The subcortical hidden side of focal motor seizures: evidence from micro-recordings and local field potentials

Abstract

Focal motor seizures are characterized by transient motor behaviour that occurs simultaneously with paroxystic activity in the controlateral motor cortex. The implication of the basal ganglia has already been shown for generalized seizure but the propagation pathways from the motor cortex towards the basal ganglia during focal motor seizures are largely unknown. With a better knowledge of those pathways, a therapeutic modulation for reducing drug resistant motor epilepsy could be considered. Here, we recorded single-unit activities and local field potentials in the basal ganglia of two Macaca fascicularis in which acute focal motor seizures were induced by the injection of penicillin over the arm motor cortex territory. Each neuron was characterized using its mean firing rate and its type of firing pattern during interictal periods and seizures. Time-frequency analyses of local field potentials and electroencephalographic signals were used to assess dynamic changes occurring during seizure at a larger spatial level. The firing rate of neurons of input stages of basal ganglia (subthalamic nucleus and putamen) and those from the external part of the globus pallidus were significantly higher during seizures as compared to interictal periods. During seizures, the proportion of oscillatory neurons in subthalamic nucleus (71%), external globus pallidus (45%) and putamen (53%) significantly increased in comparison to interictal periods. Rhythmic activity was synchronized with ictal cortical spikes in external globus pallidus and subthalamic nucleus, but not in the putamen which oscillated faster than motor cortex. In contrast, no significant modification of the firing rate of the output stages of basal ganglia (internal part of the globus pallidus, substantia nigra pars reticulata) could be found during seizures. The local field potentials of subthalamic nucleus and external globus pallidus changed abruptly at the onset of the seizure, showing synchronization with the cortical activity throughout the seizure. In putamen, the synchronization appeared only by the end of seizures and for the two output structures, despite some increase of the oscillatory activity, the synchronization with the cortex was not significant. Our results suggest that the subthalamo-(external)-pallidal pathway is the main subcortical route involved during ictal motor seizures. Surprisingly, ictal activity did not propagate to the output structure of basal ganglia in that model. This finding may be important for clinical decisions of targeting when considering anti-epileptic neuromodulation in human beings suffering from disabling, drug resistant motor epilepsy.

On the Role of the Pedunculopontine Nucleus and Mesencephalic Reticular Formation in Locomotion in Nonhuman Primates

“…The precise assessment of microelectrode trajectories and recording site were performed with methods commonly used in NHP electrophysio-logical studies of the basal ganglia or PPN area in our laboratory and by other groups using ventricular landmarks (Wichmann et al, 1994;Matsumura et al, 1997;Devergnas et al, 2012). To improve the localization of microelectrode trajectories and recording sites in the brainstem, we combined these standard methods with MRI and histological data obtained for each primate.…”

The primate pedunculopontine nucleus region: towards a dual role in locomotion and waking state

“…The electrocorticography (EcoG) signal was recorded from 3 epidural titanium screw electrodes implanted in the frontal and parietal brain regions, amplified, sampled at 6 kHz and analogically band-pass filtered (1-300 Hz). Assessment of microelectrode trajectories and recording site were performed with methods commonly used in NHP electrophysiological studies of the basal ganglia or PPN area in our lab and by other groups using ventricular landmarks (Wichmann et al 1994;Matsumura et al 1997;Devergnas et al 2012). In order to improve the localization of micoelectrode trajectories and recording sites in the brainstem, we combined these standard methods with MRI and immuno-histological data obtained for each primate.…”

Subcortical SISCOM hyperperfusion: Should we pay more attention to it?

“…Although focal epilepsy is considered a cortical disease, the subcortical regions such as the basal ganglia, thalamus and cerebellum are important pathways for seizure propagation and regulation [13][14][15][16][17][18]. Unfortunately, scalp EEG cannot correctly reflect the involvement of deep structures.…”