Antiseizure effects of Anacyclus pyrethrum in socially isolated rats with and without a positive handling strategy.

OBJECTIVE: Aqueous extract of Anacyclus pyrethrum (AEAPR) is used in traditional medicine to treat epilepsy, but whether it has antiseizure properties has not been established. Because extracts of the plant have antioxidant properties, we hypothesized that it may be particularly potent in conditions associated with oxidative stress, in particular social isolation. METHODS: We addressed these objectives in the pilocarpine experimental model of epilepsy using socially isolated rats maintaining contacts with (handled) and without (unhandled) positive handling strategy. Both groups were further divided into treated (AEAPR was added to the drinking water) and untreated groups. Continuous (24/7) electroencephalography (EEG) recordings started in the sixth week after status epilepticus (SE) with a predrug control period of 3 weeks, followed by 3 weeks of daily treatment with AEAPR or water, and finally a postdrug control period of 3 weeks. At the end of the experimental procedure, we measured lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities in the hippocampus to assess oxidative stress. RESULTS: A. pyrethrum treatment significantly reduced seizure frequency by 51% and 57%, duration by 30% and 33%, and severity by 31% and 26% in isolated handled and unhandled rats, respectively. The beneficial effects on seizures were still present 3 weeks after the end of the treatment. The treatment reduced lipid peroxidation as well as SOD, GPx, and catalase activities. SIGNIFICANCE: We conclude that A. pyrethrum has antiseizure and antioxidant properties, even in social isolation conditions.

Cycles in epilepsy.

Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over diverse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur.

Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain.

When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation.

Impaired consciousness during temporal lobe seizures is related to increased long-distance cortical-subcortical synchronization.

Loss of consciousness (LOC) is a dramatic clinical manifestation of temporal lobe seizures. Its underlying mechanism could involve altered coordinated neuronal activity between the brain regions that support conscious information processing. The consciousness access hypothesis assumes the existence of a global workspace in which information becomes available via synchronized activity within neuronal modules, often widely distributed throughout the brain. Re-entry loops and, in particular, thalamo-cortical communication would be crucial to functionally bind different modules together. In the present investigation, we used intracranial recordings of cortical and subcortical structures in 12 patients, with intractable temporal lobe epilepsy (TLE), as part of their presurgical evaluation to investigate the relationship between states of consciousness and neuronal activity within the brain. The synchronization of electroencephalography signals between distant regions was estimated as a function of time by using non-linear regression analysis. We report that LOC occurring during temporal lobe seizures is characterized by increased long-distance synchronization between structures that are critical in processing awareness, including thalamus (Th) and parietal cortices. The degree of LOC was found to correlate with the amount of synchronization in thalamo-cortical systems. We suggest that excessive synchronization overloads the structures involved in consciousness processing, preventing them from treating incoming information, thus resulting in LOC.