Cortical Spreading Depression In Migraine Research Articles

Updated review on the link between cortical spreading depression and headache disorders

ABSTRACT Introduction: Experimental animal studies have revealed mechanisms that link cortical spreading depression (CSD) to the trigeminal activation mediating lateralized headache. However, conventional CSD as seen in lissencephalic brain is insufficient to explain some clinical features of aura and migraine headache. Areas covered: The importance of CSD in headache development including dysfunction of the thalamocortical network, neuroinflammation, calcitonin gene-related peptide, transgenic models, and the role of CSD in migraine triggers, treatment options, neuromodulation, and future directions are reviewed. Expert opinion: The conventional understanding of CSD marching across the hemisphere is invalid in gyrencephalic brains. Thalamocortical dysfunction and interruption of functional cortical network systems by CSD may provide alternative explanations for clinical manifestations of migraine phases including aura. Not all drugs showing CSD blocking properties in lissencephalic brains have efficacy in migraine headache and monoclonal antibodies against CGRP ligand/receptors which are effective in migraine treatment, have no impact on aura in humans or CSD properties in rodents. Functional networks and molecular mechanisms mediating and amplifying the effects of limited CSD in migraine brain remain to be investigated to define new targets.

Mapping migraine to a common brain network

Inconsistent findings from migraine neuroimaging studies have limited attempts to localize migraine symptomatology. Novel brain network mapping techniques offer a new approach for linking neuroimaging findings to a common neuroanatomical substrate and localizing therapeutic targets. In this study, we attempted to determine whether neuroanatomically heterogeneous neuroimaging findings of migraine localize to a common brain network. We used meta-analytic coordinates of decreased grey matter volume in migraineurs as seed regions to generate resting state functional connectivity network maps from a normative connectome (n = 1000). Network maps were overlapped to identify common regions of connectivity across all coordinates. Specificity of our findings was evaluated using a whole-brain Bayesian spatial generalized linear mixed model and a region of interest analysis with comparison groups of chronic pain and a neurologic control (Alzheimer's disease). We found that all migraine coordinates (11/11, 100%) were negatively connected (t ≥ ±7, P < 10-6 family-wise error corrected for multiple comparisons) to a single location in left extrastriate visual cortex overlying dorsal V3 and V3A subregions. More than 90% of coordinates (10/11) were also positively connected with bilateral insula and negatively connected with the hypothalamus. Bayesian spatial generalized linear mixed model whole-brain analysis identified left V3/V3A as the area with the most specific connectivity to migraine coordinates compared to control coordinates (voxel-wise probability of ≥90%). Post hoc region of interest analyses further supported the specificity of this finding (ANOVA P = 0.02; pairwise t-tests P = 0.03 and P = 0.003, respectively). In conclusion, using coordinate-based network mapping, we show that regions of grey matter volume loss in migraineurs localize to a common brain network defined by connectivity to visual cortex V3/V3A, a region previously implicated in mechanisms of cortical spreading depression in migraine. Our findings help unify migraine neuroimaging literature and offer a migraine-specific target for neuromodulatory treatment.

The Migraine Aura.

This article discusses the basic mechanisms of migraine aura and its clinical significance based upon evidence from human studies and animal models. Prospective clinical studies have reinforced the understanding that migraine aura is highly variable from one individual to the next as well as from attack to attack in an individual. While migraine with aura clearly has a higher heritability than migraine without aura, population studies have not identified specific genes that underlie this heritability for typical migraine with aura. Imaging studies reveal hypoperfusion associated with migraine aura, although the timing and distribution of this hypoperfusion is not strictly correlated with migraine symptoms. Mapping of migraine visual aura symptoms onto the visual cortex suggests that the mechanisms underlying the aura propagate in a linear fashion along gyri or sulci rather than as a concentric wave and also suggests that aura may propagate in the absence of clinical symptoms. Cortical spreading depression in animal models continues to be a translational model for migraine, and the study of spreading depolarizations in the injured human brain has provided new insight into potential mechanisms of cortical spreading depression in migraine. Migraine with aura has multiple comorbidities including patent foramen ovale, stroke, and psychiatric disorders; the shared mechanisms underlying these comorbidities remains a topic of active investigation. Although it occurs in the minority of patients with migraine, aura may have much to teach us about basic mechanisms of migraine. In addition, its occurrence may influence clinical management regarding comorbid conditions and acute and preventive therapy.

The borderland of migraine and epilepsy in children.

To provide a review on the spectrum of migraine-epilepsy disorders in children. The migraine-epilepsy continuum covers a fascinating array of disorders that share many clinical similarities but also differ fundamentally in pathophysiology. In the pediatric population, its study can be complicated by the young age of those affected and the lack of clear understanding of the neurobiology of these disorders within the developing brain. This review serves to discuss the borderland of migraine and epilepsy in children. It will focus on epidemiology and comorbidity of the two disorders, possible mechanisms for shared pathophysiology informed by basic and translational science, and an overview of clinical similarities and differences. It will also discuss differentiation of migraine aura from childhood occipital epilepsies. Finally, the review concludes with a discussion of current classification methods for capturing cases on the migraine-epilepsy spectrum and a call for a united approach towards a better definition of this spectrum of disorders. Recent advances examining the migraine-epilepsy spectrum show clinicopathological similarities between the two disorders in children. Epidemiology demonstrates reciprocally increased incidences of epilepsy in migraineurs and of migraines in children with epilepsy, however, prospective longitudinal in children are currently lacking. Clinically, the two disorders show similarity in preictal, ictal, and postictal phenomena, with close temporal association of the two conditions described by the controversial term of "migralepsy." Basic science research has contributed significant improvements in understanding the generation of both of these episodic neurological conditions, with common links seen at a cellular level involving synaptic glutamate release and the provocation of varying propagation methods including cortical spreading depression in migraine and the paroxysmal depolarizing shift in epilepsy. Despite these significant gains in understanding, improved classification methods are required to identify and further study these interrelated conditions and move towards improved diagnosis and treatment of disorders on the migraine-epilepsy continuum in children.

The Role of Cortical Spreading Depression in Migraine

The Role of Cortical Spreading Depression in Migraine

Cortical spreading depression and migraine

Cortical spreading depression (CSD), a slowly propagated wave of depolarization followed by suppression of brain activity, is a remarkably complex event that involves dramatic changes in neural and vascular function. Since its original description in the 1940s, CSD has been hypothesized to be the underlying mechanism of the migraine aura. Substantial evidence from animal models provides indirect support for this hypothesis, and studies showing that CSD is common in humans with brain injury clearly demonstrate that the phenomenon can occur in the human brain. Considerable uncertainty about the role of CSD in migraine remains, however, and key questions about how this event is initiated, how it spreads, and how it might cause migraine symptoms remain unanswered. This Review summarizes current concepts of CSD and its potential roles in migraine, and addresses ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon.

Functional neuroimaging of migraine

This review summarizes the history of migraine imaging and key findings of studies on functional neuroimaging in migraine and describes how these data have changed our view of the disorder. Functional neuroimaging during migraine attacks and also interictally has initiated the description of “the migraine brain”. These studies have led to the demonstration of cortical spreading depression in migraine with aura, the crucial role for the brainstem during migraine attacks, and cortical hypersensitivity in migraineurs modulated by the trigeminal pathway, explaining sensory sensitization such as photophobia and osmophobia.

Minimum Conditions for the Induction of Cortical Spreading Depression: Implications for Migraine with Aura (S16.002)

Objective: Determine whether cortical spreading depression can be induced under conditions physiologically compatible with migraine. Background Cortical spreading depression (CSD) is thought to be the mechanism of the migraine aura. If so, it must occur in awake humans, be focally inducible, and not be overtly injurious. In contrast, laboratory models of CSD use conditions that are associated with brain injury in humans. It is important to define the parameters under which CSD can be triggered, and determine whether any of these are plausible in migraine aura. Design/Methods: We used a novel microfluidic device to precisely vary extracellular potassium concentration (Ke) as well as the area exposed to this increased Ke, in a mouse brain slice model. Ke was varied over a range from 15 to 140 mM above normal baseline of 3 mM. Microfluidic port radius was varied from 75 to 250 µm. Whole slice perfusion was also performed. Results: We found that CSD was inducible with small areas exposed to high Ke, and large areas exposed to lower Ke levels, in an approximately hyperbolic relationship. For elevations in Ke unlikely to be associated with tissue damage ( 300 µm (on the order of magnitude of a cortical column or penetrating artery territory). Smaller areas supported CSD when Ke was raised to levels that can only be achieved by cell lysis. Perfusion of the whole brain slice yielded the lowest CSD threshold (15 mM Ke). Conclusions: Our results show that relatively large focal regions must be depolarized to generate CSD in a manner compatible with migraine aura. However they also suggest that the induction of CSD in migraine is physiologically plausible. Supported by: NIH NS 059072, NS 070084 (KCB). Disclosure: Dr. Brennan has nothing to disclose. Dr. Tang has nothing to disclose. Dr. Lopez-Valdes has nothing to disclose. Dr. Charles has received personal compensation for activites with MAP Pharmaceuticals and Merck & Co., Inc. Dr. Charles has received research support from MAP Pharmaceuticals. Dr. Ju has nothing to disclose.

Cortical-spreading depression: at the razor’s edge of scientific logic

For over 60 years, cortical spreading depression (CSD) has mesmerized neurologists immersed in headache research. While science and logic are (or, at least, should be) inseparable, CSD—a largely experimental physiological reality—has dissociated the two in headache-related research. Although the need for a fresh pathophysiologic approach to migraine and other primary headaches unrelated to the neuronal (neural) or vascular theories has been voiced two decades ago [1, 2], and the issue has been questioned again recently [3, 4], the fascination for CSD as the basis for migraine remains largely undimmed. Currently, the pathogenetic role of CSD in migraine is widely accepted as an immutable fact or truth, and, any challenge to its role is regarded as almost heretical. In this issue of TJHP, Yu and colleagues present an interesting facet of the mechanism of action of flunarizine in a rat model of CSD. The key finding is that flunarizine can alleviate cerebral mitochondrial injury under both normal and hypoxic conditions, a not unexpected effect attributed likely to blockade of voltage-gated calcium channels. However, hypoxia attenuated the protective effect of flunarizine on the CSD amplitude. In a nutshell, CSD leads to oxidative stress, or aggravated hypoxic conditions in the brain, and, these changes can be attenuated by flunarizine. In extrapolating these experimental results in rats to humans, and, in particular, to migraine pathophysiology, certain features need careful consideration. The role of flunarizine in migraine therapeutics is itself uncertain. While flunarizine is used (albeit, with low-grade evidence) for migraine prophylaxis in several countries, it has yet to be approved for this indication by the United States Food and Drug Administration. Whereas the US FDA looks for evidences from randomized clinical trials (RCT) to stamp its approval of drugs such as flunarizine, the RCT itself is not without flaws, and, its utility in migraine is limited by the very nature of the disorder [5]. At a more fundamental level, flunarizine is a potent vasodilator of the cerebral vessels. Alcohol and nitroglycerin are well-established vasodilators that precipitate migraine predictably without any known effect(s) on CSD. There is, however, a significant clinical difference between sustained prophylactic cerebral vasodilatation (flunarizine) and relatively sudden cerebral vasodilatation (alcohol, nitroglycerin). Nevertheless, evidence that flunarizine can provide extended, satisfactory prophylaxis for most migraine patients is conspicuously sparse. The limitations of CSD as a pathogenetic model for human neurological illnesses, particularly migraine, have been discussed almost exhaustively; additionally, a large and growing body of evidence indicates that CSD is biologically adaptive or neuroprotective [4]. There is not a single description of homonymously distributed migrainous scintillating scotoma; the scotoma has always been described as spreading towards the temporal field, right or left. Even Lashley [6] did not describe spread of his own migrainous scotoma towards the nasal field. As a neuropathologic concept, CSD has spawned much confusion and speculation, and, has outlived its usefulness. The time is, perhaps, ripe to bid farewell to an enduring and revered notion in neurology. Only then, we might step out of the maze of clinical and therapeutic assumptions that sustain a prominent role for CSD in human neuropathology. Such comprehension would also mark the beginning of the end of the stalemate that has gripped migraine research for over half a century.

Migraine preventive drugs differentially affect cortical spreading depression in rat

Cortical spreading depression (CSD) is the most likely cause of the migraine aura. Drugs with distinct pharmacological properties are effective in the preventive treatment of migraine. To test the hypothesis that their common denominator might be suppression of CSD we studied in rats the effect of three drugs used in migraine prevention: lamotrigine which is selectively effective on the aura but not on the headache, valproate and riboflavin which have a non-selective effect. Rats received for 4 weeks daily intraperitoneal injections of one of the three drugs. For valproate and riboflavin we used saline as control, for lamotrigine its vehicle dimethyl sulfoxide. After treatment, cortical spreading depressions were elicited for 2 h by occipital KCl application. We measured CSD frequency, its propagation between a posterior (parieto-occipital) and an anterior (frontal) electrode, and number of Fos-immunoreactive nuclei in frontal cortex. Lamotrigine suppressed CSDs by 37% and 60% at posterior and anterior electrodes. Valproate had no effect on posterior CSDs, but reduced anterior ones by 32% and slowed propagation velocity. Riboflavin had no significant effect at neither recording site. Frontal Fos expression was decreased after lamotrigine and valproate, but not after riboflavin. Serum levels of administered drugs were within the range of those usually effective in patients. Our study shows that preventive anti-migraine drugs have differential effects on CSD. Lamotrigine has a marked suppressive effect which correlates with its rather selective action on the migraine aura. Valproate and riboflavin have no effect on the triggering of CSD, although they are effective in migraine without aura. Taken together, these results are compatible with a causal role of CSD in migraine with aura, but not in migraine without aura.

The borderland of epilepsy: A clinical and molecular view, 100 years on

The diagnosis of phenomena that mimic epilepsy is anongoingchallengefortheclinicalneurologist.SirWilliamGowers published his classic book The Border-land ofEpilepsyin1907,basinghisanalysisanddifferentialdiag-noses solely on clinical information. He focused on faints,vagal and vasovagal attacks (which he differentiated fromfaints), migraine, vertigo, and some sleep symptoms,particularly narcolepsy. Over the last 100 years, majorinvestigative advances—including electroencephalogra-phy(EEG),imaging,and,morerecently,moleculargenet-ics—have revolutionized the clinical and basic sciencesrelevant to Gowers’ borderland. We have revisited theepilepsy borderland, from the clinical and molecularviewpoints, focusing on syncope, migraine, parasomnias,and some rarer disorders including the paroxysmal dyski-nesias and organic causes of nonepileptic convulsions(Crompton & Berkovic, 2009). Many of the basic clinicaltenets of Gowers’ analysis from a century ago remain,although the importance of vertigo as an epileptic mimichas diminished and the clinical approach to syncope hasbeen considerably modified. Interestingly, nonepilepticseizures (pseudo seizures) were not regarded as a signifi-cantclinicalissuebyGowers.A major advance in scientific thinking, made possibleby molecular genetics, is that the epilepsies are, at least inpart, afamily ofchannelopathies. Ion channeldysfunctionis the major known mechanism of the inherited idiopathicepilepsies, and roles in the acquired epilepsies (‘‘acquiredchannelopathies’’) are also likely. It is of interest to notethat when analyzing the mechanisms of disorders withinthe epilepsy borderland, ion channels also featurestrongly.The clinical distinction of epileptic seizures fromsyncope, particularly convulsive syncope, is a commonclinical problem which, just like in Gowers’ era, remainslargely based on the clinical history. In certain cardiacdisorders causing syncope, such as arrhythmias includingthe long QT syndrome and Brugada syndrome, the majormechanisms are of inherited cardiac ion channel dysfunc-tion. Remarkably, epileptic seizures and cardiac channel-opathies causing syncope rarely coexist. This is becauseion channel subunits present in the heart are generally notexpressedinthebrainandviceversa.However,themolec-ular and cellular mechanisms of electrical instability aresimilar, thus illustrating the parsimony of nature in termsofmechanismsofparoxysmaldisordersaffectingdifferentorgans.Migraine and epilepsy are usually easily distinguished,but a complex clinical overlap of migraine and epilepsydoes occur, as shown by epidemiologic studies, by analy-sis of certain families segregating both disorders, and byspecific but uncommon migraine–epilepsy syndromes.The molecular mechanisms of migraine are slowly beingunravelled, particularly in the autosomal dominantfamilial forms. Again, the genetic culprits are largely ionchannel subunits. Indeed, dysfunction of certain ion chan-nels can cause both migraine and epilepsy, although themolecular mechanisms, cortical-spreading depression inmigraine aura, and paroxysmal high frequency dischargesin epileptic seizures, are quite different. This paradox hasyettobefullyexplainedatamolecularlevel.Theparasomniasprovideanextremelychallengingareaof clinical differential diagnosis from nocturnal epilepticseizures. Moreover, there appears to be a genetic relation-ship between what are regarded as nocturnal seizures andparasomnias.Thediscoveryofacetylcholinereceptorsub-unit mutations in some families with autosomal dominantnocturnal frontal lobe epilepsy has provided a windowinto this issue, although the mechanism of seizure genesishas not been elucidated. Mouse models with humanmutations may show spontaneous epileptic seizures, butapparently nonepileptic phenomena can occur as well,furthercomplicatingthisfascinatingborderland.Paroxysmal dyskinesias are uncommon disorders,often familial, where the underlying molecular defects

Cortical Spreading Depression—New Insights and Persistent Questions

Since its original extensive description by Leao in 1944, thousands of publications have characterized the phenomenon of cortical spreading depression (CSD). Despite the attention that CSD has received over more than six decades, however, many fundamental questions regarding its initiation, propagation, functional consequences, and relationship to migraine and other human disorders remain unanswered. Advances in genetics and cellular imaging have led to important insights into the basic mechanisms of CSD, with increasing attention focused on specific neuronal ion channels, neurotransmitters and neuromodulators. In addition, there is growing recognition that astrocytes and the vasculature may play an active, rather than simply a passive or reactive role in CSD. Several recent descriptions of CSD in humans in the setting of brain injury provide definitive evidence that this phenomenon can occur and have important functional consequences in the human brain. Although the exact role of CSD in migraine has yet to be conclusively established, there is strong evidence that the investigation of CSD in animal models can provide meaningful information about migraine that can be translated into the clinical setting. This review will briefly address the extensive work that has been done on CSD over more than half a century, but focus primarily on more recent studies with a particular emphasis on relevance to migraine.

Cortical spreading depression in migraine.

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis as well as efflux of excitatory amino acids from nerve cells and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine. This paper will, based on the experience related to the detection of CSD in humans, discuss pitfalls and possible strategies for detection of CSD in man. Development of reliable methods for detection of CSD in humans will determine the extent to which the large body of experimental findings from animal studies of CSD can be applied to the investigation and treatment of human brain disease. The paper is based on the experience that has been gained from two decades of studies of CSD in relation to clinical neurological diseases.

Cortical Spreading Depression in Migraine

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis as well as efflux of excitatory amino acids from nerve cells and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine. This paper will, based on the experience related to the detection of CSD in humans, discuss pitfalls and possible strategies for detection of CSD in man. Development of reliable methods for detection of CSD in humans will determine the extent to which the large body of experimental findings from animal studies of CSD can be applied to the investigation and treatment of human brain disease. The paper is based on the experience that has been gained from two decades of studies of CSD in relation to clinical neurological diseases.

Cortical spreading depression in migraine

Cortical spreading depression in migraine

Effects of Ca2+ channel blockers on cortical hypoperfusion and expression of c‐Fos‐like immunoreactivity after cortical spreading depression in rats

1. We examined the effects of two Ca2+ channel blockers, lomerizine (KB-2796) and flunarizine, on the cortical hypoperfusion (measured by hydrogen clearance and laser Doppler flowmetry methods) and cortical c-Fos-like immunoreactivity that follow KCl-induced cortical spreading depression in anaesthetized rats. Cortical spreading depression was induced by application of 1 M KCl for 30 s to the cortical surface, 3.0 mm posterior to the area of cerebral blood flow measurement. 2. In control rats, KB-2796 (0.3 and 1 mg kg-1, i.v.) dose-dependently increased cerebral blood flow significantly at 30 min and 15 min, respectively, after its administration. Flunarizine (1 mg kg-1, i.v.) significantly increased cerebral blood flow 15 min after its administration. In contrast, dimetotiazine (3 mg kg-1, i.v.), a 5-HT2 and histamine H1 antagonist, failed to affect cerebral blood flow significantly. 3. After KCl application to the cortex, cerebral blood flow monitored by the laser Doppler flowmetry method increased transiently, for a few minutes, then fell and remained approximately 20 to 30% below control for at least 60 min. Cerebral blood flow monitored by the hydrogen clearance method was also approximately 20 to 30% below baseline for at least 60 min after KCl application. KB-2796 (0.3 and 1 mg kg-1, i.v.) and flunarizine (1 and 3 mg kg-1, i.v.) administered 5 min before KCl application inhibited the cortical hypoperfusion that followed KCl application, but dimetotiazine (1 and 3 mg kg-1, i.v.) did not. 4. An indicator of neuronal activation, c-Fos-like immunoreactivity, was detected in the ipsilateral, but not in the contralateral frontoparietal cortex 2 h after KCl application. No c-Fos-like immunoreactivity was seen on either side of the brain in the hippocampus, thalamus, striatum or cerebellum. 5. KB-2796 (1 mg kg-1, i.v.) and flunarizine (3 mg kg-1, i.v.), but not dimetotiazine (3 mg kg-1, i.v.), significantly attenuated the expression of c-Fos-like immunoreactivity in the ipsilateral frontoparietal cortex. 6. These findings suggest that the inhibitory effects of KB-2796 and flunarizine on the cortical hypoperfusion and expression of c-Fos-like immunoreactivity induced by spreading depression are mediated via the effects of Ca(2+)-entry blockade, which may include an increase in cerebral blood flow and the prevention of excessive Ca2+ influx into brain cells. KB-2796 and flunarizine may prove useful as inhibitors of cortical spreading depression in migraine.

Spreading depression induces prolonged reduction of cortical blood flow reactivity in the rat

The purpose of the present study was to examine the dynamic aspects of the cerebrovascular events occurring during and up to 2 h following cortical spreading depression (CSD) in the rat, using the mass spectrometry technique which enables continuous measurements of the cortical tissue PO 2 and PCO 2 and repeated blood flow measurements (CoBF) by helium clearance. We mostly sought to determine whether cortical perforation by a stimulation electrode induced long-lasting perturbation of the cortical vasoreactivity to hypercapnia and basal forebrain electrical stimulation. Cortical perforation in the animal under α-chloralose anesthesia, chronically implanted with mass spectrometry probes, was associated with biphasic changes in tissue gases. PO 2 first briefly decreased (−7.8%) and then strongly increased (+79%) while PCO 2 changed in the opposite direction (+7%, −13%) in the ipsilateral frontal cortex. Qualitatively similar changes occurred in the ipsilateral parietal cortex. The CoBF measurements showed a marked vasodilation (131 and 108% in the frontal and parietal cortex, respectively) in parallel with the PO 2 increase, followed by a prolonged (60 min), moderate hypoperfusion (maximum −17% at 20 min after CSD). There was a pronounced reduction of vascular reactivity to both hypercapnia (20.3% of the control response) and substantia innominata stimulation ( 1 6 of the response obtained 80 min later) at 10 min after CSD. Both reactivities progressively recovered in approximately 2 h. Since the issue of CSD in human has become a popular hypothesis for migraine, the reduced cerebrovascular reactivity could constitute the basis of a test for the involvement of CSD in migraine.

Detection of cortical spreading depression in the anaesthetised rat by impedance measurement with scalp electrodes: implications for non-invasive imaging of the brain with electrical impedance tomography.

The possible use of impedance measurement with scalp electrodes to detect intracranial events non-invasively was investigated by measuring the localised impedance changes during cortical spreading depression (CSD) in anaesthetised rats. Impedance was measured over ipsilateral fronto-parietal cortex by a four electrode method operating at 50 kHz with electrodes spaced 0.5 mm apart. Cortical impedance increased by 39% of the resting level during CSD. With scalp electrodes placed on abraded skin, an unexpected impedance decrease of 0.8% occurred, which correlated spatially and temporally with CSD. CSD was accompanied by a small rise in temperature; when scalp temperature was held constant by warming the scalp, no impedance change greater than baseline variability (+/- 0.1% of the resting impedance level) was observed. The non-invasive detection of CSD in migraine in humans may be possible by measuring the characteristic temperature-related impedance changes with Electrical Impedance Tomography and scalp electrodes.