- Email: [email protected]
Magnetoencephalography (MEG) in the study of human brain functions
S.03 Functional imaging: promises andpiifalls [5] Silbersweig, D.A., Stem, E., Frith, C., Cahill, C.. Schnorr, L., Groontook, S., Spinks, T., Clark, J., Frackowiak, R., Jones, T. (1993) Detection of thirty-second cognitive activations in single subjects witb positron emissiontomography: a new low-dose H21s a regional cerebral blood flow three-dimensional imaging technique. Journal of Cerebral BloodFlowand Metabolism 13, 617--629.
IS,03.04! Magnetoencephalography (MEG) in thestudy of human brain functIons
M. Sams . Department of Psychology. University of Tampere, P.O. Box
607,33101Tampere, Finland Magnetoencephalography (MEG, for a comprehensive review. see HiimiiHiinen et al., 1993; hnp:/lboojum.hut.fi/researchlbrainlindex.html) allows totally noninvasive studies of healthy, awake humans. MEG provides spatial resolution of about 5 rnm for cortical sources and a temporal resolution of I ms, thus allowing studies the dynamics of cortical activation. The combination of good temporal and spatial resolution characterize MEG. The 2Q-year history of MEG has seen the development from single-channel instruments to those with sensors covering both hemispheres. In a typical experiment, various sensory stimuli are delivered and the responses time-locked to these stimuli are obtained by averaging . Magnetic field pattern on the head surface can be calculated at different latencies. On the basis of the measured field, the 3-d location , strength and orientation of the equivalent current dipole (ECD) in the brain is estimated. When the data of whole-head recordings is examined , multidipole models are used and the source strengths of all dipoles as a function of time are evaluated . The volume conductor model has been a sphere, the dimensions of which are found from magnetic resonance images (MR!). The coordinate systems of MEG and MRl are aligned with the help of markers . In the Brain Research Unit of the Low Temperature Laboratory , Helsinki University of Technology (Espoo, Finland ) MEG has been used to study the basic mechanisms the human cortical functions . Among other things, we have studied the cortical mechanisms of cognitive functions and the processing of information in the auditory cortical areas. Clinical use of MEG is emerging. It has been used in the localization of irritative epileptic and has potential for studies of, e.g., maturation and dysfunctions of the central nervous system . In our recent study, neuroruagnetic responses were recorded from 7 subjects to pictures of faces and to various control stimuli (Sams et al., in press) . In 4 subjects, faces elicited a specific response, not seen with the other stimulus categories. The combination of information from MEG and MRl suggests that the face-specific activity was generated in the inferior occipito-temporal cortex . All 4 subjects showed this response in the right hemisphere; one of these also in the left. We have also recorded neuromagnetic responses of the human brain when the subjects both hears and sees speech (Sams et al., 1991). When we presented infrequent deviant discordant pairings (auditory Ipal together with visual /kat) among frequent concordant stimuli (auditory and visual Ipal), the deviants elicited a specific response , which was argued to be generated in the auditory cortex . In another experiment, the subjects were experienced lip readers and the concordant and discordant stimuli were also delivered equiprobably. The measured MEG signals were complex and showed a lot of individual variability. However, some subject s showed a distinct response to a discordant stimulus both when presented equiprobably with concordant stimuli and when presented as an infrequent deviant The response was rather late, emerging about 200 ms from the onset of the auditory stimul us. We suggest that the perisylvian cortex, close to the source area for the IOD-ms response (MlOO), may be activated by the discordant stimuli .
References Hamalalnen, M., Han. R., Ilmoniemi, RJ.• Knuutila, J., and Lounasmaa, a.v. (1993) Magnetoencephalography - theory, instrumentation, and applications to noninvasive studiesof the working humanbrain.Rev. Mod. Phys., 65, 413-497. Sams, M., Aulanlro, R., Hlimliliiinen, M., Hari, R., Lounasmaa, a.v., Lu, S.-T., and Simola, J. Seeing speech: visualinformation from lip movements modifies activity in \be humanauditory cortex. Neurosci. Lett., 1991,127:141-145. Sams, M., Hietanen, J., Hari, R., Ilmoniemi, R. and Lounasmaa, a.v. (1996) Face-specific responses from the humaninferior occipito-temporal cortex. Neuroscience, in press.
54-9
I8,03.051 Event related potentials as indicators of central serotonergic activity
U. Hegerl , G. Juckel, H.-J. Moller. Lab. of Clinical Neurophysiology.
Department of Psychiatry, Ludwig-Maximilians Universitas, D-80336 Miinchen Indicators of the central serotonergic function are urgently needed in psychiatry, because patients with a dysfunction e.g. in the serotonin system could be identified and could be treated more specifically. Event related potentials (ERP) are of interest in this context because they reflect directly postsynaptic effects of cortical neurotransmitters (e.g. GABA , glutamate) and indirectly modulating effects of neuromodulators (e.g. serotonin, acetylcholine). Converging evidence from recent clinical and preclinical studies [1,2] suggest that a pronounced loudness dependence of the auditory evoked NIIP2 component (LDAEP) reflects low central serotonergic neurotransmission and vice versa. Dipole source analysis represents an important methodological advance in this context, because NllP2-subcomponents generated mainly in the primary auditory cortex (tangential dipoles) can be separated at least in part from those generated in secondary auditory areas (radial dipoles) . Since the serotonergic innervation is very high in primary but low in secondary auditory cortices, only the tangential dipoles are suppo sed to reflect aspects of serotonergic neurotransmission. In 40 health y subjects retested after 3 weeks an excellent test-retest reliability of the loudness dependence of these dipoles (r = 0.91) was found. Some of the arguments for a close relationship between LDAEP and clinically relevant aspects of central serotonergic neurotransmission will be presented : Serotonin and modulation of sensory cortical function: The knowledge about the serotonergic system and its involvement in sensory processing supports the assumption of a tonic modulating role of this system in sensory processing. The highest concentrations of cortical serotonin and the highest synthesis rates have consistently been found in the primary sensory cortices , especially the primary auditory cortex in the superior temporal plane. Furthermore, serotonergic neurons of the raphe dorsalis are characterized by a very regular and stable discharge in the awake and behaving animal , which is not influenced by environmental stressors (e.g. loud white noise). Serotonergic neurons are therefore well suited for a tonic regulatory effect on cortical sensory processing. LDAEP and central serotonergic function: I) In patients with major depression, but not in healthy subjects, intraindividual changes of blood serotonin concentration under a single dose of ISO mg f1uvoxamine as well as under a one week phototherapy were both negatively correlated with corresponding changes in LDAEP. 2) Ethanol acutely given increases serotonergic neurotransmission. LDAEP (tangential dipoles) was measured in 28 alcoholic patients in the intoxication phase and after one week withdrawal. An increase of LDAEP from intoxicated to abstinent state was observed. Correspondingly, a decrease ofLDAEP was found in healthy subjects when recorded after a load with ethanol (I g1kg p.o.), compared to the recording without ethanol challenge [3]. 3) Personality traits like "Sensation Seeking", "Impulsivity" and antisocial tendencies have been related to low 5-HlAA concentrations in CSF. It is a robust finding that these personality factors are also related to a pronounced LDAEP [4). 4) In depressed patients treated with selective serotonin reuptake inhibitors (SSRI) , serotonin related side effects were assessed with the serotonin symptom scale. A significant negative correlation was found between the LDAEP (tangential dipoles) and the severity of the serotonin related side effects (serotonin syndrome score) . 5) In cats serotonin antagonists increase and agonists decrease the LDAEP [2].
LDAEP and prediction of clinical respanse to serotonin agonists: 1) Lithium has serotonin-agonistic effects, which are supposed to be relevant for its prophylactic effects in patient s with recurrent affective disorders. Therefore, it can be assumed that especially patients with a pronounced LDAEP will be lithium responders. In three retrospective studies it was consistently found that lithium responders were characterized by a pronounced LDAEP [5]. First results of a prospective study support the predictive quality of the LDAEP in preventive lithium treatment. 2) Autistic children responding to the serotonin agonist fenflurarnine had a more pronounced LDAEP than nonresponders. 3) Reports in the literature (6) as well as one results indicate , that a pronounced LDAEP predicts a favorable response to SSRI. In summary, the LDAEP is one of the best validated indicators of
IS,03.04! Magnetoencephalography (MEG) in thestudy of human brain functIons
M. Sams . Department of Psychology. University of Tampere, P.O. Box
607,33101Tampere, Finland Magnetoencephalography (MEG, for a comprehensive review. see HiimiiHiinen et al., 1993; hnp:/lboojum.hut.fi/researchlbrainlindex.html) allows totally noninvasive studies of healthy, awake humans. MEG provides spatial resolution of about 5 rnm for cortical sources and a temporal resolution of I ms, thus allowing studies the dynamics of cortical activation. The combination of good temporal and spatial resolution characterize MEG. The 2Q-year history of MEG has seen the development from single-channel instruments to those with sensors covering both hemispheres. In a typical experiment, various sensory stimuli are delivered and the responses time-locked to these stimuli are obtained by averaging . Magnetic field pattern on the head surface can be calculated at different latencies. On the basis of the measured field, the 3-d location , strength and orientation of the equivalent current dipole (ECD) in the brain is estimated. When the data of whole-head recordings is examined , multidipole models are used and the source strengths of all dipoles as a function of time are evaluated . The volume conductor model has been a sphere, the dimensions of which are found from magnetic resonance images (MR!). The coordinate systems of MEG and MRl are aligned with the help of markers . In the Brain Research Unit of the Low Temperature Laboratory , Helsinki University of Technology (Espoo, Finland ) MEG has been used to study the basic mechanisms the human cortical functions . Among other things, we have studied the cortical mechanisms of cognitive functions and the processing of information in the auditory cortical areas. Clinical use of MEG is emerging. It has been used in the localization of irritative epileptic and has potential for studies of, e.g., maturation and dysfunctions of the central nervous system . In our recent study, neuroruagnetic responses were recorded from 7 subjects to pictures of faces and to various control stimuli (Sams et al., in press) . In 4 subjects, faces elicited a specific response, not seen with the other stimulus categories. The combination of information from MEG and MRl suggests that the face-specific activity was generated in the inferior occipito-temporal cortex . All 4 subjects showed this response in the right hemisphere; one of these also in the left. We have also recorded neuromagnetic responses of the human brain when the subjects both hears and sees speech (Sams et al., 1991). When we presented infrequent deviant discordant pairings (auditory Ipal together with visual /kat) among frequent concordant stimuli (auditory and visual Ipal), the deviants elicited a specific response , which was argued to be generated in the auditory cortex . In another experiment, the subjects were experienced lip readers and the concordant and discordant stimuli were also delivered equiprobably. The measured MEG signals were complex and showed a lot of individual variability. However, some subject s showed a distinct response to a discordant stimulus both when presented equiprobably with concordant stimuli and when presented as an infrequent deviant The response was rather late, emerging about 200 ms from the onset of the auditory stimul us. We suggest that the perisylvian cortex, close to the source area for the IOD-ms response (MlOO), may be activated by the discordant stimuli .
References Hamalalnen, M., Han. R., Ilmoniemi, RJ.• Knuutila, J., and Lounasmaa, a.v. (1993) Magnetoencephalography - theory, instrumentation, and applications to noninvasive studiesof the working humanbrain.Rev. Mod. Phys., 65, 413-497. Sams, M., Aulanlro, R., Hlimliliiinen, M., Hari, R., Lounasmaa, a.v., Lu, S.-T., and Simola, J. Seeing speech: visualinformation from lip movements modifies activity in \be humanauditory cortex. Neurosci. Lett., 1991,127:141-145. Sams, M., Hietanen, J., Hari, R., Ilmoniemi, R. and Lounasmaa, a.v. (1996) Face-specific responses from the humaninferior occipito-temporal cortex. Neuroscience, in press.
54-9
I8,03.051 Event related potentials as indicators of central serotonergic activity
U. Hegerl , G. Juckel, H.-J. Moller. Lab. of Clinical Neurophysiology.
Department of Psychiatry, Ludwig-Maximilians Universitas, D-80336 Miinchen Indicators of the central serotonergic function are urgently needed in psychiatry, because patients with a dysfunction e.g. in the serotonin system could be identified and could be treated more specifically. Event related potentials (ERP) are of interest in this context because they reflect directly postsynaptic effects of cortical neurotransmitters (e.g. GABA , glutamate) and indirectly modulating effects of neuromodulators (e.g. serotonin, acetylcholine). Converging evidence from recent clinical and preclinical studies [1,2] suggest that a pronounced loudness dependence of the auditory evoked NIIP2 component (LDAEP) reflects low central serotonergic neurotransmission and vice versa. Dipole source analysis represents an important methodological advance in this context, because NllP2-subcomponents generated mainly in the primary auditory cortex (tangential dipoles) can be separated at least in part from those generated in secondary auditory areas (radial dipoles) . Since the serotonergic innervation is very high in primary but low in secondary auditory cortices, only the tangential dipoles are suppo sed to reflect aspects of serotonergic neurotransmission. In 40 health y subjects retested after 3 weeks an excellent test-retest reliability of the loudness dependence of these dipoles (r = 0.91) was found. Some of the arguments for a close relationship between LDAEP and clinically relevant aspects of central serotonergic neurotransmission will be presented : Serotonin and modulation of sensory cortical function: The knowledge about the serotonergic system and its involvement in sensory processing supports the assumption of a tonic modulating role of this system in sensory processing. The highest concentrations of cortical serotonin and the highest synthesis rates have consistently been found in the primary sensory cortices , especially the primary auditory cortex in the superior temporal plane. Furthermore, serotonergic neurons of the raphe dorsalis are characterized by a very regular and stable discharge in the awake and behaving animal , which is not influenced by environmental stressors (e.g. loud white noise). Serotonergic neurons are therefore well suited for a tonic regulatory effect on cortical sensory processing. LDAEP and central serotonergic function: I) In patients with major depression, but not in healthy subjects, intraindividual changes of blood serotonin concentration under a single dose of ISO mg f1uvoxamine as well as under a one week phototherapy were both negatively correlated with corresponding changes in LDAEP. 2) Ethanol acutely given increases serotonergic neurotransmission. LDAEP (tangential dipoles) was measured in 28 alcoholic patients in the intoxication phase and after one week withdrawal. An increase of LDAEP from intoxicated to abstinent state was observed. Correspondingly, a decrease ofLDAEP was found in healthy subjects when recorded after a load with ethanol (I g1kg p.o.), compared to the recording without ethanol challenge [3]. 3) Personality traits like "Sensation Seeking", "Impulsivity" and antisocial tendencies have been related to low 5-HlAA concentrations in CSF. It is a robust finding that these personality factors are also related to a pronounced LDAEP [4). 4) In depressed patients treated with selective serotonin reuptake inhibitors (SSRI) , serotonin related side effects were assessed with the serotonin symptom scale. A significant negative correlation was found between the LDAEP (tangential dipoles) and the severity of the serotonin related side effects (serotonin syndrome score) . 5) In cats serotonin antagonists increase and agonists decrease the LDAEP [2].
LDAEP and prediction of clinical respanse to serotonin agonists: 1) Lithium has serotonin-agonistic effects, which are supposed to be relevant for its prophylactic effects in patient s with recurrent affective disorders. Therefore, it can be assumed that especially patients with a pronounced LDAEP will be lithium responders. In three retrospective studies it was consistently found that lithium responders were characterized by a pronounced LDAEP [5]. First results of a prospective study support the predictive quality of the LDAEP in preventive lithium treatment. 2) Autistic children responding to the serotonin agonist fenflurarnine had a more pronounced LDAEP than nonresponders. 3) Reports in the literature (6) as well as one results indicate , that a pronounced LDAEP predicts a favorable response to SSRI. In summary, the LDAEP is one of the best validated indicators of