Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40–60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.
Absence seizures are characterized by a brief behavioural impairment including apparent loss of consciousness. Neuronal mechanisms determining the behavioural impairment of absence seizures remain unknown, and their elucidation might highlight therapeutic options for reducing seizure severity. However, recent studies have questioned the similarity of animal spike-wave-discharges (SWD) to human absence seizures both behaviourally and neuronally. Here, we report that Genetic Absence Epilepsy Rats from Strasbourg recapitulate the decreased neuroimaging signals and loss of consciousness characteristic of human absence seizures. Overall neuronal firing is decreased but rhythmic in the somatosensory cortex and thalamus during these seizures. Interestingly, individual neurons in both regions tend to consistently express one of four distinct patterns of seizure-associated activity. These patterns differ in firing rate dynamics and in rhythmicity during seizure. One group of neurons showed a transient initial peak in firing at SWD onset, accounting for the brief initial increase in overall neuronal firing seen in cortex and thalamus. The largest group of neurons in both cortex and thalamus showed sustained decreases in firing during SWD. Other neurons showed either sustained increases or no change in firing. These findings suggest that certain classes of cortical and thalamic neurons may be particularly responsible for the paroxysmal oscillations and consequent loss of consciousness in absence epilepsy.
People with epilepsy face serious driving restrictions, determined using retrospective studies. To relate seizure characteristics to driving impairment, we aimed to study driving behavior during seizures with a simulator. Patients in the Yale New Haven Hospital undergoing video-electroencephalographic monitoring used a laptop-based driving simulator during ictal events. Driving function was evaluated by video review and analyzed in relation to seizure type, impairment of consciousness/responsiveness, or motor impairment during seizures.Fifty-one seizures in 30 patients were studied. In terms of seizure type, we found that focal to bilateral tonic-clonic or myoclonic seizures (5/5) and focal seizures with impaired consciousness/responsiveness (11/11) always led to driving impairment; focal seizures with spared consciousness/responsiveness (0/10) and generalized nonmotor (generalized spike-wave bursts; 1/19) usually did not lead to driving impairment. Regardless of seizure type, we found that seizures with impaired consciousness (15/15) or with motor involvement (13/13) always led to impaired driving, but those with spared consciousness (0/20) or spared motor function (5/38) usually did not. These results suggest that seizure types with impaired consciousness/responsiveness and abnormal motor function contribute to impaired driving. Expanding this work in a larger cohort could further determine how results with a driving simulator may translate into real world driving safety.
As a non-invasive detection method and an advanced imaging method, magnetic resonance imaging (MRI) has been widely used in the research of schizophrenia. Although a large number of neuroimaging studies have confirmed that MRI can display abnormal brain phenotypes in patients with schizophrenia, no valid uniform standard has been established for its clinical application. On the basis of previous evidence, we argue that MRI is an important tool throughout the whole clinical course of schizophrenia. The purpose of this commentary is to systematically describe the role of MRI in schizophrenia and to provide references for its clinical application.
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