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Healthy aging limits the activities of daily living and personal independence. Furthermore, cognitive-motor interference in dual-task (e.g., walking while talking) appears to be more pronounced in the elderly. Transcranial direct current stimulation (tDCS), a form of the non-invasive brain stimulation technique, is known to modify cortical excitability and has been investigated as a tool for enhancing motor and cognitive performance in health and disease. The present study examined whether tDCS targeting the dorsolateral prefrontal cortex (DLPFC) could improve dual-task performance in healthy older adults. The effects of tDCS, among other factors, depend on stimulation polarity (anodal vs. cathodal), electrode setup (unilateral vs. bilateral) and the time of application (off-line vs. on-line). We therefore explored the effects of unilateral and simultaneous bilateral tDCS (anodal and cathodal) of left DLPFC while performing (on-line) the Grooved Pegboard Test (GPT) and Serial Seven Subtraction Test (SSST) alone or together (dual-tasking). The number of pegs and the number of correct subtractions were recorded before, during and 30 min after tDCS. The dual-task performance was measured as the percent change from single- to the dual-task condition (dual-task cost DTC). Only bilateral, anode left tDCS, induced a significant increase in subtracted numbers while dual-tasking, i.e., it reduced the DTC of manual dexterity (GPT) to a cognitive task. Significant changes 30 min after the stimulation were only present after bilateral anode right (BAR) tDCS on GPT dual-task costs. These findings suggest that anodal tDCS applied on-line interacts with a dual-task performance involving demanding cognitive and manual dexterity tasks. The results support the potential use of non-invasive brain stimulation for improvement of cognitive functioning in daily activities in older individuals.

Rats develop hyperalgesia and allodynia in the hind paw after L5 spinal nerve ligation. Phosphorylated extracellular regulated kinase (pERK) was used as a pain marker to investigate the potential role of adjacent uninjured L4 nerve in the development of heat hyperalgesia after L5 nerve injury. Left L5 nerve was ligated and sectioned in rats. Three days later, rats were randomly assigned to five groups; each had both hind paws immersed in water at different temperatures (no heat, 37, 42, 47, and 52 °C) under sevoflurane anesthesia for 2 minutes. Five minutes after stimulation the rats were sacrificed and sections of L3-L6 spinal segments were stained immunocytochemically with pERK antibody. pERK immunoreactivity, which is not detectable in the normal spinal cord, was discernible in neurons (not glia) of the superficial dorsal horn after noxious heat stimuli. pERK-positive neurons clearly overlapped in laminae I-II with normal unmyelinated and thin myelinated afferents labeled with calcitonin gene-related peptide and isolectin B4, and injured unmyelinated afferents labeled with vasoactive intestinal polypeptide. There was a linear increase in pERK immunoreactivity on both sides with an increase in temperature. Importantly, the number of positive pERK neurons was significantly higher in the ipsilateral side of L4 spinal segment, which receives innervation from uninjured L4 nerve, compared with the contralateral control side, which receives both uninjured L4 and L5 spinal nerves. The data demonstrate that the uninjured L4 nerve plays an important role in the development of heat hyperalgesia at the spinal cord level after L5 nerve injury.

© 2017 by the authors. We are glad to introduce the fourth Journal Club. This edition is focused on several relevant studies published in the last few years in the field of musculoskeletal disorders, chosen by our Editorial Board members. We hope to stimulate your curiosity in this field. The Editorial Board members wish you an inspiring lecture.

Objective Little is known whether and how chronic exposure to dopaminergic treatment alters physiological mechanisms in Parkinson’s disease (PD). Methods Two clinically similar groups of PD patients, one consisting of drug-naive patients and another of patients already on chronic dopaminergic medication (when off medication), were compared to each other and to a control group. Plasticity and excitability of the hand primary motor cortex of the more affected side were evaluated using transcranial magnetic stimulation (TMS) techniques. Results There was little difference between two patient groups, and both groups showed similar differences in comparison to controls: decreased facilitatory sensory-motor plasticity (as measured by paired associative stimulation [PAS] protocol), impaired short-interval intracortical inhibition (SICI), and diminished slope of input–output curves at higher TMS intensities. The exception was that 30 min after PAS, intracortical facilitation (ICF) was significantly reduced in drug-naive patients, whereas it changed much less in other two groups. Conclusions Chronic exposure to dopaminergic drugs does not affect substantially the features of motor cortex excitability and plasticity in PD. There is little interaction between plasticity and excitability features of motor cortex in PD. Significance Reduced response to facilitatory PAS protocol, reduced SICI, and reduced slope of the input–output curve at higher TMS pulse intensities, seem to be physiological markers for the presence of the pathological disease process in PD. Long term treatment does not seem to change the underlying physiology of the disease.

The complex interplay between hypernatremic osmotic disturbances and cerebral lesions is yet to be clarified. In this review, we discuss, on the basis of the reported data of hypernatremic CNS challenge in the adult population, the clinical and radiologic features of the condition. Our search captured 20 case studies and 1 case series with 30 patients in total who acquired acute hypernatremia due to different etiologies and developed CNS lesions. We explored the associations between premorbid conditions, clinical presentation, hypernatremic state, correction rate, and radiologic appearance, including the localization of brain lesions and the outcomes. The results revealed that altered mental status was the most commonly reported symptom and osmotic demyelination syndrome in the form of extrapontine myelinolysis was the prevailing radiologic pattern. Finally, we contrasted, when appropriate, clinical and experimental data related to hypernatremic and hyponatremic osmotic insults to aid the understanding of the pathophysiology of CNS osmotic brain injury.

We are glad to introduce the third Journal Club. The third edition is focused on several relevant studies published in the last years in the field of Gait and Posture, chosen by our Editorial Board members. We hope to stimulate your curiosity in this field and to share with you a passion for sport seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture., Journal of Functional Morphology and Kinesiology, 1 (4)

Background The dorsolateral prefrontal cortex (DLPFC) plays an important role in the regulation of food intake. Several previous studies demonstrated that a single session of transcranial direct current stimulation (tDCS) of the DLPFC reduces food craving and caloric intake. Objectives We hypothesized that repeated tDCS of the right DLPFC cortex may exert long-term changes in food craving in young, healthy adults and that these changes may differ between normal and overweight subjects. Methods Thirty healthy individuals who reported frequent food cravings without a prior history of eating disorders were initially recruited. Subjects were randomized into an ACTIVE group who received 5 days of real tDCS (20 minutes, anode right-cathode left montage, 2 mA with current density kept at 0.06 mA/cm2, 1 min ramp-up/ramp-down), and a SHAM group, who received one day of real tDCS, on the first day (same parameters), followed by 4 days of sham tDCS. Food craving intensity was examined by Food Craving Questionnaires State and Trait and Food Craving Inventory before, during, (5-days) and one month (30-days) after tDCS. Results Single session of tDCS significantly reduced the intensity of current food craving (FCQ-S). Five days of active tDCS significantly reduced habitual experiences of food craving (FCQ-T), when compared to baseline pre-stimulation levels. Furthermore, both current (FCQ-S) and habitual craving (FCQ-T) were significantly reduced 30 days after active tDCS, while sham tDCS, i.e. a single tDCS session did not have significant effects. Also, active tDCS significantly decreased craving for fast food and sweets, and to a lesser degree for fat, while it did not have significant effects on craving for carbohydrates (FCI). There were no significant differences between individual FCQ-T subscales (craving dimensions) after 5 or 30 days of either sham or active tDCS. Changes in craving were not significantly associated with the initial weight, or with weight changes 30 days after the stimulation in the subjects. Conclusions The results confirm earlier findings that single session of tDCS has immediate effects in reducing food craving. They also show that repeated tDCS over the right DLPFC may increase the duration of its effects, which may be present 30 days after the stimulation. These results support further investigation of the use of tDCS in obesity.

Experimental and clinical data suggest that high-frequency deep brain stimulation (DBS) of different subcortical structures can be used to control or modulate epileptic seizures. Recent studies showed that DBS of the substantia nigra reticulata (SNr) in rats has an anticonvulsant effect on forebrain clonic seizures. The aim of this study was to determine whether DBS of SNr could also suppress tonic epileptic seizures evoked in hindbrain structures. DBS with high frequency often mimics the effects of surgical ablation of a particular area of the brain. However, the optimal parameters of DBS stimulation to induce ablation-like effects on seizures are not well defined. Consequently, in the first experiment we examined the effects of different stimulation frequencies (80, 130, 260 and 390 Hz) on neuronal activation induced in SNr, using c-fos immunocytochemistry. The results showed that the stimulation of the SNr with 80 Hz has no inhibitory effect while stimulation with 130, 260 and 390 Hz produced a remarkable suppressive effect compared with the control unstimulated side. The aim of the second experiment was to determine whether bilateral inhibition of SNr with DBS could suppress tonic seizures induced by electric shock. Statistical analysis showed that the mean tonic seizure scores following SNr stimulation with either 130 or 260 Hz were not significantly different from scores following the application of the electrode without current. The data suggest that DBS of the SNr produces neuronal inhibition but fails to suppress tonic seizures. We conclude, therefore, that DBS of SNr with frequencies used in this study might not be effective for treatment of patients who suffer from tonic epileptic seizures.

Diabetic patients show a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. Their electrocardiograms may show several alterations from normal patterns, many of them related to the QT. Various diastolic and systolic abnormalities are frequently reported in diabetic patients, and the severity of the abnormalities depend on the patients' age and the duration of diabetes. The aim of this experimental study has been to clarify the progressive effects on heart rhythm in neonatal alloxan (ALX) (induced at 5 days of age) diabetic male rats. Cardiac biopotential data were acquired in vivo with a biotelemetry system. After an overnight fast blood glucose in diabetic rats, compared to age-matched controls, was elevated before and at 60, 120 and 180min after a glucose challenge at 2 and 8 months of age. Heart rate and heart rate variability were modestly reduced and QT interval modestly prolonged in diabetic rats, compared to controls, at 2, 6 and 8 months of age. There was also an age-dependent decline in heart rate and prolongation in QT interval. At 8 months heart rate was 296±8bpm in diabetic compared to 311±10bpm in controls and heart rate variability was 27±3bpm in diabetic rats compared to 32±4bpm in controls. Physical activity was significantly reduced in diabetic rats, compared to controls, at 6 and 8 months of age. Body temperature was modestly reduced in diabetic rats, compared to controls, at 2, 6 and 8 months. In conclusion, the neonatal ALX-induced diabetes mellitus was associated with disturbances in heart rate, heart rate variability, QT interval which in turn may be associated with changes in physical activity and body temperature.

Recent evidence suggests that the dynamic-scaling behavior of the time-series of signals extracted from separate peaks of tremor spectra may reveal existence of multiple independent sources of tremor. Here, we have studied dynamic characteristics of the time-series of hand tremor movements in essential tremor (ET) patients using the detrended fluctuation analysis method. Hand accelerometry was recorded with (500 g) and without weight loading under postural conditions in 25 ET patients and 20 normal subjects. The time-series comprising peak-to-peak (PtP) intervals were extracted from regions around the first three main frequency components of power spectra (PwS) of the recorded tremors. The data were compared between the load and no-load condition on dominant (related to tremor severity) and non-dominant tremor side and with the normal (physiological) oscillations in healthy subjects. Our analysis shows that, in ET, the dynamic characteristics of the main frequency component of recorded tremors exhibit scaling behavior. Furthermore, they show that the two main components of ET tremor frequency spectra, otherwise indistinguishable without load, become significantly different after inertial loading and that they differ between the tremor sides (related to tremor severity). These results show that scaling, a time-domain analysis, helps revealing tremor features previously not revealed by frequency-domain analysis and suggest that distinct oscillatory central circuits may generate the tremor in ET patients.

Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions.

s / Brain Stimulation 8 (2015) 395e411 398 at 5Hz intervals). After this patient remitted following TBS-20Hz, this parameter was then successfully applied to other patients with treatment refractory MDD who had failed TBS-50Hz. We began to use TBS-20Hz as our initial treatment parameter after multiple patients failed TBS-50Hz but remitted after TBS-20Hz. Results: 9 of 10 MDD patients treated with TBS-20Hz remitted, with an average BDI-II score drop of 20 points (s.d.1⁄416.8), or 64.3%. Our only non-remitter had suffered a CVA several years prior, possibly altering the position of the LDLPFC target location. Discussion: The strong response seen after TBS-20Hz suggests this and perhaps other alternate pulse parameters could improve the efficacy and durability of TMS treatment for depression. Therefore, a larger controlled trial is warranted to confirm and expand upon these results.

In decerebrate cats, changes in the monosynaptic reflex (MSR) of gastrocnemius–soleus (G–S) motoneurones were studied after fatiguing stimulation (FST) of the G–S muscles. Monosynaptic reflexes were evoked by stimulation of Ia fibres in the G–S nerve and recorded from a filament of ventral root (VR) L7. FST (intermittent 40 s−1 stimulation for 10–12 min) was applied to the distal part of the cut VR S1. FST reduced MSR amplitudes to 0.64 ± 0.04 (mean ±s.e.m.) of the prefatigue values. The suppression remained stable for approximately 25 min and then MSR amplitudes gradually returned towards the normal. To test for the involvement of presynaptic and recurrent inhibition, MSRs were conditioned by stimulation of the nerve to the posterior biceps and semitendinosus (PBSt) muscles or a filament of VR L7, respectively. The intensity of presynaptic inhibition (reduction of the normalized value of MSR amplitude during conditioning) increased from 0.19 ± 0.02 in prefatigue to 0.44 ± 0.04 within a 5.3–18.2 min interval after FST, followed by a recovery. In contrast, the intensity of recurrent inhibition first diminished from 0.23 ± 0.02 in prefatigue to 0.15 ± 0.01 within 15.6–30.1 min after FST and then gradually recovered. Both primary afferent depolarization and the intensity of antidromic discharges in primary afferents increased with the presynaptic inhibition intensity. These results demonstrate a fatigue-related suppression of Ia excitation of synergistic motoneurones, probably arising from the activation of group III and IV afferents. The effects could in part be due to increased presynaptic inhibition, while recurrent inhibition plays a minor role.

We study the interspike intervals (ISI) time series of the spontaneous fusimotor neuron activity by applying the detrended fluctuation analysis that is a modification of the random walk model analysis. Thus, we have found evidence for the white noise characteristics of the ISI time series, which means that the fusimotor activity does not possess temporal correlations. We conclude that such an activity represents the requisite noisy component for occurrence of the stochastic resonance mechanism in the neural coordination of muscle spindles.

Background/Aim. Transcranial magnetic stimulation (TMS) is a standard technique for noninvasive assessment of changes in central nervous system excitability. The aim of this study was to examine changes in responses to TMS in patients suffering from Parkinson's disease (PD) during sustained submaximal isometric voluntary contraction [60% of maximal voluntary contraction (MVC)] of the adductor pollicis muscle, as well as during a subsequent recovery period. Methods. Cortical excitability was tested by single TMS pulses of twice of the motor threshold intensity applied over the vertex. Testing was carried out during the sustained contraction phase every 10 s before and every 5 s after the endurance point, as well as at rest and during brief 60% MVC contractions before (control), immediately after the sustained contraction, and at 5 min intervals during the recovery period. Results. Although the PD patients could sustain the contraction at the required level for as long period of time as the healthy subjects (though contraction level subsided more rapidly after the endurance point), effects of muscle fatigue on the responses to TMS were different. In contrast to the findings observed in the healthy people where motor evoked potentials (MEP) and EMG silent period (SP) in fatigued muscle gradually diminished during contraction up to the endurance point, and increased thereafter, in the majority of patients no changes occurred in MEP size (peak and area) of the adductor pollicis muscle, either before or after the endurance point. On the other hand, changes in the SP of this muscle differed among the subjects, showing a gradual increase, a decrease or no changes in duration. The trends of changes in both MEP size and SP duration in the musculus brachioradialis varied among the tested PD patients, without any consistent pattern, which was in contrast with the findings in the healthy people where both measures showed a gradual increase from the beginning of the sustained contraction. A complete dissociation between changes in MEP and SP during fatigue was also of note, which differed sharply from the findings in the healthy people in who fatigue induced changes in these measures followed identical patterns. Conclusion. These results in the PD patients suggest the presence of impairment and/or compensatory changes in mechanisms responsible for adaptation of voluntary drive as well as for matching between cortical excitation and inhibition which become manifest in demanding motor tasks such as those imposed by muscle fatigue. Uvod/Cilj. Transkranijalna magnetna stimulacija (TMS) je standardna tehnika za neinvazivnu procenu promena ekscitabilnosti centralnog nervnog sistema. Cilj rada je bio da se prikažu promene odgovora na TMS kod obolelih od Parkinsonove bolesti (PB) za vreme trajanja submaksimalne voljne izometrijske kontrakcije [60% maksimalne voljne kontrakcije (MVK)] mišića adductor pollicis, kao i tokom perioda oporavka. Metode. Kortikalna ekscitabilnost testirana je TMS pulsevima dvostruko većeg intenziteta od motornog praga. Testiranje je vršeno za vreme održavanja kontrakcije na svakih 10 s do tačke izdržljivosti i na svakih 5 s posle toga, a, takođe, u miru kao i za vreme kratkotrajnih 60% MVK u periodu pre (kontrola), neposredno posle održavanja kontrakcije, i u intervalima od pet minuta za vreme perioda oporavka. Rezultati. Iako su bolesnici sa PB mogli da održavaju zahtevani nivo kontrakcije jednako dugo kao i zdravi ispitanici (mada je nivo opadao brže nakon tačke izdržljivosti), efekti mišićnog zamora na odgovor izazvan TMS-om bili su različiti. Za razliku od zdravih ispitanika kod kojih se motorni evocirani potencijali (MEP) i trajanje perioda EMG tišine (PT) u zamaranom mišiću postepeno smanjuju tokom kontrakcije do tačke izdržljivosti, a zatim rastu, kod većine bolesnika nije došlo do promena veličine (maksimalna amplituda i površina) MEP mišića adductor pollicis, bilo pre ili posle tačke izdržljivosti. S druge strane, promene PT ovog mišića su se razlikovale među ispitanicima, pokazujući bilo postepeno povećanje, smanjenje ili odsustvo promena. Promene kako amplitude MEP tako i trajanje PT u EMG mišića brahioradialisa varirale su među bolesnicima sa PB, bez nekog dominantnog obrasca, po čemu su se, takođe, razlikovale od promena nađenih kod zdravih ispitanika, kod kojih su se oba parametra postepeno povećavala od početka održavanja tonične kontrakcije. Upadljiva je, takođe, i potpuna disocijacija između promena MEP i PT tokom zamora, što je u oštroj suprotnosti sa nalazom kod zdravih ispitanika gde su promene ovih parametara pratile identičan obrazac. Zaključak. Rezultati kod bolesnika sa PB ukazuju na postojanje oštećenja i/ili kompenzatornih promena mehanizmima odgovornih za adaptaciju voljne pobude i usklađivanja kortikalne eksitacije i inhibicije, koji se manifestuju tokom mišićnog zamora i u drugim zahtevnim motornim zadacima.

Objective Motor learning is the core cognitive function in neurorehabilitation and in various other skill-training activities (e.g. sport, music). Therefore, there is an increasing interest in the use of transcranial magnetic stimulation (TMS) methods for its enhancement. However, although usually assumed, a potential placebo effect of TMS methods on motor learning has never been systematically investigated. Methods Improvement of performance on the Purdue Pegboard Task over three test-blocks (T0, T1, and T2), separated by >20 min, was used to evaluate motor learning. In Experiment-1, two groups of 10 participants each were compared: one group immediately before T1 received a sham intermittent theta burst stimulation procedure (P-iTBS group), while another did not have any intervention at all (control – CON group). In Experiment-2, a third group of participants (six subjects) who received sham high-frequency repetitive TMS procedure before T1 (P-rTMS group) was compared with P-iTBS group. Results All three groups showed significant learning over time, but without any difference between them, either in Experiment-1 between P-iTBS and CON, or in Experiment-2 between P-rTMS and P-iTBS. Conclusion The results suggest lack of any placebo effect of TMS on motor learning. Significance The results may help in designing further TMS–motor learning studies and in interpreting their results.

The aim of this study was to examine whether the changes of the motor cortex excitability induced by muscle fatigue could be affected by prior or subsequent intervention protocol supposed to induce opposing excitability changes. For this purpose we used paired associative stimulation (PAS) method, where peripheral nerve stimuli were associated with transcranial magnetic stimulation (TMS) of the motor cortex at a fixed interstimulus interval of 25 ms. The PAS protocol used is known to produce a long lasting, long-term potentiation (LTP) like change of cortical plasticity manifested by significant increase in motor evoked potentials (MEPs) amplitude. In this study, we confirmed significant MEP size reduction following fatigue, which had been already reported in the literature. When PAS was applied either immediately before or after muscle fatigue protocol, the excitability changes were largely occluded and MEP sizes remained close to baseline levels. However, in spite of the effects on cortical excitability, conditioning with PAS did not cause any change in target fatigue measure, the endurance point, which remained the same as when fatiguing protocol was applied alone. The present results demonstrate that fatigue-related changes in cortical excitability can be modulated by either prior or subsequent excitability promoting activity. They also suggest that muscle fatigue associated changes in motor cortical excitability probably represent non-specific activity-related plasticity, rather than a direct expression of the so-called central fatigue.

We have studied the stimulated discharge dynamics of fusimotor neurons by applying the wavelet transform technique and by adopting that the neuronal discharge dynamics is manifested by the random time series of interspike intervals. We found two different power-law type behaviors along interspike intervals (ISI) time scale (which implies existence of two different types of neuronal noise), which are separated by a crossover region. Our results reveal that complex neuronal dynamics, in the presence of external stimulation, is manifested with long-range correlated noise in the region before the crossover, on the ISI time scale.

We have studied the discharge dynamics of dorsal horn neurons by applying the detrended fluctuation analysis and the wavelet transform technique. We have adopted that the neuronal discharge dynamics is manifested by the random time series of interspike intervals. In all cases studied, we found two different power-law type behaviors across interspike intervals enumeration scale, that are separated by crossover regions (which implies existence of two different types of neuronal noise). Our results reveal that complex neuronal dynamics may change in the presence of external stimulation, manifested by changing of the noise characteristics that appear before crossover.

Previously we showed that neuropeptide Y (NPY), a sympathetic vasoconstrictor neurotransmitter, stimulates endothelial cell migration, proliferation, and differentiation in vitro. Here, we report on NPY's actions, receptors, and mediators in ischemic angiogenesis. In rats, hindlimb ischemia stimulates sympathetic NPY release (attenuated by lumbar sympathectomy) and upregulates NPY-Y2 (Y2) receptor and a peptidase forming Y2/Y5-selective agonist. Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance. NPY-mediated ischemic angiogenesis is not prevented by a selective Y1 receptor antagonist but is reduced in Y2(-/-) mice. Nonischemic muscle vascularity is also lower in Y2(-/-) mice, whereas it is increased in NPY-overexpressing rats compared with their WT controls. Ex vivo, NPY-induced aortic sprouting is markedly reduced in Y2(-/-) aortas and spontaneous sprouting is severely impaired in NPY(-/-) mice. NPY-mediated aortic sprouting, but not cell migration/proliferation, is blocked by an antifetal liver kinase 1 antibody and abolished in mice null for eNOS. Thus, NPY mediates neurogenic ischemic angiogenesis at physiological concentrations by activating Y2/Y5 receptors and eNOS, in part due to release of VEGF. NPY's effectiveness in revascularization and restoring function of ischemic tissue suggests its therapeutic potential in ischemic conditions.

We have studied the discharge dynamics of dorsal horn neurons (DHN) by applying the detrended fluctuation analysis (DFA) and the wavelet transform (WT) technique. We have adopted that discharge dynamics is manifested by the random time series of the interspike intervals (ISI), that is, by intervals between two consecutive neuronal electrical activities. In all cases studied, we found two different power-law type behaviors across ISI enumeration scale, that are separated by a crossover region. Our results reveal that complex neuronal dynamics may change in the presence of external stimulation, which is manifested by changing the noise characteristics that appear before the crossover region (the noise after the crossover region is of the 1/ f type).

Previous reports showed that sympathetic stimulation affects the activity of muscle spindle afferents (MSAs). The aim of the present work is to study the characteristics of sympathetic modulation of MSA response to stretch: (i) on the dynamic and static components of the stretch response, and (ii) on group Ia and II MSAs to evaluate potentially different effects. In anaesthetised rabbits, the peripheral stump of the cervical sympathetic nerve (CSN) was stimulated at 10 impulses s(-1) for 45-90 s. The responses of single MSAs to trapezoidal displacement of the mandible were recorded from the mesencephalic trigeminal nucleus. The following characteristic parameters were determined from averaged trapezoidal responses: initial frequency (IF), peak frequency at the end of the ramp (PF), and static index (SI). From these, other parameters were derived: dynamic index (DI = PF - SI), dynamic difference (DD = PF - IF) and static difference (SD = SI - IF). The effects of CSN stimulation were also evaluated during changes in the state of intrafusal muscle fibre contraction induced by succinylcholine and curare. In a population of 124 MSAs, 106 units (85.4 %) were affected by sympathetic stimulation. In general, while changes in resting discharge varied among different units (Ia vs. II) and experimental conditions (curarised vs. non-curarised), ranging from enhancement to strong depression of firing, the amplitude of the response to muscle stretches consistently decreased. This was confirmed and detailed in a quantitative analysis performed on 49 muscle spindle afferents. In both the non-curarised (23 units) and curarised (26 units) condition, stimulation of the CSN reduced the response amplitude in terms of DD and SD, but hardly affected DI. The effects were equally present in both Ia and II units; they were shown to be independent from gamma drive and intrafusal muscle tone and not secondary to muscle hypoxia. Sympathetic action on the resting discharge (IF) was less consistent. In the non-curarised condition, IF decreased in most Ia units, while in II units decreases and increases occurred equally often. In the curarised condition, IF in group II units mostly increased. The results have important functional implications on the control of motor function in a state of 'high' sympathetic activity, like excessive stress, as well as in certain pathological conditions such as sympathetically maintained pain.

We study the interspike intervals (ISI) time series of the spontaneous fusimotor neuron activity by applying the wavelet transform analysis and confirm the existence of the white noise characteristics of the ISI time series. This means that the neuron activity may serve as the requisite noisy component for occurrence of the stochastic resonance mechanism in the neural coordination of muscle spindles. Besides, we apply the multifractal formalism adapted for the wavelet transform time series analysis. Thus, we have established the multifractality of the ISI data and achieved an additional insight into fusimotor discharge dynamics.

We have tested the hypothesis that agonist and antagonist muscle fatigue could affect the final position of rapid, discrete movements. Six subjects performed consecutive elbow flexion and extension movements between two targets, with their eyes closed prior to, and after fatiguing the elbow extensor muscles. The results demonstrate that elbow extension movements performed in the post-test period systematically undershot the final position as compared to pre-test movements. However, attainment of the aimed final position in elbow flexion movements was unaffected by fatiguing of the extensor muscles. Undershoot of the final position obtained in extension movements was associated with agonist muscle fatigue, a result that was expected from the point of view of current motor control theories, and that could be explained by a reduced ability of the shortening muscle to exert force. On the other hand, the absence of the expected overshoot of the final position when the antagonist is fatigued, indicates the involvement of various reflex and/or central mechanisms operating around the stretched muscle that could contribute to returning the limb to the standard final position after a brief prominent overshoot.

Responses of fusimotor neurons to lengthening vs isometric contractions have been studied in decerebrate cats. Spike discharges of fusimotor neurons to the medial gastrocnemius muscle were recorded From this muscle nerve filament during sequences of contractions and/or stretches of the lateral gastrocnemius and soleus muscles. The sequences lasted for 250-450 s (duty cycle 4:2 s). Isometric contractions were elicited by electrical stimulation (40 Hz, 1.3 times motor threshold) of the muscle nerves. Lengthening contractions were elicited in the same way while the muscles were stretched by 4 mm at a velocity of 1 mm/s. Of 25 fusimotor neurons studied, 23 responded to muscle contractions with an increase in firing rate, subsiding towards the end of the sequence. The increase was either modulated with each subsequent contraction or smooth throughout the sequence. Approximately 64% of fusimotor neurons, responding to muscle contractions, responded in a similar way to the sequences of muscle stretches, applied alone. Responses to sequences of the lengthening contractions were significantly larger, on average, than those to the isometric ones, but smaller than the sum of the responses to the contractions and stretches applied separately. On the other hand, they were also larger in fusimotor units, showing no overt responses to muscle stretches alone.

Interaction of cutaneous and small-diameter, primarily fatigue-induced, muscle afferent inputs on fusimotor neurons has been studied in decerebrate cats. Spike discharges of fusimotor neurons to medial gastrocnemius were recorded from filaments dissected free from this muscle nerve. Non-noxious mechanical stimuli (10 Hz, 2 mm vibration) were applied to the skin area on the lateral side of the heel, innervated by sural nerve, during long-lasting (250 s) fatiguing contraction of lateral gastrocnemius and soleus muscles, elicited by electrical stimulation (40 Hz, 1.3 x motor threshold) of the muscle nerves. In 15 units (58%) the pattern of responses to muscle contraction and/or fatigue (initial transient, and late long-lasting increase in firing rate, respectively) was preserved in the presence of skin vibration which, by itself, provoked either a slight increase or no changes in fusimotor discharge rate. Pattern of the response to skin vibration prevailed in the presence of muscle contraction and fatigue only if the vibration by itself induced marked increase in fusimotor discharge rate (three units). In the remaining eight units the responses to both stimuli applied simultaneously were dissimilar in pattern to the response to either stimulus applied alone: the initial, tension-related, increase in firing rate was prolonged, while the late, fatigue-induced one was attenuated and its post-contraction part almost abolished. Possible mechanisms and functional role of interaction between cutaneous and muscle afferent inflows are discussed.

Changes in silent period (SP) duration following transcranial magnetic stimulation (TMS) set at 20% above the motor threshold were studied in six subjects suffering from writer's cramp, while performing dystonic movement and during voluntary isometric contraction of the muscles mostly involved in the dystonic movement. Dependency of SP duration on the intensity of preceding muscle contraction was compared on both affected and healthy side. In all subjects SP duration during dystonic contraction was shorter than during voluntary contraction of the similar strength performed with the same hand. Also, in five subjects, SP duration during dystonic contraction was shorter than during voluntary contraction of the similar strength performed with the healthy hand. In addition, the SP duration on the affected side was negatively associated with the intensity of the preceding contraction (i.e. the stronger contraction the shorter SP), while on the healthy side it was not the case. It is concluded that central inhibitory mechanisms are abnormal in writer's cramp.

The aim of this study was to investigate the effects of agonist and antagonist muscle fatigue on the performance of rapid, self-terminating movements. Six subjects performed rapid, consecutive elbow flexion and extension movements between two targets prior to and after fatiguing either the elbow flexor or elbow extensor muscles. The experiments demonstrated consistent results. Agonist muscle fatigue was associated with a decrease in peak velocity and peak deceleration, while a decrease in peak acceleration was particularly prominent. Antagonist muscle fatigue, however, was associated with a decrease in peak deceleration, while a decrease in both the peak velocity and peak acceleration was modest and, in some tests, non-significant. The relative acceleration time (i.e. acceleration time as a proportion of the total movement time) increased when agonists were fatigued, but decreased when antagonists were fatigued. Taken together, these results emphasize the mechanical roles of the agonist and antagonist muscles; namely, the fatigue of each muscle group particularly affected the movement phase in which that group accelerated a limb, while changes of the movement kinematics pattern provided more time for action of the fatigued muscles. In addition, the results presented suggest that agonist muscle fatigue affects movement velocity more than antagonist muscle fatigue, even in movements that demonstrate prominently both mechanical and myoelectric activity of the antagonist muscles, such as rapid, self-terminating movements.