Converging PET and fMRI evidence for a common area involved in human focal epilepsies

Objectives: Experiments in animal models have identified specific subcortical anatomic circuits, which are critically involved in the pathogenesis and control of seizure activity. However, whether such anatomic substrates also exist in human epilepsy is not known. Methods: We studied 2 separate groups of patients with focal epilepsies arising from any cortical location using either simultaneous EEG-fMRI (n = 19 patients) or [11C]flumazenil PET (n = 18). Results: Time-locked with the interictal epileptiform discharges, we found significant hemodynamic increases common to all patients near the frontal piriform cortex ipsilateral to the presumed cortical focus. GABAA receptor binding in the same area was reduced in patients with more frequent seizures. Conclusions: Our findings of cerebral blood flow and GABAergic changes, irrespective of where interictal or ictal activity occurs in the cortex, suggest that this area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery.

[1]  J. H. Cross,et al.  Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009 , 2010, Epilepsia.

[2]  John-Dylan Haynes,et al.  Odor quality coding and categorization in human posterior piriform cortex , 2009, Nature Neuroscience.

[3]  Robert A Gross,et al.  Levels of evidence , 2008, Neurology.

[4]  G. Gronseth,et al.  Lost in a jungle of evidence: we need a compass. , 2008, Neurology.

[5]  G. Gronseth,et al.  Invited Article: Practice parameters and technology assessments , 2008, Neurology.

[6]  A. Kleinschmidt,et al.  Temporal lobe interictal epileptic discharges affect cerebral activity in “default mode” brain regions , 2006, Human brain mapping.

[7]  W. D. Penny,et al.  Random-Effects Analysis , 2002 .

[8]  M. Morrell Brain stimulation for epilepsy: can scheduled or responsive neurostimulation stop seizures? , 2006, Current opinion in neurology.

[9]  Dan C McIntyre,et al.  Parahippocampal networks, intractability, and the chronic epilepsy of kindling. , 2006, Advances in neurology.

[10]  David H. Zald,et al.  On the scent of human olfactory orbitofrontal cortex: Meta-analysis and comparison to non-human primates , 2005, Brain Research Reviews.

[11]  Alexander Hammers,et al.  Periventricular White Matter Flumazenil Binding and Postoperative Outcome in Hippocampal Sclerosis , 2005, Epilepsia.

[12]  M. Steriade Sleep, epilepsy and thalamic reticular inhibitory neurons , 2005, Trends in Neurosciences.

[13]  François Mauguière,et al.  Seizure-related short-term plasticity of benzodiazepine receptors in partial epilepsy: a [11C]flumazenil-PET study. , 2005, Brain : a journal of neurology.

[14]  N. Bye,et al.  Glucocorticoid regulation of glial responses during hippocampal neurodegeneration and regeneration , 2005, Brain Research Reviews.

[15]  A. Biraben,et al.  Involvement of the basal ganglia in refractory epilepsy: an 18F-fluoro-L-DOPA PET study using 2 methods of analysis. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  F. Fornai,et al.  AMPA receptor desensitization as a determinant of vulnerability to focally evoked status epilepticus , 2005, The European journal of neuroscience.

[17]  K. D.,et al.  Chemoconvulsant seizures: Advantages of focally-evoked seizure models , 2005, The Italian Journal of Neurological Sciences.

[18]  Colin Studholme,et al.  Positive and negative network correlations in temporal lobe epilepsy. , 2004, Cerebral cortex.

[19]  G. Douaud,et al.  PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy , 2004, Neurology.

[20]  Donald A. Wilson,et al.  Olfactory perceptual learning: the critical role of memory in odor discrimination , 2003, Neuroscience & Biobehavioral Reviews.

[21]  M. Richardson,et al.  Grey and white matter flumazenil binding in neocortical epilepsy with normal MRI. A PET study of 44 patients. , 2003, Brain : a journal of neurology.

[22]  S. Spencer Neural Networks in Human Epilepsy: Evidence of and Implications for Treatment , 2002, Epilepsia.

[23]  W. Penny,et al.  Random-Effects Analysis , 2002 .

[24]  L. Haberly,et al.  A new subdivision of anterior piriform cortex and associated deep nucleus with novel features of interest for olfaction and epilepsy , 2001, The Journal of comparative neurology.

[25]  L. Haberly,et al.  Parallel-distributed processing in olfactory cortex: new insights from morphological and physiological analysis of neuronal circuitry. , 2001, Chemical senses.

[26]  K. Gale,et al.  Evoked epileptiform discharges in the rat anterior piriform cortex: generation and local propagation , 2000, Brain Research.

[27]  Karl J. Friston,et al.  Multisubject fMRI Studies and Conjunction Analyses , 1999, NeuroImage.

[28]  D. Born,et al.  Development of a Model of Status epilepticus in Pigtailed Macaque Infant Monkeys , 1999, Developmental Neuroscience.

[29]  M. Mizobuchi,et al.  Unidirectional Olfactory Hallucination Associated with Ipsilateral Unruptured Intracranial Aneurysm , 1999, Epilepsia.

[30]  D. Coulter,et al.  Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy , 1998, Nature Medicine.

[31]  Peter Somogyi,et al.  Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses , 1998, Nature.

[32]  C. Deransart,et al.  The role of basal ganglia in the control of generalized absence seizures , 1998, Epilepsy Research.

[33]  Helen M. Byrne,et al.  Suppression of Noise Artifacts in Spectral Analysis of Dynamic PET Data , 1998 .

[34]  W. Löscher,et al.  THE ROLE OF THE PIRIFORM CORTEX IN KINDLING , 1996, Progress in Neurobiology.

[35]  Karl J. Friston,et al.  Cerebral benzodiazepine receptors in hippocampal sclerosis. An objective in vivo analysis. , 1996, Brain : a journal of neurology.

[36]  Karl J. Friston,et al.  Movement‐Related effects in fMRI time‐series , 1996, Magnetic resonance in medicine.

[37]  W. Löscher,et al.  Basic mechanisms of seizure propagation: targets for rational drug design and rational polypharmacy. , 1996, Epilepsy research. Supplement.

[38]  K. Gale Chemoconvulsant seizures: Advantages of focally-evoked seizure models , 1995, Italian journal of neurological sciences.

[39]  Antoine Depaulis,et al.  Endogenous control of epilepsy: The nigral inhibitory system , 1994, Progress in Neurobiology.

[40]  Karl J. Friston,et al.  Assessing the significance of focal activations using their spatial extent , 1994, Human brain mapping.

[41]  T. Jones,et al.  Spectral Analysis of Dynamic PET Studies , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  T. F. Murray,et al.  Amino acid neurotransmitter interactions in 'area tempestas': an epileptogenic trigger zone in the deep prepiriform cortex. , 1992, Epilepsy research. Supplement.

[43]  J. Bower,et al.  Olfactory cortex: model circuit for study of associative memory? , 1989, Trends in Neurosciences.

[44]  B. Meldrum,et al.  Focal injection of 2-amino-7-phosphonoheptanoic acid into prepiriform cortex protects against pilocarpine-induced limbic seizures in rats , 1986, Neuroscience Letters.

[45]  K. Gale,et al.  Anticonvulsant action of 2-amino-7-phosphonoheptanoic acid and muscimol in the deep prepiriform cortex. , 1986, European journal of pharmacology.

[46]  K. Gale,et al.  A crucial epileptogenic site in the deep prepiriform cortex , 1985, Nature.