Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode

Rational selection of electrical stimulus parameters for an electronic retinal prosthesis requires knowledge of the electrophysiological responses of retinal neurons to electrical stimuli. In this study, we examined the effects of cathodal and anodal current pulses on the extracellularly recorded responses of OFF and ON rabbit retinal ganglion cells (RGCs) in an in vitro preparation. Current pulses (1 msec duration), delivered by a 125 microm electrode placed on the inner retinal surface within the receptive field of a RGC, produced both short-latency (< or =5 msec) and long-latency (8-60 msec) responses. The long-latency responses, but not the short-latency responses, were abolished upon application of the glutamate receptor antagonists CNQX and NBQX, thus indicating that the long-latency responses of RGCs are due to activation of presynaptic neurons in the retina. The latency of the long-latency response depended upon the polarity of the stimulus. For OFF RGCs, the average latency was 11 msec for a cathodal stimulus and 24 msec for an anodal stimulus. For ON RGCs, the average latency was 25 msec for a cathodal stimulus and 16 msec for an anodal stimulus. The threshold current also depended upon the polarity of the stimulus, at least for OFF RGCs. The average threshold current for evoking a long-latency response in OFF RGCs was 10 microA for a cathodal stimulus and 21 microA for an anodal stimulus. In ON RGCs, the average threshold current was 13 microA for a cathodal stimulus and 15 microA for an anodal stimulus.     

Modelling magnetic coil excitation of human cerebral cortex with a peripheral nerve immersed in a brain-shaped volume conductor: the significance of fiber bending in excitation.

To help elucidate some basic principles of magnetic coil (MC) excitation of cerebral cortex, a model system was devised in which mammalian phrenic nerve, or amphibian sciatic nerve with its branches was suspended in appropriate Ringer's solution in a human brain-shaped volume conductor, an inverted plastic skull. The nerve was recorded monophasically out of the volume conductor. The site of nerve excitation by the MC was identified by finding where along the nerve a bipolar electrical stimulus yielded a similar action potential latency. MC excitation of hand-related corticospinal (CT) neurons was modelled by giving the distal end of nerve attached to the lateral skull an initial radial (perpendicular) trajectory, with subsequent bends towards the base and posterior part of the skull; this nerve was optimally excited by a laterally placed figure 8 or round MC when the induced electric field led to outward membrane current at the initial bend. By contrast, nerve given a trajectory modelling CT neurons related to the foot was optimally excited when the coil windings were across the midline, but again when membrane current flowed outward at the first bend. Corticocortical fibers were modelled by placing the nerve in the anteroposterior axis lateral to the midline; with the round MC vertex-tangentially orientated, optimal excitation occurred at the bend nearest the interaural line, i.e., near the peak electric field. The findings emphasize the importance of orientation and direction of current in the MC and fiber bends in determining nerve excitation. The findings in the peripheral nerve-skull model help explain (1) why lateral and vertex-tangentially orientated MCs preferentially excite arm-related CT neurons directly and indirectly (through corticocortical fibers), respectively, and (2) why the MC orientations for optimally exciting directly arm and leg-related CT neurons differ.     

Effects of acute stimulation through contacts placed on the motor cortex for chronic stimulation.

OBJECTIVES: We tried to determine which neural elements were activated in awake subjects by stimulation through contacts placed chronically on the motor cortex. METHODS: We recorded the motor effects of stimulation through 4 disc contacts placed in the subdural space over the motor cortex in 9 patients undergoing chronic stimulation for the control of pain or for the control of the rigidity of multiple system atrophy. RESULTS: Single stimuli could elicit short latency motor evoked potentials or facilitate active motoneurons in the contralateral limbs. The responsible neural elements had a short chronaxie (the pulse duration necessary to reach threshold with a stimulus intensity twice that required to reach threshold at the longest pulse duration used) and refractory period implying that they were myelinated axons. The facilitation was larger with cathodal than with anodal monopolar stimulation. The short latency facilitation in response to the second of two stimuli was greater at condition test intervals of 2-5 ms. This enhancement could be demonstrated with conditioning stimuli subthreshold for the excitation of active motoneurons suggesting that it arose, in part, at the level of the cortex. Single cortical stimuli could result in inhibition of voluntarily activated motoneurons. The inhibition was larger with cathodal than anodal monopolar stimulation. The responsible neural elements also had a short chronaxie and refractory period. CONCLUSIONS: Stimulation in awake subjects through contacts placed chronically over the motor cortex appears to activate axons in the cortex, which excite both corticospinal neurons and inhibitory neurons.     

Focal stimulation of human cerebral cortex with the magnetic coil: a comparison with electrical stimulation

Percutaneous stimulation of human motor cortex electrically (focal anode) and with magnetic coils (MCs) of various designs is compared. The theoretical prediction was confirmed that positioning the standard round MC laterally and orientating it more towards the vertical induces an electric field appropriate for directly exciting corticospinal neurons (cf., the conventional tangential orientation at the vertex). Thus, during voluntary contraction, minimal latency compound motor action potentials (CMAPs) in contralateral arm were elicited both by focal anodic and appropriately orientated MC stimulation. Conduction time from motor cortex to motoneuron was estimated by subtracting peripheral conduction time and monosynaptic delay at the motoneuron from the overall CMAP latency, yielding an estimated corticospinal conduction velocity as high as 66 m/sec. Discontinuous latency variations observed in population CMAPs or individual motor units approximated mono- or polysynaptic cortical synaptic delays and, therefore, are attributed to the intervals between direct and early, or late indirect corticospinal discharges. A TV computer system was used to track movements of individual digits and the hand following MC stimulation. An appropriately orientated MC readily elicited movements predominantly of a single digit, implying focal activation of motor cortex. A double square and a small pointed MC proved especially convenient for eliciting reproducibly single digit movements. Stronger stimulation revealed a topographical gradient in the responses of the different digits. Responses to a given MC stimulus a little above threshold were variable in amplitude, which could not be explained by the relationship of stimulus to phase of the cardiac or respiratory cycle. Overall, our findings indicate the importance of appropriately orientating a standard round MC and using a specially designed MC to obtain the various types of motor response to stimulation of cerebral cortex.     

Modeling direct activation of corticospinal axons using transcranial electrical stimulation

Corticospinal axons can be directly activated using anodal transcranial electrical stimulation. The purpose of this work was to find the location of the direct activation. The response to stimulation was modeled with a spherical head model and an active model of a corticospinal nerve. The nerve model had a deep bend at a location corresponding to a corticospinal fiber entering the midbrain. The threshold activation initiated close to brain surface; the exact location depended on whether the cell body located in the surface layers of the brain or in the bank of the central sulcus. The stimulation time constant was 44 μs. When the stimulus amplitude was increased, the site of activation shifted gradually to deeper level, until the activation initiated directly at the bend causing a half millisecond latency jump at spinal level. These results support the theory that the corticospinal axons can be directly activated at deep locations using anodal transcranial electrical stimulation. However, the high amplitude needed for the direct activation suggests that not only the bends on the fibers, but also the shape of surrounding volume conductor (intracranial cavity) favor activation at this location.     

EMG responses in the soleus muscles evoked by unipolar galvanic vestibular stimulation

This study compared the effects of transmastoid galvanic stimulation with unilateral galvanic stimulation of vestibular afferents. We recorded the effects on soleus EMG occurring at short (SL) and medium (ML) latency, both in normal subjects and in patients with previous unilateral vestibular neurectomy. Unipolar cathodal and anodal stimulation on the same side produced opposite effects for both SL and ML responses. Responses to unilateral cathodal or anodal stimulation were smaller, but otherwise resembled those of transmastoid stimulation with the cathode or the anode placed on the same side, respectively. Unilateral cathodal stimulation resulted in a larger SL response, which occurred at shorter latency than unilateral anodal stimulation. With unipolar stimulation on the side of previous vestibular nerve section, typical SL and ML responses were absent. With stimulation of the intact side, the patients showed smaller SL responses than normal subjects with unilateral stimulation. The larger responses to unilateral cathodal compared to unilateral anodal stimulation are consistent with previous reports that cathodal stimulation produces an increase and anodal a decrease in vestibular nerve firing. The smaller SL responses in the patients may be a consequence of central nervous system reorganization following unilateral vestibular nerve section.     

An analysis of peripheral motor nerve stimulation in humans using the magnetic coil

We compared conventional electrical and magnetic coil (MC) stimulation of distal median nerve in 10 normal subjects and 1 patient. Orthogonal (90 degrees to volar forearm)-longitudinal (the plane of the MC aligned with the long axis of nerve or wire), tilted (to 45 degrees) longitudinal, and tangential edge orientations elicited maximal or near maximal compound motor axon potentials (CMAPs) without simultaneous co-activation of ulnar nerve. Transverse and symmetrical tangential orientations were inefficient. A simulation study of an ideal volume conductor confirmed these findings by predicting that the maximum current density was near the outer edge of the MC and not at the center where the magnetic flux intensity is maximal. An orthogonal-longitudinal MC induces a current in the adjacent volume conductor (for example elbow or wrist), which flows in the same circular direction as in the MC. This differs from a tangentially orientated MC which classically elicits current flow in the volume conductor opposite in circular direction to that in the MC. Amplitude and latency of the CMAP were both altered, but not identically, by changing the intensity of MC and cathodal stimuli. Rotating an orthogonal-longitudinal MC through 180 degrees, thus reversing the direction of current flow, elicited single fiber muscle action potentials whose peak latencies differed at most by 100 microseconds. Thus, the (virtual) cathode and anode are significantly closer (i.e., 5-6 mm) with MC than with electrical stimulation where they are at least 20 mm apart. A disadvantage of MC stimulation is the imprecision in defining exactly where the distally propagating nerve impulse originates. In different subjects, using maximum output and orthogonal or tilted (to 45 degrees) longitudinal orientations, the calculated site of excitation in the median nerve varied 2-15 mm distal to the midpoint of the contacting edge of the MC. This limits the usefulness of the MC in its current configuration for determining distal motor latencies. Future advances in MC design may overcome these difficulties.     

Transcranial magnetic and electrical stimulation compared: Does TES activate intracortical neuronal circuits?

OBJECTIVE: To determine whether, and under which conditions, transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) can activate similar neuronal structures of the human motor cortex, as indicated by electromyographic recordings. METHODS: Focal TMS was performed on three subjects inducing a postero-anterior directed current (p-a), TES with postero-anteriorly (p-a) and latero-medially (l-m) oriented electrodes. We analyzed the onset latencies and amplitudes (single-pulse) and intracortical inhibition and excitation (paired-pulse). RESULTS: TMS p-a and TES p-a produced muscle responses with the same onset latency, while TES l-m led to 1.4-1.9 ms shorter latencies. Paired-pulse TMS p-a and TES p-a induced inhibition at short inter-stimulus intervals (ISI) (maximum: 2-3 ms) and facilitation at longer ISIs (maximum: 10 ms). No inhibition but a strong facilitation was obtained from paired-pulse TES l-m (ISIs 1-5 ms). CONCLUSIONS: Our findings support the hypothesis, that current direction is the most relevant factor in determining the mode of activation for both TMS and TES: TMS p-a and TES p-a are likely to activate the corticospinal neurons indirectly. In contrast, TES l-m may preferentially activate the corticospinal fibres directly, distant of the neuronal body. SIGNIFICANCE: TES is a suitable tool to induce intracortical inhibition and excitation.     

Responses of human single motor units to transcranial magnetic stimulation

Transcranial electromagnetic brain stimuli elicit a complex response in the electromyogram of active human hand muscles. Relatively weak stimuli evoke a short-latency primary response via a presumably monosynaptic corticospinal path. This is followed by a silent period that is terminated by a second peak at a latency of 50–80 ms. The responses evoked in single motor units in flexor digitorum profundus (FDP) were recorded. Responses were elicited at the second-peak latency only in trials in which no primary response was elicited in that unit, and only when the stimulus was given during the first half of the interspike interval (ISI). When given during the second half of the ISI, the same stimulus evoked a primary response but no second peak response. Stronger stimuli suppressed the second peak by evoking a primary response in more trials. Having discharged at about 20 ms latency, the parent motoneurone was unable to discharge again at second-peak latency, 30–60 ms later. The response at second-peak latency was not modified by disengaging both FDP and the extensors of the distal interphalangeal joint. Hence, this response is not secondary to a stretch reflex provoked by activation of the finger extensors, nor is it the result of a cutaneous signal resulting from movement of the finger. The latencies suggest that the corticospinal volley evokes a β-motoneurone-mediated twitch in FDP muscle spindles, which elicits an afferent volley that activates the motoneurone reflexly. The first 100 ms or so of the silent period is due to the realignment of the first post-stimulus spike in most trials to corticospinal latency; i.e. this is not necessarily the result of an inhibitory or disfacilitatory process. Still stronger stimuli increase the duration of the ISI in which the stimulus is given, indicating the presence of an inhibitory/disfacilitatory process.     

Variability in Response to Transcranial Direct Current Stimulation of the Motor Cortex

BackgroundResponses to a number of different plasticity-inducing brain stimulation protocols are highly variable. However there is little data available on the variability of response to transcranial direct current stimulation (TDCS).ObjectiveWe tested the effects of TDCS over the motor cortex on corticospinal excitability. We also examined whether an individual's response could be predicted from measurements of onset latency of motor evoked potential (MEP) following stimulation with different orientations of monophasic transcranial magnetic stimulation (TMS).MethodsFifty-three healthy subjects participated in a crossover-design. Baseline latency measurements with different coil orientations and MEPs were recorded from the first dorsal interosseous muscle prior to the application of 10 min of 2 mA TDCS (0.057 mA/cm²). Thirty MEPs were measured every 5 min for up to half an hour after the intervention to assess after-effects on corticospinal excitability.ResultsAnodal TDCS at 2 mA facilitated MEPs whereas there was no significant effect of 2 mA cathodal TDCS. A two-step cluster analysis suggested that approximately 50% individuals had only a minor, or no response to TDCS whereas the remainder had a facilitatory effect to both forms of stimulation. There was a significant correlation between the latency difference of MEPs (anterior–posterior stimulation minus latero-medial stimulation) and the response to anodal, but not cathodal TDCS.ConclusionsThe large variability in response to these TDCS protocols is in line with similar studies using other forms of non-invasive brain stimulation. The effects highlight the need to develop more robust protocols, and understand the individual factors that determine responsiveness.     

Selective augmentation of corticospinal motor drive with trans-spinal direct current stimulation in the cat

BackgroundA key outcome for spinal cord stimulation for neurorehabilitation after injury is to strengthen corticospinal system control of the arm and hand. Non-invasive, compared with invasive, spinal stimulation minimizes risk but depends on muscle-specific actions for restorative functions.ObjectiveWe developed a large-animal (cat) model, combining computational and experimental techniques, to characterize neuromodulation with transcutaneous spinal direct current stimulation (tsDCS) for facilitation of corticospinal motor drive to specific forelimb muscles.MethodsAcute modulation of corticospinal function by tsDCS was measured using motor cortex-evoked muscle potentials (MEPs). The effects of current intensity, polarity (cathodal, anodal), and electrode position on specific forelimb muscle (biceps vs extensor carpi radialis, ECR) MEP modulation were examined. Locations of a key target, the motoneuron pools, were determined using neuronal tracing. A high-resolution anatomical (MRI and CT) model was developed for computational simulation of spinal current flow during tsDCS.ResultsEffects of tsDCS on corticospinal excitability were robust and immediate, therefore supporting MEPs as a sensitive marker of tsDCS targeting. Varying cathodal/anodal current intensity modulated MEP enhancement/suppression, with higher cathodal sensitivity. Muscle-specificity depended on cathode position; the rostral position preferentially augmented biceps responses and the caudal position, ECR responses. Precise anatomical current-flow modeling, supplemented with target motor pool distributions, can explain tsDCS focality on muscle groups.ConclusionAnatomical current-flow modeling with physiological validation based on MEPs provides a framework to optimize muscle-specific tsDCS interventions. tsDCS targeting of representative motor pools enables muscle- and response-specific neuromodulation of corticospinal motor drive.     

The effects of transcranial direct current stimulation on conscious perception of sensory inputs from hand palm and dorsum

Conscious perception of sensory signals depends in part on stimulus salience, relevance and topography. Letting aside differences at skin receptor level and afferent fibres, it is the CNS that makes a contextual selection of relevant sensory inputs. We hypothesized that subjective awareness (AW) of the time at which a sensory stimulus is perceived, a cortical function, may be differently modified by cortical stimulation, according to site and type of the stimulus. In 24 healthy volunteers, we examined the effects of transcranial direct current stimulation (tDCS) on the assessment of AW to heat pain or weak electrical stimuli applied to either the hand palm or dorsum. We also recorded the vertex‐evoked potentials to the same stimuli. The assessment was done before, during and after cathodal or anodal tDCS over the parietal cortex contralateral to the hand receiving the stimuli. At baseline, AW to thermal stimuli was significantly longer for palm than for dorsum (P < 0.01), while no differences between stimulation sites were observed for the electrical stimuli. Both cathodal and anodal tDCS caused a significant shortening of AW to thermal stimuli in the palm but not in the dorsum, and no effects on AW to electrical stimuli. Longer AW in the palm than in the dorsum may be attributable to differences in skin thickness. However, the selectivity of the effects of tDCS on AW to thermal stimulation of the glabrous skin reflects the specificity of CNS processing for site and type of sensory inputs.     

Spinal cord-evoked potentials and muscle responses evoked by transcranial magnetic stimulation in 10 awake human subjects.

Transcranial magnetic stimulation (TCMS) causes leg muscle contractions, but the neural structures in the brain that are activated by TCMS and their relationship to these leg muscle responses are not clearly understood. To elucidate this, we concomitantly recorded leg muscle responses and thoracic spinal cord-evoked potentials (SCEPs) after TCMS for the first time in 10 awake, neurologically intact human subjects. In this report we provide evidence of direct and indirect activation of corticospinal neurons after TCMS. In three subjects, SCEP threshold (T) stimulus intensities recruited both the D wave (direct activation of corticospinal neurons) and the first I wave (I1, indirect activation of corticospinal neurons). In one subject, the D, I1, and I2 waves were recruited simultaneously, and in another subject, the I1 and I2 waves were recruited simultaneously. In the remaining five subjects, only the I1 wave was recruited first. More waves were recruited as the stimulus intensity increased. The presence of D and I waves in all subjects at low stimulus intensities verified that TCMS directly and indirectly activated corticospinal neurons supplying the lower extremities. Leg muscle responses were usually contingent on the SCEP containing at least four waves (D, I1, I2, and I3).     

Generation of spike latency tuning by thalamocortical circuits in auditory cortex

In many sensory systems, the latency of spike responses of individual neurons is found to be tuned for stimulus features and proposed to be used as a coding strategy. Whether the spike latency tuning is simply relayed along sensory ascending pathways or generated by local circuits remains unclear. Here, in vivo whole-cell recordings from rat auditory cortical neurons in layer 4 revealed that the onset latency of their aggregate thalamic input exhibited nearly flat tuning for sound frequency, whereas their spike latency tuning was much sharper with a broadly expanded dynamic range. This suggests that the spike latency tuning is not simply inherited from the thalamus, but can be largely reconstructed by local circuits in the cortex. Dissecting of thalamocortical circuits and neural modeling further revealed that broadly tuned intracortical inhibition prolongs the integration time for spike generation preferentially at off-optimal frequencies, while sharply tuned intracortical excitation shortens it selectively at the optimal frequency. Such push and pull mechanisms mediated likely by feedforward excitatory and inhibitory inputs respectively greatly sharpen the spike latency tuning and expand its dynamic range. The modulation of integration time by thalamocortical-like circuits may represent an efficient strategy for converting information spatially coded in synaptic strength to temporal representation.     

Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for spinal cord stimulation permitted to study the descending volleys generated by EMCS in order to better appraise the neural circuits involved in EMCS effects. Direct and indirect volleys (D- and I-waves) were produced depending on electrode polarity and montage and stimulus intensity. At low-intensity, anodal monopolar EMCS generated D-waves, suggesting direct activation of corticospinal fibers, whereas cathodal EMCS generated I2-waves, suggesting transsynaptic activation of corticospinal tract. The bipolar electrode configuration used in chronic EMCS to produce maximal pain relief generated mostly I3-waves. This result suggests that EMCS induces analgesia by activating top–down controls originating from intracortical horizontal fibers or interneurons but not by stimulating directly the pyramidal tract. The descending volleys elicited by bipolar EMCS are close to those elicited by transcranial magnetic stimulation using a coil with posteroanterior orientation. Different pathways are activated by EMCS according to stimulus intensity and electrode montage and polarity. Special attention should be paid to these parameters when programming EMCS for pain treatment.     

Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats: II. Membrane factors underlying paired-pulse response profiles

Two subtypes of neurons in the striatum have been defined on the basis of their different response patterns to paired-impulse stimulation of corticostriatal afferents, with type I cells showing a longer spike latency, facilitation at short intervals, and inhibition at long intervals, and type II cells defined by the facilitation occurring at long interstimulus intervals. Nevertheless, the companion report has shown that this distinction of cell types cannot be accounted for by differences in the basic physiological properties of these cells, but instead is likely to be due to differences in their synaptic connectivity. The experiments performed in this study were directed at examining in detail the membrane factors and synaptic responses that may contribute to these distinct response patterns. When pairs of stimuli were delivered to the corticostriatal fibers at 10-30 ms interstimulus intervals, the EPSPs elicited in type I neurons exhibited a temporal summation, resulting in a facilitation of spike firing to the second stimulus relative to the first. In contrast, type II cells showed decreased EPSP amplitude at short intervals, and in cells showing a short-interval inhibition, there was a significant increase in spike threshold (+5.3 ± 1.4 mV) during the second response. All type II neurons recorded with KCl-filled microelectrodes showed short-interval facilitation with little or no change in spike threshold. Although the use of KCI electrodes did not alter the facilitation at short intervals in type I neurons it did increase the rate of rise of the EPSP, causing spikes to be triggered at a latency similar to that of type II cells. Paired stimuli delivered at 75–150 ms interstimulus intervals showed inverse effects on type I and type II cells with respect to the probability of spike firing. In type I cells, the evoked EPSP was followed by a long-latency membrane hyperpolarization that prevented the second EPSP from reaching spike threshold. In contrast, the smaller-amplitude hyperpolarization evoked in type II cells enabled the second stimulus to activate an EPSP at the same membrane potential as the first stimulus, resulting in a facilitation of spiking. Therefore, despite the similarity in the basic physiological properties of type I and type II cells, the differences in their spike latencies and paired impulse response profiles appear to be dependent on the timing of their GABAergic inhibition at short intervals: A GABA-mediated conductance change occurs simultaneously with the EPSP in type I cells leading to a delay in triggering the evoked spike, whereas a later-developing GABA conductance change in type II cells results in an inhibition of spiking at short intervals. In contrast, the pronounced long-duration membrane hyperpolarization of type I cells appears to underlie the inhibition of spiking at long intervals, whereas in the type II cells the GABA-mediated decrease in cell excitability necessitated the use of larger-amplitude stimulation pulses to reach threshold with respect to the first stimulus, resulting in a higher probability of spike discharge to the second stimulus at long intervals. © 1994 Wiley-Liss, Inc.     

Transcranial direct current stimulation preconditioning modulates the effect of high-frequency repetitive transcranial magnetic stimulation in the human motor cortex

Experimental studies emphasize the importance of homeostatic plasticity as a mean of stabilizing the properties of neural circuits. In the present work we combined two techniques able to produce short-term (5-Hz repetitive transcranial magnetic stimulation, rTMS) and long-term (transcranial direct current stimulation, tDCS) effects on corticospinal excitability to evaluate whether and how the effects of 5-Hz rTMS can be tuned by tDCS preconditioning. Twelve healthy subjects participated in the study. Brief trains of 5-Hz rTMS were applied to the primary motor cortex at an intensity of 120% of the resting motor threshold, with recording of the electromyograph traces evoked by each stimulus of the train from the contralateral abductor pollicis brevis muscle. This interventional protocol was preconditioned by 15 min of anodal or cathodal tDCS delivered at 1.5 mA intensity. Our results showed that motor-evoked potentials (MEPs) increased significantly in size during trains of 5-Hz rTMS in the absence of tDCS preconditioning. After facilitatory preconditioning with anodal tDCS, 5-Hz rTMS failed to produce progressive MEP facilitation. Conversely, when 5-Hz rTMS was preceded by inhibitory cathodal tDCS, MEP facilitation was not abolished. These findings may give insight into the mechanisms of homeostatic plasticity in the human cerebral cortex, suggesting also more suitable applications of tDCS in a clinical setting.     

Climbing fiber action on the responsiveness of Purkinje cells to parallel fiber inputs

Recent work in our laboratory has demonstrated that spontaneous or evoked climbing fiber inputs are associated with an increased responsiveness of Purkinje cells to mossy fiber inputs activated by natural peripheral stimuli. These experiments were designed to test the hypothesis that this increased responsiveness occurs in the cerebellar cortex. In decerebrate, unanesthetized cats Purkinje cells in the surface folium were isolated and their simple and complex spikes discriminated. A bipolar concentric stimulating electrode was placed on the surface of the folium to activate the parallel fiber volley and modulate the Purkinje cell's simple spike discharge. The cell's simple spike discharge was evaluated when the surface stimulus was presented randomly and when this stimulus was timed to occur at a fixed interval after the spontaneous complex spike activity. When the surface stimulus was timed to occur at short intervals after the spontaneous complex spike, the response to the surface stimulus was accentuated. This increase in simple spike modulation occurred independent of whether the simple spike discharge increased or decreased in response to the surface stimulus. These results support the hypothesis that the climbing fiber input changes the gain of Purkinje cells' simple spike responses to mossy fiber inputs due to interactions occurring in the cerebellar cortex.     

Early malnutrition followed by nutritional restoration lowers the conduction velocity and excitability of the corticospinal tract

The physiological sequelae of undernutrition were investigated in rats that were undernourished from day 1–21 and subsequently free-fed to 75 days of age. Population responses were recorded in the corticospinal tract following surface stimulation of the motor cortex, which activates corticospinal cells directly, and also indirectly via cortical synapses. The conduction velocity of the fastest corticospinal fibers in 15 malnourished rats was 16.9 m/s, significantly slower (P < 0.001) than the 20.0 m/s observed in 26 controls. In addition, the excitability of corticospinal neurons to direct stimulation was reduced as much as 67% in malnourished rats, while no effect on synaptic activation was observed. Our findings suggest that early malnutrition reduces the number of large fibers in the adult corticospinal tract. These results are discussed with respect to known morphological and behavioral effects of malnutrition in rats and their relevance to humans.     

Contrast invariance of orientation tuning in the lateral geniculate nucleus of the feline visual system

Responses of most neurons in the primary visual cortex of mammals are markedly selective for stimulus orientation and their orientation tuning does not vary with changes in stimulus contrast. The basis of such contrast invariance of orientation tuning has been shown to be the higher variability in the response for low‐contrast stimuli. Neurons in the lateral geniculate nucleus (LGN), which provides the major visual input to the cortex, have also been shown to have higher variability in their response to low‐contrast stimuli. Parallel studies have also long established mild degrees of orientation selectivity in LGN and retinal cells. In our study, we show that contrast invariance of orientation tuning is already present in the LGN. In addition, we show that the variability of spike responses of LGN neurons increases at lower stimulus contrasts, especially for non‐preferred orientations. We suggest that such contrast‐ and orientation‐sensitive variability not only explains the contrast invariance observed in the LGN but can also underlie the contrast‐invariant orientation tuning seen at the level of the primary visual cortex.