Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation
Introduction
Cortical dysgenesis (CD) is a heterogeneous disorder of cerebral cortex development frequently associated with epilepsy (Raymond et al., 1995). In patients who underwent epilepsy surgery for intractable seizures, neuropathological studies and intraoperative as well as in vitro electrophysiological investigations have shown striking cytoarchitectonic changes and intrinsic epileptogenicity of dysgenic cortex, respectively (Palmini et al., 1995, Preul et al., 1997). Moreover, studies in animal models suggested altered connections between dysgenic areas and other cortical regions (Colacitti et al., 1998).
Transcranial magnetic stimulation (TMS) provides a non-invasive evaluation of distinct excitatory and inhibitory functions of the human cerebral cortex (for recent review, see Rossini and Rossi (1998)). In particular, the TMS-induced post-excitatory suppression of the voluntary EMG activity mainly depends on interneuronal inhibition within the contralateral primary motor cortex (M1) (Fuhr et al., 1991, Cantello et al., 1992, Inghilleri et al., 1993, Roick et al., 1993). These inhibitory circuits are modulated by various cortical and subcortical areas projecting to the M1 (von Giesen et al., 1994, Classen et al., 1997). Recently, interictal modifications of this cortical silent period (CSP) have been described in patients with cryptogenic motor cortex epilepsy (Cincotta et al., 1998).
In reference to CD patients, limited information about motor evoked potentials (MEPs) is available (Di Capua et al., 1993, Maegaki et al., 1995). On the contrary, to our knowledge, data addressing the CSP have not been previously reported. We present 3 consecutive adult patients with focal CD located outside the M1.
Section snippets
Subjects
Patient 1, a 24-year-old man, had had 4 complex partial seizures consisting of vertiginous sensation followed by loss of consciousness since the age of 17 years. MRI showed right parietal/temporal heterotopia and parietal gyral simplification associated with a retrocerebellar arachnoid cyst (Fig. 1). He became seizure-free after introduction of carbamazepine (CBZ) at 600 mg/day. The present neurophysiological studies were performed at least 13 months after the last seizure.
Patient 2, a
Results
Neurophysiological findings are given in Table 1. In all 3 patients, ET, as well as peripheral and corticospinal motor conduction studies, were within normal limits on both sides; however, the ET was shifted toward the upper limit of the normal range in patients 1 and 2. In patients 1 and 2, the CSP in the left FDI was significantly prolonged at both stimulus intensities. In patient 1, the CSP in the right FDI was normal at both stimulus intensities, although a shift toward the higher normal
Discussion
The principal finding of the present study is that the CSP was significantly prolonged in each patient with focal CD located outside the M1. Patient 1 was treated with CBZ and patient 2 was on CBZ and VGB. In normals, a single CBZ dose lengthens the CSP duration by up to 30 ms, whereas VGB is ineffective (Ziemann et al., 1996, Mavroudakis et al., 1997). Moreover, both patients 1 and 2 showed a bilateral shift of the ET toward the higher normal values, probably resulting from CBZ treatment (
Acknowledgements
We are grateful to Dr M. Hallett and Dr N.J. Patronas for helpful advice and criticism and to Ms A. Minnis for skilful language revision.
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2015, Journal of Neuroscience MethodsCitation Excerpt :In addition, iSP duration traditionally increases as stimulation intensity raises (Chen et al., 2003): however, in our experiment, iSP shortened after anodal tsDCS, when paradoxically higher TMS intensities were applied compared with baseline and sham condition. Second, although iSP has been proposed as a synonymous of transcallosal inhibition (Chen et al., 2003; Cincotta et al., 1996, 2000; Trompetto et al., 2004; Wassermann et al., 1994), no conclusive remark has been reached so far. Another possibility is that iSP could be generated, at least in part, within subcortical motor tracts with bilateral projections to brainstem or spinal cord through a complex interneuronal network with inhibitory effects on alpha motorneurons (Gerloff et al., 1998; Mazevet et al., 1996).
A meta-analysis of the cortical silent period in epilepsies
2015, Brain StimulationCitation Excerpt :The CSP lengthens with the TMS intensity up to a duration in the order of hundreds of milliseconds [7,8]. Spinal mechanisms may contribute to the first part of the CSP, whereas the latter part depends on inhibitory phenomena in the M1 [3,9–11] and is modulated by various cortical and subcortical areas [12]. Neuropharmacologic data suggest that the CSP mainly reflects GABAB-mediated inhibition (for review, see Tassinari et al., Cincotta et al., and Ziemann et al., [3,4,13]).
Epilepsy
2013, Handbook of Clinical NeurologyCitation Excerpt :Increased cortical excitability in patients with juvenile myoclonic epilepsy has been shown by a spTMS–EEG protocol, and an interesting extension of these data may be to test whether extramotor LICI TMS–EEG abnormalities are present in the epilepsy population (Del Felice et al., 2011). However, as number of TMS–EMG experiments show motor cortex abnormalities in patients with extramotor and generalized epilepsies, further studies are required to test whether interrogating focal cortical excitability outside of the motor cortex by TMS–EEG is of any greater clinical value than checking TMS–EMG measures (Cincotta et al., 2000; Loscher et al., 2007; Groppa et al., 2008). Another interesting role for TMS–EEG in epilepsy may be as a neurological stressor to provoke epileptiform activity in a vulnerable patient or in a vulnerable cortical region.
Changes in intracortical excitability after successful epilepsy surgery
2008, Epilepsy ResearchCitation Excerpt :The mechanisms underlying these changes remain to be elucidated; a lower local inhibitory level caused by the presence of an excitatory epileptic focus may be hypothesized. This finding is not unique; several studies with focal epileptic patients support the notion that the focus exerts bilateral effects which may even be stronger on the non-focal hemisphere (Classen et al., 1995; Cincotta et al., 1998, 2000; Cicinelli et al., 2000; Fong et al., 1993; Hamer et al., 2005; Inghilleri et al., 1998). Our data based on a comparison of pre- and postsurgical stimulation support this notion.
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2008, Clinical NeurophysiologyCitation Excerpt :Finally, interhemispheric difference in MT can be exaggerated in patients with asymmetric motor seizures (Aguglia et al., 2000), supporting a role for interhemispheric imbalance of cortical excitability in mediating lateralized ictal events. Prolonged SP was reported in patients with untreated IGE (Macdonell et al., 2001) and in patients with partial motor seizures, whether the lesion was located within or outside the primary motor cortex (Classen et al., 1995; Cincotta et al., 1998, 2000). These findings may be due to spread of epileptic hyperexcitability to corticospinal inhibitory networks, or alteration in motor control independent of epilepsy.