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While prefrontal cortex dysfunction has been implicated in high food cravings, other cortical regions, like the parietal cortex, are potentially also involved in regulating craving. This study explored the effects of stimulating the inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) on food craving state and trait. Transcranial direct current stimulation (tDCS) was administered at 1.5 mA for 5 consecutive days. Participants received 20 min of IPL, DLPFC, or sham stimulation (SHAM) each day which consisted of two rounds of 10-min stimulation, divided by a 10-min mindfulness task break. In addition, we studied inhibition and subjective psychological aspects like body image and self-esteem state and trait. To decompose immediate and cumulative effects, we measured the following on days 1 and 5: inhibition through the Go/No-go task; and food craving, self-esteem, and body appreciation through a battery of questionnaires. We found that false alarm errors decreased in the participants receiving active stimulation in the DLPFC (DLPFC-group). In contrast, false alarm errors increased in participants receiving active stimulation in the IPL (IPL-group). At the same time, no change was found in the participants receiving SHAM (SHAM-group). There was a trending reduction in craving trait in all groups. Momentary craving was decreased in the DLPFC-group and increased in IPL-group, yet a statistical difference was not reached. According to time and baseline, self-esteem and body perception improved in the IPL-group. Furthermore, self-esteem trait significantly improved over time in the DLPFC-group and IPL-group. These preliminary results indicate that tDCS modulates inhibition in frontoparietal areas with opposite effects, enhancing it in DLPFC and impairing it in IPL. Moreover, craving is moderately linked to inhibition, self-esteem, and body appreciation which seem not to be affected by neuromodulation but may rely instead on broader regions as more complex constructs. Finally, the fractionated protocol can effectively influence inhibition with milder effects on other constructs.

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.

Deep brain stimulation applied at high frequency (HFS) to the subthalamic nucleus (STN) is used to ameliorate the symptoms of Parkinson's disease. The mechanism by which this is achieved remains controversial. In particular, it is uncertain whether HFS has a suppressive or excitatory action locally within the STN. Brief exposure of rats to ether anesthesia evokes pathological burst firing and associated expression of the immediate early gene c-Fos in STN neurons. We used this ether model of STN activation to test the effect of a range of HFS parameters on c-Fos expression evoked by the anesthetic. The elevated baseline of c-Fos expression afforded the possibility of detecting further excitatory, or suppressive effects of STN HFS. Four HFS protocols were examined; 130, 200 and 260 Hz with 60 µs, and 130 Hz with 90 µs pulse width (HFS intensity:150-300 µA). All HFS protocols were applied for 20 min while the animals were exposed to ether. Ether-evoked expression of c-Fos immunoreactivity was suppressed by HFS at 200 and 260 Hz with a pulse width of 60 µs, and by 130 Hz when the pulse width was increased to 90 µs. HFS at 130 Hz with the 60 µs pulse width had no significant effect and HFS alone caused negligible c-Fos expression in the STN. These findings suggest that HFS of the STN causes significant suppression of evoked neuronal activity. It remains to be determined whether this locally suppressive property of HFS is associated with the efficacy of STN deep brain stimulation to relieve the symptoms of Parkinson's disease.

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.

We have investigated the effects of changing the coil-to-skull distance on the motor-evoked responses (MEP) induced with two different magnetic stimulator coils (80 mm round and figure-of-eight coil) at rest and during voluntary muscle contraction. The changes in MEP latency, amplitude and silent period (SP) duration induced by stimulation directly upon the skull, and 1 cm away from the skull were analyzed by computing the probability density distribution (PDD) for the responses obtained from all subjects. This measure corresponds to the finite probability that the event occurs within a given area. Overall, the results were consistent with a distance-induced decrease in magnetic field strength. However, the increase in coil-to-skull distance induced a higher probability of longer latencies in active muscle when stimulating with either coil. Also, stimulating at a distance with the figure-of-eight coil increased the probability of a longer SP duration. The stimulation strength at the two distances was comparable because it was set based on the motor threshold obtained for each distance. Therefore, our results are not entirely compatible with the established exponential drop in magnetic field with increasing distance. Rather, they suggest that a more complex set of interactions occurs in the cortex. The results imply that distinct patterns of cortical network activation may exist related to the distance-induced alterations when the coil is moved away from the skull. Further studies are required to elucidate the precise nature of the distance-related interactions of the magnetic field with the cortex.

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.

The objective of this preliminary study was to quantify changes in complexity of EEG using fractal dimension (FD) alongside linear methods of spectral power, event-related spectral perturbations, coherence, and source localization of EEG generators for theta (4–7 Hz), alpha (8–12 Hz), and beta (13–23 Hz) frequency bands due to a memory load effect in an auditory–verbal short-term memory (AVSTM) task for words. We examined 20 healthy individuals using the Sternberg’s paradigm with increasing memory load (three, five, and seven words). The stimuli were four-letter words. Artifact-free 5-s EEG segments during retention period were analyzed. The most significant finding was the increase in FD with the increase in memory load in temporal regions T3 and T4, and in parietal region Pz, while decrease in FD with increase in memory load was registered in frontal midline region Fz. Results point to increase in frontal midline (Fz) theta spectral power, decrease in alpha spectral power in parietal region—Pz, and increase in beta spectral power in T3 and T4 region with increase in memory load. Decrease in theta coherence within right hemisphere due to memory load was obtained. Alpha coherence increased in posterior regions with anterior decrease. Beta coherence increased in fronto–temporal regions. Source localization delineated theta activity increase in frontal midline region, alpha decrease in superior parietal region, and beta increase in superior temporal gyrus with increase in memory load. In conclusion, FD as a nonlinear measure may serve as a sensitive index for quantifying dynamical changes in EEG signals during AVSTM tasks.

Deep-brain stimulation at high frequencies (HFS) directed to the subthalamic nucleus (STN) is used increasingly to treat patients with Parkinson's disease. However, the mechanism of action by which HFS of the STN achieves its therapeutic effects remains unresolved. Insofar as lesions of the STN have similar therapeutic benefit, a favored hypothesis is that HFS acts by suppressing neural activity in the STN. The purpose of the present study was to exploit prior observations that exposure to ether anesthesia in a rodent model evokes c-fos expression (a marker of neural activation) in the STN and its efferent structures, the globus pallidus, entopeduncular nucleus and substantia nigra. We showed first that exposure to ether induced a profound oscillatory pattern of neural activity in the STN and SNr, which could explain the marked induction of c-fos immunoreactivity in these structures. Secondly, inhibition of the STN by local injections of the GABA agonist, muscimol, suppressed ether-evoked c-fos expression in all target structures. This showed that excitation of target structures in the ether model originated, at least in part, from the STN. Thirdly, and contrary to expectation, HFS of the STN increased further the expression of c-fos in the STN target structures of animals treated with ether. Finally, we demonstrated, in the absence of ether treatment, that HFS and chemical stimulation of the STN with local injections of kainic acid both induced c-fos expression in the globus pallidus, entopeduncular nucleus and substantia nigra. Together these results suggest that the principal action of STN stimulation at high frequencies is to excite rather than inhibit its efferent targets. Given that Parkinsonism has been associated with increased levels of inhibitory output activity from the basal ganglia, it is unlikely that excitation of output structures revealed in this study provides a basis for deep-brain stimulation's therapeutic action.

The distribution of Fos-immunoreactive (Fos-ir) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-reactive neurons in the rat lumbar spinal cord was examined following muscle fatigue caused by intermittent high-rate (100 s(-1)) electrical stimulation of the triceps surae muscle or the ventral root L5 (VRL5) for 30 min. Following both types of stimulation, the fatigue-related c-fos gene expression was more extensive in the L2-L5 segments on the stimulated side, and the majority of Fos-ir neurons were concentrated in the dorsal horn. After direct muscle stimulation, the highest number of Fos-ir neurons were detected in two regions: layer 5, and superficial layers (1 and 2(o)), although many labeled cells were also found in layers 3, 4, 6, and 7. In response to VRL5 stimulation, the maximal density of Fos-ir neurons was detected in the middle and lateral parts of layers 1 and 2(o), the zone of termination of high-threshold muscle afferents(.) Statistically significant prevalence of Fos-ir cell number was also found in layers 5 and 7 on the stimulated side. A few Fos-ir neurons were detected in the ventral horn (layer 8 and area 10) on both sides. The lamellar distribution of NADPH-d-reactive neurons was similar over all experimental groups of animals. In the L3-L6 segments, such reactive cells were arranged in two distinct regions: dorsal horn (layers 2(i), 3, and 5) and area 10; in the L1 and L2 segments, an additional cluster of NADPH-d positive cells was found in the intermediolateral cell column (IML). Double-labeled cells were not detected. We suggest that c-fos expression in response to muscle fatigue reveals activity of functionally different types of spinal neurons which could operate together with NOS-containing cells in pre-motoneuronal networks to modulate the motoneuron output.

Effects of low- and high-frequency fatigue were studied on muscle dynamics in isometric conditions of the cat gastrocnemius. Fatiguing sessions consisted of 25-28 repetitions of the standard tests that included an 18-s interval of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions. The rate of the continuous part was changed in accordance with a symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10s(-1); between these phases, each lasting for 4s, the rate changed linearly within a 2-s interval. The following modes of muscle activation were applied: (i) stimulation of single filaments constituting approximately one-fifth to one-seventh of the total cross-section of the L(7) and S(1) ventral roots; (ii) the distributed stimulation of five similar filaments; and (iii) direct stimulation of muscle through bipolar wire electrodes. A relative drop in tension, the fatigue index, expressed as the ratio at the end of a fatigue session over its value at the beginning of the test, was used to quantify fatigue effects. The fatigue indices during low-rate stimulation were 0.56+/-0.03 (mean+/-S.D.) at the first phase and 0. 64+/-0.02 at the third phase, while during high-rate stimulation this parameter was only 0.32+/-0.02. The high-rate stimulation noticeably increased the mean tension during low-rate stimulation; the ratio between the reactions at the third and the first phases could be as much as two to three times greater than that at the beginning of the fatigue session. It was demonstrated that the potentiation was connected with after-effects of the rate-tension hysteresis. The hysteresis decreased with fatigue, the fatigue index for the rate-tension loop areas ranging from 0.39 to 0.52 (0.45+/-0. 05, mean+/-S.D.). The fatigue processes developed more quickly and intensively in the previously fatigued muscles: the obtained fatigue indices were 0.73+/-0.05 and 0.70+/-0.10 at the first and third phases, and 0.62+/-0.06 (mean+/-S.D.) at the second phase of stimulation, respectively. In the cases of distributed and direct stimulation applied to muscles in a fresh state, fatigue dynamics did not differ significantly from those observed during single-filament stimulation. In experiments with distributed stimulation applied to previously fatigued muscles, a powerful depression of the high-rate components was registered in several cases, which seemed to be connected with depressive effects at the level of nerve-muscle synaptic transmission. The effects of low- and high-frequency fatigue were studied in isometric conditions of muscle contraction. In addition to the well-known differentiation between low- and high-frequency fatigue effects, the complex pattern of efferent stimulation used allowed us to identify additional fatigue-related changes in the rate-tension hysteresis. This hysteresis seems to be one of the possible mechanisms directed to compensate for low-frequency fatigue in the muscle contraction.

The aim of this study was to examine whether single-pulse transcranial magnetic stimulation (spTMS) affects the pattern of corticospinal activity once voluntary drive has been restored after spTMS-induced EMG silence. We used fractal dimension (FD) to explore the ‘complexity’ of the electromyography (EMG) signal, and median frequency of the spectra (MDF) to examine changes in EMG spectral characteristics. FD and MDF of the raw EMG epochs immediately before were compared with those obtained from epochs after the EMG silence. Changes in FD and MDF after spTMS were examined with three levels of muscle contraction corresponding to weak (20–40 %), moderate (40–60 %) and strong (60–80 % of maximal voluntary contraction) and three intensities of stimulation set at 10, 20 and 30 % above the resting motor threshold. FD was calculated using the Higuchi fractal dimension algorithm. Finally, to discern the origin of FD changes between the CNS and muscle, we compared the effects of spTMS with the effects of peripheral nerve stimulation (PNS) on FD and MDF. The results show that spTMS induced significant decrease in both FD and MDF of EMG signal after stimulation. PNS did not have any significant effects on FD nor MDF. Changes in TMS intensity did not have any significant effect on FD or MDF after stimulation nor had the strength of muscle contraction. However, increase in contraction strength decreased FD before stimulation but only between weak and moderate contraction. The results suggest that the effects of spTMS on corticospinal activity, underlying voluntary motor output, outlast the TMS stimulus. It appears that the complexity of the EMG signal is reduced after spTMS, suggesting that TMS alters the dynamics of the ongoing corticospinal activity most likely temporarily synchronizing the neural network activity. Further studies are needed to confirm whether observed changes after TMS occur at the cortical level.

Changes in discharge rate of fusimotor neurones to pretibial flexor muscles were recorded during and after long-lasting fatiguing isometric and/or isotonic contractions of triceps surae in decerebrate cats. The contractions were elicited by electrical stimulation of the nerves to triceps. Fusimotor spikes were recorded from nerve filaments dissected free from the peroneal nerve. Responses of the fusimotor neurones were diverse. In isometric regime, 22 out of 40 units recorded exhibited an initial increase at the onset of muscle contraction, different in amplitude and duration among the units. In seven of these units an additional brisk burst of spike discharges, of different duration, occurred at the end of the contraction. In 15 fusimotor neurones (14 units with the initial response and an additional unit without it) a slow increase in discharge rate developed, starting during the contraction and outlasting it. In another eleven units the initial response was a decrease in discharge rate, lasting in six of them throughout the contraction. Another six units exhibited a sustained increase in discharge rate throughout the contraction, as well as, at a lower level, but still above the spontaneous one, thereafter. Similar patterns of changes in discharge rate, recorded in 31 of the units, were encountered during isotonic triceps contractions. It should be mentioned that many (about 20) additional silent neurones, responding to manipulating the skin and paw and/or stroking the fur, but not to triceps contractions were encountered. The majority of changes in discharge rate of fusimotor neurones to pretibial flexors differed markedly from those found previously in fusimotor neurones to triceps and hamstring muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in discharge rate of 21 fusimotor neurons to medial gastrocnemius muscle during long-lasting fatiguing contractions of lateral gastronemius and soleus muscles were recorded in decerebrate cats with innervation of the same hindlimb preserved. Both the spontaneous activity and reflex responses of fusimotor neurons differed from those found previously in preparations with denervated hindlimb. Higher proportion of units fired at rest at rates above 20 impulses/s, the initial increase in discharge rate at the onset of muscle contraction was markedly prolonged, lasting in the majority of units throughout the muscle contraction, while the late increase in discharge rate developing with muscle fatigue was either absent or short-lasting. It is suggested that the increase in spontaneous firing rate occurs in dynamic fusimotor neurons being supported by afferent inflow from secondary muscle spindle endings from non-contracting muscles, the enhancement of the early responses to be primarily due to recurrent disinhibition and the differences in changes of early and late responses to reflect their partly different origin. The possibility is raised that the late reflex responses are lacking more often in static than in dynamic fusimotor neurons. From the functional point of view the differences in fusimotor reflex responses in innervated versus denervated hindlimb may indicate their susceptibility to modifications by changes in afferent inflow according, supposedly, to the current demands of motor control of the active and/or fatigued muscle.

It has been well established that repetitive motor performance and skill learning alter the functional organization of human corticomotoneuronal system. Over the past decade, transcranial magnetic stimulation (TMS) has helped to demonstrate motor practice and learning-related changes in corticomotoneuronal excitability and representational plasticity. It has also provided some insights into the mechanisms underlying such plasticity. TMS-derived indices show that motor practice, skill acquisition and learning are associated with an increase in cortical excitability and a modulation of intracortical inhibition partly related to the amount of GABA-related inhibition. It has been suggested that these changes in excitability might be related to learning and motor memory formation in the motor cortex. However, it has proved difficult to relate different aspects of TMS-derived representational plasticity with specific behavioral outcomes. A better understanding of the relationship between TMS measurements of practice-related cortical plasticity and underlying mechanisms, in the context of associated changes in behavior, will facilitate the development of techniques and protocols that will allow predictable modulation of cortical plasticity in health and disease.

Recently, it has been shown that the subthalamic nucleus (STN) has anticonvulsant effects on epileptic seizures originating from the forebrain. The aim of the present study was to determine whether the anticonvulsant properties of the STN extend to the suppression of tonic seizures originating from the brainstem elicited by electroshock in rats. Three different procedures were used to manipulate activity in the STN and in each case the duration of tonic hindlimb extension elicited by electroshock was used as a measure of seizure-severity. Under general anesthesia, two groups of rats received chronic implants of either bilateral stainless steel guide cannulae or bilateral bipolar stimulating electrodes stereotaxically implanted and aimed at the STN. After 3 days of recovery, each rat in the first group was tested with electroshock on three consecutive days after having received 220 nl bilateral microinjections into the STN of either 200 or 400 pmol of muscimol (a GABA agonist) dissolved in saline or the same volume of normal saline. In the second group the electroshock test was conducted, again on three consecutive days, immediately following high frequency electrical stimulation (HFS) of the STN at 130 or 260 Hz or a no current control condition. In the third group, rats were tested with electroshock before and after bilateral excitotoxic lesions of the STN with either kainic or ibotenic acids. None of these manipulations produced significant suppression of the tonic hind limb extension elicited by electroshock compared with the relevant control conditions. This suggests that, within the limitations of the current procedures, the anticonvulsant properties of the STN appear to be ineffective against tonic seizures originating in the brainstem.

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.

The concept of fatigue refers to a class of acute effects that can impair motor performance, and not to a single mechanism. A great deal is known about the peripheral mechanisms underlying the process of fatigue, but our knowledge of the roles of the central structures in that process is still very limited. During fatigue, it has been shown that peripheral apparatus is capable of generating adequate force while central structures become insufficient/sub-optimal in driving them. This is known as central fatigue, and it can vary between muscles and different tasks. Fatigue induced by submaximal isometric contraction may have a greater central component than fatigue induced by prolonged maximal efforts. We studied the changes in regional cerebral blood flow (rCBF) of brain structures after sustained isometric muscle contractions of different submaximal force levels and of different durations, and compared them with the conditions observed when the sustained muscle contraction becomes fatiguing. Changes in cortical activity, as indicated by changes in rCBF, were measured using positron emission tomography (PET). Twelve subjects were studied under four conditions: (1) rest condition; (2) contraction of the m. biceps brachii at 30% of MVC, sustained for 60 s; (3) contraction at 30% of MVC, sustained for 120 s, and; (4) contraction at 50% of MVC, sustained for 120 s. The level of rCBF in the activated cortical areas gradually increased with the level and duration of muscle contraction. The fatiguing condition was associated with predominantly contralateral activation of the primary motor (MI) and the primary and secondary somatosensory areas (SI and SII), the somatosensory association area (SAA), and the temporal areas AA and AI. The supplementary motor area (SMA) and the cingula were activated bilaterally. The results show increased cortical activation, confirming that increased effort aimed at maintaining force in muscle fatigue is associated with increased activation of cortical neurons. At the same time, the activation spread to several cortical areas and probably reflects changes in both excitatory and inhibitory cortical circuits. It is suggested that further studies aimed at controlling afferent input from the muscle during fatigue may allow a more precise examination of the roles of each particular region involved in the processing of muscle fatigue.

The present work was designed to check for the possibility of interactions between mechanical innocuous and chemically induced noxious muscle afferent inputs on discharge behavior of nociceptive superficial dorsal horn neurons (SDHNs) of the spinal cord in decerebrated cats. The innocuous and noxious stimuli were applied separately and in combination, so that the effects of the innocuous stimulus on nociceptive processing could be evaluated. The innocuous stimulus consisted of ramp-and-hold stretches of the gastrocnemius muscles, whereas the noxious stimulus consisted of i.a. injections of bradykinin (BK; 0.5-1 ml, 50 microg/ml) into the arterial circulation of same muscles. Only neurons up to approximately 1mm depth and those that responded to noxious pinch of the gastrocnemius muscles were selected for further analysis. The activity of 16 dorsal horn neurons was recorded extracellularly with high-impedance glass microelectrodes, out of which seven responded to stretch, while 12 neurons responded to bradykinin injections. The bradykinin injections induced three types of responses: excitatory, inhibitory and mixed. The majority of the neurons that showed excitatory and mixed responses to bradykinin were also influenced by stretches applied directly after the bradykinin injection. In these neurons, the stretch usually counteracted the bradykinin-induced response, i.e. shortening and reducing bradykinin-induced excitation and re-exciting the cells after bradykinin-induced inhibition. The mechanism of the stretch modulation is proposed to reside in a segmental spinal control of the nociceptive transmission.

A positron emission tomography imaging study was performed on 16 healthy volunteers to reveal changes in cortical activation during acute muscle pain induced by intra-muscular injection of hypertonic saline into the left triceps brachii muscle. Changes in regional cerebral blood flow (rCBF) were measured with the use of [(15)O] labelled water during 'Rest1', 'Needle' (insertion of a needle without injection), 'Rest2' and 'Pain' conditions. Differences in rCBF were found in the comparison of Pain and Needle, and Pain and Rest2 conditions, revealing activation of the contralateral insula and putamen. The results are discussed with respect to possible differences in brain processing of muscle and cutaneous noxious inputs.

It has been shown that the primary and secondary somatosensory cortex, as well as the supplementary motor area (SMA), are involved in central processing of proprioceptive signals during passive and active arm movements. However, it is not clear whether different cortical areas are involved in processing of different proprioceptive inputs (skin, joint, muscle receptors), what their relative contributions might be, where kinesthetic sensations are formed within the CNS, and how they interact when the full peripheral proprioceptive machinery acts. In this study we investigated the representation of the brain structures involved in the perception of passive limb movement and illusory movement generated by muscle tendon vibration. Changes in cortical activity as indicated by changes in regional cerebral blood flow (rCBF) were measured using positron emission tomography (PET). Twelve subjects were studied under four conditions: (1) passive flexion-extension movement (PM) of the left forearm; (2) induced illusions of movements (VI) similar to the real PM, induced by alternating vibration of biceps and triceps tendons (70-80 Hz) at the elbow; (3) alternating vibration of biceps and triceps tendons (with 20-50 Hz) without induced kinesthetic illusions (VN); and (4) rest condition (RE). The results show different patterns of cortex activation. In general, the activation during passive movement was higher in comparison with both kinds of vibration, and activation during vibrations with induced illusions of movement was more prominent than during vibrations without induced illusions. When the PM condition was contrasted with the other conditions we found the following areas of activation -- the primary motor (MI) and somatosensory area (SI), the SMA and the supplementary somatosensory area (SSA). In conditions where passive movements and illusory movements were contrasted with rest, some temporal areas, namely primary and associative auditory cortex, were activated, as well as secondary somatosensory cortex (SII). Our data show that different proprioceptive inputs, which induce sensation of movement, are associated with differently located activation patterns in the SI/MI and SMA areas of the cortex. In general, the comparison of activation intensities under different functional conditions indicates the involvement of SII in stimulus perception generation and of the SI/MI and SMA areas in the processing of proprioceptive input. Activation of the primary and secondary auditory cortex might reflect the interaction between somatosensory and auditory systems in movement sense generation. SSA might also be involved in movement sense generation and/or maintenance.

Intramuscular injection of hypertonic saline (HS) is a procedure widely adopted to experimentally induce deep muscle pain in humans. This study was undertaken to test whether intramuscular injections of HS (5%) influence the activity of primary and secondary muscle spindle afferents (MSAs) from homonymous as well as heteronymous muscles. The experiments were performed on six cats anaesthetised with alpha-chloralose. Usually responses of two to nine MSAs from gastrocnemius medialis (GM) and/or gastrocnemius lateralis (GL) muscles were recorded simultaneously, while HS was injected either into the receptor-bearing muscle (homonymous responses) or into a close (GM/GL) or remote synergistic muscle (posterior biceps, PB, heteronymous responses). The mean rate of discharge and the depth of modulation of the MSA responses to sinusoidal stretching of the receptor-bearing muscle were calculated. Out of the 42 afferents tested (7 from GM and 35 from GL), 38 (90%) exhibited statistically significant responses to injections of HS into homonymous and/or heteronymous muscles. With injections into the homonymous muscle, the average maximal increase in mean rate of discharge was 74% and the average decrease in depth of modulation was --18%. The mean duration of the effects was 2.1 min. The corresponding values for heteronymous injections into a close synergist were 87%, -17% and 2.1 min (GM or GL), and for injections into PB 52%, -11%, and 1.8 min. The majority of the responses (72%) were compatible with reflex action on static fusimotor neurones, whereas 20% of the responses could be attributed to mixed static and dynamic fusimotor action. The remaining 8% of the responses were attributed to inhibition of fusimotor activity. There were no statistically significant differences between the responses following injections into homonymous or heteronymous muscles. Injections of Tyrode's solution did not induce any significant alterations in MSA responses, implying that they were not induced by direct and/or injury effects of the injections. HS-related changes in MSA activity were completely abolished after the nerves to corresponding muscles were cut, confirming the reflex nature of the effects. Thus, intramuscular injections of HS induce reflex changes in MSA activity from both homonymous and heteronymous muscles, most likely via fusimotor reflexes. Predominantly static fusimotor neurones were activated. The possible role of the fusimotor-muscle spindle system in altered motor control during experimentally induced muscle pain is discussed.

Changes in the compound muscle action potentials of cat gastrocnemius muscle were studied during low- and high-frequency fatigue. Fatiguing session consisted of 25–28 repetitions of the standard single fatigue tests (1.5 min interval between the tests) that included the part of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions in the muscle. The rate of the continuous part was changed in accordance with symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10 s −1 ; between these phases of 4 s duration the rate changed linearly within a 2 s interval. During fatigue relative changes in compound muscle action potential waves were usually smaller than changes in tension. Within the same fatigue procedure applied to a fresh muscle, the drop in tension was as much as 35% for high-rate stimulation and 59–71% for low-rate stimulation, whereas the decrease of the peak-to-peak compound muscle action potential waves amplitudes did not exceed 10–20%. Compound muscle action potential waves underwent the most pronounced depression during high-rate stimulation, the decrease proceeding during the following phase of low-rate stimulation. The tension changes during long-lasting activation were different for low- and high-frequency fatigue, with more pronounced depression during low-rate stimulation. As a rule, compound muscle action potential waves changes followed opposite patterns. Compound muscle action potential waves progressively split up, which was probably associated with a continuous slowing of the action potentials in the most fatigable motor units and the subsequent disappearance of the reactions at least in part of the motor units. Hysteresis effects in muscle contraction seem to be able, at least in part, to compensate for some of the depressive effects appearing during conduction of action potentials in muscle fibres. Changes in the compound muscle action potentials were studied during development of the muscle fatigue. These changes showed pronounced dependency on stimulation rate allowing differentiating effects of low- and high-frequency stimulation of the efferents supplying muscle under study. At the same time the fatigue-related changes in the action potentials were noticeably smaller than changes in tension, thus supporting existing concepts in the field arguing that fatigue effects are mainly connected with corresponding activity-dependent changes in muscle contraction machinery.

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.

Changes in responses to transcranial magnetic stimulation (TMS) during submaximal isometric voluntary contraction (60% of maximal voluntary contraction (MVC) of the adductor pollicis muscle and the subsequent recovery period have been studied in healthy volunteers. TMS at twice the motor threshold was applied during the sustained contraction, as well as at rest and during short-lasting (2 s) 60% MVCs before and immediately after the sustained contraction, and at 5 min intervals during the recovery period. Both motor evoked potential (MEP) magnitude (peak and area) and silent period (SP) duration in electromyographic activity (EMG) of the adductor pollicis muscle showed a gradual decrease up to the endurance point and an increase thereafter. MEPs elicited at rest immediately after the fatiguing contraction were larger, whereas those elicited later on during the recovery period did not differ significantly from the controls. It is suggested that the changes in responses to TMS, divergent from those in ongoing voluntary EMG during the sustained 60% MVC, indicate complex processes at levels preceding the motor cortex output cells in an attempt to maintain a submaximal contraction of the fatigued muscle. The increase in MEP magnitude after the sustained 60% MVC may indicate residual changes in cortical activity after fatiguing contraction.