Blood Oxygenation Level-dependent Signal Changes Research Articles

Changes preceding interictal epileptic EEG abnormalities: Comparison between EEG/fMRI and intracerebral EEG

In simultaneous scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), blood oxygen level dependent (BOLD) changes occurring before the spike have been sometimes described but could not be explained. To characterize the origin of this prespike BOLD signal change, we looked for electrographic changes in stereo-EEG (SEEG) possibly preceding the scalp spike in patients that showed early BOLD response in EEG/fMRI. We studied four patients with drug-resistant focal epilepsy who underwent EEG/fMRI, showed a prespike BOLD response, and were then studied with depth electrodes for presurgical localization of the epileptic generator. Early BOLD responses in the region of the spike field were analyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike. SEEG recordings in the period and location corresponding to the early HRF responses were analyzed to detect if electrographic changes were present in the SEEG before the scalp abnormality. One of the four patients presented a SEEG interictal discharge in the period corresponding to the early BOLD response. In the other three, no electrographic changes were detected in the SEEG in the period corresponding to early BOLD changes. Although the early BOLD activity may sometimes be explained by a synchronized neural discharge detectable with SEEG but not visible on the scalp EEG, in most cases the early BOLD response reflects a metabolic phenomenon that does not appear to result from a synchronized neuronal discharge. Prespike metabolic responses can result from synchronized or nonsynchronized neuronal activity, or from nonneuronal mechanisms including glia.

Refractive surgery in anisometropic adult patients induce plastic changes in primary visual cortex

To prospectively study the effect of refractive surgery in the primary visual cortex of adult anisometropic and isometropic myopic patients. Two anisometropic and two isometropic myopic patients were examined with multifocal functional magnetic resonance imaging technique (mffMRI) before refractive surgery and at 3, 6, 9 and 12 months postoperatively. Two controls without refractive surgery were also examined with mffMRI in the beginning and in the end of the study. Anisometropic patients had only their more myopic eye operated to correct the anisometropia. The myopic isometropic patients had their both eyes operated. Operated anisometropic eyes showed 65% reduced amount of active voxels in foveal data at 12 months postoperatively compared with the preoperative situation. In unoperated anisometropic eyes, the corresponding value was 86% and in myopic patients and controls 31% and 1%, respectively. To confirm this finding, the number of activated voxels representing the innermost ring of the stimulus was also calculated, and an exactly similar phenomenon was encountered in the anisometropic patients. Both anisometropic patients improved the best-spectacle-corrected visual acuity in the operated eye after refractive surgery. Our results suggest that plastic changes may take place in the primary visual cortex of anisometropic adult patients after refractive surgery.

Electrophysiology and Functional MRI in Post-Acute Mild Traumatic Brain Injury

Symptoms persisting beyond the acute phase (>2 months) after a mild traumatic brain injury (MTBI) are often reported, but their origin remains controversial. Some investigators evoke dysfunctional cerebral mechanisms, while others ascribe them to the psychological consequences of the injury. We address this controversy by exploring possible cerebral dysfunction with functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) in a group of patients during the post-acute phase. Fourteen MTBI symptomatic patients (5.7±2.9 months post-injury) were tested with fMRI and ERP using a visual externally ordered working memory task, and were compared with 23 control subjects. Attenuated blood oxygen level dependent (BOLD) signal changes in the left and right mid-dorsolateral prefrontal cortex (mid-DLPFC), the putamen, the body of the caudate nucleus, and the right thalamus were found in the MTBI group compared with the control group. Moreover, symptom severity and BOLD signal changes were correlated: patients with more severe symptoms had lower BOLD signal changes in the right mid-DLPFC. For ERP, a group×task interaction was observed for N350 amplitude. A larger amplitude for the working memory task than for the control task was found in control subjects, but not in MTBI subjects, who had weak amplitudes for both tasks. This study confirms that persistent symptoms after MTBI cannot be uniquely explained by psychological factors, such as depression and/or malingering, and indicates that they can be associated with cerebral dysfunction. ERP reveals decreased amplitude of the N350 component, while fMRI demonstrates that the more severe the symptoms, the lower the BOLD signal changes in the mid-DLPFC.

Microstructure of Frontoparietal Connections Predicts Cortical Responsivity and Working Memory Performance

We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.

Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process. Nine healthy, normal weight subjects underwent blood oxygenation level dependent (BOLD) fMRI measurements during either intravenous (IV) glucose (0.3 mg/kg), fructose (0.3 mg/kg) or saline, administered over 2 min in a randomized, double-blind, crossover study. Blood was sampled every 5 min during a baseline period and following infusion for 60 min in total for glucose, fructose, lactate and insulin levels. No significant brain BOLD signal changes were detected in response to IV saline. BOLD signal in the cortical control areas increased during glucose infusion (p = 0.002), corresponding with increased plasma glucose and insulin levels. In contrast, BOLD signal decreased in the cortical control areas during fructose infusion (p = 0.006), corresponding with increases of plasma fructose and lactate. Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus. In normal weight humans, cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose. Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake.

Independent component analysis (ICA) of generalized spike wave discharges in fMRI: Comparison with general linear model‐based EEG‐fMRI

Most EEG-fMRI studies in epileptic patients are analyzed using the general linear model (GLM), which assumes a known hemodynamic response function (HRF) to epileptic spikes. In contrast, independent component analysis (ICA) can extract blood-oxygenation level dependent (BOLD) responses without imposing constraints on the HRF. ICA might therefore detect responses that vary in time and shape, and that are not detected in the GLM analysis. In this study, we compared the findings of ICA and GLM analyses in 12 patients with idiopathic generalized epilepsy. Spatial ICA was used to extract independent components from the functional magnetic resonance imaging (fMRI) data. A deconvolution method identified component time courses significantly related to the generalized EEG discharges, without constraining the shape of the HRF. The results from the ICA analysis were compared to those from the GLM analysis. GLM maps and ICA maps showed significant correlation and revealed BOLD responses in the thalamus, caudate nucleus, and default mode areas. In patients with a low rate of discharges per minute, the GLM analysis detected BOLD signal changes within the thalamus and the caudate nucleus that were not revealed by the ICA. In conclusion, ICA is a viable alternative technique to GLM analyses in EEG-fMRI studies related to generalized discharges. This study demonstrated that the BOLD response largely resembles the standard HRF and that GLM analysis is adequate. However, ICA is more dependent on a sufficient number of events than GLM analysis.

Transcranial direct current stimulation over the primary motor cortex during fMRI

Measurements of motor evoked potentials (MEPs) have shown that anodal and cathodal transcranial direct current stimulations (tDCS) have facilitatory or inhibitory effects on corticospinal excitability in the stimulated area of the primary motor cortex (M1). Here, we investigated the online effects of short periods of anodal and cathodal tDCS on human brain activity of healthy subjects and associated hemodynamics by concurrent blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Using a block design, 20s periods of tDCS at 1mA intensity over the left M1 altered with 20s periods without tDCS. In different fMRI runs, the effect of anodal or cathodal tDCS was assessed at rest or during finger tapping. A control experiment was also performed, in which the electrodes were placed over the left and right occipito-temporo-parietal junction. Neither anodal nor cathodal tDCS over the M1 for 20s stimulation duration induced a detectable BOLD signal change. However, in comparison to a voluntary finger tapping task without stimulation, anodal tDCS during finger tapping resulted in a decrease in the BOLD response in the supplementary motor area (SMA). Cathodal stimulation did not result in significant change in BOLD response in the SMA, however, a tendency toward decreased activity could be seen. In the control experiment neither cathodal nor anodal stimulation resulted in a significant change of BOLD signal during finger tapping in any brain area including SMA, PM, and M1. These findings demonstrate that the well-known polarity-dependent shifts in corticospinal excitability that have previously been demonstrated using measurements of MEPs after M1 stimulation are not paralleled by analogous changes in regional BOLD signal. This difference implies that the BOLD signal and measurements of MEPs probe diverse physiological mechanisms. The MEP amplitude reflects changes in transsynaptic excitability of large pyramidal neurons while the BOLD signal is a measure of net synaptic activity of all cortical neurons.

Clinical utility of cerebrovascular reactivity mapping in patients with low grade gliomas

To evaluate neurovascular uncoupling (NVU) associated with low grade gliomas (LGG) using blood oxygen level dependent (BOLD) cerebrovascular reactivity mapping. Seven patients with low grade gliomas referred by neurosurgeons for presurgical mapping were included in this pilot study. Cerebrovascular reactivity (CVR) mapping was performed by acquiring BOLD images while patients performed a block-design breath-hold (BH) hypercapnia task. CVR mapping was expressed as BOLD percentage signal change (PSC) from baseline associated with performance of the BH hypercapnia task. Standard T2* Dynamic Susceptibility Contrast perfusion imaging was performed and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) maps were generated. Structural T1 weighted MR images were also acquired. A correlation analysis between intratumoral normalized (via ratio with contralateral homologous regions) BOLD BH PSC [referred to as (n(CVR))] and intratumoral normalized resting state rCBV (rCBF) values (i.e., n(CBV) and n(CBF), respectively) was performed. No significant correlation was seen between the normalized BOLD BH PSC (i.e., n(CBV)) and n(CBV) or n(CBF). However, the average n(CVR) (median = 0.50, z = -2.28, P = 0.01) was significantly less than 1.0, indicating abnormally reduced vascular responses in the tumor regions relative to normal contralesional homologous regions, whereas the average n(CBV) (median = 0.94, z = -0.92, P = 0.375) and n(CBF) (median = 0.93, z = -1.16, P = 0.25) were not significantly higher or lower than 1.0, indicating iso-perfusion in the tumor regions relative to normal contralesional homologous regions. These findings suggest that in LGG, hyperperfusion that is seen in high grade gliomas is not present, but, nevertheless, abnormally decreased regional CVR is present within and adjacent to LGG. Since the patients all demonstrated at least some residual function attributable to the cortical regions of impaired CVR, but were incapable of producing a BOLD response in these regions regardless of the tasks performed, such regionally decreased CVR is indicative of NVU. The low n(CVR) ratios indicate high prevalence of NVU in this LGG cohort, which is an important consideration in the interpretation of clinical presurgical mapping with functional magnetic resonance (MR) imaging. Our preliminary study shows that BH CVR mapping is clinically feasible and demonstrates an unexpectedly high prevalence of NVU in patients with LGG.

Functional MRI evidence for the importance of visual short‐term memory in logographic reading

Logographic symbols are visually complex, and thus children's abilities for visual short-term memory (VSTM) predict their reading competence in logographic systems. In the present study, we investigated the importance of VSTM in logographic reading in adults, both behaviorally and by means of fMRI. Outside the scanner, VSTM predicted logographic Kanji reading in native Japanese adults (n=45), a finding consistent with previous observations in Japanese children. In the scanner, participants (n=15) were asked to perform a visual one-back task. For this fMRI experiment, we took advantage of the unique linguistic characteristic of the Japanese writing system, whereby syllabic Kana and logographic Kanji can share the same sound and meaning, but differ only in the complexity of their visual features. Kanji elicited greater activation than Kana in the cerebellum and two regions associated with VSTM, the lateral occipital complex and the superior intraparietal sulcus, bilaterally. The same regions elicited the highest activation during the control condition (an unfamiliar, unpronounceable script to the participants), presumably due to the increased VSTM demands for processing the control script. In addition, individual differences in VSTM performance (outside the scanner) significantly predicted blood oxygen level-dependent signal changes in the identified VSTM regions, during the Kanji and control conditions, but not during the Kana condition. VSTM appears to play an important role in reading logographic words, even in skilled adults, as evidenced at the behavioral and neural level, most likely due to the increased VSTM/visual attention demands necessary for processing complex visual features inherent in logographic symbols.

Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression

BackgroundWomen have approximately twice the risk of major depressive disorder (MDD) than men, yet this difference remains largely unexplained. Previous MDD research suggests high rates of endocrine dysfunction, which may be related to deficits in brain activity in stress response circuitry [hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC)]. This functional magnetic resonance imaging (fMRI) study investigated the relationship between hypothalamic–pituitary–gonadal (HPG)-axis hormones and stress response circuitry dysfunction in MDD in women. MethodsDuring the late follicular/midcycle phase of the menstrual cycle, female participants (10 with extensive histories of MDD, in remission, 10 healthy controls) were scanned while viewing negative and neutral arousal pictures. Group differences in blood oxygen-level dependent (BOLD) signal changes were analyzed using SPM2. Baseline gonadal hormones included estradiol, progesterone, and testosterone. ResultsfMRI results showed greater BOLD signal intensity changes in controls versus MDD in hypothalamus, amygdala, hippocampus, OFC, ACC, and subgenual ACC, findings unrelated to medication status. MDD women had a lower serum estradiol and higher serum progesterone compared to controls. Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone. LimitationsGeneralizability of our findings is limited by small sample size and restriction to females, although this did not affect the internal validity of the results. ConclusionsHypoactivation of the stress response circuitry in MDD women is associated with dysregulation of the HPG-axis. Associations between brain activity deficits and hormonal disruption in MDD may ultimately contribute to understanding sex differences in MDD.

Aging and the neural correlates of source memory: over-recruitment and functional reorganization

Behavioral evidence suggests that memory for context (i.e., source memory) is more vulnerable to age-related decline than item memory. It is not clear, however, whether this pattern reflects a specific age-related deficit in context memory or a more general effect of task difficulty. In the present study, we used event-related functional magnetic resonance imaging (fMRI) with healthy younger and older adults to dissociate the effects of age, task (item vs. source memory), and task difficulty (1 vs. 2 study presentations) on patterns of blood oxygen level-dependent (BOLD) signal changes during memory retrieval. Behavioral performance was similar in both age groups, but was sensitive to task and difficulty (item > source; easy > difficult). Data-driven multivariate analyses revealed age differences consistent with age-related overrecruitment of frontoparietal regions during difficult task conditions, and age-related functional reorganization in bilateral frontal and right-lateralized posterior regions that were sensitive to difficulty in younger adults, but to task (i.e., context demand) in older adults. These findings support the hypothesis of a specific context memory deficit in older adults.

Spontaneous recovery of visually-triggered saccades after focal lesions of the frontal and parietal eye fields: A combined longitudinal oculomotor and fMRI study

Objective To analyze oculomotor recovery in a patient with ischemic lesions restricted to the left frontal eye field (FEF) and the left parietal eye field (PEF). Methods Two, three, and four weeks after the stroke, saccades were measured and mean gain and latency were calculated. At the same time intervals and 2 months after stroke, the same oculomotor paradigm was performed during fMRI. Bilateral FEF and PEF were identified and defined as volumes of interest (VOI). Both cluster size and mean percentage blood oxygenation level-dependent (BOLD) signal changes were computed for each VOI. Results Initially, rightward saccades were hypometric and showed bilaterally increased latencies that recovered within 4 weeks ( Talairach and Tournoux, 1988). FMRI revealed important changes in cluster size and percentage BOLD signal change in the contralesional and ipsilesional hemisphere. A persisting high activation was found in the contralesional intact FEF and PEF, whereas in the lesioned FEF and PEF, the initially absent or reduced activity increased. Two months after stroke symmetric activations in both FEF and PEF were found. Conclusions Saccade deficits completely and rapidly recovered due to functional rearrangements within the ipsi- and contralesional hemispheric oculomotor network. Significance This study shows the importance of the contralesional and ipsilesional hemispheres in oculomotor recovery.

Aging of human supraspinal locomotor and postural control in fMRI

Standing, walking, and running are sensorimotor tasks that develop during childhood. Thereafter they function automatically as a result of a supraspinal network that controls spinal pattern generators. The present study used functional magnetic resonance imaging (fMRI) to investigate age-dependent changes in the supraspinal locomotor and postural network of normal subjects during mental imagery of locomotion and stance. Sixty healthy subjects (ages: 24–78 years), who had undergone a complete neurological, neuro-ophthalmological, and sensory examination to rule out disorders of balance and gait, were trained for the conditions lying, standing, walking, and running in order to imagine these conditions on command in 20-second sequences with the eyes closed while lying supine in an magnetic resonance imaging (MRI) scanner. The following blood oxygen level-dependent (BOLD) signal changes during locomotion and stance were found to be independent of age: (1) prominent activations in the supplementary motor areas, the caudate nuclei, visual cortical areas, vermal, and paravermal cerebellum; (2) significant deactivations in the multisensory vestibular cortical areas (posterior insula, parietoinsular vestibular gyrus, superior temporal gyrus), and the anterior cingulate during locomotion. The following differences in brain activation during locomotion and stance were age-dependent: relative increases in the cortical BOLD signals in the multisensory vestibular cortices, motion-sensitive visual cortices (MT/V5), and somatosensory cortices (right postcentral gyrus). In advanced age this multisensory activation was most prominent during standing, less during walking, and least during running. In conclusion, the functional activation of the basic locomotor and postural network, which includes the prefrontal cortex, basal ganglia, brainstem, and cerebellar locomotor centers, is preserved in the elderly. Two major age-dependent aspects of brain activation during locomotion and stance were found: the mechanism of cortical inhibitory reciprocal interaction between sensory systems during locomotion and stance declines in advanced age; and consequently, multisensory cortical control of locomotion and stance increases with age. These findings may indicate a more conscious locomotor and postural strategy in the elderly.

Different BOLD Responses to Intragastric Load of L-glutamate and Inosine Monophosphate in Conscious Rats

In this study, we compared the blood oxygen level-dependent (BOLD) signal changes between intragastric load of monosodium L-glutamate (MSG) and inosine monophosphate (IMP), which elicit the umami taste. An intragastric load of 30 mM IMP or 60 mM MSG induced a BOLD signal increase in several brain regions, including the nucleus of the solitary tract (NTS), lateral hypothalamus (LH), and insular cortex. Only MSG increased the BOLD signal in the amygdala (AMG). The time course of the BOLD signal changes in the NTS and the LH in the IMP group was different from that of the MSG group. We further compared the brain regions correlated with the BOLD signal change in the NTS between MSG and IMP groups. The BOLD responses in the hippocampus and the orbital cortex were associated with activation of the NTS in both MSG and IMP groups, but the association in the AMG and the pyriform was only in MSG group. These results indicate that gut stimulation with MSG and IMP evoked BOLD responses in distinct regions with different temporal patterns and that the mechanism of perception of L-glutamate and IMP in the gastrointestinal tract differed from that in the taste-sensing system.

Assessment of brain responses to innocuous and noxious electrical forepaw stimulation in mice using BOLD fMRI

Functional magnetic resonance imaging (fMRI) using the blood oxygen level-dependent (BOLD) contrast was used to study sensory processing in the brain of isoflurane-anesthetized mice. The use of a cryogenic surface coil in a small animal 9.4T system provided the sensitivity required for detection and quantitative analysis of hemodynamic changes caused by neural activity in the mouse brain in response to electrical forepaw stimulation at different amplitudes. A gradient echo-echo planar imaging (GE-EPI) sequence was used to acquire five coronal brain slices of 0.5mm thickness. BOLD signal changes were observed in primary and secondary somatosensory cortices, the thalamus and the insular cortex, important regions involved in sensory and nociceptive processing. Activation was observed consistently bilateral despite unilateral stimulation of the forepaw. The temporal BOLD profile was segregated into two signal components with different temporal characteristics. The maximum BOLD amplitude of both signal components correlated strongly with the stimulation amplitude. Analysis of the dynamic behavior of the somatosensory ‘fast’ BOLD component revealed a decreasing signal decay rate constant koff with increasing maximum BOLD amplitude (and stimulation amplitude). This study demonstrates the feasibility of a robust BOLD fMRI protocol to study nociceptive processing in isoflurane-anesthetized mice. The reliability of the method allows for detailed analysis of the temporal BOLD profile and for investigation of somatosensory and noxious signal processing in the brain, which is attractive for characterizing genetically engineered mouse models.

Non-neural BOLD variability in block and event-related paradigms

Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability.

BOLD signal changes preceding negative responses in EEG‐fMRI in patients with focal epilepsy

In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level-dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus. Eighty-two patients with focal epilepsy who underwent EEG-fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike. Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of -5 to -9 s. This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs.

Absence seizures: Individual patterns revealed by EEG‐fMRI

Absences are characterized by an abrupt onset and end of generalized 3-4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences. Seventeen absences from nine patients with absence epilepsy and classical pattern of 3-4 Hz GSWs during EEG-fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen-level dependent (BOLD) response maps. Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient-specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses. Like a fingerprint, patient-specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific.

The core network in absence epilepsy

We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and wave events and to explore the timing of activity in these regions. Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level-dependent (BOLD) signal prior to and immediately following events of interest in these ROIs. Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity. In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.

Cortical and Subcortical Connectivity Changes during Decreasing Levels of Consciousness in Humans: A Functional Magnetic Resonance Imaging Study using Propofol

While ubiquitous, pharmacological manipulation of consciousness remains poorly defined and incompletely understood (Prys-Roberts, 1987). This retards anesthetic drug development, confounds interpretation of animal studies conducted under anesthesia, and limits the sensitivity of clinical monitors of cerebral function to intact perception. Animal and human studies propose a functional "switch" at the level of the thalamus, with inhibition of thalamo-cortical transmission characterizing loss of consciousness (Alkire et al., 2000; Mashour, 2006). We investigated the effects of propofol, widely used for anesthesia and sedation, on spontaneous and evoked cerebral activity using functional magnetic resonance imaging (fMRI). A series of auditory and noxious stimuli was presented to eight healthy volunteers at three behavioral states: awake, "sedated" and "unresponsive." Performance in a verbal task and the absence of a response to verbal stimulation, rather than propofol concentrations, were used to define these states clinically. Analysis of stimulus-related blood oxygenation level-dependent signal changes identified reductions in cortical and subcortical responses to auditory and noxious stimuli in sedated and unresponsive states. A specific reduction in activity within the putamen was noted and further investigated with functional connectivity analysis. Progressive failure to perceive or respond to auditory or noxious stimuli was associated with a reduction in the functional connectivity between the putamen and other brain regions, while thalamo-cortical connectivity was relatively preserved. This result has not been previously described and suggests that disruption of subcortical thalamo-regulatory systems may occur before, or even precipitate, failure of thalamo-cortical transmission with the induction of unconsciousness.