Where fMRI and electrophysiology agree to disagree: corticothalamic and striatal activity patterns in the WAG/Rij rat.

The relationship between neuronal activity and hemodynamic changes plays a central role in functional neuroimaging. Under normal conditions and in neurological disorders such as epilepsy, it is commonly assumed that increased functional magnetic resonance imaging (fMRI) signals reflect increased neuronal activity and that fMRI decreases represent neuronal activity decreases. Recent work suggests that these assumptions usually hold true in the cerebral cortex. However, less is known about the basis of fMRI signals from subcortical structures such as the thalamus and basal ganglia. We used WAG/Rij rats (Wistar albino Glaxo rats of Rijswijk), an established animal model of human absence epilepsy, to perform fMRI studies with blood oxygen level-dependent and cerebral blood volume (CBV) contrasts at 9.4 tesla, as well as laser Doppler cerebral blood flow (CBF), local field potential (LFP), and multiunit activity (MUA) recordings. We found that, during spike-wave discharges, the somatosensory cortex and thalamus showed increased fMRI, CBV, CBF, LFP, and MUA signals. However, the caudate-putamen showed fMRI, CBV, and CBF decreases despite increases in LFP and MUA signals. Similarly, during normal whisker stimulation, the cortex and thalamus showed increases in CBF and MUA, whereas the caudate-putamen showed decreased CBF with increased MUA. These findings suggest that neuroimaging-related signals and electrophysiology tend to agree in the cortex and thalamus but disagree in the caudate-putamen. These opposite changes in vascular and electrical activity indicate that caution should be applied when interpreting fMRI signals in both health and disease from the caudate-putamen, as well as possibly from other subcortical structures.

Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures.

PURPOSE: Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3-4-Hz spike-wave discharges (SWDs) on electroencephalography (EEG). Prior EEG-functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated. METHODS: We performed EEG-fMRI with simultaneous behavioral testing in 37 children with typical childhood absence epilepsy (CAE). Attentional vigilance was evaluated by a continuous performance task (CPT), and simpler motor performance was evaluated by a repetitive tapping task (RTT). RESULTS: SWD episodes were obtained during fMRI scanning from 9 patients among the 37 studied. fMRI signal increases during SWDs were observed in the thalamus, frontal cortex, primary visual, auditory, somatosensory, and motor cortex, and fMRI decreases were seen in the lateral and medial parietal cortex, cingulate gyrus, and basal ganglia. Omission error rate (missed targets) with SWDs during fMRI was 81% on CPT and 39% on RTT. For those seizure epochs during which CPT performance was impaired, fMRI changes were seen in cortical and subcortical structures typically involved in SWDs, whereas minimal changes were observed for the few epochs during which performance was spared. DISCUSSION: These findings suggest that typical absence seizures involve a network of cortical-subcortical areas necessary for normal attention and primary information processing. Identification of this network may improve understanding of cognitive impairments in CAE, and may help guide development of new therapies for this disorder.

Imaging onset and propagation of ECT-induced seizures.

PURPOSE: Regions of seizure onset and propagation in human generalized tonic-clonic seizures are not well understood. Cerebral blood flow (CBF) measurements with single photon emission computed tomography (SPECT) during electroconvulsive therapy (ECT)-induced seizures provide a unique opportunity to investigate seizure onset and propagation under controlled conditions. METHODS: ECT stimulation induces a typical generalized tonic-clonic seizure, resembling spontaneous generalized seizures in both clinical and electroencephalogram (EEG) manifestations. Patients were divided into two groups based on timing of ictal (during seizure) SPECT tracer injections: 0 s after ECT stimulation (early group), and 30 s after ECT (late group). Statistical parametric mapping (SPM) was used to determine regions of significant CBF changes between ictal and interictal scans on a voxel-by-voxel basis. RESULTS: In the early injection group, we saw increases near the regions of the bitemporal stimulating electrodes as well as some thalamic and basal ganglia activation. With late injections, we observed increases mainly in the parietal and occipital lobes, regions that were quiescent 30 s prior. Significant decreases occurred only at the later injection time, and these were localized to the bilateral cingulate gyrus and left dorsolateral frontal cortex. CONCLUSIONS: Activations in distinct regions at the two time points, as well as sparing of intermediary brain structures, suggest that ECT-induced seizures propagate from the site of initiation to other specific brain regions. Further work will be needed to determine if this propagation occurs through cortical-cortical or cortico-thalamo-cortical networks. A better understanding of seizure propagation mechanisms may lead to improved treatments aimed at preventing seizure generalization.

Neocortical and thalamic spread of amygdala kindled seizures.

PURPOSE: Amygdala kindling is an epilepsy model involving long-term network plasticity in the nervous system. In this model, repeated weak stimulation of the amygdala eventually leads to severe motor seizures. The mechanisms for worsening behavioral seizures, and the possible role of enhanced connectivity between the amygdala and other structures have not been thoroughly investigated. METHODS: We performed simultaneous field potential recordings from the amygdala, frontal cortex, and medial thalamus during kindling in rats. Seizures were analyzed for signal power compared with baseline and for correlation between recording sites. Interictal signals were analyzed for changes in coherence between electrode contacts in kindled animals compared with sham kindled controls. RESULTS: We found that increased behavioral severity of seizures was related to increased seizure duration and to increased signal power in the frontal cortex and medial thalamus. Kindling was associated with increased connectivity between the amygdala and frontal cortex, based on increased amygdala-frontal signal correlation during seizures. In addition, during the interictal period, increased coherence was noted between amygdala and frontal contacts in kindled animals compared with controls. CONCLUSIONS: We found evidence for increased connectivity between the amygdala and frontal cortex both during seizures and in the interictal period, as a result of kindling. Enhanced connections between limbic and neocortical circuits may be important for the development of epilepsy, as well as for normal long-range network plasticity in the nervous system.