Early ReportFocal cortical release of endogenous opioids during reading induced seizures
Introduction
Cerebral glucose metabolism and regional cerebral blood flow reflect synaptic activity. 18F-fluorodeoxyglucose and 15O-H2O positron-emission tomography (PET) activation studies have increased our understanding of the functional anatomy of the brain in health and disease. The release of neurotransmitters, is a pivotal event in neuroregulation but has been very difficult to study non-invasively: PET studies have focused on pharmacological manipulations and changes in the number of receptors available to radioligands.1, 2, 3, 4
Studies have suggested that the release of opioid peptides is involved in the termination of seizures:5, 6, 7 in animals there is an increase in the number of δ-opioid receptor occupied after a seizure.8 Raised concentrations of leuenkephalin in the cerebrospinal fluid of epilepsy patients are indirect evidence of an endogenous opiate-receptor-mediated anticonvulsant system in human beings.9 Also, interictal PET studies have shown raised μ-opioid receptor binding in the lateral temporal neocortex adjacent to mesial temporal foci that suggest focal epilepsy may be associated with abnormal opioid transmission.10 A diffuse release of cerebral opioids, as evidenced by displacement of 11C-diprenorphine (DPN) binding has been seen in the cerebral-association cortex after repeated absence seizures.11
Reading epilepsy is a localisation-related reflex epilepsy in which seizures are usually myoclonic jerks restricted to the jaw or throat.12 Reading epilepsy is, therefore, an ideal model to study dynamic neurotransmitter changes in specific brain areas with focal seizure activity. The biochemical and anatomical bases of reading epilepsy are not well understood.13 Electroencephalogram (EEG) changes during seizures are predominantly seen in the temporo-parietal cortex of the language-dominant hemisphere but are also found in other cortical areas functionally activated by reading.14
Developments in the sensitivity of PET scanners and image analyses now allow measurement not only of the resting regional neuroanatomical distribution of opioid receptors but can also localise neurotransmitter release in response to focal epileptic activity and specific cognitive activation in man.15, 16 We measured acute changes in cerebral opioid-receptor availability during reading-induced seizures to investigate the neural networks and neurotransmitter release in this form of localised epilepsy and its specific trigger, reading.
Section snippets
Methods
Five right-handed patients with reading epilepsy and six age-matched, right-handed, healthy volunteers (controls) without a previous history of neurological or psychiatric disease had two 11C-DPN-PET scans, to measure μ-, k- and δ-opioid receptor availability. All patients had a diagnosis of reading epilepsy confirmed by video-EEG monitoring. A sixth patient had a secondary generalised seizure while he was reading before his first scan and was not studied because of the risk of other seizures.
Results
Patient details are shown in Table 1. Two patients were women. The median (range) age of the controls was 33 years (26–45). Reading induced frequent myoclonic jaw jerks (>20 seizures over 30 min) in two patients, less frequent seizures (<10 seizures) in two patients, and no visible or self-reported seizures in one patient. There were no differences in 11C-DPN binding on the baseline scans between patients and controls. Within an individual, there was no significant change in 11C-DPN binding for
Discussion
This is the first time that focal cortical release of neurotransmitters in response to specific brain activity has been shown in human beings. We found that, with reading, opioid-receptor binding in the left parieto-temporo-occipital cortex increases in controls and decreases in patients with reading epilepsy.
The left posterior temporal and the left inferior parietal cortex are known to be associated with word processing.22, 23 Price and colleagues24 reported increased blood flow to the left
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2017, NeuroImageCitation Excerpt :DPN is a competitive, non-subtype selective opioid antagonist that has been used in binding studies in animal models that have shown it is displaced by opioid peptide ligands and also in response to activation of the endogenous opioid system (Neumaier and Chavkin, 1989; Ruiz-Gayo et al., 1992; Stein et al., 1990). Reduction of DPN binding has been reported in human volunteers after painful stimulation (Sprenger et al., 2006) and also in patients following reading-induced seizures (Koepp et al., 1998). Although DPN is less specific for mu opioid receptors and perhaps less sensitive than Carfentanil in detecting agonist evoked changes in binding (Quelch et al., 2014) this appears to have not been a limiting factor in detecting the DBS-evoked change in [11C]DPN VT.
Reflex seizures, traits, and epilepsies: From physiology to pathology
2016, The Lancet NeurologyCitation Excerpt :During adolescence and adulthood, activation of widespread, well connected networks by complex sensory, motor, or cognitive tasks results in generalised seizures. Examples include activation of the supplementary motor area, prefrontal cortex, and motor cortex through induction by praxis in patients with juvenile myoclonic epilepsy,95,97 activation of the inferior frontal and temporoparieto-occipital cortex, predominantly on the left, in patients with reading epilepsy,73 and activation of the orbitofrontal and lateral and mesial temporal areas, predominantly on the right, in patients with musicogenic seizures.112,113 Methods and concepts derived from the theory of non-linear dynamical systems and bifurcation theory can help to shed light on the aforementioned findings114–117 and to derive improved mathematical-physical models of generation, spread, and termination of seizures.118–123
Quantification of opioid receptor availability following spontaneous epileptic seizures: Correction of [<sup>11</sup>C]diprenorphine PET data for the partial-volume effect
2013, NeuroImageCitation Excerpt :Interictal studies suggest increased MOP and DOP receptor availability in the ipsilateral temporal lobe during the interictal period in temporal lobe epilepsy (TLE; (Frost et al., 1988; Madar et al., 1997; Mayberg et al., 1991)). Ictal studies of reading-induced and absence epilepsies suggest decreased opioid MOP-, DOP- and KOP-receptor availability during seizures (Bartenstein et al., 1993; Koepp et al., 1998). Post-ictal opioid peptide receptor availability is increased in the ipsilateral temporal lobe in TLE (Hammers et al., 2007a).
Functional imaging: PET
2013, Handbook of Clinical Neurology