I3 Waves Research Articles

Interneuronal networks mediate cortical inhibition and facilitation

ObjectiveRecruitment of interneuronal circuits generating later indirect (I) waves seem to be important in short-interval intracortical inhibition (SICI) and facilitation (SICF) development. This study assessed whether individual variations in intracortical inhibition and facilitation could be explained by variation in recruitment of interneuronal networks. MethodsCortical excitability was assessed using a figure of eight coil, with motor evoked responses recorded over the contralateral abductor pollicis brevis (APB) muscle. I-wave recruitment was inferred from the measurement of motor evoked potential (MEP) onset latencies, with coil positioned in posterior-to-anterior (early I waves) and anterior-to-posterior (later I waves) directions. ResultsSubtle variability in the recruitment of later I-waves (I3) was evident across subjects. Importantly, mean SICI (P < 0.05) was significantly greater in subjects recruiting I3 waves, as were the two SICI peaks at interstimulus intervals of 1 ms (P < 0.05) and 3 ms (P < 0.05). In addition, mean SICF was significantly greater in participants exhibiting an AP-to-LM latency differences of <4 ms (P < 0.01). There was no significant correlation between I-wave recruitment and intracortical facilitation, motor evoked potential amplitude or cortical silent period duration. ConclusionsDifferential recruitment of interneuronal networks appears to underlie the generation and individual variations in intracortical inhibition and facilitation. SignificanceInvestigating cortical interneuronal networks in human diseases may yield novel pathophysiological insights.

Breaking down the human motor cortex: the layer-specific measurement of corticospinal neuronal activity.

Breaking down the human motor cortex: the layer-specific measurement of corticospinal neuronal activity.

Increased facilitation of the primary motor cortex in de novo Parkinson's disease

IntroductionPaired-pulse transcranial magnetic stimulation (TMS) is useful to estimate the balance between inhibitory and facilitatory circuits of the primary motor cortex (M1) in Parkinson's disease (PD). Results of earlier studies are, however, incongruent: some reports describe normal short-interval intracortical inhibition (SICI), but others describe reduced SICI. We hypothesize that exaggerated intracortical facilitation masks normal inhibition, and that a triple-pulse method can reveal masked inhibition in PD. MethodsTen PD patients who had not been exposed to dopaminergic medications were enrolled. Results were compared with those obtained from 10 age-matched healthy volunteers. We measured TMS-elicited motor evoked potential (MEP) as an index of M1 excitability. We tested SICI, intracortical facilitation (ICF), and short-interval intracortical facilitation (SICF), which has three distinct facilitatory peaks, using the paired-pulse TMS paradigm. A triple-pulse protocol, SICI + SICF, was investigated as described in our earlier study. This protocol examined SICF in the presence of SICI, thereby allowing our test of true inhibitory influence on a specific component of MEP-generating mechanism known as I3 wave. ResultsIn PD patients, SICI estimated using the conventional method was decreased, whereas SICF was enhanced around its second peak out of the three. Results for SICI + SICF were comparable between PD patients and healthy controls, suggesting normal inhibition of I3 waves in PD patients. ConclusionWe confirmed the SICF enhancement in drug naïve PD patients. We propose that I3 wave inhibition by a subthreshold pulse shown by SICI paradigm is unaffected in PD. The triple-pulse method can reveal masked inhibition.

Modulation of amplitude and latency of motor evoked potential by direction of transcranial magnetic stimulation

The present study analyzed the effects of monophasic magnetic stimulation to the motor cortex. The effects of magnetic stimulation were evaluated by analyzing the motor evoked potentials (MEPs). The amplitude and latency of MEPs on the abductor pollicis brevis muscle were used to evaluate the effects of repetitive magnetic stimulation. A figure eight-shaped flat coil was used to stimulate the region over the primary motor cortex. The intensity of magnetic stimulation was 120% of the resting motor threshold, and the frequency of magnetic stimulation was 0.1 Hz. In addition, the direction of the current in the brain was posterior-anterior (PA) or anterior-posterior (AP). The latency of MEP was compared with PA and AP on initial magnetic stimulation. The results demonstrated that a stimulus in the AP direction increased the latency of the MEP by approximately 2.5 ms. MEP amplitude was also compared with PA and AP during 60 magnetic stimulations. The results showed that a stimulus in the PA direction gradually increased the amplitude of the MEP. However, a stimulus in the AP direction did not modulate the MEP amplitude. The average MEP amplitude induced from every 10 magnetic pulses was normalized by the average amplitude of the first 10 stimuli. These results demonstrated that the normalized MEP amplitude increased up to approximately 150%. In terms of pyramidal neuron indirect waves (I waves), magnetic stimulation inducing current flowing backward to the anterior preferentially elicited an I1 wave, and current flowing forward to the posterior elicited an I3 wave. It has been reported that the latency of the I3 wave is approximately 2.5 ms longer than the I1 wave elicitation, so the resulting difference in latency may be caused by this phenomenon. It has also been reported that there is no alteration of MEP amplitude at a frequency of 0.1 Hz. However, this study suggested that the modulation of MEP amplitude depends on stimulation strength and stimulation direction.

Transcranial direct current stimulation effects on I-wave activity in humans

Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability noninvasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation and cathodal tDCS to inhibition of motor cortex excitability. To further elucidate the underlying physiological mechanisms, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 5-min period of anodal or cathodal tDCS in eight conscious patients who had electrodes implanted in the cervical epidural space for the control of pain. The effects of anodal tDCS were evaluated in six subjects and the effects of cathodal tDCS in five subjects. Three subjects were studied with both polarities. Anodal tDCS increased the excitability of cortical circuits generating I waves in the corticospinal system, including the earliest wave (I1 wave), whereas cathodal tDCS suppressed later I waves. The motor evoked potential (MEP) amplitude changes immediately following tDCS periods were in agreement with the effects produced on intracortical circuitry. The results deliver additional evidence that tDCS changes the excitability of cortical neurons.

Influence of current direction in transcranial magnetic stimulation (TMS) on MEP amplitude and latency – opportunity of I wave specific evaluation and stimulation

Introduction: It has been shown from invasive epidural recordings that in transcranial magnetic stimulation (TMS) a current in the brain flowing from a posterior to an anterior (p.a.) direction mainly evokes I1, I2 and I3 waves whereas a current flowing from an anterior to a posterior direction mainly evokes I3 waves. This leads to the hypotheses that in p.a. current direction the motor threshold (MT) is lower, motor evoked potentials (MEPs) are higher and latency is shorter than in a.p. direction. The aim of this study was to re-evaluate the inconsistent results in literature by means of a stimulation technique that enabled us to change the current direction without turning the coil. Methods: We investigated n=23 healthy subjects (female: n=12; mean age: 26.2±1.9 years). We recorded the MT, MEP amplitude to target 400µV (SI400µV), MT adapted IO curves and maximum stimulator output (MSO) adapted IO curves in a.p. and p.a. current direction (monophasic waveform) with the P-Stim 160 stimulator (Mag and More, Germany). Results: MT was significantly lower (p=0.003), MEP amplitudes (SI400µV) were significantly higher (p<0.001) and latencies significantly shorter (p<0.001) in p.a. current direction. RmANOVA revealed a significant influence of current direction in MSO adapted IO curves on both, MEP amplitude and latency. We observed a significant influence of current direction on latencies in MT adapted recording of IO-curves but not on MEP amplitudes. Discussion: Our results consistently demonstrate for the first time a significant influence of current direction on MT, MEP amplitude and latency at fixed stimulus intensities as well as in IO curves due to the hypotheses generated from the specific I-wave pattern. The high consistency of the results when changing the current direction without altering coil position offers the opportunity of I wave specific evaluation and stimulation in TMS.

Influence of Short-Interval Intracortical Inhibition on Short-Interval Intracortical Facilitation in Human Primary Motor Cortex

Using the paired-pulse paradigm, transcranial magnetic stimulation (TMS) has revealed much about the human primary motor cortex (M1). A preceding subthreshold conditioning stimulus (CS) inhibits the excitability of the motor cortex, which is named short-interval intracortical inhibition (SICI). In contrast, facilitation is observed when the first pulse (S1) is followed by a second one at threshold (S2), named short-interval intracortical facilitation (SICF). SICI and SICF have been considered to be mediated by different neural circuits within M1, but more recent studies reported relations between them. In this study, we performed triple-pulse stimulation consisting of CS-S1-S2 to further explore putative interactions between these two effects. Three intensities of CS (80-120% of active motor threshold: AMT) and two intensities of S2 (120 and 140% AMT) were combined. The SICF in the paired-pulse paradigm exhibited clear facilitatory peaks at ISIs of 1.5 and 3 ms. The second peak at 3 ms was significantly suppressed by triple-pulse stimulation using 120% AMT CS, although the first peak was almost unaffected. Our present results obtained using triple-pulse stimulation suggest that each peak of SICF is differently modulated by different intensities of CS. The suppression of the second peak might be ascribed to the findings in the paired-pulse paradigm that CS mediates SICI by inhibiting later I waves such as I3 waves and that the second peak of SICF is most probably related to I3 waves. We propose that CS might inhibit the second peak of SICF at the interneurons responsible for I3 waves.

Influence of current direction in transcranial magnetic stimulation (TMS) on MEP amplitude and latency – opportunity of I wave specific evaluation and stimulation

Introduction: It has been shown from invasive epidural recordings that in transcranial magnetic stimulation (TMS) a current in the brain flowing from a posterior to an anterior (p.a.) direction mainly evokes I1, I2 and I3 waves whereas a current flowing from an anterior to a posterior direction mainly evokes I3 waves. This leads to the hypotheses that in p.a. current direction the motor threshold (MT) is lower, motor evoked potentials (MEPs) are higher and latency is shorter than in a.p. direction. The aim of this study was to re-evaluate the inconsistent results in literature by means of a stimulation technique that enabled us to change the current direction without turning the coil. Methods: We investigated n=23 healthy subjects (female: n=12; mean age: 26.2±1.9 years). We recorded the MT, MEP amplitude to target 400µV (SI400µV), MT adapted IO curves and maximum stimulator output (MSO) adapted IO curves in a.p. and p.a. current direction (monophasic waveform) with the P-Stim 160 stimulator (Mag and More, Germany). Results: MT was significantly lower (p=0.003), MEP amplitudes (SI400µV) were significantly higher (p<0.001) and latencies significantly shorter (p<0.001) in p.a. current direction. RmANOVA revealed a significant influence of current direction in MSO adapted IO curves on both, MEP amplitude and latency. We observed a significant influence of current direction on latencies in MT adapted recording of IO-curves but not on MEP amplitudes. Discussion: Our results consistently demonstrate for the first time a significant influence of current direction on MT, MEP amplitude and latency at fixed stimulus intensities as well as in IO curves due to the hypotheses generated from the specific I-wave pattern. The high consistency of the results when changing the current direction without altering coil position offers the opportunity of I wave specific evaluation and stimulation in TMS.

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.

Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways

We explored interhemispheric facilitation (IHF) between (a) left and right primary motor cortex (M1) and (b) left dorsal premotor (dPM) and right M1 in 20 right-handed healthy human subjects using a paired pulse transcranial magnetic stimulation (TMS) protocol. A conditioning TMS pulse (CP) applied to left M1 or dPM with an intensity of 80% and 60% active motor threshold (CP(80%AMT) and CP(60%AMT), respectively) was followed by a test pulse (TP) over right M1 induced by anterior-posterior- or posterior-anterior- (TP(AP), TP(PA)) directed currents in the brain at interstimulus intervals (ISIs) of 3-8 and 10 ms. EMG was recorded from left first dorsal interosseous muscle. In the main experimental condition IHF was evoked by CP(80%AMT) over left M1 and TPAP at ISIs of 6 and 8 ms. The same CP(80%AMT) produced IHF at an ISI of 8 ms when applied over left dPM but only with TP(PA). In addition, when CP(60%AMT) was given to M1, IHF was present at an ISI of 6 ms (but not 8 ms) when followed by TP(PA), indicating that IHF elicited over dPM was not caused by current spread of the conditioning pulse to M1. We conclude that IHF can be induced differentially by conditioning M1 and dPM using subthreshold CP. These facilitatory interactions depended on the intensity and ISI of the CP as well as the current flow direction of the TP. We suggest that not only do the CPs activate separate anatomical pathways but also that these pathways project to different populations ofinterneurons in the receiving M1. These may correspond to elements involved in the generation of I3 and I1 waves, respectively.

Theta‐burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex

In four conscious patients who had electrodes implanted in the cervical epidural space for the control of pain, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex before and after a 20 s period of continuous theta-burst stimulation (cTBS). It has previously been reported that this form of repetitive TMS reduces the amplitude of motor-evoked potentials (MEPs), with the maximum effect occurring at 5-10 min after the end of stimulation. The present results show that cTBS preferentially decreases the amplitude of the corticospinal I1 wave, with approximately the same time course. This is consistent with a cortical origin of the effect on the MEP. However, other protocols that lead to MEP suppression, such as short-interval intracortical inhibition, are characterized by reduced excitability of late I waves (particularly I3), suggesting that cTBS suppresses MEPs through different mechanisms, such as long-term depression in excitatory synaptic connections.

Transcranial DC Stimulation and Corticospinal Transmission

Transcranial DC stimulation (tDCS) is a non-invasive technique for the induction of long-lasting changes in neuronal excitability. tDCS of the human motor cortex leads to polarity-specific changes in corticospinal excitability: anodal tDCS facilitates TMS-evoked MEP while cathodal tDCS inhibits them. Here we report on an experiment on tDCS and corticospinal transmission in a patient with electrodes implanted in the high cervical epidural space for the relief of pain. TMS-evoked descending volleys and MEP from the right FDI were recorded before and after 5min of anodal tDCS of the left motor cortex. MEP amplitudes after tDCS were facilitated for about 5min before they returned to baseline level. Cervical recordings before tDCS revealed that at 110% RMT PA magnetic stimulation evoked three negative waves and the first had a latency of 3.8 ms. This was 1.2 ms longer than the earliest volley evoked by LM magnetic stimulation. Since the earliest volley elicited by LM stimulation is probably a D-wave we have termed this volley as the I1 wave. After tDCS, the I1 wave was unchanged regarding amplitude and latency. However, for the period of tDCS-induced MEP-facilitation an increase in number and amplitude of the later I waves was recorded. This observation supports the theory that tDCS-induced modulation of MEP arises from changes in excitatory circuits in the human motor cortex.

Macaque ventral premotor cortex exerts powerful facilitation of motor cortex outputs to upper limb motoneurons.

The ventral premotor area (F5) is part of the cortical circuit controlling visuomotor grasp. F5 could influence hand motor function through at least two pathways: corticospinal projections and corticocortical projections to primary motor cortex (M1). We found that stimulation of macaque F5, which by itself evoked little or no detectable corticospinal output, could produce a robust modulation of motor outputs from M1. Arrays of fine microwires were implanted in F5 and M1. During terminal experiments under chloralose anesthesia, single stimuli delivered to M1 electrodes evoked direct (D) and indirect (I1,I2, and I3) corticospinal volleys. In contrast, single F5 shocks were ineffective; double shocks (3 msec separation) evoked small I waves but no D wave. However, when the test (T) M1 shock was conditioned (C) by single or double F5 shocks, there was strong facilitation of I2 and I3 waves from M1, with C-T intervals of <1 msec. Intracellular recordings from 79 arm and hand motoneurons (MNs) revealed no postsynaptic effects from single F5 shocks. In contrast, these stimuli produced a robust facilitation of I2 and I3 EPSPs evoked from M1 (60% of MNs); this was particularly marked in hand muscle MNs (92%). Muscimol injection in M1 reduced I waves from F5 and abolished the F5-induced facilitation of late I waves from M1, and of EPSPs associated with them. Thus, some motor effects evoked from F5 may be mediated by corticocortical inputs to M1 impinging on interneurons generating late corticospinal I waves. Similar mechanisms may allow F5 to modulate grasp-related outputs from M1.

The effect on corticospinal volleys of reversing the direction of current induced in the motor cortex by transcranial magnetic stimulation.

Descending corticospinal volleys were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects after monophasic transcranial magnetic stimulation over the motor cortex with a figure-of-eight coil. We examined the effect of reversing the direction of the induced current in the brain from the usual posterior-anterior (PA) direction to an anterior-posterior (AP) direction. The volleys were compared with D waves evoked by anodal electrical stimulation (two subjects) or medio-lateral magnetic stimulation (two subjects). As reported previously, PA stimulation preferentially recruited I1 waves, with later I waves appearing at higher stimulus intensities. AP stimulation tended to recruit later I waves (I3 waves) in one of the subjects, but, in the other three, I1 or D waves were seen. Unexpectedly, the descending volleys evoked by AP stimulation often had slightly different peak latencies and/or longer duration than those seen after PA stimulation. In addition the relationship between the size of the descending volleys and the subsequent EMG response was often different for AP and PA stimulation. These findings suggest that AP stimulation does not simply activate a subset of the sites activated by PA stimulation. Some sites or neurones that are relatively inaccessible to PA stimulation may be the low-threshold targets of AP stimulation.

A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation

The purpose of this method is to establish a single motor unit recording technique to study the differential activation of corticospinal volleys by various types of transcranial magnetic stimulation (TMS). TMS is performed with various coil orientations over the hand or leg motor areas and surface EMG, and single motor unit recordings are made either from the studied hand or leg muscle. Transcranial electrical stimulation (TES) is also performed over the motor cortex as well as at the foramen magnum level to determine the latency of D waves. The intensity of stimulation is set just above the motor threshold for each type of stimulation. This method makes it possible to activate some I volleys (especially I1 and I3 waves) preferentially, if not selectively, from the hand and leg motor areas. The obtained results accord well with recent epidural recording studies, which lends support to the validity of this method.

Predominant activation of I1-waves from the leg motor area by transcranial magnetic stimulation

We performed transcranial magnetic stimulation (TMS) to elucidate the D- and I-wave components comprising the motor evoked potentials (MEPs) elicited from the leg motor area, especially at near-threshold intensity. Recordings were made from the tibialis anterior muscle using needle electrodes. A figure-of-eight coil was placed so as to induce current in the brain in eight different directions, starting from the posterior-to-anterior direction and rotating it in 45° steps. The latencies were compared with those evoked by transcranial electrical stimulation (TES) and TMS using a double cone coil. Although the latencies of MEPs ranged from D to I3 waves, the most prominent component evoked by TMS at near-threshold intensity represented the I1 wave. With the double cone coil, the elicited peaks always represented I1 waves, and D waves were evoked only at very high stimulus intensities, suggesting a high effectiveness of this coil in inducing I1 waves. Using the figure-of-eight coil, current flowing anteriorly or toward the hemisphere contralateral to the recorded muscle was more effective in eliciting large responses than current flowing posteriorly or toward the ipsilateral hemisphere. The effective directions induced I1 waves with the lowest threshold, whereas the less effective directions elicited I1 and I2 waves with a similar frequency. Higher stimulus intensities resulted in concomitant activation of D through I3 waves with increasing amount of D waves, but still the predominance of I1 waves was apparent. The amount of I waves, especially of I1 waves, was greater than predicted by the hypothesis that TMS over the leg motor area activates the output cells directly, but rather suggests predominant transsynaptic activation. The results accord with those of recent human epidural recordings.

Intracortical inhibition after paired transcranial magnetic stimulation depends on the current flow direction

Objectives: To assess whether cortico-cortical inhibition (CCI) induced by paired-pulse transcranial magnetic stimulation (TMS) is influenced by ‘preferential’ or ‘non-preferential’ activation of the motor cortex.Methods: Paired-pulse TMS (conditioning-test paradigm with interstimulus intervals of 2–5 ms) with a round coil centered over the vertex was performed in 10 normal subjects using opposite current flow directions. The amount of CCI in the opponens pollicis and first dorsal interosseus muscles was determined.Results: When a clockwise current was induced in the brain (side A of the coil uppermost) a ‘preferential’ activation of the left hemisphere (right hand muscles) was observed, but the suppression of the test response by the conditioning stimulus (i.e. the CCI) was significantly greater in the left hand muscles. The situation was reversed when an anticlockwise current (side B of the coil uppermost) was induced in the brain. These effects occurred independently of the interstimulus interval, or of the absolute conditioning stimulus strength.Conclusions: CCI is more effective in the ‘non-preferentially’ stimulated hemisphere, and the neural elements generating the indirect I3 wave are more sensitive to intracortical inhibition than those generating the I1 wave.

Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves.

1. In paired-pulse cortical stimulation experiments, conditioning subthreshold stimuli suppress the electromyographic (EMG) responses of relaxed muscles to suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1-5 ms) and facilitate them at long ISIs (8-15 ms). 2. We made paired-pulse magnetic stimulation studies on the response of the first dorsal interosseous muscle (FDI) produced by I1 or I3 waves using our previously reported method which preferentially elicits one group of I waves when subjects make a slight voluntary contraction. In some experiments the conditioning and test stimuli were oppositely directed, in the others they were oriented in the same direction. Single motor unit responses were recorded with a concentric needle electrode, and surface EMG responses with cup electrodes. 3. In post-stimulus time histograms (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves were decreased by a subthreshold conditioning stimulus that preferentially elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on the intensity of the conditioning stimulus. The stronger the conditioning stimulus, the greater the suppression. In contrast, the peaks produced by I1 waves were little affected by any type of subthreshold conditioning stimulus, given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold conditioning stimulus slightly decreased the size of the peak produced by the I3 waves, but did not affect the peaks evoked by I1 waves. 4. Surface EMGs showed that a subthreshold conditioning stimulus suppressed the responses produced by I3 waves irrespective of its current direction (anterior or posterior). Both the amount and duration of suppression depended on the intensity of the conditioning stimulus, but not on its current direction. Both parameters increased when the intensity increased. At a high intensity conditioning stimulus, suppression was evoked at ISIs of 1-20 ms, compatible with the duration of GABA-mediated inhibition found in animal experiments. Responses produced by I1 waves were little affected by any type of subthreshold conditioning stimulus. 5. We conclude that a subthreshold conditioning stimulus given over the motor cortex moderately suppresses I3 waves but does not affect I1 waves. The duration of suppression of the I3 waves supports the idea that this is an effect of GABAergic inhibition within the motor cortex.

Comparative effect of thiopental sodium on cortical evoked potentials of different origin

The minimal doses of thiopental sodium (TS) to suppress each of seven varieties of cortical evoked potentials tested were determined in experiments on cats. The preparation had the strongest effect on the following responses: interzonal, arising in the motor cortex to stimulation of somatosensory area I; the reflex pyramidal and late components of the direct pyramidal response. The oligosynaptic transcallosal potential is less sensitive than the above responses but more so than the callosal response. The action of TS on the response depends on the complexity of its organization. The level at which the given cortical response takes place must also be considered. Comparison of the action of TS on the I1 wave of the pyramidal response and on the dendritic component of the direct cortical response showed that, given equal complexity of its organization, the response arising in deep layers of the cortex is depressed more by TS than the response arising wholly at the level of surface layer I.