Cortico-thalamic mechanisms underlying generalized spike-wave discharges of absence epilepsy. A lesional and signal analytical approach in the WAG/Rij rat

Contains fulltext : mmubn000001_379772221.pdf (publisher's version ) (Closed access)168 p

Thalamic lesions in a genetic rat model of absence epilepsy: Dissociation between spike-wave discharges and sleep spindles

Contains fulltext : 77295.pdf (publisher's version ) (Closed access)Recent findings have challenged the traditional view that the thalamus is the primary driving source of generalized spike-wave discharges (SWDs) characteristic for absence seizures, and indicate a leading role for the cortex instead. In light of this we investigated the effects of thalamic lesions on SWDs and sleep spindles in the WAG/Rij rat, a genetic model of absence epilepsy. EEG was recorded from neocortex and thalamus in freely moving rats, both before and after unilateral thalamic ibotenic acid lesions. Complete unilateral destruction of the reticular thalamic nucleus (RTN) combined with extensive destruction of the thalamocortical relay (TCR) nuclei, resulted in the bilateral abolishment of SWDs and ipsilateral abolishment of sleep spindles. A suppression of both types of thalamocortical oscillations was found when complete or extensive damage to the RTN was combined with minor to moderate damage to the TCR nuclei. Lesions that left the rostral pole of the RTN and part of the TCR nuclei intact, resulted in an ipsilateral suppression of sleep spindles, but a large increase of bilateral SWDs. These findings demonstrate that the thalamus in general and the RTN in particular are a prerequisite for both the typical bilateral 7–11 Hz SWDs and natural occurring sleep spindles in the WAG/Rij rat, but suggest that different intrathalamic subcircuits are involved in the two types of thalamocortical oscillations. Whereas the whole RTN appears to be critical for the generation of sleep spindles, the rostral pole of the RTN seems to be the most likely part that generates SWDs

Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory

Contains fulltext : 55480.pdf (publisher's version ) (Closed access)Four main theories on the pathophysiology of generalized absence seizures have been proposed. The "centrencephalic" theory, proposed in 1954, suggested that discharges originate from a deep-seated diffusely projecting subcortical pacemaker in the midline thalamus. This concept was refined in 1991 with the "thalamic clock". theory, implying that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, imposing its rhythm to the cortex. According to other investigators, however, the cortex seems to play a leading role. They suggested that spike-wave discharges have a focal onset in the cortex and are generalized through a rapid propagation. In the "corticoreticular" theory, postulated in 1968, spike-wave discharges are linked to the thalamocortical mechanisms that generate spindles. Rhythmic spindle oscillations generated in the thalamus are transformed into spike-wave discharges when the cortex is hyperexcitable. A 2002 study confirmed in epileptic rats that a functionally intact thalamocortical network is required for the generation of spike-wave discharges. The corticothalamic interrelationships were investigated by means of nonlinear association signal analyses of multiple spike-wave discharges. This showed a consistent focus within the perioral region of the somatosensory cortex. From this focus, seizure activity generalizes rapidly over the cortex. During the first cycles of the seizure the cortex drives the thalamus, while thereafter cortex and thalamus drive each other, thus amplifying and maintaining the rhythmic discharge. In this way the "cortical focus" theory for generalized absence epilepsy bridges cortical and thalamic theories

Evolving concepts on the pathophysiology of generalised absence seizures: the cortical focus theory

Item does not contain fulltextThree major theories concerning the pathophysiology of generalised absence seizures have been proposed. Penfield and Jasper (1947) put forward the 'centrencephalic' theory, suggesting that the discharges originate from a deep-seated central subcortical pacemaker in the midline thalamus, which diffusely projects to the cortex. This concept was refined by Buzsáki (1991) who proposed that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, which imposes its rhythm to the cortex. According to proponents of the cortical theory (Gibbs and Gibbs, 1952; Bancaud, 1969; Lüders et al., 1984; Niedermeyer, 1969), however, the cortex plays a leading role. They found evidence that generalised spike-wave discharges have a focal onset in the frontal cortex. They suggested that seizures became secondarily generalised through a rapid propagation over the cortex. The cortico-reticular theory, postulated by Gloor (1968), formed a reconciliation between the thalamic and cortical theory. Work on the 'feline penicillin generalised epilepsy' model showed that the mechanisms responsible for the spike-wave discharges were linked to the thalamocortical mechanisms that generate spindles. Gloor (1968) demonstrated that rhythmic spindle oscillations generated in the thalamus could be transformed into spike-wave discharges when the cortex was made hyperexcitable. In that case the cortex initiates abnormal hypersynchronous oscillations in the thalamocortical network. Experiments performed in genetically epileptic rats by Meeren et al. (2002) confirmed that a functionally intact thalamocortical network is required for the generation of generalised spike-wave discharges. They investigated the cortico-cortical, intrathalamic and cortico-thalamic interrelationships during spontaneous absence seizures using the advanced signal analysis method of nonlinear association analysis. The analyses revealed a consistent cortical 'focus' within the peri-oral region of the somatosensory cortex. From here, seizure activity spreads rapidly over the cortex, which gives the discharges their generalized appearance. During the first few cycles of the seizure the cortex drives the thalamus, which subsequently becomes entrained into the oscillation. Thereafter cortex and thalamus form a unified network in which both structures drive each other, thus amplifying and maintaining the rhythmic paroxysmal discharges. In this way Meeren's et al. (2002) cortical focus theory for generalised absence epilepsy forms a synthesis between the cortical and the cortico-reticular theory

Learning from each other’s struggles

Sociology has always been in dialogue with social movements, from Tocqueville, Marx and Durkheim to Angela Davis, Herbert Marcuse, Frances Piven and Toni Negri. As a young activist, wanting to understand the movements I was involved in and see how we could take them further, sociology was the obvious starting-point. I had grown up around human rights and anti-apartheid, the peace and ecology movements. Travel and study around Europe showed me whole movement scenes and subcultures – feminist, libertarian, socialist – with roots in the 1960s and 1970s and still generating new movements in the 1980s and 1990s. I started to research where these shared histories and cultures had come from, and how we could draw on them to build new alliances. My PhD, on the potential for radical alliances developing the everyday popular rationalities expressed by these cultures, was written against the background of the Zapatistas and submitted just in time to see the Seattle protests against the WTO validate its conclusions and change the movement landscape across the industrialised North. Writing the thesis went hand-in-hand with editing an activist magazine which tried to make those links in practical ways, and with small gatherings of activists from different movements – around the possibility of a new left, networking independent media, reviving the older alternative movements and trying to create cross-movement dialogues