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In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1038/srep03798">doi:10.1038/srep03798</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/24445927">pmid:24445927</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3896905/">pmcid:PMC3896905</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/lez7tqf4afgnpoddyu64wqwfdi">fatcat:lez7tqf4afgnpoddyu64wqwfdi</a> </span>
more »... along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways. E pilepsy is one of the most common and devastating neurologic diseases affecting over 2.5 M Americans. Seizure control with antiepileptic drugs (AEDs) has been proven to decrease morbidity and mortality and remains the only treatment option for the majority of patients. Nevertheless, despite progress in antiepileptic drug development, at least 30% of all epilepsy cases remain resistant to current therapeutics 1,2 . For patients without complete seizure control, the sudden, unforeseen occurrence represents one of the most debilitating aspects of epilepsy. Amongst the types of epileptic seizures, generalized tonic-clonic seizures are the most dangerous form, which has the potential to cause severe injuries or even death 3,4 . However, by providing appropriate and timely prevention, the risk factor can be significantly reduced 5 . In the absence of completely controlling a patient's epilepsy, predicting seizures is an important goal of clinical management and treatment. A question of fundamental importance to seizure prediction is to better understand the brain dynamics during the transition from interictal to the seizure state. A promising and widely studied candidate for seizure precursor is high frequency oscillations (HFOs). Recent studies have shown that HFOs occur in advance of impending seizures indicating its strong relationship with the seizure onset zone 6,7 . Most seizure prediction methods are based on mathematically extracting specific features from multiscale intracranial electroencephalogram (IEEG) recordings 8 . Although studies have focused on prospectively testing these methods, no study to date has yet confirmed the ability of any method to predict seizures better than random 9 . Invasive intracranial electrodes are required to detect oscillations generated in very localized or deep brain regions. Owing to the IEEG's insufficient spatial sampling, a barrier to obtaining better seizure predictive rates has been the inconsistency in identifying the earliest changes prior to seizure onset. A deeper understanding of the regional interactions at the beginning and during the evolution of a seizure may help identify the earliest seizure susceptible brain regions 10-12 . To advance our knowledge about seizure initiation, functional brain imaging techniques like single-photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) are used to answer questions regarding whether so-called 'preictal states' can be distinguished from the ictal period and the functional networks in the brain responsible for seizure generation. With SPECT's ability to capture a "snapshot" of cerebral blood flow, studies in 13,14 observed cerebral blood flow (CBF) increases a few seconds to several minutes preceding clinical electroencephalographic (EEG) seizure onset in temporal lobe partial seizures. With fMRI's high spatial resolution and its combination with EEG, fMRI studies recently reported that blood-oxygen-leveldependent (BOLD) changes occur minutes prior to seizure onset, either in animals or in humans 4,15,16 . However, due to relatively low temporal resolution and lack of portability, such techniques are not suitable for rigorous OPEN SUBJECT AREAS: APPLIED PHYSICS NEUROSCIENCE BIOMEDICAL ENGINEERING APPLIED OPTICS
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