Search

Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Study Objectives: Daytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness, and vigilance performance., Methods: Sixty healthy older individuals (mean age: 69 years, 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-hour multiple nap protocol (10 cycles of 80 minutes of sleep opportunity alternating with 160 minutes of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness, and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities., Results: The circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day- compared to nighttime naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases., Discussion: Our data indicate that napping is associated with an altered circadian sleep-wake propensity rhythm. They thereby contribute to the understanding of the biological correlates underlying napping and/or sleep-wake cycle fragmentation during healthy aging. Altered circadian sleep-wake promotion can lead to a less distinct allocation of sleep into nighttime and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Objectives: The ability to generate slow waves (SW) during non-rapid eye movement (NREM) sleep decreases as early as the 5th decade of life, predominantly over frontal regions. This decrease may concern prominently SW characterized by a fast switch from hyperpolarized to depolarized, or down-to-up, state. Yet, the relationship between these fast and slow switcher SW and cerebral microstructure in ageing is not established., Methods: We recorded habitual sleep under EEG in 99 healthy late midlife individuals (mean age = 59.3 ± 5.3 years; 68 women) and extracted SW parameters (density, amplitude, frequency) for all SW as well as according to their switcher type (slow vs. fast). We further used neurite orientation dispersion and density imaging (NODDI) to assess microstructural integrity over a frontal grey matter region of interest (ROI)., Results: In statistical models adjusted for age, sex, and sleep duration, we found that a lower SW density, particularly for fast switcher SW, was associated with a reduced orientation dispersion of neurites in the frontal ROI (p = 0.018, R2β* = 0.06). In addition, overall SW frequency was positively associated with neurite density (p = 0.03, R2β* = 0.05). By contrast, we found no significant relationships between SW amplitude and NODDI metrics., Conclusions: Our findings suggest that the complexity of neurite organization contributes specifically to the rate of fast switcher SW occurrence in healthy middle-aged individuals, corroborating slow and fast switcher SW as distinct types of SW. They further suggest that the density of frontal neurites plays a key role for neural synchronization during sleep., Trial Registration Number: EudraCT 2016-001436-35., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The frontoparietal semantic network, encompassing the inferior frontal gyrus and the posterior middle temporal cortex, is considered to be involved in semantic control processes. The explicit versus implicit nature of these control processes remains however poorly understood. The present study examined this question by assessing regional brain responses to the semantic attributes of an unattended stream of auditory words while participants' top-down attentional control processes were absorbed by a demanding visual search task. Response selectivity to semantic aspects of verbal stimuli was assessed via a functional magnetic resonance imaging response adaptation paradigm. We observed that implicit semantic processing of an unattended verbal stream recruited not only unimodal and amodal cortices in posterior supporting semantic knowledge areas, but also inferior frontal and posterior middle temporal areas considered to be part of the semantic control network. These results indicate that frontotemporal semantic networks support incidental semantic (control) processes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer's disease (AD). Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset., Methods: We computed whole-genome PRS for AD and extensively phenotyped sleep under different sleep conditions, including baseline sleep, recovery sleep following sleep deprivation, and extended sleep opportunity, in a carefully selected homogenous sample of 363 healthy young men (22.1 years ± 2.7) devoid of sleep and cognitive disorders., Results: AD PRS was associated with more slow-wave energy, that is, the cumulated power in the 0.5-4 Hz EEG band, a marker of sleep need, during habitual sleep and following sleep loss, and potentially with larger slow-wave sleep rebound following sleep deprivation. Furthermore, higher AD PRS was correlated with higher habitual daytime sleepiness., Conclusions: These results imply that sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative, and support the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence., Methods: Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MT sat ), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MT sat , and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ - OZ), and the area of recurrence (RZ = EZ - OZ)., Results: Thirty-one patients with HGG who underwent gross-total resection were enrolled. MT sat and R1 were the most strongly associated with tumor progression. MT sat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI., Conclusions: HGG recurrence was associated with hMRI parameters' variation after initial surgery, weeks to months before overt recurrence., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

While efficient treatments for Alzheimer's disease (AD) remain elusive, a growing body of research has highlighted sleep-wake regulation as a potential modifiable factor to delay disease progression. Evidence accumulated in recent years is pointing toward a tight link between sleep-wake disruption and the three main hallmarks of the pathogenesis of AD, i.e. abnormal amyloid-beta (Aβ) and tau proteins accumulation, and neurodegeneration. However, all three hallmarks are rarely considered together in the same study. In this review, we gather and discuss findings in favor of an association between sleep-wake disruption and each AD hallmark in animal models and in humans, with a focus on the preclinical stages of the disease. We emphasize that these relationships are likely bidirectional for each of these hallmarks. Altogether, current findings provide strong support for considering sleep-wake disruption as a true risk factor in the early unfolding of AD, but more research integrating recent technical advances is needed, particularly with respect to tau protein and neurodegeneration. Interventional longitudinal studies among cognitively healthy older individuals should assess the practical use of improving sleep-wake regulation to slow down the progression of AD pathogenesis., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Patients with glioblastoma (GBM) have an overall median survival of 15 months despite multimodal therapy. These catastrophic survival rates are to be correlated to systematic relapses that might arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. In this line, it has recently been demonstrated that GSCs are able to escape the tumor mass and preferentially colonize the adult subventricular zone (SVZ). At a distance from the initial tumor site, these GSCs might therefore represent a high-quality model of clinical resilience to therapy and cancer relapses as they specifically retain tumor-initiating abilities., Method: While relying on recent findings that have validated the existence of GSCs in the human SVZ, we questioned the role of the SVZ niche as a potential GSC reservoir involved in therapeutic failure., Results: Our results demonstrate that (i) GSCs located in the SVZ are specifically resistant to radiation in vivo, (ii) these cells display enhanced mesenchymal roots that are known to be associated with cancer radioresistance, (iii) these mesenchymal traits are specifically upregulated by CXCL12 (stromal cell-derived factor-1) both in vitro and in the SVZ environment, (iv) the amount of SVZ-released CXCL12 mediates GBM resistance to radiation in vitro, and (v) interferes with the CXCL12/CXCR4 signalling system, allowing weakening of the tumor mesenchymal roots and radiosensitizing SVZ-nested GBM cells., Conclusion: Together, these data provide evidence on how the adult SVZ environment, through the release of CXCL12, supports GBM therapeutic failure and potential tumor relapse., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val(158)Met) has received increasing attention as a possible modulator of executive functioning and its neural correlates. However, this attention has generally centered on the prefrontal cortices because of the well-known direct impact of COMT enzyme on these cerebral regions. In this study, we were interested in the modulating effect of COMT genotype on anterior and posterior brain areas underlying interference resolution during a Stroop task. More specifically, we were interested in the functional connectivity between the right inferior frontal operculum (IFop), an area frequently associated with inhibitory efficiency, and posterior brain regions involved in reading/naming processes (the 2 main non-executive determinants of the Stroop effect). The Stroop task was administered during functional magnetic resonance imaging scanning to 3 groups of 15 young adults divided according to their COMT Val(158)Met genotype [Val/Val (VV), Val/Met (VM), and Met/Met (MM)]. Results indicate greater activity in the right IFop and the left middle temporal gyrus in homozygous VV individuals than in Met allele carriers. In addition, the VV group exhibited stronger positive functional connectivity between these 2 brain regions and stronger negative connectivity between the right IFop and left lingual gyrus. These results confirm the impact of COMT genotype on frontal functions. They also strongly suggest that differences in frontal activity influence posterior brain regions related to a non-executive component of the task. Particularly, changes in functional connectivity between anterior and posterior brain areas might correspond to compensatory processes for performing the task efficiently when the available dopamine level is low., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Memory reactivation appears to be a fundamental process in memory consolidation. In this study we tested the influence of memory reactivation during rapid eye movement (REM) sleep on memory performance and brain responses at retrieval in healthy human participants., Participants: Fifty-six healthy subjects (28 women and 28 men, age [mean ± standard deviation]: 21.6 ± 2.2 y) participated in this functional magnetic resonance imaging (fMRI) study., Methods and Results: Auditory cues were associated with pictures of faces during their encoding. These memory cues delivered during REM sleep enhanced subsequent accurate recollections but also false recognitions. These results suggest that reactivated memories interacted with semantically related representations, and induced new creative associations, which subsequently reduced the distinction between new and previously encoded exemplars. Cues had no effect if presented during stage 2 sleep, or if they were not associated with faces during encoding. Functional magnetic resonance imaging revealed that following exposure to conditioned cues during REM sleep, responses to faces during retrieval were enhanced both in a visual area and in a cortical region of multisensory (auditory-visual) convergence., Conclusions: These results show that reactivating memories during REM sleep enhances cortical responses during retrieval, suggesting the integration of recent memories within cortical circuits, favoring the generalization and schematization of the information.

Interactions between the neural correlates of short-term memory (STM) and attention have been actively studied in the visual STM domain but much less in the verbal STM domain. Here we show that the same attention mechanisms that have been shown to shape the neural networks of visual STM also shape those of verbal STM. Based on previous research in visual STM, we contrasted the involvement of a dorsal attention network centered on the intraparietal sulcus supporting task-related attention and a ventral attention network centered on the temporoparietal junction supporting stimulus-related attention. We observed that, with increasing STM load, the dorsal attention network was activated while the ventral attention network was deactivated, especially during early maintenance. Importantly, activation in the ventral attention network increased in response to task-irrelevant stimuli briefly presented during the maintenance phase of the STM trials but only during low-load STM conditions, which were associated with the lowest levels of activity in the dorsal attention network during encoding and early maintenance. By demonstrating a trade-off between task-related and stimulus-related attention networks during verbal STM, this study highlights the dynamics of attentional processes involved in verbal STM.

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.

The 'default network' is defined as a set of areas, encompassing posterior-cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal junctions, that show more activity at rest than during attention-demanding tasks. Recent studies have shown that it is possible to reliably identify this network in the absence of any task, by resting state functional magnetic resonance imaging connectivity analyses in healthy volunteers. However, the functional significance of these spontaneous brain activity fluctuations remains unclear. The aim of this study was to test if the integrity of this resting-state connectivity pattern in the default network would differ in different pathological alterations of consciousness. Fourteen non-communicative brain-damaged patients and 14 healthy controls participated in the study. Connectivity was investigated using probabilistic independent component analysis, and an automated template-matching component selection approach. Connectivity in all default network areas was found to be negatively correlated with the degree of clinical consciousness impairment, ranging from healthy controls and locked-in syndrome to minimally conscious, vegetative then coma patients. Furthermore, precuneus connectivity was found to be significantly stronger in minimally conscious patients as compared with unconscious patients. Locked-in syndrome patient's default network connectivity was not significantly different from controls. Our results show that default network connectivity is decreased in severely brain-damaged patients, in proportion to their degree of consciousness impairment. Future prospective studies in a larger patient population are needed in order to evaluate the prognostic value of the presented methodology.

Neuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements. Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modem neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans.

In addition to classical visual effects, light elicits nonvisual brain responses, which profoundly influence physiology and behavior. These effects are mediated in part by melanopsin-expressing light-sensitive ganglion cells that, in contrast to the classical photopic system that is maximally sensitive to green light (550 nm), is very sensitive to blue light (470-480 nm). At present, there is no evidence that blue light exposure is effective in modulating nonvisual brain activity related to complex cognitive tasks. Using functional magnetic resonance imaging, we show that, while participants perform an auditory working memory task, a short (18 min) daytime exposure to blue (470 nm) or green (550 nm) monochromatic light (3 x 10(13) photons/cm2/s) differentially modulates regional brain responses. Blue light typically enhanced brain responses or at least prevented the decline otherwise observed following green light exposure in frontal and parietal cortices implicated in working memory, and in the thalamus involved in the modulation of cognition by arousal. Our results imply that monochromatic light can affect cognitive functions almost instantaneously and suggest that these effects are mediated by a melanopsin-based photoreceptor system.

Neural activity elicited during the encoding and retrieval of source information was investigated with event-related functional magnetic resonance imaging (efMRI). During encoding, 17 subjects performed a natural/artificial judgement on pictures of common objects which were presented randomly in one of the four quadrants of the display. At retrieval, old pictures were mixed with new ones and subjects judged whether each picture was new or old and, if old, indicated in which quadrant it was presented at encoding. During encoding, study items that were later recognized and assigned a correct source judgement elicited greater activity than recognized items given incorrect judgements in a variety of regions, including right lateral occipital and left prefrontal cortex. At retrieval, regions showing greater activity for recognized items given correct versus incorrect source judgements included the right hippocampal formation and the left prefrontal cortex. These findings indicate a role for these regions in the encoding and retrieval of episodic information beyond that required for simple item recognition.

H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness.

The first aim of our PET study was to replicate previous findings concerning the brain areas activated by a verbal working memory task. The second aim was to specify the neural basis of the central executive, using a task of working memory updating. Our data confirm that the lower left supramarginal gyrus and premotor area are the key regions subserving short-term verbal memory processes. They also suggest that the updating memory task is related to middorsolateral prefrontal activation, most probably responsible for the updating function of the central executive. An unexpected, predominantly right activation occurred in the inferior parietal region during the verbal memory updating task, which we related to a visuospatial strategy used to maintain the information in short-term memory. A third purpose was to explore the brain regions activated by a nonverbal, visual memory task, and our results confirm the importance of the superior occipital gyrus in the visual short-term memory.

The Landau-Kleffner syndrome (LKS) and the syndrome of continuous spike-and-wave discharges during slow sleep (CSWS) were originally described, and are still considered, separately. The former combines an acquired aphasia with spike-and-wave discharges that are activated by slow wave sleep, behavioural disturbances, and sometimes epileptic seizures. The latter is characterized by continuous spike-and-wave discharges during slow wave sleep, usually combined with global intellectual deterioration and epileptic seizures. These two syndromes share many common features: (i) onset during childhood; (ii) deterioration of cognitive functions that were previously normally acquired; (iii) seizure type; (iv) EEG pattern; (v) pharmacological reactivity; (vi) regression of the neuropsychological symptoms, of the EEG abnormalities and of the seizures before the end of adolescence; (vii) absence of obvious structural lesion detected by CT or MRI scan. Therefore, we postulated that these patients might, in fact, be presenting several facets of a single process associating the deterioration of cognitive functions and continuous spike-and-wave discharges during slow wave sleep. The pathogenesis of this syndrome remains unknown. Seven patients, presenting CSWS associated with neuropsychological deterioration (isolated aphasia, three cases; language disturbances with more widespread cognitive deterioration, three cases; isolated apraxia, one case) were studied using PET with [18F]fluorodeoxyglucose (FDG). We hoped to find metabolic arguments in favour of a unifying hypothesis, and to reveal clues as to pathogenesis. We present the retrospective analysis of 21 studies performed between 1986 and 1993, 12 of which were done during sleep. For three of these patients, follow-up studies were obtained until recovery. The metabolic patterns were very variable from one patient to another and in the same patient over time. Among the six patients studied during the active phase of the affection, our results showed unilateral, focal or regional increase in glucose metabolism of the cortex in five patients. This hypermetabolism was observed during sleep with continuous spike-and-wave discharges, but also persisted during wakefulness. In the last patient, the metabolic pattern was different: decreased regional glucose metabolism was observed during wakefulness, whereas during sleep, the metabolic pattern in the temporal areas varied during the course of the affection. After recovery, the metabolic pattern in four children (including the seventh patient) was either normal or showed focal or regional, uni- or bilateral decrease in cortical glucose metabolism. Despite this apparent disparity, four basic metabolic characteristics formed a common pattern in all patients, in line with our unifying postulate: (i) the metabolism of the cortical mantle was higher than in the subcortical structures, especially in the thalamic nuclei. This metabolic pattern is characteristic of an immature brain. (ii) The metabolic abnormalities involved focal or regional areas of the cortex. This finding is in good agreement with recent neurophysiological data suggesting a focal origin of the spike-and-wave discharges. (iii) The metabolic disturbances predominantly involved associative cortices. The pattern of neuropsychological deterioration is in good agreement with the topography of the disturbances of cortical glucose metabolism. (iv) The thalamic nuclei remained symmetrical despite significant cortical asymmetries, suggesting either that cortico-thalamic neurons do not participate in the generation of spike-and-wave discharges or that they are inhibited by the pathologic mechanisms. We hypothesize that the acquired deterioration of cognitive function with CSWS is caused by an alteration of the maturation of one or several associative cortices, primarily involving local interneurons and cortico-cortical associative neurons.