Epilepsia 44 Suppl. 9 :41 (Abst. 1.109 ), 2003
PARALLEL INCREASES IN NEURONAL FIRING AND CEREBRAL BLOOD FLOW DURING SPIKE-WAVE SEIZURES, TONIC-CLONIC SEIZURES, AND SOMATOSENSORY PROCESSING
Authors: Hrachya Nersesyan, Peter Herman, Natasja Maandag, Fahmeed Hyder, Hal Blumenfeld Neurology, Yale University School of Medicine, New Haven, CT; Diagnostic Radiology, Yale University School of Medicine, New Haven, CT; Neurobiology, Yale University School of Medicine, New Haven, CT
Recent studies have shown that cerebral blood flow (CBF) is usually coupled to cerebral metabolic demand, which in turn, is proportional to neuronal spiking frequency. However, the data is very controversial, especially concerning coupling of CBF to increased neuronal activity during absence seizures. Some investigators have shown increased CBF during spike-wave discharges (SWD) compared to interictal basal levels, while others have shown the opposite. We have used laser Doppler flowmetry (LDF) in a rodent model of absence seizures to determine the relationship between capillary CBF changes and simultaneously recorded multiunit neuronal firing during SWD, somatosensory stimulation, and generalized tonic-clonic seizures.
We used a custom-built combination probe to perform simultaneous tissue LDF and extracellular multiunit recordings from the same region at a cortical depth of 1mm. Experiments used WAG/Rij rats under fentanyl/haloperidol anesthesia and measured changes in neuronal firing (ΔΝ/Ν) and CBF (ΔF/F) during SWDs, whisker stimulation, and bicuculline-induced generalized tonic-clonic seizures. Because prior electrophysiological recordings have shown the primary somatosensory (S1BF) cortex to be intensely involved in SWDs while primary visual (V1M) cortex is spared, we focused our combined recordings on these two regions.
Increases in CBF occurred during SWD, whisker stimulation, and generalized tonic-clonic seizures, which directly paralleled increases in neuronal firing rate. During SWD and whisker stimulation, we observed increases in S1BF but not V1M, while during generalized tonic-clonic seizures increases also involved V1M. During SWD, mean maximal increases in ΔΝ/Ν and ΔF/F in S1BF were 92%[plusmn]18% (mean[plusmn]SD) and 29%[plusmn]10%, respectively, compared to baseline. Interestingly, ΔΝ/Ν and ΔF/F during whisker stimulation were even larger than during SWD (p<0.008, p<0.04 for ΔΝ/Ν and ΔF/F, respectively). Increases in neuronal firing and CBF were larger still during generalized tonic-clonic seizures, at least 5 times higher than during SWD (p<0.0004, p<0.0001 for ΔΝ/Ν and ΔF/F, respectively).
Spike-wave seizures are accompanied by approximately proportional increases in neuronal firing and CBF in primary somatosensory cortex, but not in primary visual cortex. However, these increases are much smaller than during generalized tonic-clonic seizures, and are also smaller than the increases seen during normal somatosensory information processing in the same region.
[Supported by: NIH NS02060, NIH NS037203, NIH MH067528, and the Patterson Trust]
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