning ASD and ADHD (n = 15), and of typically developed controls (TD; n = 36). With FreeSurfer, an automated brain imaging processing and analyzing suite, we reconstructed the cerebral cortex and calculated gray matter volumes as well as cortical surface parameters in terms of cortical thickness and mean curvature.Results: A significant main effect of the factor ADHD was detected for the left inferior frontal gyrus (Pars orbitalis) volume, with the ADHD group exhibiting smaller Pars orbitalis volumes. Dimensional measures of autism (SRS total raw score) and ADHD (DISYPS-II FBB-ADHD score) had no significant influence on the left Pars orbitalis volume. Both, ASD and ADHD tended to have an effect on cortical thickness or mean curvature, which did not survive correction for multiple comparisons.Conclusion: Our results underline that ADHD rather than ASD is associated with volume loss in the left inferior frontal gyrus (Pars orbitalis). This area might play a relevant role in modulating symptoms of inattention and/or impulsivity in ADHD. The effect of comorbid ADHD in ASD samples and vice versa, on cortical thickness and mean curvature, requires further investigation in larger samples

The longitudinal changes of BOLD response and cerebral hemodynamics from acute to subacute stroke. A fMRI and TCD study

<p>Abstract</p> <p>Background</p> <p>By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke.</p> <p>This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response.</p> <p>We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.</p> <p>Results</p> <p>As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01).</p> <p>Conclusions</p> <p>The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.</p

Detection of motor changes in huntington's disease using dynamic causal modeling

Deficits in motor functioning are one of the hallmarks of Huntington's disease (HD), a genetically caused neurodegenerative disorder. We applied functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to assess changes that occur with disease progression in the neural circuitry of key areas associated with executive and cognitive aspects of motor control. Seventy-seven healthy controls, 62 pre-symptomatic HD gene carriers (preHD), and 16 patients with manifest HD symptoms (earlyHD) performed a motor finger-tapping fMRI task with systematically varying speed and complexity. DCM was used to assess the causal interactions among seven pre-defined regions of interest, comprising primary motor cortex, supplementary motor area (SMA), dorsal premotor cortex, and superior parietal cortex. To capture heterogeneity among HD gene carriers, DCM parameters were entered into a hierarchical cluster analysis using Ward's method and squared Euclidian distance as a measure of similarity. After applying Bonferroni correction for the number of tests, DCM analysis revealed a group difference that was not present in the conventional fMRI analysis. We found an inhibitory effect of complexity on the connection from parietal to premotor areas in preHD, which became excitatory in earlyHD and correlated with putamen atrophy. While speed of finger movements did not modulate the connection from caudal to pre-SMA in controls and preHD, this connection became strongly negative in earlyHD. This second effect did not survive correction for multiple comparisons. Hierarchical clustering separated the gene mutation carriers into three clusters that also differed significantly between these two connections and thereby confirmed their relevance. DCM proved useful in identifying group differences that would have remained undetected by standard analyses and may aid in the investigation of between-subject heterogeneity

Development of Planning Abilities in Normal Aging: Differential Effects of Specific Cognitive Demands

In line with the frontal hypothesis of aging, the ability to plan ahead undergoes substantial change during normal aging. Although impairments on the Tower of London planning task were reported earlier, associations between age-related declines and specific cognitive demands on planning have not been studied. Here we investigated the impact of search depth and goal ambiguity on planning, which impose demands on the depth and breadth of look-ahead processes, respectively. Besides an overall age-related decline in planning accuracy of 106 healthy older adults, differential search depth effects were found: Whereas planning accuracy of subjects in the early 60s was not affected by variations in search depth, between the ages of 65 and 76 years, accuracy was significantly decreased for high versus low levels of search depth. For subjects older than 76, different search depth levels did not further impact on accuracy, which was lowest overall. This nonlinear pattern may reflect differential impairments in fluid abilities and working memory capacity across various stages of older age. As no age-related effects of goal ambiguity were found, normal aging seems to be specifically sensitive to planning demands on the depth but not the breadth of anticipatory search processes. Hence, cognitive functions subserved by the prefrontal cortex experience differential development over the course of normal aging

Planning Decrements in Healthy Aging: Mediation Effects of Fluid Reasoning and Working Memory Capacity

Objectives: Although age-related differences in planning ability are well known, their cognitive foundations remain a matter of contention. To elucidate the specific processes underlying planning decrements in older age, the relative contributions of fluid reasoning, working memory (WM) capacity, and processing speed to accuracy on the Tower of London (TOL) planning task were investigated. Method: Mediation analyses were used to relate overall and search depth-related TOL accuracy from older (N = 106; 60-89 years) and younger adults (N = 69; 18-54 years) to age and measures of fluid reasoning, WM capacity, and speed. Results: For overall planning, fluid abilities mediated the effects of age, WM capacity, and speed in older adults. By contrast, fluid abilities and WM capacity mediated each other in younger adults. For planning accuracy under low demands on the depth of search, WM capacity was specifically important in older age, whereas younger adults recruited both WM capacity and fluid reasoning. Under high search-depth-demands, fluid abilities underlay the cognitive operations critical for resolving move interdependencies in both age groups. Discussion: Fluid abilities and WM capacity undergo significant changes from younger to older age in their unique contribution to planning, which might represent a mechanism whereby planning decrements in older age are brought about

Dissociable stages of problem solving (I): Temporal characteristics revealed by eye-movement analyses

Understanding the functional neuroanatomy of planning and problem solving may substantially benefit from better insight into the chronology of the cognitive processes involved. Based on the assumption that regularities in cognitive processing are reflected in overtly observable eye-movement patterns, here we recorded eye movements while participants worked on Tower of London (TOL) problems that comprised an experimental manipulation of different task demands. Single-trial saccade-locked analyses revealed that higher demands on forming an internal problem representation were associated with an increased number of gaze alternations between start state and goal state, but did not show any effect on the durations of these inspections of the states. In contrast, higher demands on actual planning in terms of mental manipulations of working memory contents coincided with a prolonged duration of the very last inspection of the start state (i.e., immediately preceding movement execution) but did not show any effect on the number of gaze alterations. Differential task demands on internalization and planning processes during problem solving hence selectively affect different eye-movement parameters. Moreover, these findings complement previous neuroimaging data on dissociable contributions of left and right dorsolateral prefrontal cortex in problem solving with novel evidence for a corresponding dissociation in the eye-movement patterns reflecting the associated cognitive processes. (C) 2012 Elsevier Inc. All rights reserved