EEG–fMRI of idiopathic and secondarily generalized epilepsies

We used simultaneous EEG and functional MRI (EEG–fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG–fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG–fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG–fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity

Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

Background: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings: Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACE

The mapping of cortical activation by near infra-red spectroscopy might be a biomarker related to the severity of fibromyalgia

The delta value of oxyhemoglobin (Δ-HbO) determined by functional near-infrared spectroscopy at prefrontal cortex (PFC) and motor cortex (MC) based on primary (25 °C) and secondary (5 °C) thermal stimuli presented a larger peak latency at left MC in fibromyalgia than in controls. The difference between HbO concentration 15 s after the thermal stimuli ending and HbO concentration before the thermal stimuli onset (Δ-HbO*) at left PFC increased 47.82% in fibromyalgia and 76.66% in controls. This value had satisfactory discriminatory properties to differentiate cortical activation in fibromyalgia versus controls. A receiver operator characteristics (ROC) analysis showed the Δ-HbO* cutoffs of − 0.175 at left PFC and − 0.205 at right PFC offer sensitivity and specificity of at least 80% in screening fibromyalgia from controls. In fibromyalgia, a ROC analysis showed that these cutoffs could discriminate those with higher disability due to pain and more severe central sensitization symptoms (CSS). The ROC with the best discriminatory profile was the CSS score with the Δ-HbO* at left PFC (area under the curve = 0.82, 95% confidence interval = 0.61–100). These results indicate that cortical activation based on Δ-HbO* at left PFC might be a sensitive marker to identify fibromyalgia subjects with more severe clinical symptoms

Reversible cooling-induced deactivations to study cortical contributions to obstacle memory in the walking cat

On complex, naturalistic terrain, sensory information about an environmental obstacle can be used to rapidly adjust locomotor movements for avoidance. For example, in the cat, visual information about an impending obstacle can modulate stepping for avoidance. Locomotor adaptation can also occur independent of vision, as sudden tactile inputs to the leg by an expected obstacle can modify the stepping of all four legs for avoidance. Such complex locomotor coordination involves supraspinal structures, such as the parietal cortex. This protocol describes the use of reversible, cooling-induced cortical deactivation to assess parietal cortex contributions to memory-guided obstacle locomotion in the cat. Small cooling loops, known as cryoloops, are specially shaped to deactivate discrete regions of interest to assess their contributions to an overt behavior. Such methods have been used to elucidate the role of parietal area 5 in memory-guided obstacle avoidance in the cat

Effects of cranial electrotherapy stimulation on resting state brain activity

Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec “on” alternating with 22 sec of baseline (device was “off”). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment

Effects of core auditory cortex deactivation on neuronal response to simple and complex acoustic signals in the contralateral anterior auditory field

Interhemispheric communication has been implicated in various functions of sensory signal processing and perception. Despite ample evidence demonstrating this phenomenon in the visual and somatosensory systems, to date, limited functional assessment of transcallosal transmission during periods of acoustic signal exposure has hindered our understanding of the role of interhemispheric connections between auditory cortical fields. Consequently, the present investigation examines the impact of core auditory cortical field deactivation on response properties of contralateral anterior auditory field (AAF) neurons in the felis catus. Single-unit responses to simple and complex acoustic signals were measured across AAF before, during, and after individual and combined cooling deactivation of contralateral primary auditory cortex (A1) and AAF neurons. Data analyses revealed that on average: 1) interhemispheric projections from core auditory areas to contralateral AAF neurons are predominantly excitatory, 2) changes in response strength vary based on acoustic features, 3) A1 and AAF projections can modulate AAF activity differently, 4) decreases in response strength are not specific to particular cortical laminae, and 5) contralateral inputs modulate AAF neuronal response thresholds. Collectively, these observations demonstrate that A1 and AAF neurons predominantly modulate AAF response properties via excitatory projections

Electrocortical and Autonomic Alteration by Administration of a Pleasant and an Unpleasant Odor

The present study was designed to investigate whether there is a consistent response in ongoing EEG due to repetitive olfactory stimulation. Two odors of different hedonic quality were presented bilaterally to five male subjects at suprathreshold levels. A room-air blank served as the control stimulus. Each odor was presented six times to each subject in each of three sessions. Electrocortical activity, heart rate, skin conductance and breathing cycle were recorded continuously. EEG variables assessed were difference scores of absolute power in the frequency bands theta, alpha1, alpha2 and beta1 at eight locations. Phenylethyl alcohol was rated pleasant, while valeric acid was judged unpleasant. Within 8 s after stimulus release, valeric acid increased alpha2 power, whereas phenylethyl alcohol did not. No further frequency bands were affected by olfactory stimulation. These findings suggest that smelling an unpleasant odor leads to a cortical deactivation. Chem. Senses 20: 505-515, 199

Age-related changes in prefrontal cortex function: links between sleep EEG and cognition

Healthy ageing has been found to be accompanied by changes in slow wave activity (SWA) and cognitive function. Furthermore, these changes have been seen predominantly in the prefrontal cortex (PFC) compared to other regions of the cortex. Current theories of cognitive ageing propose that this occurs due to a specified deterioration of neuronal substrates of the PFC, and as such, changes in SWA and cognitive function may decline at similar rates due to similar underlying aetiology. The main aim of the current thesis was to explore age-related differences in electroencephalographic (EEG) SWA during the first NREM period and cognitive performance that relies on the integrity of the PFC: executive function and social cognition. The extent to which executive function (reliant on dorsolateral PFC areas) and social cognitive function (reliant on ventromedial PFC regions) show similar age-related deterioration was investigated in Study 1. Here, 16 young (22.2 years) and 16 older (71.5 years) adults were administered with a cognitive testing battery including executive function measures: Verbal Fluency (VF) and Tower of London (TOL); as well as measures of social cognition: Go/No-go, Emotional Prosody and Ekman 60 Faces. Not all measures of PFC function were affected to the same extent. The older group performed significantly worse on the TOL, but not on the VF test. Additionally, simple aspects of social cognition did not display differences between the groups, but the older group performed significantly worse than the young group on more complex aspects of recognition of emotion from facial expression (Ekman 60 Faces) and Emotional Prosody. As most studies of cognitive ageing are cross-sectional and show large agerelated changes, the remainder of this thesis focused on age-related changes using a longitudinal design over a relatively small ageing period (mean = 6.29 years). The average age of participants at baseline was 67.1 years and the average age at follow-up was 73.4 years. In Study 2, in a sample of 11 participants, performance on executive function tests was measured (TOL, VF and Wisconsin Card Sorting Test: WCST). As found in the cross-sectional analyses reported in Study 1, the TOL task was found to be the most sensitive indicator of age-related changes, as this showed a decline with age; whereas, VF and WCST remained stable over time. Furthermore, in Study 3, localised SWA was recorded via EEG, and significant declines were found in low frequency delta (0.5 – 1 Hz), which was localised to the left frontal region. (Continues...)