Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

Background and PurposeIt is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry) influences the blood oxygenation level dependent (BOLD) contrast changes induced by neuronal activation and measured by functional MRI (fMRI). We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE).Material and MethodsTwenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL) activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level.ResultsIn TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P < 0.001). Activation over the supposedly normal MTL, i.e. contralateral to the seizure onset of TLE patients, was smaller than the averaged MTL activation in healthy controls (P < 0.005). Age, duration of epilepsy, side of seizure onset, and intelligence were not correlated to the extent of the significant BOLD-response over both MTL in patients with TLE.ConclusionsIn TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

[1]  M. James,et al.  Pharmacological magnetic resonance imaging: a new application for functional MRI. , 2000, Trends in pharmacological sciences.

[2]  A R McIntosh,et al.  Neural correlates of the episodic encoding of pictures and words. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. A. Frost,et al.  Language dominance in neurologically normal and epilepsy subjects , 1999 .

[4]  M. Trimble,et al.  Anticonvulsant serum levels: relationship to impairments of cognitive functioning. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[5]  Friedrich G. Woermann,et al.  Memory fMRI lateralizes temporal lobe epilepsy , 2001, Neurology.

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

[7]  S. Hyman,et al.  Acute Effects of Cocaine on Human Brain Activity and Emotion , 1997, Neuron.

[8]  R G Hoffmann,et al.  Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. , 1998, The American journal of psychiatry.

[9]  E. Ross The evolving role of antiepileptic drugs in treating neuropathic pain. , 2000, Neurology.

[10]  A. Grinvald,et al.  Interactions Between Electrical Activity and Cortical Microcirculation Revealed by Imaging Spectroscopy: Implications for Functional Brain Mapping , 1996, Science.

[11]  C. Büchel,et al.  Functional magnetic resonance imaging in spontaneous attacks of SUNCT: Short‐lasting neuralgiform headache with conjunctival injection and tearing , 1999, Annals of neurology.

[12]  J. Cramer,et al.  A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. , 1992, The New England journal of medicine.

[13]  P E Roland,et al.  Does mental activity change the oxidative metabolism of the brain? , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  A. Kleinschmidt,et al.  Effects of sedation, stimulation, and placebo on cerebral blood oxygenation: a magnetic resonance neuroimaging study of psychotropic drug action , 1999, NMR in biomedicine.

[15]  J A Sorenson,et al.  Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine. , 1997, The Journal of clinical psychiatry.

[16]  J. A. Frost,et al.  Side of seizure focus predicts left medial temporal lobe activation during verbal encoding , 1998, Neurology.

[17]  L. Altshuler,et al.  Antiepileptic drugs in affective illness. Clinical and theoretical implications. , 1991, Advances in neurology.

[18]  M. D’Esposito,et al.  Functional MRI lateralization of memory in temporal lobe epilepsy , 1998, Neurology.

[19]  E. Maguire,et al.  Knowing Where Things Are: Parahippocampal Involvement in Encoding Object Locations in Virtual Large-Scale Space , 1998, Journal of Cognitive Neuroscience.

[20]  Jens Frahm,et al.  The Effect of Acetazolamide on Regional Cerebral Blood Oxygenation at Rest and under Stimulation as Assessed by MRI , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

[22]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[23]  Deborah A Yurgelun-Todd,et al.  Neuroimaging in bipolar disorder: what have we learned? , 2000, Biological Psychiatry.

[24]  J B Poline,et al.  Episodic memory in left temporal lobe epilepsy: a functional MRI study. , 2000, Brain : a journal of neurology.