Introduction The intricate patterns of cerebral activity associated with our sensory, motor, and cognitive functions are largely defined by neuronal connectivity. While local connections between neurons are located within the gray matter, 1 fibers in the white matter bridge func- tionally related cortical areas over long distances directly 2,3 or indirectly. 4 In neural network theories of the brain, connectionist models play a central role. 5 While positron emission tomography (PET), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG) and electroen- cephalography (EEG) are able to provide maps of the distribution of activity in the brain, they are of little use in determining corticocortical connections. We have developed a tool to evaluate non-invasively cortical reactivity and functional connections between different brain areas. 6 By locating with high-resolution EEG (HR-EEG) the changing pattern of the neuronal activity evoked by transcranial magnetic stimulation (TMS), the initial cortical response reflecting cortical reactivity as well as the spread of activation from the stimulated site to other areas can be determined. This new brain- mapping method appears promising for the study of the functional organization of the human brain. In TMS, 7,8 a changing magnetic field induces electric currents in the brain, causing depolarization of cellular membranes and thereby neuronal activa- tion. The currently available TMS devices can focus the sub-millisecond pulses on areas of 30 mm in diameter. 9,10 On the other hand, HR-EEG 11,12 enables one to follow sequential cerebral activation with millisecond temporal resolution and with spatial accuracy of about 10 mm when the number of gener- ator sources is small. If no assumption of localized distinct sources can be made, however, the spatial resolution of the EEG is on the same order as the interelectrode distance, i.e., in practice, no better than 3–5 cm. So far, TMS has been limited to observing the brain’s motor and behavioral output while conventional evoked-response EEG studies have been confined to using the sensory pathways for stimulating the cortex. The combination of TMS and EEG is free from these limitations: an arbitrary patch of superficial cortex can be stimulated and the resulting responses everywhere in the brain can be Brain Imaging p © Rapid Science Publishers Vol 8 No 16 10 November 1997 3537 MOTOR and visual cortices of normal volunteers were activated by transcranial magnetic stimulation. The elec- trical brain activity resulting from the brief electro- magnetic pulse was recorded with high-resolution electroencephalography (HR-EEG) and located using inversion algorithms. The stimulation of the left senso- rimotor hand area elicited an immediate response at the stimulated site. The activation had spread to adjacent ipsilateral motor areas within 5–10 ms and to homolo- gous regions in the opposite hemisphere within 20 ms. Similar activation patterns were generated by magnetic stimulation of the visual cortex. This new non-invasive method provides direct information about cortical reac- tivity and area-to-area neuronal connections. Key words: Connectivity; EEG; Electroencephalography; Interhemispheric transfer; Motor cortex; TMS; Trans- callosal connections; Transcranial magnetic stimulation; Visual cortex Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity Risto J. Ilmoniemi, 1,CA Juha Virtanen, 1,2,3 Jarmo Ruohonen, 1 Jari Karhu, 1,4 Hannu J. Aronen, 2 Risto Näätänen 3 and Toivo Katila 1,5 1 BioMag Laboratory, Medical Engineering Centre, and 2 Department of Radiology, Helsinki University Central Hospital, Tukholmankatu 8 F, FIN-00290 Helsinki; 3 Cognitive Brain Research Unit, Department of Psychology, University of Helsinki, Helsinki; 4 Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio; 5 Laboratory of Biomedical Engineering, Helsinki University of Technology, Espoo, Finland CA Corresponding Author Website publication 17 October 1997 NeuroReport 8, 3537–3540 (1997)