Our objective was to evaluate the brain regions showing increased and decreased metabolism in patients at the time of generalized bursts of epileptic discharges in order to understand their mechanism of generation and effect on brain function. By recording the electroencephalogram during the functional MRI, changes in the blood oxygenation level-dependent signal were obtained in response to epileptic discharges observed in the electroencephalogram of 15 patients with idiopathic generalized epilepsy. A group analysis was performed to determine the regions of positive (activation) and negative (deactivation) blood oxygenation leveldependent responses that were common to the patients. Activations were found bilaterally and symmetrically in the thalamus, mesial midfrontal region, insulae, and midline and bilateral cerebellum and on the borders of the lateral ventricles. Deactivations were bilateral and symmetrical in the anterior frontal and parietal regions and in the posterior cingulate gyri and were seen in the left posterior temporal region. Activations in thalamus and midfrontal regions confirm known involvement of these regions in the generation or spread of generalized epileptic discharges. Involvement of the insulae in generalized discharges had not previously been described. Cerebellar activation is not believed to reflect the generation of discharges. Deactivations in frontal and parietal regions remarkably followed the pattern of the default state of brain function. Thalamocortical activation and suspension of the default state may combine to cause the actual state of reduced responsiveness observed in patients during spike-and-wave discharges. This brief lapse of responsiveness may therefore not result only from the epileptic discharge but also from its effect on normal brain function.absence ͉ epilepsy ͉ thalamus T he electroencephalogram (EEG) of patients with epilepsy presents paroxysmal discharges that depend on the type of epilepsy. In epilepsy that has been termed ''idiopathic generalized'' according to the Commission on Classification and Terminology of the International League Against Epilepsy (1), the most common type of discharge is the 2-to 3-Hz spike-and-wave burst, which occurs simultaneously over wide cortical regions, most often with an anterior predominance. The origin of this discharge and of the absence seizures that often accompany spike-and-wave bursts when they last several seconds has been a subject of investigation and controversy for many years (see ref.2 for a review), particularly with respect to the involvement of subcortical structures. The recently developed method of combined EEG and functional magnetic resonance imaging (fMRI) (EEG͞fMRI) allows the investigation of the brain regions, cortical and subcortical, that are involved in metabolic changes as a result of epileptic discharges seen in the scalp EEG. In our recent publication (3), we described for each individual the patterns of increases and decreases in blood oxygenation leveldependent (BOLD) signal resulting from bu...

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

Combined EEG-fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG-fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium-enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co-registration of statistical maps with gadolinium-enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs.