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.

Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

Deep brain stimulation and motor cortical stimulation for neuropathic pain.

Deep brain stimulation (DBS) is an important treatment option for neuropathic pain. DBS has a considerable history, and it can be used successfully for a wide number of pain syndromes. Epidural motor cortex stimulation (MCS) also is a treatment option for neuropathic pain. Less invasive than DBS, MCS has been rapidly adopted and studied since first described in 1991. A growing body of literature supports the use of MCS for facial pain, though further study to better define the mechanism of action and the most appropriate patient populations is ongoing.

Radiotherapy-induced common carotid pseudoaneurysm presenting with initially occult upper airway hemorrhage and successfully treated by endovascular stent graft.

Radiation induced carotid vasculopathy may present as steno-occlusive disease or less commonly as a pseudoaneurysm. The latter most often presents with a pulsatile mass but is a potential cause of life threatening hemorrhage. We present a case of a small common carotid artery (CCA) pseudoaneurysm that was initially dismissed as the cause of the patients presenting epistaxis given its small size and location. After standard bilateral internal maxillary artery embolizations failed to prevent significant subsequent pharyngeal and tracheal blood loss and serial imaging demonstrated a progressive enlargement of the pseudoaneurysm, a stent graft was successfully placed across the lesion. At five months post stenting, follow-up imaging of the neck showed a stable obliteration of the pseudoaneurysm, good arterial patency, and the patient remained free of recurrent hemorrhage. This case demonstrates that even a small carotid pseudoaneurysm, can present with pharyngeal hemorrhage and should be treated aggressively--with endovascular stent grafting being a preferred treatment modality for arterial lesions in the irradiated neck.

An automated rat single pellet reaching system with high-speed video capture.

BACKGROUND: Single pellet reaching is an established task for studying fine motor control in which rats reach for, grasp, and eat food pellets in a stereotyped sequence. Most incarnations of this task require constant attention, limiting the number of animals that can be tested and the number of trials per session. Automated versions allow more interventions in more animals, but must be robust and reproducible. NEW METHOD: Our system automatically delivers single reward pellets for rats to grasp with their forepaw. Reaches are detected using real-time computer vision, which triggers video acquisition from multiple angles using mirrors. This allows us to record high-speed (>300 frames per second) video, and trigger interventions (e.g., optogenetics) with high temporal precision. Individual video frames are triggered by digital pulses that can be synchronized with behavior, experimental interventions, or recording devices (e.g., electrophysiology). The system is housed within a soundproof chamber with integrated lighting and ventilation, allowing multiple skilled reaching systems in one room. RESULTS: We show that rats acquire the automated task similarly to manual versions, that the task is robust, and can be synchronized with optogenetic interventions. COMPARISON WITH EXISTING METHODS: Existing skilled reaching protocols require high levels of investigator involvement, or, if ad libitum, do not allow for integration of high-speed, synchronized data collection. CONCLUSION: This task will facilitate the study of motor learning and control by efficiently recording large numbers of skilled movements. It can be adapted for use with modern neurophysiology, which demands high temporal precision.

Review: electrophysiology of basal ganglia and cortex in models of Parkinson disease.

Incomplete understanding of the systems-level pathophysiology of Parkinson Disease (PD) remains a significant barrier to improving its treatment. Substantial progress has been made, however, due to the availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons. This review discusses the in vivo electrophysiology of basal ganglia (BG), thalamic, and cortical regions after dopamine-depleting lesions. These include firing rate changes, neuronal burst-firing, neuronal oscillations, and neuronal synchrony that result from a combination of local microanatomic changes and network-level interactions. While much is known of the clinical and electrophysiological phenomenology of dopamine loss, a critical gap in our conception of PD pathophysiology is the link between them. We discuss potential mechanisms by which these systems-level electrophysiological changes may emerge, as well as how they may relate to clinical parkinsonism. Proposals for an updated understanding of BG function are reviewed, with an emphasis on how emerging frameworks will guide future research into the pathophysiology and treatment of PD.

Peripheral neuromodulation for migraine headache.

Extremely high prevalence among general population along with the high percentage of treatment-refractory cases makes migraine headaches one of the potentially largest indications for neuromodulation. Cranial peripheral nerve stimulation targeting the occipital nerve(s) alone or in combination with others appears to be both safe and efficacious for the treatment of medically intractable migraine headaches. Although initial reports of occipital nerve stimulation for migraine headaches were very encouraging, this clinical benefit was not clearly confirmed in larger-scale prospective randomized trials. Moreover, the exact mechanism of neuromodulation effect in migraine treatment remains unclear. Significant further investigation needs to be performed to optimize our knowledge concerning patient selection, stimulation targets and parameters and device programming, and further improve clinical results. At present, neurostimulation for migraine headache pain is performed in the United States on an 'off-label' basis, but based upon our experience and the increasing evidence in the medical literature, we look forward to its approval by the FDA in the near future so that patients suffering from severe, medically intractable headache pain may gain access to these potentially important therapies.

Development of spike-wave seizures in C3H/HeJ mice.

C3H/HeJ mice have been reported to have relatively early onset of spike-wave discharges (SWD), and a defective AMPA receptor subunit Gria4 as the genetic cause. We investigated the time course of SWD development through serial EEG recordings in C3H/HeJ mice to better characterize this model. We found that at immature postnatal ages of 5-15 days, rare SWD-like events were observed at an average rate of 3 per hour, and with relatively broad spikes, irregular rhythm, slow frequency (5-6 Hz), and short duration (mean 1.75 s). This was followed by a transitional period of increasing SWD incidence, which then stabilized in mature animals at age 26-62 days, with SWD at an average rate of 45 per hour, narrower spike morphology, regular rhythm, higher frequency (7-8 Hz), and longer duration (mean 3.40s). This sequence of maturational changes in SWD development suggests that effects of early intervention could be tested in C3H/HeJ mice over the course of a few weeks, rather than a few months as in rats, greatly facilitating future research on anti-epileptogenesis.