Remembering forward: neural correlates of memory and prediction in human motor adaptation.

We used functional MR imaging (FMRI), a robotic manipulandum and systems identification techniques to examine neural correlates of predictive compensation for spring-like loads during goal-directed wrist movements in neurologically-intact humans. Although load changed unpredictably from one trial to the next, subjects nevertheless used sensorimotor memories from recent movements to predict and compensate upcoming loads. Prediction enabled subjects to adapt performance so that the task was accomplished with minimum effort. Population analyses of functional images revealed a distributed, bilateral network of cortical and subcortical activity supporting predictive load compensation during visual target capture. Cortical regions--including prefrontal, parietal and hippocampal cortices--exhibited trial-by-trial fluctuations in BOLD signal consistent with the storage and recall of sensorimotor memories or "states" important for spatial working memory. Bilateral activations in associative regions of the striatum demonstrated temporal correlation with the magnitude of kinematic performance error (a signal that could drive reward-optimizing reinforcement learning and the prospective scaling of previously learned motor programs). BOLD signal correlations with load prediction were observed in the cerebellar cortex and red nuclei (consistent with the idea that these structures generate adaptive fusimotor signals facilitating cancelation of expected proprioceptive feedback, as required for conditional feedback adjustments to ongoing motor commands and feedback error learning). Analysis of single subject images revealed that predictive activity was at least as likely to be observed in more than one of these neural systems as in just one. We conclude therefore that motor adaptation is mediated by predictive compensations supported by multiple, distributed, cortical and subcortical structures.

Physical therapy workforce in the United States: forecasting nationwide shortages.

OBJECTIVE: To examine current and future physical therapy (PT) job surplus/shortage trends across the United States. DESIGN: Forecast models and grading methodology previously published for nursing were used to evaluate individual state PT job shortages from 2008 to 2030. SETTING: Not applicable. PARTICIPANTS: Not applicable. METHODS: The forecast model used to project PT job supply and demand accounted for changes in age and population size on the basis of estimates from the U.S. Census Bureau for each of the 50 states. PT shortages were assigned letter grades on the basis of shortage ratios (difference between demand and supply per 10,000 people) to evaluate PT shortages and describe the changing PT workforce in each state. RESULTS: On the basis of current trends, demand for PT services will outpace the supply of PTs within the United States. Shortages are expected to increase for all 50 states through 2030. By 2030, the number of states receiving below-average grades for their PT shortages will increase from 12 to 48. States in the Northeast are projected to have the smallest shortages, whereas states in the south and west are projected to have the largest shortages. CONCLUSION: These data serve to provide health professionals, policy makers, and stakeholders with a means of assessing current and future PT needs. Discussion of the issues surrounding PT shortages and ongoing assessment of supply and demand must ensue to mitigate projected shortages. Although our model has several limitations and may be oversimplified, it is the first attempt to use available, creditable data to examine both supply and demand for the entire country. Follow-up studies that use more complex modeling are needed to adequately forecast future trends beyond that accomplished in the current article. Monitoring trends over time is critical to maintain an appropriate balance between PT supply and demand that meets the population needs.

Neural modulation of temporal encoding, maintenance, and decision processes.

Time perception emerges from an interaction among multiple processes that are normally intertwined. Therefore, a challenge has been to disentangle timekeeping from other processes. Though the striatum has been implicated in interval timing, it also modulates nontemporal processes such as working memory. To distinguish these processes, we separated neural activation associated with encoding, working-memory maintenance, and decision phases of a time-perception task. We also asked whether neuronal processing of duration (i.e., pure tone) was distinct from the processing of identity (i.e., pitch perception) or sensorimotor features (i.e., control task). Striatal activation was greater when encoding the duration than the pitch or basic sensory features, which did not differentially engage the striatum. During the maintenance phase, striatal activation was similar for duration and pitch but at baseline in the control task. In the decision phase, a stepwise reduction in striatal activation was found across the 3 tasks, with activation greatest in the timing task and weakest in the control task. Task-related striatal activations in different cognitive phases were distinguished from those of the supplementary motor area, inferior frontal gyrus, thalamus, frontoparietal cortices, and the cerebellum. Our results were consistent with a model in which timing emerges from context-dependent corticostriatal interactions.

fMRI detection of early neural dysfunction in preclinical Huntington's disease.

Neuropsychological and neuroimaging changes have been observed in individuals with the Huntington's disease (HD) gene expansion prior to the onset of manifest HD. This cross-sectional fMRI study of preclinical HD (pre-HD) individuals was conducted to determine if functional brain changes precede deficits in behavioral performance and striatal atrophy. Twenty-six pre-HD and 13 demographically matched healthy participants performed a time reproduction task while undergoing fMRI scanning. Pre-HD participants were divided into two groups (n=13 each): FAR (>12 years to estimated onset [YEO] of manifest HD) and CLOSE (<12 YEO). The CLOSE group demonstrated behavioral deficits, striatal atrophy, and reduced neural activation in the left putamen, SMA, left anterior insula and right inferior frontal gyrus. The FAR group showed reduced neural activation in the right anterior cingulate and right anterior insula. The FAR group also demonstrated increased neural activation in the left sensorimotor, left medial frontal gyrus, left precentral gyrus, bilateral superior temporal gyri and right cerebellum. The fMRI changes in the FAR group occurred in the relative absence of striatal atrophy and behavioral performance deficits. These results suggest that fMRI is sensitive to neural dysfunction occurring more than 12 years prior to the estimated onset of manifest HD.

Design and validation of a MR-compatible pneumatic manipulandum.

The combination of functional MR imaging and novel robotic tools may provide unique opportunities to probe the neural systems underlying motor control and learning. Here, we describe the design and validation of a MR-compatible, 1 degree-of-freedom pneumatic manipulandum along with experiments demonstrating its safety and efficacy. We first validated the robot's ability to apply computer-controlled loads about the wrist, demonstrating that it possesses sufficient bandwidth to simulate torsional spring-like loads during point-to-point flexion movements. Next, we verified the MR-compatibility of the device by imaging a head phantom during robot operation. We observed no systematic differences in two measures of MRI signal quality (signal/noise and field homogeneity) when the robot was introduced into the scanner environment. Likewise, measurements of joint angle and actuator pressure were not adversely affected by scanning. Finally, we verified device efficacy by scanning 20 healthy human subjects performing rapid wrist flexions against a wide range of spring-like loads. We observed a linear relationship between joint torque at peak movement extent and perturbation magnitude, thus demonstrating the robot's ability to simulate spring-like loads in situ. fMRI revealed task-related activation in regions known to contribute to the control of movement including the left primary sensorimotor cortex and right cerebellum.

Motor timing variability increases in preclinical Huntington's disease patients as estimated onset of motor symptoms approaches.

Huntington's disease (HD) is a neurodegenerative disorder diagnosed clinically with the development of choreiform movements. However, neuropsychological studies have demonstrated cognitive and psychiatric changes during the preclinical phase (pre-HD) prior to formal diagnosis. Previous studies have demonstrated the sensitivity of time reproduction tasks to basal ganglia pathology, as seen in clinical HD and Parkinson's disease. In this study, 29 pre-HD participants, ranging from 3 to 39 years from estimated onset (YEO) of HD based on genetic testing and chronological age, were administered the paced finger-tapping task using target intervals of 600 and 1200 ms. Mean inter-response interval, a measure of timing accuracy, did not systematically deviate from the target interval as a function of YEO. In contrast, timing variability increased curvilinearly as a function of YEO, but not with chronological age alone. Motor timing variability, but not accuracy, may serve as a marker to define the earliest behavioral changes in HD. The present study is among the first to examine the relationship between behavioral measures and YEO in pre-HD.

fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington's Disease.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) has been used to probe basal ganglia function in people with presymptomatic Huntington's disease (pre-HD). A previous fMRI study in healthy individuals demonstrated activation of the basal ganglia during a time-discrimination task. The current study was designed to examine the relative sensitivity of fMRI compared with that of behavioral testing and morphometric measurements in detecting early neurodegenerative changes related to Huntington's disease (HD). METHODS: Pre-HD participants were assigned to two groups based on estimated years to diagnosis of manifest disease: close <12 years and far >or=12 years. Age at disease onset was estimated using a regression equation based on the number of trinucleotide CAG repeats. The time-discrimination task required participants to determine whether a specified interval was shorter or longer than a standard interval of 1200 milliseconds. RESULTS: Participants in the close group performed more poorly on the time-task discrimination than did control subjects; however, no differences were observed between far participants and control subjects. Similarly, close participants had reduced bilateral caudate volume relative to that of control subjects, whereas far participants did not. On functional imaging, close participants had significantly less activation in subcortical regions (caudate, thalamus) than control subjects; far participants had an intermediate degree of activation. In contrast, far participants had hyperactivation in medial hemispheric structures (anterior cingulate, pre-supplementary motor area) relative to close and control subjects. CONCLUSION: Hyperactivation of medial prefrontal regions compensated for reduced subcortical participation during time discrimination in pre-HD. This pattern of brain activation may represent an early neurobiologic marker of neuronal dysfunction.

Neural basis for impaired time reproduction in Parkinson's disease: an fMRI study.

Studies involving brain-lesioned subjects have used the paced finger tapping (PFT) task to investigate the neural systems that govern motor timing. Patients with Parkinson's disease (PD), for example, demonstrate abnormal performance on the PFT, characterized by decreased accuracy and variability changes, suggesting that the basal ganglia may play a critical role in motor timing. Consistent with this hypothesis, an fMRI study of healthy participants demonstrated that the medial frontostriatal circuit (dorsal putamen, ventrolateral thalamus, SMA) correlated with explicit time-dependent components of the PFT task. In the current fMRI study, PD patients and healthy age-matched controls were imaged while performing the PFT. PD patients underwent 2 imaging sessions, 1 on and the other off dopamine supplementation. Relative to controls, PD patients were less accurate and showed greater variability on the PFT task relative to controls. No PFT performance differences were observed between the on and off medication states despite significantly greater motor symptoms on the Unified Parkinson's Disease Rating Scale (UPDRS) in the off medication state. Functional imaging results demonstrated decreased activation within the sensorimotor cortex (SMC), cerebellum, and medial premotor system in the PD patients compared to controls. With dopamine replacement, an increase in the spatial extent of activation was observed within the SMC, SMA, and putamen in the PD patients. These results indicate that impaired timing reproduction in PD patients is associated with reduced brain activation within motor and medial premotor circuits. Despite a lack of improvement in PFT performance, PD patient's brain activation patterns were partially "normalized" with dopamine supplementation. These findings could not be attributed to greater head movement artifacts or basal ganglia atrophy within the PD group.