Cortical hot spots and labyrinths: why cortical neuromodulation for episodic migraine with aura should be personalized

Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies toward preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD) wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI) scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using noninvasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (N30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2- dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25–90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

Long-latency reductions in gamma power predict hemodynamic changes that underlie the negative BOLD signal

Studiesthat use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to “negative” hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently withtwo-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gammaband power (30 – 80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals.