Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges

To investigate the coupling between the hemodynamic and metabolic changes following functional brain activation as well as interictal epileptiform discharges (IEDs), blood oxygenation level dependent (BOLD), perfusion and oxygen consumption responses to a unilateral distal motor task and interictal epileptiform discharges (IEDs) were examined via continuous EEG-fMRI. Seven epilepsy patients performed a periodic (1 Hz) right-hand pinch grip using approximately 8% of their maximum voluntary contraction, a paradigm previously shown to produce contralateral MI neuronal excitation and ipsilateral MI neuronal inhibition. A multi-slice interleaved pulsed arterial spin labeling and T(2)*-weighted gradient echo sequence was employed to quantify cerebral blood flow (CBF) and BOLD changes. EEG was recorded throughout the imaging session and reviewed to identify the IEDs. During the motor task, BOLD, CBF and cerebral metabolic rate of oxygen consumption (CMR(O(2))) signals increased in the contra- and decreased in the ipsilateral primary motor cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of 0.46 +/- 0.05. The ratio of contra- to ipsilateral CBF changes was smaller in the present group of epilepsy patients than in the healthy subjects examined previously. IEDs produced both increases and decreases in BOLD and CBF signals. In the two case studies for which the estimation criteria were met, the coupling ratio between IED-induced CMR(O(2)) and CBF changes was estimated at 0.48 +/- 0.17. These findings provide evidence for a preserved coupling between hemodynamic and metabolic changes in response to both functional activation and, for the two case studies available, in response to interictal epileptiform activity.

[1]  S Warach,et al.  Monitoring the patient's EEG during echo planar MRI. , 1993, Electroencephalography and clinical neurophysiology.

[2]  M. Avoli,et al.  Do Interictal Discharges Promote or Control Seizures? Experimental Evidence from an In Vitro Model of Epileptiform Discharge , 2001, Epilepsia.

[3]  A. Papanicolaou,et al.  Effects of duration of epilepsy on the uncoupling of metabolism and blood flow in complex partial seizures , 1997, Neurology.

[4]  M Hallett,et al.  Inhibitory influence of the ipsilateral motor cortex on responses to stimulation of the human cortex and pyramidal tract , 1998, The Journal of physiology.

[5]  Norman R. Kreisman,et al.  Oxidative metabolic responses with recurrent seizures in rat cerebral cortex: Role of systemic factors , 1981, Brain Research.

[6]  M Rosenthal,et al.  Oxidative metabolic responses during recurrent seizures are independent of convulsant, anesthetic, or species , 1983, Neurology.

[7]  J. Mcculloch,et al.  The effects of the GABAergic agonist muscimol upon the relationship between local cerebral blood flow and glucose utilization , 1983, Brain Research.

[8]  C. N. Guy,et al.  Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[9]  J. Gotman,et al.  Electroencephalographic spiking activity, drug levels, and seizure occurence in epileptic patients , 1985, Annals of neurology.

[10]  Abbas F. Sadikot,et al.  BOLD, CBF, and CMRO2 in the human primary motor cortex , 2000, NeuroImage.

[11]  J C Mazziotta,et al.  Interictal cerebral glucose metabolism in partial epilepsy and its relation to EEG changes , 1982, Annals of neurology.

[12]  H. Lüders,et al.  Presurgical evaluation of epilepsy. , 2001, Brain : a journal of neurology.

[13]  Afraim Salek-Haddadi,et al.  Event-Related fMRI with Simultaneous and Continuous EEG: Description of the Method and Initial Case Report , 2001, NeuroImage.

[14]  W H Theodore,et al.  The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism. , 1999, Neurology.

[15]  J. Liepert,et al.  Inhibition of ipsilateral motor cortex during phasic generation of low force , 2001, Clinical Neurophysiology.

[16]  H. Jokeit,et al.  Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy , 2001, Epilepsy Research.

[17]  Anthony B Waites,et al.  fMRI “deactivation” of the posterior cingulate during generalized spike and wave , 2003, NeuroImage.

[18]  R. Buxton,et al.  Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling , 1997, NMR in biomedicine.

[19]  J. Gotman,et al.  fMRI Activation in Continuous and Spike‐triggered EEG–fMRI Studies of Epileptic Spikes , 2003, Epilepsia.

[20]  Eraldo Paulesu,et al.  Preserved functional competence of perilesional areas in drug-resistant epilepsy with lesion in supplementary motor cortex: fMRI and neuropsychological observations , 2003, NeuroImage.

[21]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[22]  Çetin Okuyaz,et al.  Brain Single Photon Emission Computed Tomographic Evaluation of Patients With Childhood Absence Epilepsy , 2003, Journal of child neurology.

[23]  Louis Lemieux,et al.  Mapping of spikes, slow waves, and motor tasks in a patient with malformation of cortical development using simultaneous EEG and fMRI. , 2003, Magnetic resonance imaging.

[24]  Massimo Cincotta,et al.  Transcranial magnetic stimulation and epilepsy , 2003, Clinical Neurophysiology.

[25]  D R Fish,et al.  Demonstration of thalamic activation during typical absence seizures using H2(15)O and PET. , 1995, Neurology.

[26]  R. Buckner,et al.  Human Brain Mapping 6:373–377(1998) � Event-Related fMRI and the Hemodynamic Response , 2022 .

[27]  Karl J. Friston,et al.  Event-related fMRI , 1997 .

[28]  D C Reutens,et al.  Interictal Spikes Increase Cerebral Glucose Metabolism and Blood Flow: A PET Study , 1999, Epilepsia.

[29]  William H. Press,et al.  The Art of Scientific Computing Second Edition , 1998 .

[30]  P. Maquet,et al.  Epilepsy: The Use of Oxygen-15-Labeled Gases , 1989, Seminars in neurology.

[31]  Ari Syngeniotis,et al.  Benign Epilepsy with Centro‐temporal Spikes: Spike Triggered fMRI Shows Somato‐sensory Cortex Activity , 2003, Epilepsia.

[32]  J S Duncan,et al.  Imaging and epilepsy. , 1997, Brain : a journal of neurology.

[33]  W H Theodore,et al.  Interictal metabolism and blood flow are uncoupled in temporal lobe cortex of patients with complex partial epilepsy , 1995, Neurology.

[34]  V. Schmithorst,et al.  High-resolution functional MRI at 3T in healthy and epilepsy subjects: hippocampal activation with picture encoding task , 2004, Epilepsy & Behavior.

[35]  Alan C. Evans,et al.  A general statistical analysis for fMRI data , 2000, NeuroImage.

[36]  Karl J. Friston,et al.  Studying spontaneous EEG activity with fMRI , 2003, Brain Research Reviews.

[37]  M. de Curtis,et al.  Activity-Dependent pH Shifts and Periodic Recurrence of Spontaneous Interictal Spikes in a Model of Focal Epileptogenesis , 1998, The Journal of Neuroscience.

[38]  J C Depresseux,et al.  Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus. , 1986, Advances in neurology.

[39]  W H Theodore,et al.  Effect of Valproate on Human Cerebral Glucose Metabolism , 1991, Epilepsia.

[40]  M. Palfreyman,et al.  Total GABA and homocarnosine in CSF as indices of brain GABA concentrations , 1983, Neuroscience Letters.

[41]  Robert M. Worth,et al.  Single photon emission computed tomography (SPECT) brain imaging using N,N,N′‐trimethyl‐N′‐(2 hydroxy‐3‐methyl‐5–123Iiodobenzyl)‐1,3‐propanediamine 2 HCl (HIPDM) , 1986, Neurology.

[42]  Jean Gotman,et al.  Using patient-specific hemodynamic response functions in combined EEG-fMRI studies in epilepsy , 2003, NeuroImage.

[43]  R. Macdonald,et al.  GABA(A) receptor epilepsy mutations. , 2004, Biochemical pharmacology.

[44]  C M Michel,et al.  EEG‐Triggered Functional MRI in Patients With Pharmacoresistant Epilepsy , 2000, Journal of magnetic resonance imaging : JMRI.

[45]  G. Bruce Pike,et al.  Hemodynamic and metabolic responses to neuronal inhibition , 2004, NeuroImage.

[46]  Jan M Warnking,et al.  Bandwidth‐modulated adiabatic RF pulses for uniform selective saturation and inversion , 2004, Magnetic resonance in medicine.

[47]  Y. Yaari,et al.  Role of intrinsic burst firing, potassium accumulation, and electrical coupling in the elevated potassium model of hippocampal epilepsy. , 1997, Journal of neurophysiology.

[48]  W H Theodore,et al.  The effect of carbamazepine on cerebral glucose metabolism , 1989, Annals of neurology.

[49]  W H Theodore,et al.  Effect of Valproate on Cerebral Metabolism and Blood Flow: An 18F‐2‐Deoxyglusose and 15O Water Positron Emission Tomography Study , 1996, Epilepsia.

[50]  D. Brooks,et al.  Demonstration of thalarnic activation during typical absence seizures using H2 15O and PET , 1995, Neurology.

[51]  W. Löscher,et al.  GABA in plasma and cerebrospinal fluid of different species. Effects of gamma-acetylenic GABA, gamma-vinyl GABA and sodium valproate. , 1979, Journal of neurochemistry.

[52]  M R Symms,et al.  EEG-triggered functional MRI of interictal epileptiform activity in patients with partial seizures. , 1999, Brain : a journal of neurology.

[53]  R. Mattson,et al.  Human brain GABA levels rise rapidly after initiation of vigabatrin therapy , 1996, Neurology.

[54]  P Gloor,et al.  Generalized epilepsy with bilateral synchronous spike and wave discharge. New findings concerning its physiological mechanisms. , 1978, Electroencephalography and clinical neurophysiology. Supplement.

[55]  J. Serratosa,et al.  Genetics of the epilepsies , 2004, Current opinion in neurology.

[56]  R. Leroy,et al.  Single photon emission computed tomography in epilepsy. , 1990, Seminars in nuclear medicine.

[57]  M. Raichle,et al.  The Effects of Changes in PaCO2 Cerebral Blood Volume, Blood Flow, and Vascular Mean Transit Time , 1974, Stroke.

[58]  L. Bettendorf,et al.  The molecular neuron-glia couple and epileptogenesis. , 1999, Advances in neurology.

[59]  G. Crelier,et al.  Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: The deoxyhemoglobin dilution model , 1999, Magnetic resonance in medicine.

[60]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[61]  M R Sperling,et al.  Cerebral Blood Flow During Spike‐Wave Discharges , 1995, Epilepsia.

[62]  P. Chauvel,et al.  Spatio-temporal characteristics of paroxysmal interictal events in human temporal lobe epilepsy , 1995, Journal of Physiology-Paris.

[63]  M. Curtis,et al.  Interictal spikes in focal epileptogenesis , 2001, Progress in Neurobiology.

[64]  U. Ziemann,et al.  Hemispheric asymmetry of transcallosalinhibition in man , 2004, Experimental Brain Research.

[65]  K. Metrakos,et al.  Genetics of convulsive disorders , 1960, Neurology.

[66]  Karl J. Friston,et al.  Functional magnetic resonance imaging of human absence seizures , 2003, Annals of neurology.

[67]  J R Ives,et al.  Echo-planar functional MR imaging of epilepsy with concurrent EEG monitoring. , 1999, AJNR. American journal of neuroradiology.

[68]  Jean Gotman,et al.  The BOLD Response to Interictal Epileptiform Discharges , 2002, NeuroImage.

[69]  W H Theodore,et al.  Positron emission tomography in generalized seizures , 1985, Neurology.

[70]  Farsin Hamzei,et al.  Reduction of Excitability (“Inhibition”) in the Ipsilateral Primary Motor Cortex Is Mirrored by fMRI Signal Decreases , 2002, NeuroImage.

[71]  P T Fox,et al.  The growth of human brain mapping , 1997, Human brain mapping.

[72]  C. A. Marsan,et al.  CORTICAL CELLULAR PHENOMENA IN EXPERIMENTAL EPILEPSY: ICTAL MANIFESTATIONS. , 1964, Experimental neurology.

[73]  J. R. Baker,et al.  Simultaneous functional magnetic resonance imaging and electrophysiological recording , 1995 .

[74]  J. R. Baker,et al.  The intravascular contribution to fmri signal change: monte carlo modeling and diffusion‐weighted studies in vivo , 1995, Magnetic resonance in medicine.

[75]  Jean Gotman,et al.  EEG‐fMRI of focal epileptic spikes: Analysis with multiple haemodynamic functions and comparison with gadolinium‐enhanced MR angiograms , 2004, Human brain mapping.

[76]  Aashit Shah,et al.  Brain Activation During Intermittent Photic Stimulation: A [15O]‐Water PET Study on Photosensitive Epilepsy , 1999, Epilepsia.

[77]  U. Ziemann,et al.  Hemispheric asymmetry of transcallosal inhibition in man. , 1995, Experimental brain research.

[78]  Terry M. Peters,et al.  3D statistical neuroanatomical models from 305 MRI volumes , 1993, 1993 IEEE Conference Record Nuclear Science Symposium and Medical Imaging Conference.

[79]  M E Phelps,et al.  Epileptic patterns of local cerebral metabolism and perfusion in humans determined by emission computed tomography of 18FDG and 13NH3 , 1980, Annals of neurology.

[80]  T. Allison,et al.  Linking hemodynamic and electrophysiological measures of brain activity: evidence from functional MRI and intracranial field potentials. , 2004, Cerebral cortex.

[81]  M. J. Jang,et al.  Disparity of Perfusion and Glucose Metabolism of Epileptogenic Zones in Temporal Lobe Epilepsy Demonstrated by SPM/SPAM Analysis on 15O Water PET, [18F]FDG‐PET, and [99mTc]‐HMPAO SPECT , 2001, Epilepsia.

[82]  G. Hagemann,et al.  Uncoupling of Blood Flow and Metabolism in Focal Epilepsy , 1998, Epilepsia.

[83]  Jean Gotman,et al.  Analysis of the EEG–fMRI response to prolonged bursts of interictal epileptiform activity , 2005, NeuroImage.

[84]  R.N.Dej.,et al.  Epilepsy and the Functional Anatomy of the Human Brain , 1954, Neurology.

[85]  Gary H. Glover,et al.  Changes of Cerebral Blood Flow, Oxygenation, and Oxidative Metabolism during Graded Motor Activation , 2002, NeuroImage.

[86]  D. Lee,et al.  Diagnostic Performance of [18F]FDG‐PET and Ictal [99mTc]‐HMPAO SPECT in Occipital Lobe Epilepsy , 2001, Epilepsia.

[87]  W. Löscher,et al.  GABA in plasma and cerebrospinal fluid of different species. Effects of γ‐acetylenic GABA, γ‐vinyl GABA and sodium valproate , 1979 .

[88]  William D. Gaillard,et al.  The effect of vigabatrin (γ-vinyl GABA) on cerebral blood flow and metabolism , 1999 .

[89]  J R Ives,et al.  EEG-triggered echo-planar functional MRI in epilepsy , 1996, Neurology.

[90]  T. L. Davis,et al.  Calibrated functional MRI: mapping the dynamics of oxidative metabolism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[91]  I Savic,et al.  MRS shows syndrome differentiated metabolite changes in human-generalized epilepsies , 2004, NeuroImage.

[92]  M E Phelps,et al.  Local cerebral metabolic rate for glucose during petit mal absences , 1985, Annals of neurology.

[93]  Babak Boroojerdi,et al.  Transcallosal inhibition in cortical and subcortical cerebral vascular lesions , 1996, Journal of the Neurological Sciences.

[94]  M Diksic,et al.  Effect of generalized spike‐and‐wave discharge on glucose metabolism measured by positron emission tomography , 1987, Annals of neurology.

[95]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[96]  C. A. Marsan,et al.  CORTICAL CELLULAR PHENOMENA IN EXPERIMENTAL EPILEPSY: INTERICTAL MANIFESTATIONS. , 1964, Experimental neurology.

[97]  K. Wienhard,et al.  Temporal lobe epilepsy: Evidence for interictal uncoupling of blood flow and glucose metabolism in temporomesial structures , 1996, Journal of the Neurological Sciences.

[98]  W H Theodore,et al.  Antiepileptic Drugs and Cerebral Glucose Metabolism , 1988, Epilepsia.

[99]  M M Haglund,et al.  Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery. , 2000, Journal of neurosurgery.

[100]  B. Day,et al.  Interhemispheric inhibition of the human motor cortex. , 1992, The Journal of physiology.

[101]  T Landis,et al.  Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography. , 1998, Electroencephalography and clinical neurophysiology.

[102]  J. Gotman,et al.  fMRI activation during spike and wave discharges in idiopathic generalized epilepsy. , 2004, Brain : a journal of neurology.

[103]  W. Löscher,et al.  Valproate induced changes in GABA metabolism at the subcellular level. , 1981, Biochemical pharmacology.

[104]  Maximilian Reiser,et al.  Focal epileptiform activity in the brain: detection with spike-related functional MR imaging--preliminary results. , 2002, Radiology.

[105]  Kazuie Iinuma,et al.  Ictal cerebral haemodynamics of childhood epilepsy measured with near-infrared spectrophotometry. , 2002, Brain : a journal of neurology.

[106]  F. Morrell,et al.  Tailored anterior temporal lobectomy. Relation between extent of resection of mesial structures and postsurgical seizure outcome. , 1995, Archives of neurology.