Most seizures stop spontaneously; however, the molecular mechanisms that terminate seizures remain unknown. Observations that seizures reduced brain pH and that acidosis inhibited seizures indicate that acidosis halts epileptic activity. Because acid-sensing ion channel 1a (ASIC1a) is exquisitely sensitive to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a, which would terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant-induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented seizure progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, required ASIC1a to interrupt tonic-clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. Our results identify ASIC1a as an important element in seizure termination when brain pH falls and suggest both a molecular mechanism for how the brain stops seizures and new therapeutic strategies.

In the course of performing electrical stimulation functional mapping (ESFM) in neurosurgery patients we identified three subjects who experienced a hearing suppression effect following stimulation of sites within the superior temporal gyrus (STG). One of these patients has long standing tinnitus that affects both ears. In all subjects, auditory event related potentials (ERPs) were recorded from chronically implanted intracranial electrodes and the results were used to localize auditory cortex fields within the STG. Hearing suppression sites were identified within anterior lateral Heschl's gyrus (HG) and posterior lateral STG, in what are likely belt and parabelt fields. Cortical stimulation suppressed hearing in both ears, and persisted beyond the period of electrical stimulation. Subjects experienced other stimulation evoked perceptions at some of these same sites, including symptoms of vestibular system activation and alteration of audio-visual speech processing. In contrast, stimulation of presumed core auditory cortex within posterior medial HG evoked sound perceptions, or in one case an increase in perceived tinnitus intensity, that affected the contralateral ear and did not persist beyond the period of stimulation. The current results provide confirmation of a rarely reported experimental observation, and for the first time correlate the brain sites associated with hearing suppression with anatomically and physiologically identified auditory cortex fields.

In this selected group of patients who underwent bilateral or bicompartmental craniectomy, 60% are independent at long-term follow-up. Patients with bifrontal injury fared best. Systemic infection and cerebrovascular injury corresponded with a worse outcome.

The highly convoluted and cytoarchitectonically diverse inferior frontal gyrus (IFG) of humans is known to be critically involved in a wide range of complex operations including speech and language processing. The neural circuitry that underlies these operations is not fully understood. We hypothesized that this neural circuitry includes functional connections within and between the three major IFG subgyri: the pars orbitalis, pars triangularis, and pars opercularis. To test this hypothesis we employed electrical stimulation tract-tracing techniques in 10 human patients undergoing surgical treatment for intractable epilepsy. The approach involved delivering repeated bipolar electrical stimuli to one site on the IFG while recording the electrical response evoked by that stimulus from a 64-contact grid overlying more distant IFG sites. In all subjects, stimulation of a site on one subgyrus evoked polyphasic potentials at distant sites, either on the same subgyrus or on an adjacent subgyrus. This provided prima facie evidence for a functional connection between the site of stimulation and the sites of the evoked response. The averaged evoked potentials tended to aggregate as response fields. The spatial spread of a response field indicated a divergent projection from the site of stimulation. When two or more sites were stimulated, the resulting evoked potentials exhibited different waveforms while the respective response fields could overlap substantially, suggesting that input from multiple sites converged but by engaging different neural circuits. The earliest deflection in the evoked potential ranged from 2 to 10 msec. No differences were noted between language-dominant and language-nondominant hemispheres.