Blunted cerebrovascular response is associated with elevated beta-amyloid.

The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR ( n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals ( n = 45, age 72.0 ± 4.9; 7.2 ± 5.0 cm/s, p < 0.001). Further, greater beta-amyloid burden was linearly associated with less CVR across all participants (b = -11.7, p < 0.001). Greater CVR and less beta-amyloid burden were associated with processing speed ( p < 0.05). This study is the first to show that CVR from rest to exercise is blunted across increased global beta-amyloid burden.

Effect of healthy aging and sex on middle cerebral artery blood velocity dynamics during moderate-intensity exercise.

Blood velocity measured in the middle cerebral artery (MCAV) increases with finite kinetics during moderate-intensity exercise, and the amplitude and dynamics of the response provide invaluable insights into the controlling mechanisms. The MCAV response after exercise onset is well fit to an exponential model in young individuals but remains to be characterized in their older counterparts. The responsiveness of vasomotor control degrades with advancing age, especially in skeletal muscle. We tested the hypothesis that older subjects would evince a slower and reduced MCAV response to exercise. Twenty-nine healthy young (25 ± 1 yr old) and older (69 ± 1 yr old) adults each performed a rapid transition from rest to moderate-intensity exercise on a recumbent stepper. Resting MCAV was lower in older than young subjects (47 ± 2 vs. 64 ± 3 cm/s, P < 0.001), and amplitude from rest to steady-state exercise was lower in older than young subjects (12 ± 2 vs. 18 ± 3 cm/s, P = 0.04), even after subjects were matched for work rate. As hypothesized, the time constant was significantly longer (slower) in the older than young subjects (51 ± 10 vs. 31 ± 4 s, P = 0.03), driven primarily by older women. Neither age-related differences in fitness, end-tidal CO2, nor blood pressure could account for this effect. Thus, MCAV kinetic analyses revealed a marked impairment in the cerebrovascular response to exercise in older individuals. Kinetic analysis offers a novel approach to evaluate the efficacy of therapeutic interventions for improving cerebrovascular function in elderly and patient populations. NEW & NOTEWORTHY Understanding the dynamic cerebrovascular response to exercise has provided insights into sex-related cerebrovascular control mechanisms throughout the aging process. We report novel differences in the kinetics response of cerebrovascular blood velocity after the onset of moderate-intensity exercise. The exponential increase in brain blood flow from rest to exercise revealed that 1) the kinetics profile of the older group was blunted compared with their young counterparts and 2) the older women demonstrated a slowed response.

Dynamics of middle cerebral artery blood flow velocity during moderate-intensity exercise.

The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAV response profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAV as supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAV baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAV that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAV during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease.NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.

Does Dopamine Replacement Medication Affect Postural Sequence Learning in Parkinson's Disease?

Deficits in sequence-specific learning (SSL) may be a product of Parkinson's disease (PD) but this deficit could also be related to dopamine replacement. The purpose of this study was to determine whether dopamine replacement affected acquisition and retention of a standing Continuous Tracking Task in individuals with PD. SSL (difference between random/repeated Root Mean Square Error across trials) was calculated over 2 days of practice and 1 day of retention for 4 groups; 10 healthy young (HY), 10 healthy elders, 10 individuals with PD on, 9 individuals with PD off their usual dosage of dopamine replacement. Improvements in acquisition were observed for all groups; however, only the HY demonstrated retention. Therefore, age appeared to have the largest effect on SSL with no significant effect of medication. Additional research is needed to understand the influence of factors such as practice amount, task difficulty, and dopamine replacement status on SSL deficits during postural tasks.

Correlations between brain activity and components of motor learning in middle-aged adults: an fMRI study.

Implicit learning may be shown by improvements in motor performance, which occur unconsciously with practice and are typically restricted to the task that was practiced. The purpose of this study was to examine behaviorally relevant brain activation associated with change in motor behavior during sequence-specific motor learning of a perceptuomotor continuous tracking (CT) task in middle-aged adults. To gain further insight into the neural structures associated with change in motor behavior, overall improvement in tracking (root mean square error; RMSE) was decomposed into two components-temporal precision and spatial accuracy. We hypothesized that individual differences in CT task performance would be evident in unique networks of brain activation that supported overall tracking behavior as well-temporal and spatial tracking accuracy. A group of middle-aged healthy individuals performed the CT task, which contains repeated and random segments for seven days. Functional magnetic resonance imaging (fMRI) data was collected on the first and seventh day while the participants performed the task. Subjects did not gain explicit awareness of the sequence. To assess behaviorally-relevant changes in the blood oxygenation level-dependent (BOLD) response associated with individual sequence-specific tracking performance, separate statistical images were created for each participant and weighted by the difference score between repeated and random performance for days 1 and 7. Given the similarity of performance for random and repeated sequences during early practice, there were no unique networks evident at day 1. On Day 7 the resultant group statistical fMRI image demonstrated a positive correlation between RMSE difference score and bilateral cerebellar activation (lobule VI). In addition, individuals who showed greater sequence-specific temporal precision demonstrated increased activation in the precentral gyrus, middle occipital gyrus, and putamen of the right hemisphere and the thalamus, cuneus, and cerebellum of the left hemisphere. Activation of this neural network further confirms its involvement in timing of movements as it has been previously associated with task performance when individuals are instructed to emphasize speed over accuracy. In the present study, behavioral performance was associated with neural correlates of individual variation in motor learning that characterized the ability to implicitly learn a sequence-specific CT task.

A novel device to measure power grip forces in squirrel monkeys.

Understanding the neural bases for grip force behaviors in both normal and neurologically impaired animals is imperative prior to improving treatments and therapeutic approaches. The present paper describes a novel device for the assessment of power grip forces in squirrel monkeys. The control of grasping and object manipulation represents a vital aspect of daily living by allowing the performance of a wide variety of complex hand movements. However, following neurological injury such as stroke, these grasping behaviors are often severely affected, resulting in persistent impairments in strength, grip force modulation and kinematic hand control. While there is a significant clinical focus on rehabilitative strategies to address these issues, there exists the need for translational animal models. In the study presented here, we describe a simple grip force device designed for use in non-human primates, which provides detailed quantitative information regarding distal grip force dynamics. Adult squirrel monkeys were trained to exceed a specific grip force threshold, which was rewarded with a food pellet. One of these subjects then received an infarct of the M1 hand representation area. Results suggest that the device provides detailed and reliable information on grip behaviors in healthy monkeys and can detect deficits in grip dynamics in monkeys with cortical lesions (significantly longer release times). Understanding the physiological and neuroanatomical aspects of grasping function following neurological injury may lead to more effective rehabilitative interventions.

Impaired grip force modulation in the ipsilesional hand after unilateral middle cerebral artery stroke.

Understanding grasping control after stroke is important for relearning motor skills. The authors examined 10 individuals (5 males; 5 females; ages 32-86) with chronic unilateral middle cerebral artery (MCA) stroke (4 right lesions; 6 left lesions) when lifting a novel test object using skilled precision grip with their ipsilesional ("unaffected") hand compared to healthy controls (n = 14; 6 males; 8 females; ages 19-86). All subjects possessed normal range of motion, cutaneous sensation, and proprioception in the hand tested and had no apraxia or cognitive deficits. Subjects lifted the object 10 times at each object weight (260 g, 500 g, 780 g) using a moderately paced self-selected lifting speed. The normal horizontal ("grip") force and vertical tangential ("lift") force were separately measured at the thumb and index finger. Regardless of the object weight or stroke location, the stroke group generated greater grip forces at liftoff of the object (> or =39%; P < or = 0.05) and across the dynamic (P < or = 0.05) and static portions (P < or = 0.05) of the lifts compared to the healthy group. Peak lift forces were equivalent between groups, suggesting accurate load force information processing occurred. These results warrant further investigation of altered sensorimotor processing or compensatory biomechanical strategies that may lead to inaccurate grip force execution after strokes.

Gains in distance walking in a 3-month follow-up poststroke: what changes?

STATEMENT OF PROBLEM: Distance walking remains compromised for many adults poststroke. The purpose of this study was to examine if the amelioration of stroke-related neuromuscular impairments, improved cardiovascular fitness, or better balance contributed to gains in distance walking. METHOD OF STUDY: The authors gathered baseline data of 92 adults at an average of 75 days poststroke and again 3 months later. Participants performed a bicycle ergometry stress test, a 6-min walk, and a Fugl-Meyer assessment for motor control, strength, and balance testing. The gain in walk distance was modeled using multiple regression with the variables of gains in peak VO2, lower limb control, plantar flexion strength, and balance. Separate analyses were done for poor performers, that is, participants who walked less than the median distance (213 m) at baseline and good performers, that is, participants who walked more than 213 m. RESULTS: For poor performers, the gain in balance was the only significant predictor of the gain in distance walking and accounted for 16% of the variance. For good performers, gains in peak VO2 and the lower limb Fugl-Meyer score were significant predictors and accounted for 28% of the variance. DISCUSSION: These results suggest that rehabilitation efforts to improve distance walking should focus on different factors depending on initial distance walked.