Alexander Papanastassiou

Fine-Scale Spatial Organization of Face and Object Selectivity in the Temporal Lobe: Do Functional Magnetic Resonance Imaging, Optical Imaging, and Electrophysiology Agree?

The spatial organization of the brains object and face representations in the temporal lobe is critical for understanding high-level vision and cognition but is poorly understood. Recently, exciting progress has been made using advanced imaging and physiology methods in humans and nonhuman primates, and the combination of such methods may be particularly powerful. Studies applying these methods help us to understand how neuronal activity, optical imaging, and functional magnetic resonance imaging signals are related within the temporal lobe, and to uncover the fine-grained and large-scale spatial organization of object and face representations in the primate brain.

Large-scale, high-resolution neurophysiological maps underlying fMRI of macaque temporal lobe

Maps obtained by functional magnetic resonance imaging (fMRI) are thought to reflect the underlying spatial layout of neural activity. However, previous studies have not been able to directly compare fMRI maps to high-resolution neurophysiological maps, particularly in higher level visual areas. Here, we used a novel stereo microfocal x-ray system to localize thousands of neural recordings across monkey inferior temporal cortex (IT), construct large-scale maps of neuronal object selectivity at subvoxel resolution, and compare those neurophysiology maps with fMRI maps from the same subjects. While neurophysiology maps contained reliable structure at the sub-millimeter scale, fMRI maps of object selectivity contained information at larger scales (>2.5 mm) and were only partly correlated with raw neurophysiology maps collected in the same subjects. However, spatial smoothing of neurophysiology maps more than doubled that correlation, while a variety of alternative transforms led to no significant improvement. Furthermore, raw spiking signals, once spatially smoothed, were as predictive of fMRI maps as local field potential signals. Thus, fMRI of the inferior temporal lobe reflects a spatially low-passed version of neurophysiology signals. These findings strongly validate the widespread use of fMRI for detecting large (>2.5 mm) neuronal domains of object selectivity but show that a complete understanding of even the most pure domains (e.g., faces vs nonface objects) requires investigation at fine scales that can currently only be obtained with invasive neurophysiological methods.

Local application of the cannabinoid receptor agonist, WIN 55,212-2, to spinal trigeminal nucleus caudalis differentially affects nociceptive and non-nociceptive neurons

&NA; Cannabinoid receptor agonists produce analgesia for pains of non‐cranial origin. However, their effectiveness for craniofacial pains is currently unclear. In the present study, the cannabinoid CB1/CB2 receptor agonist, WIN 55,212–2 (WIN), was bath applied to the brainstem while activity of spinal trigeminal nucleus caudalis (Vc) neurons evoked by transcutaneous electrical stimulation was recorded in isoflurane anesthetized rats. Neurons were characterized using mechanical and electrical stimulation of the face, and were classified as either low‐threshold mechanoreceptive (LTM) or wide dynamic range (WDR). LTM neurons responded to light brushing of the receptive field and received only A&bgr; primary afferent fiber input. WDR neurons showed a graded response to mechanical stimulation, responding maximally to noxious stimuli, and demonstrated both A‐ and C‐fiber evoked activity. In addition, WDR neurons displayed longer latency, C‐fiber mediated post‐discharge (PDC) activity after repetitive stimulation. Local bath application of 2.0 mg/ml WIN significantly reduced PDC activity (3±1% control, P<0.01), C‐fiber evoked activity (58±9% control, P<0.01), and A&bgr; evoked activity (57±10% control, P<0.01) in WDR neurons. In contrast, LTM A&bgr;‐fiber evoked activity increased after local administration of WIN (204±52% control, P<0.01). SR141716A, a CB1 receptor antagonist, prevented the effects of WIN on WDR PDC and LTM A&bgr; evoked activity. These results indicate that cannabinoid receptor agonists may be effective agents for craniofacial pain. Furthermore, the particular sensitivity of PDC activity, a measure of neuronal hyperexcitability, to cannabinoid receptor agonists may be relevant to the treatment of persistent craniofacial pain.

Chiari i malformation as a cause of trigeminal neuralgia: Case report

OBJECTIVETrigeminal neuralgia (TN) is usually associated with vascular compression of the trigeminal nerve, but some cases are associated with central lesions such as tumors, aneurysms, or arteriovenous malformations. In this article, we report the 19th case of TN associated with Chiari I malformation and review clinical outcomes and pathophysiology. CLINICAL PRESENTATIONA 63-year-old right-handed man initially presented in 1993 with left-sided lancinating facial pain in the V2 distribution of the trigeminal nerve; the pain was triggered by certain movements, tactile stimulation, or a hot shower. Magnetic resonance imaging revealed a Chiari I malformation associated with a syrinx from C1 to C3. INTERVENTIONThe patient underwent uncomplicated suboccipital craniectomy, C1 laminectomy, and duraplasty for Chiari decompression. Postoperatively, his pain resolved over a period of 1 year. CONCLUSIONChiari I malformation has been found to be associated with TN in 19 cases in the English-language literature. In patients refractory to medical treatment, suboccipital decompression leads to resolution of pain in about two-thirds of patients. Potential mechanisms for the pathogenesis of TN in the setting of Chiari I malformation are discussed. Chiari I malformation is important to consider as a rare cause of TN that responds to surgical therapy.

Multiple pilocytic astrocytomas of the cerebellum in a 17-year-old patient with neurofibromatosis type I

ObjectiveApproximately 10% of patients with neurofibromatosis I (NFI) patients will have central nervous system (CNS) tumors. The most common of these are hypothalamic–optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. While isolated pilocytic astrocytomas in NFI are well described, the appearance of multiple pilocytic astrocytomas in an individual patient is less common. The most frequent combination in NFI patients with more than one pilocytic astrocytoma is optic tract/hypothalamic and brainstem. Other combinations are exceedingly rare; multiple pilocytic astrocytomas have only been reported once in the cerebral hemispheres in a patient with NFI. This report presents the first documented case, to our knowledge, of multiple pilocytic astrocytomas in the cerebellum of a patient with NF1.MethodsCase report.ConclusionThe finding of multiple cerebellar pilocytic astrocytomas in a patient with NF1 is important because it expands the spectrum of presentations for patients with NF1 and also highlights specific diagnostic and therapeutic challenges faced by the treating physicians. The genetic and molecular basis of NF1 is reviewed. Strategies of diagnosis and treatment outlined here are relevant to both patients with NF1 and all patients with multiple posterior fossa tumors.

Functional Hemispherectomy for Refractory Status Epilepticus in 2 Adults.

BACKGROUND Status epilepticus (SE) is a medical emergency, as deleterious long-term effects are well known. Medically induced burst suppression is often required if first-line and second-line treatments fail. Surgical intervention can be considered in some patients after prolonged treatment failure of medically induced coma. Multiple surgical options for terminating SE have been demonstrated in the literature, with only 2 reports including hemispherectomy in adults. CASE DESCRIPTION We present 2 cases of adults with refractory SE who failed more conservative medical/surgical treatment but responded to functional hemispherectomy. Pertinent electroencephalography and imaging findings are discussed. In addition, all previously published pediatric and adult cases are briefly reviewed. CONCLUSIONS Functional hemispherectomy can be considered in patients, including adults, with super-refractory SE and diffuse hemispheric onset. We report acceptable outcomes and quality of life in our 2 patients.

Subdural electrode recording of generalized photoepileptic responses

We evaluated the spatiotemporal distribution of photic driving (PDR), photoparoxysmal (PPR), and photoconvulsive (PCR) responses recorded by intracranial electrodes (ic-EEG) in a patient with generalized photosensitivity and right frontal lobe cortical dysplasia. Intermittent light stimulation (ILS) was performed thirteen times in nine days. Cortical responses to ILS recorded by ic-EEG were reviewed and classified as PDRs, PPRs, and PCRs. Photic driving responses were restricted to the occipital lobe at ILS frequencies below 9 Hz, spreading to the parietal and central regions at > 9 Hz. Photoparoxysmal responses commonly presented as focal, medial occipital, and parietal interictal epileptic discharges (IEDs), the latter propagating to the sensorimotor cortices. Generalized IEDs were also generated in the setting of PPRs. Photoconvulsive responses, characterized by repetitive bilateral upper extremity myoclonus sustained until the end of the stimulus, were associated with propagation of the medial parieto-occipital discharge to the primary sensorimotor and supplementary area cortices, while generalized myoclonic seizures were associated with a generalized spike-and-wave discharge with an interhemispheric posterior cingulate onset sparing the sensorimotor cortices. Both types of PCR could occur during the same stimulus. Regardless of the pathway, PCRs only occurred when PDRs involved the parietal cortices. While there may be more than one pathway underlying PCRs, parietal lobe association cortices appear to be critical to their generation.

High-Frequency Burst Vagal Nerve Simulation Therapy in a Natural Primate Model of Genetic Generalized Epilepsy

PURPOSE Since the approval of Vagal Nerve Stimulation (VNS) Therapy for medically refractory focal epilepsies in 1997, it has been also reported to be effective for a wide range of generalized seizures types and epilepsy syndromes. Instead of conventional VNS Therapy delivered at 20-30Hz signal frequencies, this study evaluates efficacy and tolerability of high-frequency burst VNS in a natural animal model for genetic generalized epilepsy (GGE), the epileptic baboon. METHODS Two female baboons (B1 P.h. Hamadryas and B2 P.h. Anubis x Cynocephalus) were selected because of frequently witnessed generalized tonic-clonic seizures (GTCS) for VNS implantation. High-frequency burst VNS Therapy was initiated after a 4-5 week baseline; different VNS settings (0.25, 2 or 2.5mA, 300Hz, 4 vs 7 pulses, 0.5-2.5s interburst interval, and intermittent stimulation for 1-2 vs for 24h per day) were tested over the subsequent 19 weeks, which included a 4-6 week wash-out period. GTCS frequencies were quantified for each setting, while seizure duration and postictal recovery times were compared to baseline. Scalp EEG studies were performed at almost every setting, including intermittent light stimulation (ILS) to evaluate photosensitivity. Pre-ILS ictal and interictal discharge rates, as well as ILS responses were compared between trials. The Novel Object test was used to assess potential treatment effects on behavior. RESULTS High-frequency burst VNS Therapy reduced GTCS frequencies at all treatment settings in both baboons, except when output currents were reduced (0.25mA) or intermittent stimulation was restricted (to 1-2h/day). Seizure duration and postictal recovery times were unchanged. Scalp EEG studies did not demonstrate treatment-related decrease of ictal or interictal epileptic discharges or photosensitivity, but continuous treatment for 120-180s during ILS appeared to reduce photoparoxysmal responses. High-frequency burst VNS Therapy was well-tolerated by both baboons, without cardiac or behavioral changes. Repetitive muscle contractions involving the neck and left shoulder girdle were observed intermittently, most commonly at 0.5 interburst intervals, but these were transient, resolving with a few cycles of stimulation and not noted in wakefulness. CONCLUSIONS This preclinical pilot study demonstrates efficacy and tolerability of high-frequency burst VNS Therapy in the baboon model of GGE. The muscle contractions may be due to aberrant propagation of the stimulus along the vagal nerve or to the ansa cervicalis, but can be reduced by minimal adjustment of current output or stimulus duration.

Influence of Intracranial Electrode Density and Spatial Configuration on Interictal Spike Localization: A Case Study.

Purpose: Poor seizure outcomes after epilepsy surgery often reflect an incorrect localization of the epileptic sources by standard intracranial EEG interpretation because of limited electrode coverage of the epileptogenic zone. This study investigates whether, in such conditions, source modeling is able to provide more accurate source localization than the standard clinical method that can be used prospectively to improve surgical resection planning. Methods: Suboptimal epileptogenic zone sampling is simulated by subsets of the electrode configuration used to record intracranial EEG in a patient rendered seizure free after surgery. sLORETA and the clinical method solutions are applied to interictal spikes sampled with these electrode subsets and are compared for colocalization with the resection volume and displacement due to electrode downsampling. Results: sLORETA provides often congruent and at times more accurate source localization when compared with the standard clinical method. However, with electrode downsampling, individual sLORETA solution locations can vary considerably and shift consistently toward the remaining electrodes. Conclusions: sLORETA application can improve source localization based on the clinical method but does not reliably compensate for suboptimal electrode placement. Incorporating sLORETA solutions based on intracranial EEG in surgical planning should proceed cautiously in cases where electrode repositioning is planned on clinical grounds.

Temporopolar bridging veins during anteromedial temporal strip placement: a case report on complication avoidance†

Abstract Introduction Surgery for temporal lobe epilepsy is proven to be beneficial in the treatment of medically refractory temporal lobe epilepsy. Subdural electrode strips are commonly passed in a blind fashion, allowing additional EEG coverage without requiring larger exposure. However, this increases risk of complication, specifically through vascular injury. Case report We present a case of a 22-year-old male with medically refractory epilepsy. During passage of an anterior medial temporal strip electrode, resistance was encountered despite multiple attempts and redirection. This strip was abandoned. During the subsequent resection operation, a large temporopolar bridging vein complex was noted and photographed precisely where we encountered resistance. Conclusion Although much frequently less encountered than paramedian subdural strips, anterior medial temporal strip subdural electrodes may indeed injure large bridging veins. As subdural strips are passed where bony exposure is minimal, potential disastrous complications may arise if extreme caution is not used.