Presurgical Motor Mapping With Transcranial Magnetic Stimulation (TMS)

This study will be an open-label feasibility study which applies nTMS to subjects with
incoming epilepsy surgery and pre-surgical motor mapping. No study-related medication changes
are expected -- participants will remain compliant with their regular anticonvulsant regimen
throughout each study phase. All patients will have undergone a complete history and
neurological exam as part of their routine clinical care at the New York University (NYU)
Comprehensive Epilepsy Center.

Fourteen (14) patients will undergo epilepsy surgery with expected subdural grid coverage
over primary motor cortex. Potential subjects will be identified at the weekly
multi-disciplinary epilepsy conference. Subjects must have a recent (<2 years) MRI scan, and
registration of the TMS coil to the MRI scan via the Brainsight neuronavigation system will
be utilized to guide TMS coil placement (Gugino et al 2001). When a presurgical fMRI
(functional magnetic resonance imaging) is available which demonstrates the patient's hand
knob, the fMRI will be used with the Brainsight neuronavigation system. Subjects will be
recruited and consented during a presurgical clinical visit where the patient's primary
epileptologist will introduce members of the research team.

nTMS mapping

Patients will receive a session of single-pulse TMS mapping of the motor area, at the
outpatient TMS clinic at NYU Neurology Ambulatory Care Center, at 240 E 38th St 20th Floor
prior their epilepsy surgery according to the following procedures:

1. Determination of the motor threshold by (1) finding the most excitable region in the
hand knob which elicits the strongest compound muscle action potential (CMAP) in the APB
muscle; (2) finding the motor threshold by determining output stimulation intensity
which generates peak to peak CMAP response above 50 mV (Millivolts) in 5/10 stimulation
cycles (Rossini et al., 1994).

2. Concurrent EMG will be measured with electrodes placed at APB (abductor policis brevis
atrial premature beat), abductor digiti minimi, flexor carpiradialis muscles. Reference
electrode will be placed at the ipsilateral elbow above the brachial biceps muscle.

3. Mapping of the upper extremity. After determination of the MT (motor threshold), mapping
of the UE(Upper Extremity) will be performed at 110% of the rMT (resting motor
threshold). All positive and negative stimulation sites will be recorded and saved.
Patients will be closely monitored during TMS stimulation. Each subject will have a
complete neurological examined by a neurologist before and immediately after nTMS.
Patients will also be provided a side effects questionnaire after TMS mapping. Patients
will then be asked to keep a 7 day seizure diary after the nTMS session.

After epilepsy surgery patients will receive the standard care for post-operative patients
which including close monitoring in ICU overnight. Patients will be transferred to the floor
for further clinical evaluation before discharge. Clinical outcome will be evaluated in the
post-operative clinic visit within 1 month after discharge. The value of a clinical follow up
is to evaluate for any discrepancy between nTMS and DCS, to determine which modality better
predicts functional outcome. Any seizure recurrence or neurological deficit will be recorded
at the follow-up clinical visit.

The trial is designed to detect strength of spatial correlation between topographic maps of
hand motor representation obtained through noninvasive nTMS compared to direct,
extra-operative cortical stimulation obtained as part of usual clinical evaluation during
epilepsy surgery, as measured by (a) average distance between positive motor mapping sites of
DCS compared to nTMS and (b) degree of concordance between positive and negative motor
mapping sites between DCS and nTMS, to generate positive and negative predictive values, and
(c) average distance between positive motor functional sites of fMRI compared to nTMS.

Inclusion Criteria:

- 12-60 years of age

- Planned neurosurgery involving implantation subdural electrodes over the precentral
gyrus

Exclusion Criteria:

- Inability to sign informed consent .

- Hemiparesis worse than 4-/5 on the side contra lateral to the planned implant

- Inability to get an MRI, or MRI older than 2 years

- Frequent (>1 per day) motor seizures

- Prior neurosurgery

- Metal in the head, including shrapnel

- Implanted stimulation devices, including DBS (Deep Brain Stimulator), RNS (Responsive
Neurostimulator), VNS (Vagus Nerve Stimulator), PPM (Permanent Pacemaker)

- Pregnancy

- Use of a medication known to increase the risk of seizures, including certain
antipsychotics (clozapine), bronchodilators (aminophylline, theophylline),
immunomodulatory agents (cyclosporine), and antibiotics (penicillins, cephalosporins,
amphotericin, imipenem)