Relationship between amplitude of tremor and reflex responses of the human jaw-closing system

Jaw-closing force was transduced while subjects maintained a biting force of 9.8 N. To estimate the amplitude of tremor in each subject's force record, the average spectrum of the force was computed, and the definite integral of the averaged spectrum in the frequency range from 3.5 to 10 Hz was calculated. For the same subjects, the amplitude of reflex responses to innocuous mechanical stimuli delivered to intraoral and perioral sites was measured as the peak-to-peak change in jaw-closing force following application of the stimulus. Force responses produced by stimulation at each site were used to compute an average reflex response measure for each subject. Large intersubject variability was observed in the amplitudes of jaw tremor and reflex responses. A correlation coefficient computed between the tremor and reflex measures revealed that subjects with large amplitude tremor tended also to have large reflex force responses. This correlation is consistent with the suggestion that activity in cutaneous reflex pathways contributes to tremor of the human mandible.     

Relationship between amplitude of tremor and reflex response of the human jaw-closing system

Jaw-closing force was transduced while subjects maintained a biting force of 9.8 N. To estimate the amplitude of tremor in each subject's forces record, the average spectrum of the force was computed, and the definite integral of the averaged spectrum in the frequency range from 3.5 to 10 Hz was calculated. For the same sunjects, the amplitude of reflex responses to innocuous mechanical stimuli delivered to intraoral and perioral sites was measured as the peak-to-peak change in jaw-closing force following application of the stimulus. Force responses produced by stimulation at each site were used to compute an average reflex response measure for each subject. Large intersubject variability was observed in the amplitudes of jaw and reflex responses. A correlation coefficient computed between the tremor and reflex measures revealed that subjects with large amplitude tremor tended also to have a large reflex force responses. This correlation is consistent with the suggestion that activity in cutaneous reflex pathways contributes to tremor of the human mandible.     

Developmental changes of synaptojanin expression in the human cerebrum and cerebellum.

Synaptojanin is a highly abundant polyphosphoinositide phosphatase in nerve terminals, and has been thought to play roles in clathrin-mediated synaptic vesicle endocytosis and signaling. In order to determine the broader role of synaptojanin in the central nervous system, we examined synaptojanin expression in the cerebrum and cerebellum from the fetal to the adult period by means of immunohistochemical and Western blot analyses. Immunohistochemistry consistently revealed the localization of synaptojanin in Cajal--Retzius cells, cortical plate neurons, subplate neurons, intermediate neurons, germinal matrix cells and the ventricular neuroepithelium of the fetal cerebrum. In the fetal cerebellum, synaptojanin immunoreactivity was localized in the external granular cell layer, Purkinje cell layer neuropil, cytoplasm of Purkinje cells and internal granular cells. The immunoreactivity in these structures was decreased around birth. After birth, the synaptojanin immunoreactivity of cortical neurons in the cerebrum, Purkinje cell layer neuropil, and internal granular cells and Purkinje cells in the cerebellum increased and reached a plateau after 11 years of age. These results were consistent with the intensity observed on Western blot analysis. These developmental changes of synaptojanin suggest a broader role in not only synaptic vesicle recycling, but also the regulation of neuronal migration and synaptogenesis in the fetal cerebrum and cerebellum.     

Developmental and age-related changes of dopamine transporter, and dopamine D1 and D2 receptors in human basal ganglia

The developmental and age-related changes of the dopamine transporter (DAT), and the dopamine D1 and D2 receptor (D1R and D2R) subtypes were investigated in basal ganglia (BG) of human brain. DAT immunostaining was mainly observed in the neuropil, neurons, and glia of the striatum. The DAT-positive neuropil was detectable at 32 GW, a peak being reached at 9–10 years of age, with a decrease to 50–63 years of age. The developmental pattern of DAT immunoreactivity in neuron was similar to that of the neuropil. DAT-positive glia were observed in the BG at 32 GW, which increased slightly at 38–40 GW, and then did not obviously change until 6–8 months after birth. D2R-positive neurons were clearly observed at 19 GW, a peak being reached at 32 GW and 1–3 months of age in the globus pallidus and striatum, respectively, with a decrease after 9–10 years of age. D1R was expressed as early as D2R, but decreased after 6–8 months. Our results suggest that D1R and D2R expression is an intrinsic property of striatal neurons and is independent of dopaminergic innervation. D1R may play a more important role in neuronal maturation of the BG than D2R. D2R may be closely correlated with late neuronal development. The higher expression of DAT during adolescence may be related to function of the BG which learns complex behavioral patterns. The significance of the age-related decreases in DAT, D1R and D2R in the BG remains to be further investigated.     

Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum

The relationship between the postnatal development of dopaminergic (DAergic) nerve endings and the maturation of D1 DA receptors in the rat striatum was analyzed by measuring the content of DA and dihydroxyphenylacetic acid (DOPAC), two biochemical markers of DAergic nerve terminal proliferation, and the ontogenetic changes in [3H]SCH 23390 binding sites. DA-stimulated adenylate cyclase (AC) activity was also measured in order to characterize the coupling of [3H]SCH 23390 binding sites to the responses mediated by the activation of D1 DA receptors. Striatal levels of DA and DOPAC, as well as the density and affinity of [3H]SCH 23390 binding sites and DA-stimulated AC activity were also measured in senescent rats. The striatal content of DA increased slowly after birth, reaching adult levels by postnatal day 60 and remaining constant through adulthood and senescence (up to 20 months of age). The density of [3H]SCH 23390 binding sites increased 14-fold from birth to postnatal day 35, when a peak value was reached, whereas a significant decrease was observed in the striatum of aged rats. In contrast, the affinity of D1 DA receptors for [3H]SCH 23390 remained unchanged from birth through senescence. The stimulation of cyclic AMP formation induced by 100 microM DA increased 4-fold from birth to postnatal day 14, when the maximal responsiveness to DA was observed and then returned to adult levels. No significant alterations were observed in the Km values during development, whereas the stimulatory effect of 100 microM DA on AC activity was significantly decreased in senescent rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developmental changes in human dural innervation

Introduction  

There is limited published work on the abundant innervation of the human dura mater, its role and responses to injury in humans. The dura not only provides mechanical support for the brain but may also have other functions, including control of the outflow of venous blood from the brain via the dural sinuses. The trigeminal nerve supplies sensory fibres to the dura as well as the leptomeninges, intracranial blood vessels, face, nose and mouth. Its relatively large size in embryonic life suggests an importance in development; the earliest fetal reflexes, mediated by the trigeminal, are seen by 8 weeks. Trigeminal functions vital to the fetus include the coordination of sucking and swallowing and the protective oxygen-conserving reflexes. Like other parts of the nervous system, the trigeminal undergoes pruning and remodelling throughout development.     

Developmental changes in glycoproteins of the chick nervous system

Temporal changes have been noted previously in retinal glycoproteins that bind to wheat germ agglutinin by a technique in which the denatured glycoproteins are first separated according to size by polyacrylamide gel electrophoresis, and are then localized on the gel using [¹²⁵I]lectin¹⁵. As reported here this technique will also detect differences between dorsal and ventral halves of the neural retina from 8-day chick embryos, and using other lectins will detect temporal changes in the glycoprotein pattern of the optic tectum. Some of the glycoproteins detected by wheat germ agglutinin in the neural retina appear to be represented on the surface of the retinal cells since: (a) the temporal changes in retinal glycoproteins can also be observed in a plasma membrane enriched fraction prepared from neural retina cells; and (b) antibodies prepared in mice against various size categories of wheat germ lectin binding glycoproteins bind to intact retinal cells.     

Neurophysiological correlates of age-related changes in human motor function

BACKGROUND: There are well-defined and characteristic age-related deficits in motor abilities that may reflect structural and chemical changes in the aging brain. OBJECTIVE: To delineate age-related changes in the physiology of brain systems subserving simple motor behavior. METHODS: Ten strongly right-handed young (<35 years of age) and 12 strongly right-handed elderly (>50 years of age) subjects with no evidence of cognitive or motor deficits participated in the study. Whole-brain functional imaging was performed on a 1.5-T MRI scanner using a spiral pulse sequence while the subjects performed a visually paced "button-press" motor task with their dominant right hand alternating with a rest state. RESULTS: Although the groups did not differ in accuracy, there was an increase in reaction time in the elderly subjects (mean score plus minus SD, young subjects = 547 +/- 97 ms, elderly subjects = 794 +/- 280 ms, p < 0.03). There was a greater extent of activation in the contralateral sensorimotor cortex, lateral premotor area, supplementary motor area, and ipsilateral cerebellum in the elderly subjects relative to the young subjects (p < 0.001). Additional areas of activation, absent in the young subjects, were seen in the ipsilateral sensorimotor cortex, putamen (left > right), and contralateral cerebellum of the elderly subjects. CONCLUSIONS: The results of this study show that elderly subjects recruit additional cortical and subcortical areas even for the performance of a simple motor task. These changes may represent compensatory mechanisms invoked by the aging brain, such as reorganization and redistribution of functional networks to compensate for age-related structural and neurochemical changes.     

Reflex responses of the human jaw-closing system depend on the locus of intraoral mechanical stimulation

Innocuous mechanical stimuli were applied to eight sites on the tongue dorsum and palate while subjects used feedback to maintain a constant isometric biting force. Reflex responses of the jaw-closing system were measured as changes in force and in EMGs recorded from right and left masseter muscles. Stimulation at each of the eight sites produced reflex force and EMG responses in most subjects tested. The nature of the reflex responses strongly depended on the site of stimulation. Stimulation of the palate tended to produce suppression of ongoing EMG activity and decreases in background biting force. In contrast, stimulation of sites on the tongue posterior to the tip, most often resulted in excitatory EMG responses and increases in jaw-closing force. Unilateral, early excitatory responses were observed in the right masseter with stimulation of the right side of the tongue. The existence of spatially organized responses of the human jaw-closing system to innocuous intraoral stimulation is not consistent with the view that these cutaneous reflexes are primarily of protective significance.     

A magnetic resonance image study of age-related changes in human putamen nuclei.

Putamen nuclei were assessed in 36 normal volunteers using magnetic resonance imaging and a systematic sampling method. There was a significant decrease in the volume of the putamen nuclei with advancing age (r = -0.74, p less than 0.0001), and an associated decline in the volume of the caudate nuclei (r = 0.60, p less than 0.0001). The implications of these findings in age-associated motor abnormalities are discussed.     

Developmental and aging changes of Bak expression in the human brain

The gene bak regulates apoptosis. To explore its role in the human central nervous system, we examined the distribution of its protein product, Bak, in the brains at various ages, by immunochemical and immunohistochemical means. Western blotting revealed that Bak expression in the cerebrum and cerebellum is high in the brains of the fetuses and elderly subjects, but low in those of young adults. Immunostaining of the cerebellum localized Bak immunoreactivity to Purkinje cells, which was strong in the fetal period and senescence, but undetectable from infancy to adolescence. These results suggest that bak regulates neuronal death associated with the development and aging of the central nervous system.     

Developmental changes in the human visual system as reflected by the latency of the pattern reversal VEP

Pattern reversal visually evoked potentials (VEPs) were recorded from 439 infants and young children ranging in age from 1 month to 5 years in response to large and small checks. Qualitative analysis of the VEP wave form showed that the first major positive component, P1, is consistently present at all ages, while the frequency of occurrence of later positive components is more variable. The proportion of infants showing late positive components increases with age; by 1 year, the frequency of occurrence of late components for large checks is more adult-like than for small checks. The latency of P1 was analyzed quantitatively. Results showed that P1 latency decreases rapidly during the first year of life for both large and small checks and that the time course of the latency change differs as a function of check size. VEPs to large checks attain adult-like P1 latency values by about 1 year of age, while the P1 latency of VEPs to small checks has still not reached adult levels by 5 years of age. Data from 12 infants tested longitudinally between 1 and 7 months of age using both checkerboards and square wave gratings show no difference in P1 latency between checkerboards and gratings comprised of large (30-240 min) pattern elements, but for patterns with small (7.5 and 15 min) elements, P1 latency to checks is significantly longer than P1 latency to stripes. These results are explained on the basis of the difference in the fundamental spatial frequency between checks and stripes.     

Developmental changes of three phosphoinositide-specific phospholipase C isozymes in the rat nervous system.

Developmental changes of 3 phosphoinositide-specific phospholipase C isozymes (PI-PLC-beta, PI-PLC-gamma and PI-PLC-delta) in the rat nervous system were studied by immunohistochemical and immunochemical methods. PI-PLC-gamma immunoreactivity was intensely expressed in the radial fibers from the late fetal to early newborn stages, while weaker PI-PLC-beta reaction was also demonstrated in these structures. PI-PLC-beta and PI-PLC-gamma immunoreactivity appeared in neurons of various regions after the first postnatal week and then increased to the adult stage. Bergmann glia and some astrocytes also showed weak immunoreactivity for both isozymes from the newborn stage, while such immunoreactive astrocytes were relatively restricted in distribution in the white matter and hippocampus at the adult stage. PI-PLC-delta immunoreactivity appeared in astrocytes of entire cerebral regions from the second postnatal week, although weak antigenicity was also present in some neurons. Immunoblot analysis revealed that the immunoreactivities of 3 PI-PLC isozymes were present in both fetal and adult brains, with strong reactions of PI-PLC-beta and PI-PLC-delta in adult brain and that of PI-PLC-gamma in fetal brain. These results suggest that each PI-PLC isozyme plays important roles in different cell types in the course of their differentiation, and that some PI-PLC isozymes, especially PI-PLC-gamma, may be involved in cellular division and growth during the histogenesis of the central nervous system.     

Cortical excitability and age-related volumetric MRI changes.

OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.     

On the development of human corticospinal oscillations: age-related changes in EEG-EMG coherence and cumulant

Changes in coherence and cumulant calculated between electroencephalograph (EEG) recorded from the scalp over primary motor cortex and rectified surface electromyograph (EMG) recorded from the contralateral wrist extensor muscles have been studied during development in humans (48 subjects, age 0–59 years). Using the techniques of EEG–EMG coherence and cumulant analysis and pooled coherence and cumulant analysis we demonstrate that between childhood, adolescence and adulthood there are increases in the prevalence and magnitude of coherence at frequencies between 15 and 35 Hz with corresponding development of a tri-phasic feature in the EEG–EMG cumulant. The results show for the first time that changes in the cortical ∼20 Hz oscillatory drive to human motoneurone pools take place during motor development.     

Developmental changes of epidermal growth factor-like immunoreactivity in the human fetal brain

We investigated the immunohistochemical localization of epidermal growth factor (EGF) in the developing human brain from 6 weeks of gestation to 3 months postpartum. EGF-like immunoreactivity varied in its localization and intensity according to the stage of development. At 10-20 weeks of gestation, EGF-like immunoreactivity appeared in proliferating and migrating cells in the cerebrum, disappeared thereafter, and appeared again in cortical neurons after 27 weeks of gestation. Astrocytes also showed EGF-like immunoreactivity from 27 weeks of gestation. These results suggest developmental regulation of EGF expression in the human brain, suggesting Its physiological role in both neuronal and glial cells. © 1995 Wiley-Liss, Inc.     

Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle.

OBJECTIVE: To investigate the patterns of motor unit firing in single motor units from the sternocleidomastoid (SCM) muscles in response to stimuli previously shown to be capable of evoking vestibulocollic reflexes (loud clicks and electrical stimulation) and to relate these to the previously described surface potentials (VEMPs, vestibular evoked myogenic potentials) evoked by the same stimuli. METHODS: Eleven male subjects (30-43-years-old) were studied. Local anaesthetic was used to block the SCM and confirm that the surface potentials (p13n23) arose from it. At another time, fine wire or needle electrodes were used to record single motor unit activity and peristimulus time histograms were constructed. RESULTS: Local anaesthetic block reduced or abolished the p13n23 response in 5 of 6 subjects. A total of 94 histograms of motor unit discharges were recorded. The excitability changes seen were always small. Loud click stimuli given ipsilaterally evoked short latency (mean 14.2 ms, uncorrected for triggering delays), and short duration (mean 3.6 ms) inhibition. Contralaterally, the effect was excitatory (latency 11.9 ms, uncorrected, mean duration 2.3 ms). For electrical stimulation, short latency inhibition occurred ipsilateral to the cathode (average latency 14.0 ms, uncorrected, mean duration 2.9 ms) and excitation occurred contralaterally. CONCLUSIONS: We confirmed that the SCM is the sole or dominant source of the VEMPs recorded from electrodes over it. Short latency, short duration motor unit firing changes are evoked in SCM by loud clicks and electrical stimulation, stimuli known to be capable of evoking vestibulocollic reflexes. VEMPs beginning with a positivity correspond to inhibition of the underlying motor unit firing and those starting with a negativity correspond to an underlying excitation, findings consistent with intracellular recordings of otolith effects. Qualitative explanations of how the surface potentials are generated by these excitability changes and relating to other properties of the surface responses are proposed. SIGNIFICANCE: This study has shown consistent patterns of single motor unit firing which underlie VEMPs evoked by both clicks and short duration galvanic stimulation.     

Developmental changes in brain kynurenic acid concentrations.

The cerebral distribution and regulation of excitatory amino acid levels may play a crucial role in neuronal development. In the present study we examined concentrations of the endogenous excitatory amino acid antagonist kynurenic acid and related substances during development in fetal and neonatal rat brain and fetal non-human primate cerebral cortex. Kynurenic acid concentrations in rat fetal whole brain were significantly increased 4-5 fold prenatally, then declined rapidly at 1 day after birth, and reached adult concentrations at 7 days after birth. L-Kynurenine concentrations were also markedly increased prior to birth and then declined to adult concentrations at 1 day after birth. L-Tryptophan was increased 3 fold before birth, and decreased to adult concentrations 1 day after birth. In contrast concentrations of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid and homovanillic acid increased 1 day prior to birth and continued to increase following birth. Fetal baboon cerebral cortex showed significant increases in kynurenic acid concentrations both pre-term and near-term as compared with adult concentrations. These results show that marked changes in kynurenic acid concentrations occur prior to and following birth. It is possible that high levels of kynurenic acid prior to birth inhibit neurite branching and development of excitatory synapses, which then develop rapidly in parallel with the decrease in kynurenic acid levels.