Brain Activation During Passive and Volitional Pedaling After Stroke

Background: Prior work indicates that pedaling-related brain activation is lower in people with stroke than in controls. We asked whether this observation could be explained by between-group differences in volitional motor commands and pedaling performance. Methods: Individuals with and without stroke performed passive and volitional pedaling while brain activation was recorded with functional magnetic resonance imaging. The passive condition eliminated motor commands to pedal and minimized between-group differences in pedaling performance. Volume, intensity, and laterality of brain activation were compared across conditions and groups. Results: There were no significant effects of condition and no Group × Condition interactions for any measure of brain activation. Only 53% of subjects could minimize muscle activity for passive pedaling. Conclusions: Altered motor commands and pedaling performance are unlikely to account for reduced pedaling-related brain activation poststroke. Instead, this phenomenon may be due to functional or structural brain changes. Passive pedaling can be difficult to achieve and may require inhibition of excitatory descending drive

Differential detection of impact site versus rotational site injury by magnetic resonance imaging and microglial morphology in an unrestrained mild closed head injury model.

Seventy-five percent of all traumatic brain injuries are mild and do not cause readily visible abnormalities on routine medical imaging making it difficult to predict which individuals will develop unwanted clinical sequelae. Microglia are brain-resident macrophages and early responders to brain insults. Their activation is associated with changes in morphology or expression of phenotypic markers including P2Y12 and major histocompatibility complex class II. Using a murine model of unrestrained mild closed head injury (mCHI), we used microglia as reporters of acute brain injury at sites of impact versus sites experiencing rotational stress 24 h post-mCHI. Consistent with mild injury, a modest 20% reduction in P2Y12 expression was detected by quantitative real-time PCR (qPCR) analysis but only in the impacted region of the cortex. Furthermore, neither an influx of blood-derived immune cells nor changes in microglial expression of CD45, TREM1, TREM2, major histocompatibility complex class II or CD40 were detected. Using magnetic resonance imaging (MRI), small reductions in T2 weighted values were observed but only near the area of impact and without overt tissue damage (blood deposition, edema). Microglial morphology was quantified without cryosectioning artifacts using ScaleA(2) clarified brains from CX3CR1-green fluorescence protein (GFP) mice. The cortex rostral to the mCHI impact site receives greater rotational stress but neither MRI nor molecular markers of microglial activation showed significant changes from shams in this region. However, microglia in this rostral region did display signs of morphologic activation equivalent to that observed in severe CHI. Thus, mCHI-triggered rotational stress is sufficient to cause injuries undetectable by routine MRI that could result in altered microglial surveillance of brain homeostasis. Acute changes in microglial morphology reveal brain responses to unrestrained mild traumatic brain injury In areas subjected to rotational stress distant from impact site In the absence of detectable changes in standard molecular indicators of brain damage, inflammation or microglial activation. That might result in decreased surveillance of brain function and increased susceptibility to subsequent brain insults

Genetic Risk for Alzheimer\u27s Disease Alters the Five-Year Trajectory of Semantic Memory Activation in Cognitively Intact Elders

Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer\u27s disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N = 24) and non-carriers (N = 21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy

PECAM-1 engagement counteracts ICAM-1-induced signaling in brain vascular endothelial cells

Interactions between leukocytes and vascular endothelial cells are mediated by a complex set of membrane adhesion molecules which transduce bi-directional signals in both cell types. Endothelium of the cerebral blood vessels, which constitute the blood–brain barrier, strictly controls adhesion and trafficking of leukocytes into the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells, we previously documented the role of ICAM-1 in activation of the tyrosine phosphorylation of several actin-binding proteins and subsequent rearrangements of the actin cytoskeleton. In the present study, we show that, whereas PECAM-1 is known to control positively the trans-endothelial migration of leukocytes via homophilic interactions between leukocytes and endothelial cells, PECAM-1 engagement on brain endothelial surface unexpectedly counteracts the ICAM-1-induced tyrosine phosphorylation of cortactin and rearrangements of the actin cytoskeleton. We present evidence that the PECAM-1-associated tyrosine phosphatase SHP-2 is required for ICAM-1 signaling, suggesting that its activity might crucially contribute to the regulation of ICAM-1 signaling by PECAM-1. Our findings reveal a novel activity for PECAM-1 which, by counteracting ICAM-1-induced activation, could directly contribute to limit activation and maintain integrity of brain vascular endothelium

Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer's disease

Background: Neuronal and synaptic function in Alzheimer's disease (AD) is measured in vivo by glucose metabolism using positron emission tomography (PET). Objective: We hypothesized that neuronal activation as measured by PET is a more sensitive index of neuronal dysfunction than activity during rest. We investigated if the correlations between dementia severity as measured with the Mini Mental State Examination (MMSE) and glucose metabolism are an artifact of brain atrophy. Method: Glucose metabolism was measured using {[}F-18]fluorodeoxyglucose PET during rest and activation due to audiovisual stimulation in 13 mild to moderate AD patients (MMSE score >= 17). PET data were corrected for brain atrophy. Results: In the rest condition, glucose metabolism was correlated with the MMSE score primarily within the posterior cingulate and parietal lobes. For the activation condition, additional correlations were within the primary and association audiovisual areas. Most local maxima remained significant after correcting for brain atrophy. Conclusion: PET activity measured during audiovisual stimulation was more sensitive to functional alterations in glucose metabolism in AD patients compared to the resting PET. The association between glucose metabolism and MMSE score was not dependent on brain atrophy. Copyright (C) 2005 S. Karger AG, Basel

Does Physical Activity Influence Semantic Memory Activation in Amnestic Mild Cognitive Impairment?

The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI

Neural Correlates of Opponent Processes for Financial Gains and Losses

Objective: Functional imaging studies offer alternative explanations for the neural correlates of monetary gain and loss related brain activity, and their opponents, omission of gains and losses. One possible explanation based on the psychology of opponent process theory suggests that successful avoidance of an aversive outcome is itself rewarding, and hence activates brain regions involved in reward processing. In order to test this hypothesis, we compared brain activation for successful avoidance of losses and receipt of monetary gains. Additionally, the brain regions involved in processing of frustrative neutral outcomes and actual losses were compared in order to test whether these two representations are coded in common or distinct brain regions. Methods: Using a 3 Tesla functional magnetic resonance imaging machine, fifteen healthy volunteers between the ages 22 to 28 were scanned for blood oxygen level dependent signal changes while they were performing a probabilistic learning task, wherein each trial a participant chose one of the two available options in order to win or avoid losing money. Results: The results confirmed, previous findings showing that medial frontal cortex and ventral striatum show significant activation (p<0.001) not only for monetary gains but also for successful avoidance of losses. A similar activation pattern was also observed for monetary losses and avoidance of gains in the medial frontal cortex, and posterior cingulate cortex, however, there was increased activation in amygdala specific to monetary losses (p<0.001). Further, subtraction analysis showed that regardless of the type of loss (i.e., frustrative neutral outcomes) posterior insula showed increased activation. Conclusion: This study provides evidence for a significant overlap not only between gains and losses, but also between their opponents. The results suggested that the overlapping activity pattern in the medial frontal cortex could be explained by a more abstract function of medial frontal cortex, such as outcome evaluation or performance monitoring, which possibly does not differentiate between winning and losing monetary outcomes.Peer reviewedFinal Published versio