Transcallosal Response Research Articles

Dose-response relationship between the variables of unilateral optogenetic stimulation and transcallosal evoked responses in rat motor cortex.

Efficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control. We employed optogenetic stimulation to establish a framework for probing transcallosal M1–M1 interactions in rats. We performed optogenetic stimulation of excitatory neurons in right M1 of male Sprague-Dawley rats. We recorded the transcallosal evoked potential in contralateral left M1 via chronically implanted electrodes. Recordings were performed under anesthesia combination of dexmedetomidine and a low concentration of isoflurane. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1. Optogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. A combination of stimulation intensities of 5–10 mW with stimulus durations of 1–10 ms were generally sufficient to elicit a robust transcallosal response in most animal, with our optic fiber setup. Optogenetically stimulated excitatory neurons in M1 can reliably evoke a transcallosal response in anesthetized rats. Characterizing the relationship between “stimulation dose” and “response magnitude” (i.e., the gain function) of transcallosal M1-to-M1 excitatory connections can be used to optimize the variables of optogenetic stimulation and ensure stimulation efficacy.

Interhemispheric transmission times in patients with intractable epilepsy: Study of transcallosal response (TCR) during the corpus callosotomy

Interhemispheric transmission times in patients with intractable epilepsy: Study of transcallosal response (TCR) during the corpus callosotomy

GABA-B-related activity in processing of transcallosal response in cat motor cortex.

GABA-ergic characteristics of transcallosal (TC) responses were studied with specific antagonists of both GABA-A and GABA-B receptor subtypes. We used a paired-pulse paradigm to get insight into the role of GABA in interhemispheric interactions between motor cortices. 3-Amino-2-(4-chlorophenyl)-propylphosphonic acid (phaclofen) and 3-aminopropyl-diethoxymethyl-phosphinic acid (CGP 35348) were used as GABA-B antagonists and bicuculline methiodide (BMI) was used to block the GABA-A receptor. Although both GABA-A and GABA-B antagonists increased spike discharge upon transcallosal stimulation, in both pyramidal tract and non-pyramidal tract neurons, they had different effects on the responses to the first and second stimuli of paired-pulse stimulation (200 msec interval). Although the inhibition seen with the second stimulus was greatly attenuated by antagonists of the GABA-B receptor, it was maintained in the presence of the GABA-A antagonist. These finding support a presynaptic regulation of callosal transmission by GABA-B receptors in the callosal synapse of the cat motor cortex.

Study of paired-pulse inhibition of transcallosal response in the pyramidal tract neuron in vivo

The effects of a specific GABA B receptor antagonist, p-(3-aminopropyl)- p-diethoxymethyl-phosphonic acid (CGP 35348), on pyramidal tract neuron responses to transcallosal stimulation were investigated in the cat motor cortex in vivo. The paired-pulse method was used to obtain more insight into the role of GABA B receptors. At a 200-ms inter-stimulus interval the spike response was inhibited in 75% of the neurons. There was an approximately 40% depression of the mean spike value in the control. CGP 35348 reduced paired-pulse inhibition, while (−)-baclofen increased it. Stronger drug effects on the second stimulation-induced response possibly indicate their presynaptic action on GABA B receptors.

1650 GABA B receptor antagonist induced excitation and agonist induced inhibition of the transcallosal response in the motor cortex

1650 GABA B receptor antagonist induced excitation and agonist induced inhibition of the transcallosal response in the motor cortex

1621 Effects of different GABA antagonists and agonists on Paired-pulse inhibition of the transcallosal response of cortical motor neuron

The present investigation assessed the effect of chronic blockade of kainate/quisqualate binding sites with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on preproenkephalin (PPE) and preprotachykinin (PPT) mRNA abundance in the neostriatum of the rat brain. Daily injection of CNQX for seven consecutive days decreased PPE mRNA abundance approximately 25% below vehicle-injected controls in dorsolateral, dorsomedial, anterior caudate-putamen (dlCPu, dmCPu and aCPu, respectively) and nucleus accumbens (NAc). Similarly, PPT mRNA abundance was significantly decreased in dlCPu, dmCPu and aCPu but not in the accumbens. The data demonstrate that non-NMDA receptor activity modulates basal levels of expression of PPE and PPT mRNAs in the neostriatum of the rat brain.

Characterization of the transcallosal response in aged rats and its susceptibility to nootropic drugs

The transcallosal response in aged rats was recorded and its susceptibility to certain nootropic drugs was compared with adult animals, under urethane-anesthesia. The transcallosal response in 24-month old rats was significantly reduced in the amplitude of both positive and negative waves, as compared with 5-month old animals. In adult rats, intravenous administration of 100 mg/kg of calcium hopantenate augmented the amplitude of both the positive and the negative waves. Intraperitoneal administration of 300 mg/kg of calcium hopantenate or 10–100 mg/kg of aniracetam increased the amplitude of the negative wave by 20–30% above the control level but had no effect on the positive one. In aged rats, these drugs, given intraperitoneally, also increased the negative wave without affecting the positive one and the degree of augmentation was more prominent; both drugs increased the amplitude of the negative wave by about 190% of the control. These results suggest that the susceptibility to the nootropic drugs became even more striking in older animals, the functions in the brain of which are reduced by the natural ageing process.

Transcallosal response in the medial prefrontal cortex of the monkey

Transcallosal response in the medial prefrontal cortex of the monkey

Effect of DN‐1417 on Photosensitivity and Cortically Kindled Seizure in Senegalese Baboons, Papio papio

The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.

Brain Stimulation Revisited

The results of the following selected studies using magnetic coil (MC) stimulation are presented: (1) evidence for focality of MC stimulation, (2) MC stimulation of frontal areas related to speech, (3) transcallosal responses evoked by MC stimulation, and (4) suppression of visual perception with MC stimulation over occipital cortex. The authors served as subjects, and in most studies a standard Cadwell stimulator and round MC were used. Using a more vertical, rather than tangential, MC orientation and threshold stimulation, nearly isolated movements of individual digits were elicited implying focal cortical excitation. MC stimulation of frontal areas of either hemisphere elicited electromyography in contralateral laryngeal muscles. The shortest latency responses that were often accompanied by arm movement were thought to be elicited from intermediate areas of precentral gyrus and longer latency responses, from near Broca's area, extreme lateral precentral gyrus, and the supplementary motor area. MC stimulation over the occipital cortex resulted in suppression of visual perception of letters briefly flashed on a screen. The topography of suppression implicated the geniculocalcarine system as the site of MC effect. Focal MC stimulation of posterior frontal cerebral cortex elicited a transcallosal response from contralateral homologous cortex with a latency similar to that obtained with focal anodic stimulation but with considerably less excitation of cranial muscles.

Human transcallosal response evoked by contralateral transcranial magnetic coil stimulation

Human transcallosal response evoked by contralateral transcranial magnetic coil stimulation

Effect of minaprine on synaptic transmission in the neocortex of the rat in vivo

The effects of minaprine and/or excitatory amino acid antagonists on transcallosal responses were examined in urethane-anesthetized rats. The transcallosal response was recorded from the surface of the anterior neocortex, following electrical stimulation of the contralateral corpus callosum. The transcallosal response consisted of a biphasic positive-negative waveform. Intravenously-administered minaprine increased the amplitude of the positive- and negative-waves, in a dose-dependent manner. Intracortical injection of ( ± )-2-amino-5-phosphonovalerate (APV) and gamma- d-glutamylglycine (DGG) reduced the amplitude of the negative-wave, with no effects on the amplitude of the positive-wave. l-Glutamate diethylester (GDEE) had no effect on the transcallosal response. The minaprine-induced increase in the amplitude of the negative-wave was completely antagonized by simultaneous intracortical injections of APV and DGG which, per se, did not affect that transcallosal response. In contrast, APV and DGG had no effect on the increase in the amplitude of the positive-wave induced by minaprine. The enhancing effect of minaprine on the transcallosal response remained unaltered in case of an intracortical injection of GDEE. These findings indicate that the negative-wave of the transcallosal response may be related to receptors for excitatory amino acids. The possibility that the pharmacological action of minaprine on synaptic transmission in the neocortex may be linked to the excitatory amino acid receptors warrants further attention.

Action of nootropic drugs on transcallosal responses in rats

The effects of nootropic drugs and related compounds on transcallosal responses were examined in urethane-anesthetized rats. The transcallosal response was recorded from the surface of the anterior neocortex following electrical stimulation of the contralateral corpus callosum. The transcallosal response consisted of a biphasic positive-negative waveform. Hopantenate increased the amplitude of the positive- and negative-waves, without affecting the latency. Aniracetam, idebenone, bifemelane hydrochloride, TRH and meclofenoxate increased the amplitude of the negative-wave, without affecting the latencies. Vinpocetine and eburunamonine had no effect on the transcallosal response. Muscimol, amino-oxyacetic acid, diazepam and pentobarbital increased the amplitude of the positive-wave and decreased the amplitude of the negative-wave, without affecting the latencies. Bicuculline and picrotoxin increased the amplitude of the negative-wave, without affecting the latencies. Physostigmine decreased the amplitude of the negative-wave, without affecting the latency. Atropine was without effect. The pharmacological nature of the transcallosal response is discussed, based on findings with 16 different pharmacological agents.

Transcallosal response (TCR) in the chronic photosensitive baboon preparation, Papio papio. I. Premotor cortical stimulation, recovery cycle and neurotropic drug effect

Transcallosal response (TCR) and its recovery cycle were studied in the chronic photosensitive baboon, Papio papio. Bipolar premotor intracortical stimulation evoked early positive (P1) and negative (N1) sequences followed by late small positivity (P2) and large negativity (N2) in the contralateral homotopic site. The sequential pattern of P1 and N1 was similar to that previously described in acute preparations. The recovery cycle as measured by means of paired stimuli with varying inter-stimulus intervals (ISI) showed a marked supernormality of P1 and N1 at an ISI of 15–200 msec with maximal facilitation up to 250–300% of the conditioning response at an ISI of 30–50 msec. Pentobarbital (10 mg/kg) suppressed this supernormality without causing a constant TCR amplitude change. In contrast, a significant increase in both the TCR amplitude and the supernormality of the recovery cycle was observed with a subconvulsive dose (3 mg/kg) of Megimide, a presumed antagonist of pentobarbital. Our results suggest that (a) the recovery cycle is a more sensitive measure than amplitude for assessing the effect of neurotropic drugs on TCR, and (b) the P1, N1 amplitudes and the supernormality may represent different neuronal processes involved in the TCR.

Transcallosal response (TCR) in the chronic photosensitive baboon preparation, Papio papio. II. Effect of premotor cortical kindling

The chronological pattern of transcallosal response (TCR) and its recovery cycle were studied by single or paired stimulation of the homotopic primary and the secondary (contralateral) cortical site before, during and after primary site premotor cortical kindling in Papio papio. Prior to kindling, the sequential pattern of TCR was early positive (P1), negative (N1), late small positive (P2) and large negative (N2) components. The recovery cycle of both P1 and N1 showed a marked supernormal phase at an inter-stimulus interval of 15–200 msec with a peak at about 30 msec, showing maximal facilitation up to 300%. Kindling, with or without prior low frequency cortical stimulation, resulted in a long-lasting amplitude potentiation of both P1 and N1 and a significant modification of the late components. However, a transient amplitude reduction was noted immediately following completion of stage 5 kindling, presumably due to repeated generalized convulsions. These changes occurred only during primary (kindling), but not secondary, homotopic site stimulation. These findings suggest that a persistently increased callosal transmission is probably due to primary site kindling-induced functional alteration of the synaptic site at the homotopic secondary site cortex. In contrast, the supernormal phase of the TCR recovery cycle was suppressed significantly at the secondary site cortex. Since a similar suppressive effect was observed with a small dose of pentobarbital in naive baboons, kindling is considered to produce enhancement of the inhibitory mechanism. However, a diminished suppressive effect on the supernormality 20 days after the termination of kindling suggests that this suppressive effect is transient. It is probably related to the repeated kindled convulsive seizures rather than to the kindling process itself.

Ontogenesis of transcallosal responses in cats: I. Formation of interhemispheric connections in kittens in the first month of life.

In acute experiments on kittens at the age of 1 to 30 days, anaesthesized with nembutal and immobilized with diplacine, multiple transcallosal response (TCR) recording from different cortical areas was performed. In 2-15-day kittens homotopical TCRs appeared earlier, were wider represented, and revealed a greater configuration maturity and amplitude-time parameters in associative (parietal and sensorimotor) areas as compared to projection (somatosensory, visual and auditory) zones. It has been established that interhemispheric relations in the kitten associative cortex are mediated, not only by the callosal, but also by the extracallosal system, which was evidenced by the presence of late negative components preserved after callosotomy. The results of per-layer analysis of interhemispheric responses in 1 month kittens have shown that in the parietal cortex, in the course of development, the drains of surface-positive oscillation shifted from the V to the III layer, whereas the drain of surface-negative deviation remained at the level of II-III layers. The late component was registered at the depth of layers III-IV, having a drain in the I-II layers. In the sensorimotor cortex, the surface-negative oscillation had a drain in the I-II layers, whereas the surface-positive oscillation had a drain in the II and V-VI layers. The data obtained reflect the dynamics of the formation of interhemispheric relations in the first-month-of-life kittens and testify to an increased level of their integrative interaction.

Human cerebral cortical responses to contralateral transcranial stimulation

We wished to develop a noninvasive electrophysiological measure of functioning of human cerebral cortex. The response chosen was that elicited by a corticocortical afferent input, specifically the transcallosal response (TCR). We used ourselves as subjects. The large shock artifacts associated with passing large currents through the head were reduced by: stimulating percutaneously with a focal anode (5 cm2) situated midway between F4 and C4 (i.e., frontal region, standard 10-20 nomenclature) and a medially located, semicircular grounded cathode (26 cm2) no closer than 3 to 4 cm away; and recording with the focal scalp electrode over homologous left frontal cortex vs. two or more reference electrodes interconnected through variable resistors and at least 6 cm away. Transcranial stimulation with pulses of 80 to 140 mA and lasting 100 microseconds elicited a brief diphasic deflection (latency, 2 to 4 ms), followed by an initially positive, often bifid wave with a latency of 9 to 14 ms, lasting 18 to 44 ms and reaching 5 to 10 microV. The initial diphasic deflection greatly increased when the stimulating anode was moved laterally over temporalis muscle, indicating an electromyographic (EMG) origin. The EMG, but not the positive wave, was elicited when the interpolar distance was reduced to 1 cm, which greatly reduced the fraction of current traversing the cortex (epicranial stimulation); furthermore, occluding the circulation to the scalp for 30 minutes by rubber tubing above the zygomas and brows dulled sensation, reduced the EMG, but did not alter the latency or rising phase of the positive wave. Early somatosensory components, if present, were small compared with the positive wave.(ABSTRACT TRUNCATED AT 250 WORDS)

P-282 - Pharmacological properties of transcallosal response in rats: Effects of nootropic drugs

P-282 - Pharmacological properties of transcallosal response in rats: Effects of nootropic drugs

A comparison of the postnatal development of post-activation potentiation in the neocortex and dentate gyrus of the rat

The postnatal development of short-term potentiation (STP) and long-term potentation (LTP) was examined in the neocortex and dentate gyrus of rats aged 7 days to adult. STP and LTP of the transcallosal response in the neocortex could not be demonstrated until the third postnatal week. STP and LTP of the perforant path-dentate response could not be demonstrated until the second postnatal week. In both cases, STP appeared several days before LTP. Structural and neurochemical correlates of STP/LTP development, and their implications for possible STP/LTP mechanisms, are discussed.

The postnatal development of post-activation potentiation in the rat neocortex

The postnatal development of short-term potentiation (STP) and long-term potentiation (LTP) of the transcallosal response (TCR) was examined in anesthetized rats, aged 7 days (PN7) to adult (⩾ PN 180). Stimulation of callosal fibers produced a biphasic, positive-negative TCR recorded at the surface of the anterior neocortex in all age groups. The TCR showed a decrease in threshold, latency and halfwidth, and an increase in peak amplitude with age. High frequency callosal stimulation produced marked STP and LTP of the mature TCR. STP in young animals, however, could not be reliably detected until after PN16. LTP was not detected until PN18. STP and LTP approached adult levels rapidly after their initial appearance. The correlations between STP/LTP onset and development and known structural developments such as initial synaptogenesis, spine formation and myelinogenesis were not particularly strong. The implications of these results for specific hypotheses of STP/LTP mechanisms were discussed.