To clarify the mechanism underlying improvement of parkinsonian signs by high-frequency electrical stimulation (HFS) of the subthalamic nucleus (STN), we investigated the effects of STN HFS on neuronal activity of the internal and external segment of the globus pallidus (GPi and GPe, respectively) in two rhesus monkeys rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. A scaled-down version of the chronic stimulating electrode used in humans, consisting of four metal contacts 0.50 mm in length each separated by 0.50 mm, was implanted through a cephalic chamber targeting the STN. Histological reconstruction revealed that the cathode was located in the STN in both monkeys. Extracellular recordings from a total of 110 pallidal neurons during STN stimulation were performed. Poststimulus time histograms of single neurons triggered by 2 Hz STN stimulation pulses at 2.4-3.0 V revealed short-latency excitations at 2.5-4.5 and 5.5-7.0 msec after stimulation onset and inhibitions at 1.0-2.5, 4.5-5.5, and 7.0-9.0 msec for both GPe and GPi neurons. These short-latency responses were present with 136 Hz stimulation, at voltages effective for alleviation of parkinsonian signs, resulting in a significant increase in mean discharge rate and a stimulus-synchronized regular firing pattern. These results indicate that activation of the STN efferent fibers and resultant changes in the temporal firing pattern of neurons in GPe and GPi underlie the beneficial effect of HFS in the STN in Parkinson's disease and further support the role of temporal firing patterns in the basal ganglia in the development of Parkinson's disease and other movement disorders.

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Patrick SK, Noah JA, Yang JF. Interlimb coordination in human crawling reveals similarities in development and neural control With quadrupeds. J Neurophysiol 101: 603-613, 2009. First published November 26, 2008 doi:10.1152/jn.91125.2008. The study of quadrupeds has furnished most of our understanding of mammalian locomotion. To allow a more direct comparison of coordination between the four limbs in humans and quadrupeds, we studied crawling in the human, a behavior that is part of normal human development and mechanically more similar to quadrupedal locomotion than is bipedal walking. Interlimb coordination during hands-and-knees crawling is compared between humans and quadrupeds and between human infants and adults. Mechanical factors were manipulated during crawling to understand the relative contributions of mechanics and neural control. Twenty-six infants and seven adults were studied. Video, force plate, and electrogoniometer data were collected. Belt speed of the treadmill, width of base, and limb length were manipulated in adults. Influences of unweighting and limb length were explored in infants. Infants tended to move diagonal limbs together (trot-like). Adults additionally moved ipsilateral limbs together (pace-like). At lower speeds, movements of the four limbs were more equally spaced in time, with no clear pairing of limbs. At higher speeds, running symmetrical gaits were never observed, although one adult galloped. Widening stance prevented adults from using the pace-like gait, whereas lengthening the hind limbs (hands-and-feet crawling) largely prevented the trot-like gait. Limb length and unweighting had no effect on coordination in infants. We conclude that human crawling shares features both with other primates and with nonprimate quadrupeds, suggesting similar underlying mechanisms. The greater restriction in coordination patterns used by infants suggests their nervous system has less flexibility.

Clinical assessment of rigidity in parkinsonian patients is largely qualitative. The reliability and validity of the assessments are sometimes in doubt. Several "engineering" methods of quantifying rigidity have been described, but none has been adopted into general clinical practice. A possible reason is that these methods differ in crucial aspects from the clinical exam. We therefore tackled the problem by monitoring the clinical exam itself, using small sensors to measure the forces and displacements applied. Limb impedance (Z) was computed using parameter identification methods and compared to raters' verbalized ratings of rigidity based on a 5-point scale: the Unified Parkinson's Disease Rating System. The qualitative and quantitative estimates of impedance covaried over a fourfold range, depending on the forces imposed and the subject's motor set. Raters differed by up to 1 full point in their mean qualitative ratings and sometimes disagreed on whether levodopa reduced rigidity. This was not due to any significant differences in the overall range of rigidity they evoked, but rather to the way they scored this range [the ratio of mean rating to mean impedance (R/Z) varied between raters and subjects]. On the other hand, the R/Z ratio was reproducible over separate sets of ratings and may therefore serve to convert measured impedance into a standardized rating. Our results indicate that the current clinical exam may be too abbreviated to detect the sometimes quite small reductions in rigidity after levodopa. We conclude that a device that conveniently quantifies the clinical assessment of rigidity is now available and will lead to more standardized protocols for rating rigidity in the near future.

Objectives-To examine diary-based, laboratory-based, and actigraphic measures of sleep in a group of healthy older women and men (≥75 years of age) without sleep/wake complaints and to describe sleep characteristics which may be correlates of health-related quality of life in old age.Design-Cross-sectional, descriptive study. Setting-University-based sleep and chronobiology program. Intervention-None.Participants-Sixty-four older adults (30 women, 34 men; mean age 79) Measurements-We used diary-, actigraphic-, and laboratory-based measures of sleep, healthrelated quality of life, mental health, social support, and coping strategies. We used two-group t-tests to compare baseline demographic and clinical measures between men and women, followed by ANOVA on selected EEG measures to examine first-night effects as evidence of physiological adaptability. Finally, we examined correlations between measure of sleep and health-related quality of life.Results-We observed that healthy men and women aged 75 and older can experience satisfactory nocturnal sleep quality and daytime alertness, especially as reflected in self-report and diary-based measures. Polysomnography (psg) suggested the presence of a first-night effect, especially in men, consistent with continued normal adaptability in this cohort of healthy older adults. Continuity and depth of sleep in older women were superior to that of men. Diary-based measures of sleep quality (but not psg measures) correlated positively (small to moderate effect sizes) with physical and mental health-related quality of life.Conclusions-Sleep quality and daytime alertness in late life may be more important aspects of successful aging than previously appreciated. Good sleep may be a marker of good functioning across a variety of domains in old age. Our observations suggest the need to study interventions which protect sleep quality in older adults to determine if doing so fosters continued successful aging. Sleep quality is an important parameter of health-related quality of life in older adults, and it is possibly a correlate of continuing adaptability in later life. 1,2 However, sleep disturbances are common in later life, particularly beyond 75 years, with loss of nocturnal sleep continuity and depth. [1][2][3] Diminution in sleep quality may presage a decline in overall health status. Thus, as Shakespeare's Macbeth observed of "sleep that knits the raveled sleeve of care," (Macbeth, Act II, Scene II), learning how to protect sleep in later life may be important to continued healthy aging.According to Rowe and Kahn, 4 "successful aging" can be characterized by avoidance of disease, maintenance of high cognitive and physical function, and continued engagement with life. Given the evidence that behavioral factors like diet, smoking, and exercise affect one's ability to age successfully, 5 studying the effect of sleep on adaptability and overall well-being observed in healthy aging may also be informative. As the discussion of how to define "healthy aging" continues, 6 this ...