Neocortical and Thalamic Spread of Amygdala Kindled Seizures

Abstract

Summary:Purpose: Amygdala kindling is an epilepsy model involving long-term network plasticity in the nervous system. In this model, repeated weak stimulation of the amygdala eventually leads to severe motor seizures. The mechanisms for worsening behavioral seizures, and the possible role of enhanced connectivity between the amygdala and other structures have not been thoroughly investigated.Methods: We performed simultaneous field potential recordings from the amygdala, frontal cortex, and medial thalamus during kindling in rats. Seizures were analyzed for signal power compared with baseline and for correlation between recording sites. Interictal signals were analyzed for changes in coherence between electrode contacts in kindled animals compared with sham kindled controls.Results: We found that increased behavioral severity of seizures was related to increased seizure duration and to increased signal power in the frontal cortex and medial thalamus. Kindling was associated with increased connectivity between the amygdala and frontal cortex, based on increased amygdalafrontal signal correlation during seizures. In addition, during the interictal period, increased coherence was noted between amygdala and frontal contacts in kindled animals compared with controls.Conclusions: We found evidence for increased connectivity between the amygdala and frontal cortex both during seizures and in the interictal period, as a result of kindling. Enhanced connections between limbic and neocortical circuits may be important for the development of epilepsy, as well as for normal long-range network plasticity in the nervous system.

Does the region of epileptogenicity influence the pattern of change in cortical excitability?

“…Another explanation is that the more extensive inter-hemispheric synaptic connections between extra-temporal lobe regions facilitate the spread or propagation of epileptic activity between these hemispheres when the focus is in these regions. This is supported by evidence from EEG-fMRI studies (Yu et al, 2009;Kobayashi et al, 2006) (Tyvaert et al, 2008) as well as human and animal data (Keller and Roberts, 2008;Blumenfeld et al, 2007); (Holmes et al, 1999;Zilles et al, 1998;Silva-Barrat et al, 1986) which show regional as well as distant cortical and subcortical changes associated with focal interictal spikes, being more so in patients with extra-temporal foci. It also would correlate well with the described increased incidence of bilateral features in extra-temporal lobe seizure semiologies (Luders et al, 1998;Gastaut, 1970) and of bilateral interictal and ictal discharges seen in patients with extra-TLE (Bautista et al, 1998;Taylor et al, 2003;Gibbs and Gibbs, 1955) as opposed to TLE where most reports show that even if bilateral interictal discharges are recorded, they are predominant over the side with seizure onset in 60-70% of patients (Hirsch et al, 1991;Williamson et al, 1993).…”

Is Epilepsy a Preventable Disorder? New Evidence from Animal Models

“…Progressive mossy fiber sprouting is a well-known ultrastructural change, which has been observed in kindling, and may contribute to abnormal excitability by forming recurrent excitatory synapses in the dentate gyrus (Sutula and Dudek 2007). On a network level, kindling results in increased connectivity as measured by both ictal and interictal EEG signal coherence between limbic and neocortical regions, specifically between the amygdala and the frontal cortex and medial thalamus (Blumenfeld and others 2007). GABA(A) receptor density is progressively increased in the dentate gyrus and acutely downregulated but chronically upregulated in CA1 and CA3 (Liu and others 2009).…”

Large scale brain networks in epilepsy

“…The performance of the commonly used WOSA coherence estimator may be extremely poor for small values of nd, and the coupling of poor estimation and statistical testing can result in inaccuracy in the measurement of MSC. In our previous work we have described the statistical properties of the coherence estimator [13], defined upper bounds of the effect of a scalp reference electrode on coherence measurements of icEEGs [14], and demonstrated the utility of this measure for measuring network change [2]. Fig 1(a) displays, in a single patient with right MTLE, all pairs of electrode contacts with delta MSC > 0.6.…”

“…Pairwise measures of relationship have been used to study seizures and the peri-seizure interval, typically in studies of seizure spread, seizure onset, and seizure prediction, and on interictal or background icEEG (ongoing activity between seizures). In a recent study of the background icEEG we demonstrated increased long-range theta coherence, between amygdala and the frontal lobe, accompanies the process of kindling in a rat model of epilepsy [2]. Further, Towle and coworkers, used the coherence of the background icEEG to define the functional borders of brain regions [3].…”