Spatiotemporal dynamics of optogenetically induced and spontaneous seizure transitions in primary generalized epilepsy

Transitions into primary generalized epileptic seizures occur abruptly and synchronously across the brain. Their potential triggers remain unknown. We used optogenetics to causally test the hypothesis that rhythmic population bursting of excitatory neurons in a local neocortical region can rapidly trigger absence seizures. Most previous studies have been purely correlational, and it remains unclear whether epileptiform events induced by rhythmic stimulation (e.g., sensory/electrical) mimic actual spontaneous seizures, especially regarding their spatiotemporal dynamics. In this study, we used a novel combination of intracortical optogenetic stimulation and microelectrode array recordings in freely moving WAG/Rij rats, a model of absence epilepsy with a cortical focus in the somatosensory cortex (SI). We report three main findings: 1) Brief rhythmic bursting, evoked by optical stimulation of neocortical excitatory neurons at frequencies around 10 Hz, induced seizures consisting of self-sustained spike-wave discharges (SWDs) for about 10% of stimulation trials. The probability of inducing seizures was frequency-dependent, reaching a maximum at 10 Hz. 2) Local field potential power before stimulation and response amplitudes during stimulation both predicted seizure induction, demonstrating a modulatory effect of brain states and neural excitation levels. 3) Evoked responses during stimulation propagated as cortical waves, likely reaching the cortical focus, which in turn generated self-sustained SWDs after stimulation was terminated. Importantly, SWDs during induced and spontaneous seizures propagated with the same spatiotemporal dynamics. Our findings demonstrate that local rhythmic bursting of excitatory neurons in neocortex at particular frequencies, under susceptible ongoing brain states, is sufficient to trigger primary generalized seizures with stereotypical spatiotemporal dynamics.

Sustained Mnemonic Response in the Human Middle Frontal Gyrus during On-Line Storage of Spatial Memoranda

The mapping of cognitive functions to neural systems is a central goal of cognitive neuroscience. On the basis of homology with lesion and physiological studies in nonhuman primates, Brodmann's area (BA) 46/9 in the middle frontal gyrus (MFG) has been proposed as the cortical focus for both the storage as well as processing components of working memory in the human brain, but the evidence on the segregation of these components and their exact areal localization has been inconsistent. In order to study this issue and increase the temporal resolution of functional mapping, we disambiguated the storage component of working memory from sensory and motor responses by employing functional magnetic resonance imaging (fMRI) in spatial delayed-response (DR) tasks with long delay intervals and different conditions of demand. We here show that BA 46 can support a sustained mnemonic response for as long as 24 sec in a high-demand task and the signal change in this area exceeded that in the other prefrontal areas examined. Our findings support a conservation of functional architecture between human and nonhuman primate in showing that the MFG is prominently engaged in the storage of spatial information.

Subcortical Modulation of High-Frequency (Gamma Band) Oscillating Potentials in Auditory Cortex

Brett, Barbara and Daniel S. Barth. Subcortical modulation of high-frequency (gamma band) oscillating potentials in auditory cortex. J. Neurophysiol. 78: 573–581, 1997. The purpose of this study was to use depth electrical stimulation and retrograde horseradish peroxidase (HRP) labeling to determine what role certain subcortical nuclei play in the neurogenesis of high-frequency gamma (∼40 Hz) oscillations in rat auditory cortex. Evoked and spontaneous electrocortical oscillations were recorded with the use of a high-spatial-resolution multichannel epipial electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) region of the ventral acoustic thalamus and to the centrolateral nucleus (CL) and the nucleus basalis (NB), which have been previously implicated in the production of cortical gamma oscillations. PIL stimulation consistently evoked gamma oscillations confined to a location between primary and secondary auditory cortex, corresponding to the region where spontaneous gamma oscillations were also recorded. Stimulation of the CL and NB did not evoke gamma oscillations in auditory cortex. HRP placed in the cortical focus of evoked gamma oscillations labeled cell bodies in the PIL, and in more lateral regions of the ventral acoustic thalamus, which on subsequent stimulation also evoked gamma oscillations in auditory cortex. No cells were labeled in either the CL or NB. These results indicate that the PIL and the lateral regions of ventral acoustic thalamus provide anatomically distinct input to auditory cortex and may play an exclusive and modality-specific role in modulating gamma oscillations in the auditory system.