Disruption of Rolandic Gamma-Band Functional Connectivity by Seizures is Associated with Motor Impairments in Children with Epilepsy

Abstract

Although children with epilepsy exhibit numerous neurological and cognitive deficits, the mechanisms underlying these impairments remain unclear. Synchronization of oscillatory neural activity in the gamma frequency range (>30 Hz) is purported to be a mechanism mediating functional integration within neuronal networks supporting cognition, perception and action. Here, we tested the hypothesis that seizure-induced alterations in gamma synchronization are associated with functional deficits. By calculating synchrony among electrodes and performing graph theoretical analysis, we assessed functional connectivity and local network structure of the hand motor area of children with focal epilepsy from intracranial electroencephalographic recordings. A local decrease in inter-electrode phase synchrony in the gamma bands during ictal periods, relative to interictal periods, within the motor cortex was strongly associated with clinical motor weakness. Gamma-band ictal desychronization was a stronger predictor of deficits than the presence of the seizure-onset zone or lesion within the motor cortex. There was a positive correlation between the magnitude of ictal desychronization and impairment of motor dexterity in the contralateral, but not ipsilateral hand. There was no association between ictal desynchronization within the hand motor area and non-motor deficits. This study uniquely demonstrates that seizure-induced disturbances in cortical functional connectivity are associated with network-specific neurological deficits.

Altered Rolandic Gamma-Band Activation Associated with Motor Impairment and Ictal Network Desynchronization in Childhood Epilepsy

“…The analysis of ictal synchrony involving Rolandic cortex in this group of epilepsy patients has been previously reported [22]. To summarize, subdural electrode grids were surgically implanted and motor cortex was localized in each patient using extra-operative mapping [32].…”

“…We investigated motor ability and functional responses from Rolandic cortex in a group of children with FCD in whom the relationship between ictal Rolandic desynchronization and motor impairment has previously been established [22]. Children were excluded from this group if median nerve stimulation was performed under general anesthetic, because this is known to alter cortical responses [28].…”

“…Digital filtering was then used to divide these reconstructed time series into delta (1–4 Hz), theta (5–8 Hz), alpha (8–13 Hz), beta (14–30 Hz), gamma1 (36–44 Hz), gamma2 (45–80 Hz), HFO1 (81–150 Hz) and HFO2 (151–200 Hz) frequency ranges. These frequency ranges were selected in order to facilitate comparison with the iEEG results [22]. We then calculated the analytic signal of the filtered waveforms for each epoch to obtain the instantaneous amplitude at each time point.…”

“…Previously, we demonstrated that seizure-induced alterations in oscillatory synchronization involving Rolandic cortex were associated with motor impairment in a group of children with focal cortical dysplasia (FCD) who were undergoing evaluation for surgery for intractable epilepsy [22]. This effect was evident in multiple frequency ranges, but was stronger at higher frequencies including the gamma-band.…”

“…Excessive high frequency oscillations (HFOs; >80 Hz) are increasingly being accepted as biomarkers of epileptogenic cortex as they appear to be most prominent within epileptogenic brain regions [19]–[21]. As well, epilepsy is associated with atypical oscillatory dynamics in several other frequency ranges, including gamma oscillations below the HFO range [22], [23]. Altered neural oscillations in multiple frequency ranges, including the gamma-band, have been associated with difficulties in cognitive development in pediatric epilepsy [24], and transient psychological alterations are associated with the desynchronization of functional networks in patients with epilepsy [25].…”