The effect of experimentally induced seizure activity on the functional reorganization of motor maps has not previously been investigated. Furthermore, while the functional reorganization of motor maps has been thought to involve increases in synaptic communication, there has yet to be a test of this hypothesis. Here we show that repeated seizure activity (kindling), that is accompanied by increased synaptic strength within adult rat motor cortex, results in a doubling of the caudal forelimb motor area. We measured neo-cortical evoked potentials in the right hemisphere prior to 25 days of electrical kindling of the medial frontal corpus callosum or amygdala and re-measured them either 1 or 21 days following the last kindling session. Then, using high resolution intracortical microstimulation (ICMS), the caudal forelimb area in the left hemisphere was mapped. This is the first report of any procedure causing a motor representation to double in size. Furthermore, this expansion was related to the enhanced area of a neocortical polysynaptic field potential and not the motor convulsions per se. Moreover, both the motor map and field potential enhancements were persistent in nature and could be driven from either cortical or limbic sites. The data have implications for human populations with epilepsy.
The presence of a highly ordered somatotopic map of movement representations within the human precentral gyrus has been known for decades (Penfield and Rasmussen, 1950). Much of the initial characterization of these motor maps came from intra-cortical stimulation experiments conducted on human patients prior to surgery intended to alleviate epileptic seizures. Recent work has shown that stimulation evoked movements in some people with epilepsy could be elicited from regions well outside the classic motor strip located along the Rolandic fissure (Uematsu et al., 1992). These data suggest that changes in the topography of movement representations within the primary motor cortex may occur in response to recurrent seizure activity. They also suggest that the classic depictions of cortical representations that have been found to be biased (Servos et al., 1999) may be due to the fact that they were obtained from tissue exposed to chronic epileptiform activity.
Functional reorganization of motor maps in non-humans has been observed in response to a number of experimental manipulations including differential motor training (Nudo et al., 1996; Kleim et al., 1998, 2000, 2001), tactile experience (Keller et al., 1996; Huntley, 1997), sensory deafferentation (Donoghue et al., 1990; Wu and Kaas, 1999), ischemic stroke (Nudo and Milliken, 1996) and focal intracortical micro-stimulation (Nudo et al., 1996). Although the neural mechanisms underlying this reorganization remain to be determined, enhanced synaptic strength has been proposed (Hess and Donoghue, 1994). Indeed, behavioral manipulations that result in motor map reorganization (Kleim et al., 1998, 2000, 2001) have also been shown to induce synaptic potentiation within motor cortex (Rioult-Pedotti et al., 1998, 2000). Thus, repeated seizure activity (kindling), which is known to induce enhanced synaptic responses (deJonge and Racine, 1987; Racine et al., 1991, 1995; Teskey et al., 1999), should also be directly related to changes in motor map organization. In the present experiment, we test the hypothesis that kindling-induced synaptic potentiation within the motor cortex is related to the topography of cortical movement representations. The caudal forelimb area (CFA) was specifically chosen for analysis because of previous work showing the capacity for reorganization in response to various behavioral manipulations (Kleim et al., 2001; Remple et al., 2001). We also explored whether alternations in the CFA motor map were persistent in nature, could be driven from cortical and limbic sites and the role of motor convulsions in the absence of synaptic enhancement.
Materials and Methods
The data of this report are based on 15 male rats weighing 370–560 g at the time of initial surgery. All rats were of the Long–Evans hooded variety and were obtained from the University of Calgary Breeding Colonies. Animals were housed individually in clear plastic cages in a colony room that was maintained on a 12 h on/12 h off light cycle. All experimentation was conducted in the light phase. Rats were maintained on Lab Diet #5001 (PMI Feeds Inc., St Louis, MO) and water ad libitum. The rats were handled and maintained according to the Canadian Council for Animal Care guidelines.
Twisted wire bipolar stimulating and recording electrodes were prepared from Teflon-coated stainless steel wire, 178 μm in diameter (A-M Systems, Everett, WA). Uninsulated ends of the electrodes were connected to gold-plated male amphenol pins. The two poles of the electrodes were separated by 1.0 mm. Animals were anesthetized with 58.83 mg/kg ketamine (85%) and xylazine (15%) at 0.5 ml/kg, injected intramuscularly. Lidocaine 2% (Austin, Joliette, QC), a local anesthetic, was administered subcutaneously at the incision site.
Two bipolar electrodes were chronically implanted in the left hemi-sphere according to the stereotaxic coordinates of Swanson (Swanson, 1992). The stimulating electrode was implanted 1.0 mm anterior to bregma on the midline in the callosal white matter, which was approximately the mid-coronal plane of the caudal forelimb area. The recording electrode was implanted 1.0 mm anterior to bregma and 4.0 mm lateral to midline in the frontal neocortex. Five animals that had callosal and neocortical electrodes also received a third electrode implanted 1.0 mm anterior to bregma, 6.0 mm lateral to midline and 8.0 mm ventral to surface in the amygdala. Electrophysiological monitoring was performed during the surgery so that the dorsal–ventral placements could be adjusted for maximal evoked response amplitude.
Gold-plated male amphenol pins connected to the electrodes were inserted into a nine-pin McIntyre connector plug, adhered to the skull with four stainless steel screws and dental cement. One of the stainless steel screws served as the ground reference. Experimental procedures commenced no earlier than 7 days post surgical implantation.
The rats with electrodes in the callosum and neocortex were divided into four groups: those receiving 25 kindling sessions and mapped 1 day (n = 3) or 21 days (n = 3) following the last seizure and the electrode implanted non-kindled control rats mapped 1 (n = 2) or 21 days (n = 2) following the last sham seizure. The group of amygdala-kindled animals were mapped 1 day following the last seizure (n = 5).
Baseline input–output (I/O) measures were conducted for two consecutive days prior to kindling. This was accomplished by administering pulses of increasing intensity to the callosal white matter and recording the resultant evoked potentials from the frontal neocortical electrode. The stimulation pulses consisted of biphasic rectangular waves, 200 μs in duration and separated by 200 μs. Ten stimulation pulses were delivered at each of the ascending logarithmic intensities (10, 32, 46, 68, 100, 147, 215, 316, 464, 681 and 1000 μA) at a frequency of 0.1 Hz. Stimulation voltages were computer generated, then converted to an amperage via a current constant current and isolation unit (World Precision Instruments, Sarasota, FL). The recorded signals were filtered, at half amplitude, below 1 Hz and above 100 Hz and then amplified 1000 or 2000 times (Grass Neurodata Acquisition System Model 12). The analog signals were digitized at a sampling rate of five points per ms and the averaged evoked potential, at each intensity, was stored to computer hard disk (Datawave, Denver, CO). Only animals that had a stable baseline I/O were used for experimentation. There were two additional rats that underwent the kindling protocol and were rejected from subsequent evoked potential and mapping analysis. All I/O measures were conducted while the animals were immobile. This was necessary because ongoing behavior can dramatically effect the size and shape of the evoked potentials (Teskey and Valentine, 1998).
Following the second I/O, an afterdischarge threshold (ADT) was determined for each animal in the kindling groups. The ADTs were defined as the weakest current required to induce an afterdischarge (AD). The current delivered commenced at 100 μA, increasing in steps of 50 μA and was delivered at 60 s intervals until an AD of at least 4 s or longer was recorded. The EEG signal was filtered as described above. Kindling stimulation was delivered to awake, freely moving rats.
Once daily, kindling stimulation was delivered through the electrode positioned in the callosal white matter or amygdala, depending on group designation. Stimulation consisted of a 1 s train of 60 Hz biphasic rectangular wave pulses, 1 ms in duration and separated by 1 ms, at an intensity 100 μA greater than ADT levels. A paper record of the resultant AD was obtained from both electrodes and the seizure behaviors were noted.
A single follow-up I/O was obtained 24 h or 20 days after the last kindling session. The AD from the neocortical recording electrode was scored for duration. The seizure behaviors were monitored and scored according to a five-stage scale (Racine, 1972) as well as tonic turning and twisting of the head and torso (Racine, 1975; Burnham, 1978).
Evoked Potential Analysis
Evoked potentials obtained pre- and post-neocortical kindling were measured for change in the area of the EPSP late component. The EPSP late component was chosen for analysis because it displays the largest and most consistent change (Trepel and Racine, 1998). The late component was designated as the surface negative component occurring between 12 and 40 ms post stimulation. The late component area score was calculated by summing all the difference values (every 200 μs) from the two evoked potentials, between the two crossing points (12–40 ms), and then dividing by the amount of amplification (Teskey and Valentine, 1998). Only potentials evoked with 681 μA were statistically analyzed. Refer to Figure 2a for an illustration of the evoked potentials and late component area.
Motor Cortex Mapping
Standard intracortical microstimulation (ICMS) techniques were used to generate detailed maps of forelimb regions of the motor cortex (Kleim et al., 2001) by experimenters that were unaware of the rats treatment condition. Prior to this surgery, rats were anaesthetized with ketamine hydrochloride (70 mg/kg i.p.) and xylazine (5 mg/kg i.p.), receiving acepromazine (0.02 mg/kg i.m.) and ketamine (20 mg/kg i.p.) as needed. A craniotomy was performed over the right motor cortex contralateral to the kindling electrode assembly and the dura removed. The exposed cortex was then covered with warm (37.4°C) silicone oil. A small puncture was also made in the cisterna magna to reduce cortical edema. A glass microelectrode (controlled by a hydraulic microdrive) was used to make penetrations to a depth of ~1550 μm (corresponding to cortical layer V) with an interpenetration distance of 375 μm. Stimulation consisted of 13, 200 μm cathodal pulses delivered at 350 Hz from an electrically isolated stimulation circuit. Animals were maintained in a prone position, with the limb supported in a consistent position. At each penetration site, the minimal threshold required to elicit a movement was recorded, and sites where no movement was detected at ≤60 μA were recorded as unresponsive. Level of anesthesia was assessed by both monitoring breathing rate and by revisiting positive response sites to check for changes in movement threshold as mapping progressed. To further assess the effects of kindling on movement representations, the stimulating current was gradually increased from the threshold at which the primary movement was detected until a second, additional movement was observed or the current reached 60 μA. Forelimb movements were classified as either distal (wrist/digit) or proximal (elbow/shoulder) and representational maps were generated from the pattern of electrode penetrations. An image analysis program (CANVAS v. 3.5) was used to calculate the areal extent of the caudal forelimb area (CFA). The CFA is separated from the rostral forelimb area (RFA) by a band of neck/whisker representations (Kleim et al., 1998) and was chosen for analysis because of previous work showing the capacity for reorganization in response to various behavioral manipulations (Kleim et al., 2001; Remple et al., 2001). Changes in the topography of movement representations within the RFA has been more difficult to detect (Kleim et al., 1998). The proportion of both distal and proximal movement categories that occupied the CFA was then calculated. The mean stimulation threshold for each movement category was also calculated.
Statistical significance was determined with a two-factor mixed design ANOVA for AD duration and behavioral convulsions. A between-subjects t-test was used on the current intensity for eliciting a movement (thresh-old) and amount of anesthetic data. Non-parametric Mann–Whitney U tests were performed on map area measures. A linear regression analysis was performed on late component and map area measures. All statistical testing was done with an a priori alpha level of 0.05%.
Effects of Kindling
The mean AD threshold and associated standard errors for the callosum and amygdala-kindled rats were 328.6 ± 74.7 and 216.7 ± 30.7 μA, respectively. Afterdischarge durations and seizure stages for rats electrically kindled in the medial frontal corpus callosum and amygdala are summarized in Figure 1.
The callosum-kindled group displayed a relatively shallow increase in AD duration with repeated stimulation. This group displayed an initial AD duration of 16.8 ± 2.7 s (SEM), which increased to 29.8 ± 8.14 s following the 25th stimulation. The amygdala-kindled group displayed a more steeply graded in-crease in AD duration with repeated stimulation. The amygdala group had an initial AD duration of 17.7 ± 3.3 s, which increased to 46.0 ± 8.0 s following the 25th stimulation. An ANOVA on the AD duration (Group × Time) revealed a significant main effect of Time [F(24, 264) = 3.03, P < 0.0001] and Group [F(1,11) = 14.17, P = 0.003] as well as a significant [F(24, 264) = 2.17, P = 0.002] Time × Group interaction. Both the callosum- and amygdala-kindled groups showed progressive increases in their AD durations with repeated stimulations.
Callosal kindling stimulation evoked a stimulation-bound forced motor response in all animals. The animals would roll to one side and display a tonic extension of one or both forelimbs, and an open mouth. Callosum-kindled rats displayed stage 3 seizure behaviors on the first kindling day. The initial short clonic or focal seizure, consisted of mouth movements and forelimb clonus. The focal seizures became more intense with repeated stimulations, with a tonic component developing and eventually a late clonic component that generalized into a limbic-type stage 5 seizure. The callosum-kindled group displayed an initial seizure stage of 3.0 ± 0.3 (SEM), which increased to 4.6 ± 0.2 following the 25th stimulation. The amygdala-kindled group displayed an initial seizure stage of 0.5 ± 0.2, which increased to all animals displaying a stage 5 following the 25th stimulation. An ANOVA on the seizure stage behaviors (Group × Time) revealed a significant main effect of Time [F(24, 264) = 17.7, P < 0.0001] and a significant [F(24, 264) = 4.96, P < 0.0001] Time × Group interaction. There was no significant main effect of Group, however the callosum and amygdala groups did show significantly [t(12) = 6.6, P < 0.0001] different seizure stages on the first kindling session. The callosum- and amygdala-kindled groups showed progressive increases in seizure severity with repeated stimulations.
Effects of Kindling on Synaptic Potentiation
Brief stimulation of the corpus callosum gave rise to a stable and reliable waveform composed of an EPSP/IPSP sequence that has been described previously (Racine et al., 1995; Chapman et al., 1998; Teskey et al., 1999). The thresholds for the evoked potentials ranged from 46 to 100 μA and reached maximum levels at 1000 μA. In most animals, the late component of the evoked potential was not clearly present in the pre-kindling responses but was reliably present in all of the cortically kindled animals and three out of five amygdala-kindled animals (Fig. 2a). A comparison of the field potentials and I/O curves before and after 25 kindling stimulations showed that there were no changes in the threshold intensity for obtaining an evoked potential and that the largest changes in the late component area were usually found to be evoked by 484 and 681 μA of current. There was a decrease in the late component area for sham rats over time (Fig. 2b). Twenty-five days of callosal kindling resulted in a significantly larger late component area of the callosal–neocortical evoked potential, 1 and 21 days after the last seizure (P < 0.05, both cases). Twenty-five days of amygdala kindling also resulted in a larger late component area of the callosal–neocortical evoked potential in three of five of those rats (P < 0.05).
Effects of Kindling on Motor Representations
The mean ± SD amounts of ketamine, as a function of body weight and duration of surgery, administered to the control and kindled rats, were 0.0013 ± 0.0004 and 0.0011 ± 0.0004 ml/kg per min, respectively, and were not significantly (P = 0.48) different. Furthermore, the mean ± SD current intensities (thresholds) required to elicit forelimb motor responses between the control and kindled rats were 25.25 ± 3.99 and 22.01 ± 7.26 μA, respectively, and were also not significantly (P = 0.23) different.
The cortical area that elicited digit, wrist, elbow and shoulder movements in the forelimbs, as well as the number of dual site and bilateral responses were analyzed in kindled and electrode implanted non-kindled control rats. We observed significant (U = 2.47, P < 0.05, all comparisons) increases in the total caudal forelimb area in the kindled rats, that displayed cortical kindling-induced potentiation, 1 and 21 days following the last seizure, as compared to non-kindled controls (Figs 3a,b and 4a). The caudal forelimb area in kindled rats expanded in the rostral, caudal, medial and lateral directions relative to the kindling electrode. The total forelimb area in these kindled rats was 197% of the control non-kindled rats. This kindling-induced expansion was due to a significant (U = 2.47, P < 0.05, for all groups) increase in the wrist/digit area representation (Fig. 4b). The elbow/shoulder area representations were not significantly different following kindling (Fig. 4c).
When ICMS intensities were increased, more dual site responses were observed in kindled animals relative to non-kindled control rats (Fig. 3c,d). When the increased map area of the kindled rats was taken into account, there was a trend to proportionately more dual-site responses in kindled rats, but this did not reach statistical significance (P = 0.07). However, kindling did result in bilateral motor responses in three callosum-kindled rats, a result that was not observed in any of the control rats.
A linear regression analysis revealed a significant (P < 0.0001) relationship between the evoked potential late component area and caudal forelimb motor map area that is described by the equation Y = 8.5X – 35.6 (Fig. 5). An r value of 0.86 indicated a high positive correlation between the evoked potential late component area and forelimb motor map area. Thus, knowledge of the evoked potential late component area accounted for 74% of the variance in forelimb motor map area, leaving only 26% of the variance unaccounted for.
The present results have shown that the repeated elicitation of seizures in the anterior callosum and amygdala lead to progressively enhanced AD duration and more severe behavioral seizures which confirm previous observations (Racine, 1972, 1975; Seidel and Corcoran, 1986; Racine et al., 1991, 1995; Teskey et al., 1999). In association with the kindled seizures, we observed synaptic potentiation of the callosal–neocortical evoked potential late component in all the rats kindled in the callosum and three of five rats kindled in the amygdala. These same rats also displayed expanded caudal forelimb movement representations in the rostral, caudal, medial and lateral directions, that went well beyond the boundaries determined in the non-potentiated kindled rats and non-kindled control rats. The dramatically expanded forelimb movement representations in the kindled potentiated rats were not a result of alterations in anesthetic levels, stimulation sensitivity (thresholds) or a simple expansion into the rostral forelimb region. Thus, it appears that changes in the topography of cortical movement representations may be mediated by synaptic enhancement. Because there are a number of electrophysiological, anatomical and neurochemical similarities between the synaptic potentiation and expanded movement representations measures, a common mechanism is suggested.
From an electrophysiological perspective, the threshold for eliciting an evoked potential, as well as the ICMS threshold for eliciting a movement, were equivalent for the non-kindled and kindled rats. When evoked potential thresholds are equivalent, before and after kindling, this indicates that the number of fibers activated has remained constant (deJonge and Racine, 1987), and that kindling did not result in either sensitization or desensitization of the tissue. Likewise, the equivalent ICMS currents required to elicit a movement representation in the non-kindled and kindled rats indicate that kindling did not alter the basic threshold sensitivity of the tissue (Kleim et al., 1998). We also observed that the kindling-induced enhanced synaptic potentiation and expanded caudal forelimb motor map were expressed both 1 and 21 days after the last seizure. In neither case was there a significant decrement in either the size of the synaptic potentiation or size of movement representations over the recording time period. While previous studies have shown short-term boundary changes within forelimb area, this is the first report of both expanded and persistent forelimb area maps. Kleim, Barbay and Nudo showed that motor skill learning of a reaching task resulted in an expansion of wrist/digit representations, but only at the expense of elbow/shoulder representations (Kleim et al., 1998). Using repetitive ICMS, Nudo, Jenkins and Merzenich also showed a short-term expansion and subsequent retraction of boundaries within forelimb motor cortex (Nudo et al., 1990). Our observation of persistent evoked potential and movement representations also indicates that these effects were not directly seizure related and transiently expressed but were related to the more long-term nature of kindling (Goddard et al., 1969; Dennison et al., 1995).
From an anatomical perspective, a previous study using current source density analysis revealed the callosal–neocortical potentiated late component to have a sink in upper layer V and a source located in deep layer V (Chapman et al., 1998). This source is likely polysynaptic in nature because it failed to be expressed when stimulations were delivered at high frequencies (Chapman et al., 1998). Because ICMS appears to elicit movement by stimulating horizontal fibers within the cortex rather than via direct stimulation of corticospinal neurons (Jankowska et al., 1975; Lemon et al., 1987), the enhanced polysynaptic response may be responsible for the expanded motor representations as well as the increased dual site and bilateral movement representations. Stimulation-induced potentiation of horizontal fibers has been demonstrated in vitro and has been proposed as the mechanism underlying functional reorganization within motor cortex (Hess and Donoghue, 1994). ICMS-induced movements are most easily elicited when the stimulating electrode is located within layer V and it is likely that map expansion is primarily mediated by potentiated layer V currents. While we have shown that late component potentiation currents correlate with expanded motor maps, it is possible that there are other contributions, such as increased monosynaptic drive onto layer V neurons, other cells that polysynaptically activate layer V, and potentiation of other intracortical horizontal connections, that may contribute to the observed changes.
The callosal–neocortical evoked potential is primarily a glutamate-mediated EPSP to GABA-mediated IPSP sequence (Metherate and Ashe, 1994; Trepel and Racine, 1998). From a neurochemical perspective, kindling has been shown to result in alterations of both glutamatergic and GABAergic transmission, the two dominant excitatory and inhibitory intracortical neuro-transmitters within motor cortex (Keller, 1993). Kindling has been shown to be associated with the recruitment of previously ‘dormant’ NMDA receptors (Mody and Heinemann, 1987; Mody et al., 1988) which manifest prolonged openings, bursts, clusters and superclusters of NMDA channel activity (Köhr et al., 1993). Following kindling, there is also an increase in glutamate agonist potency (Köhr and Mody, 1994) mediated through reduced affinity of the channel pore to Mg2 + and an enhanced phosphorylation state of the channels that last for at least as long as 60 days after kindling (Köhr et al., 1993). A role for altered glutamate neurotransmission in the motor map expansion is possible because application of NMDA antagonists has been shown to block motor cortex map plasticity induced by passive limb movements (Qiu et al., 1990). With respect to long-term changes in GABA-mediated neurotransmission following kind-ling, there is a report of a kindling-induced loss of GABAergic inhibition (Lopes da Silva et al., 1995), although this result has not been reported for all brain sites investigated (Tuff et al., 1983). Thus, a potential neurochemical mechanism for motor cortex reorganization is that adjacent cortical regions expand when preexisting lateral excitatory connections are unmasked by decreased intracortical inhibition (Jacobs and Donoghue, 1991). This potentiation has also been shown to depend upon the presence of GABA antagonists (Hess et al., 1996). Thus, both suppression of GABAergic synapses and enhancement of glutamatergic-mediated currents may underlie the synaptic potentiation and increase in movement representations observed in the kindled animals.
While previous work has shown that kindling-induced seizure activity can occur without synaptic potentiation (Giacchino et al., 1984; Maru, 1991), this is the first report of kindling-induced potentiation of the callosal–neocortical evoked late component in animals kindled in the amygdala. The failure to find kindling-induced potentiation in some of the rats that displayed well-developed seizures is also important because we can conclude that it is not the seizure-related motor activity that results in expanded motor representation but the potentiated synaptic responses. This is consistent with the observation that synaptic potentiation of horizontal afferents (Rioult-Pedotti, 1998, 2000) and reorganization of movement representations (Kleim et al., 1998, 2001) have been observed within rat motor cortex following skilled forelimb training but did not occur in animals experiencing increased motor activity in the absence of skilled training (Kleim et al., 2000).
It is important to point out that the area of cortex defined as forelimb motor cortex is highly dependent upon the methods used during mapping. Stimulation parameters such as current intensity, pulse train, stimulation frequency as well as anesthetic can all affect the size of the motor map (Donoghue and Wise, 1982). Thus, baseline maps reported in any experiment are dependent upon the techniques used. The topography of movement representations in control animals in the present experiment are consistent with those of previous experiments using similar stimulation parameters (Gioanni and Lamarche, 1985; Kleim et al., 1998; Castro-Alamancos and Borrel, 1995). The primary finding of the study is that under identical stimulation parameters, kindled animals exhibited a profound increase in the area of cortex from which forelimb movements could be elicited. This is not to say that the expanded areas necessarily represents ‘new’ areas of forelimb motor cortex. Rather, these areas have undergone some functional change due to the kindling experience. This functional change facilitates the ability to elicit forelimb movements from regions of cortex that would not previously produce movements in response to similar stimulation.
Taken together, our observations of changes in the topography of cortical movement representations appear to be mediated by synaptic enhancement. In contrast to the doubling of map size observed in kindled animals, training-induced map reorganization is characterized by an expansion of ‘trained’ movement representations into ‘untrained’ representations, without an overall increase in the size of the map. This suggests that behaviorally driven changes in map topography involve specific changes in synaptic strength and, thus, the distribution of movement representations that reflects the training experience. Seizure-driven map reorganization may involve more ‘indiscriminant’ synaptic plasticity that results in an overall expansion of movement representations. Alternatively, it may be the case that the neocortex is reorganized as a compensatory response to epileptiform activity so that functional movement representations are not lost to a developing pathological focus. Our observations of expanded motor representations in kindled rats are similar to observations from epileptic patients that were stimulated through subdural electrodes. Uematsu et al. found that 12 out of 35 patients with seizure disorders had motor responses that were distributed outside the classic motor strip immediately anterior to the Rolandic fissure (Uematsu et al., 1992). Likewise, Urasaki et al. reported that paradoxical tongue motor responses occurred in 9 out of 28 epileptic patients without organic lesions (Urasaki et al., 1994). Thus, it appears that repeated seizure activity in humans and non-humans can alter functional reorganization of motor cortex. Future studies should determine the details of the mechanisms responsible for the synaptic potentiation and movement representation expansion and further determine why some non-humans and humans show the seizure-induced enhancements while others do not.
Supported by an NSERC grant to G.C.T. and by AHFMR, CFN, NSERC and CIHR grants to J.A.K.