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Woodhall, G. L.

Publications and source records attributed to Woodhall, G. L..

2 recordsLinked to original sources

Entropy of the resting state cortex in epilepsy

BackgroundEpilepsy has long been conceptualised as a disorder in which aberrant brain dynamics extend beyond the epileptogenic zone. Evidence demonstrates that loss of entropy is a generic feature of pathological dynamics in the brain, including the ictal state. However, the impact of recurrent seizures on entropy in the interictal state remains unknown. MethodsResting state magnetoencephalography (MEG) scans and resection masks of 32 individuals with epilepsy who had Engel I outcome post-surgery were retrospectively retrieved. Using co-registered FreeSurfer parcellations, we reconstructed the source localised MEG time series and computed sample entropy for 114 regions of interest. We then tested the association of entropy with the resected volume of the brain, and additional clinical variables including the age of seizure onset, seizure frequency and duration of epilepsy. To further understand the temporal relationship between seizure onset and entropy in the interictal state, we collected and computed sample entropy for week-long EEG traces from leucine-rich glioma inactivated 1 monoclonal antibody (LGI1-mAb) rodent models of autoimmune encephalitis (n=5) and control rats (n=5). ResultsIn individuals with epilepsy, a lower age of seizure onset was associated with lower mean sample entropy of the whole cortex (Spearmans rho =0.60, p<0.001; partial correlation =0.41, p=0.021). Entropy did not differ between the resected and non-resected regions of the brain. Furthermore, LGI1-mAb treated rodents showed a persistent decrease in sample entropy as compared to control rats, after the onset of seizures, and this difference was greatest during periods of highest seizure frequency (p<0.001). ConclusionRecurrent seizures are associated with a persistent decrease in entropy, even in the interictal state, and this decrease was found to be most profound and affecting the whole cortex in patients who had a lower age of seizure onset.

neuroscience↗

In vitro characterisation and neurosteroid treatment of an N-Methyl-D-Aspartate receptor antibody-mediated seizure model

Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR-Ab) encephalitis, a distinct neuro-immunological disorder in which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization and a state of NMDAR hypofunction. To further understand ictogenesis in this disorder, and to test a novel treatment compound, we developed an NMDAR-Ab mediated rat seizure model that displays spontaneous epileptiform activity in vivo and in vitro. Using a combination of electrophysiological and dynamic causal modelling techniques we show that, contrary to expectation, reduction of synaptic excitatory, but not inhibitory, neurotransmission underlies the ictal events through alterations in the dynamical behaviour of microcircuits in brain tissue. Moreover, in vitro application of an NMDAR-specific neurosteroid, pregnenolone sulfate, that upregulates NMDARs, reduced established ictal activity. This proof-of-concept study highlights the complexity of circuit disturbances that may lead to seizures and the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy.

neuroscience↗