The relationship between peripheral and early cortical activation induced by transcranial magnetic stimulation

The purpose of this study was to assess the relationship between peripheral muscle responses (motor evoked potentials, MEP) evoked by transcranial magnetic stimulation (TMS) and the early components of the TMS-evoked EEG response, both of which reflect cortical excitability. Left primary motor cortex of five healthy volunteers was stimulated with 100% of the motor threshold. The relationship between MEP amplitudes and the peak-to-peak amplitudes of the N15–P30 complex of the evoked EEG signal was determined at the single-trial level. MEP and N15–P30 amplitudes were significantly correlated in all five subjects. The results support the view that the amount of direct activation of neurons in M1 evoked by TMS affects both subsequent cortical activation and the activation of the target muscle. Cortical excitability is altered in some neuronal disorders and modulated locally during various tasks. It could thus be used as a marker of the state of health in many cases and as a method to study brain function. The present results improve our understanding of the early components of the TMS-evoked EEG signal, which reflect cortical excitability, and may thus have widespread use in clinical and scientific studies.     

Tracking speech comprehension in space and time

A fundamental challenge for the cognitive neuroscience of language is to capture the spatio-temporal patterns of brain activity that underlie critical functional components of the language comprehension process. We combine here psycholinguistic analysis, whole-head magnetoencephalography (MEG), the Mismatch Negativity (MMN) paradigm, and state-of-the-art source localization techniques (Equivalent Current Dipole and L1 Minimum-Norm Current Estimates) to locate the process of spoken word recognition at a specific moment in space and time. The magnetic MMN to words presented as rare "deviant stimuli" in an oddball paradigm among repetitive "standard" speech stimuli, peaked 100-150 ms after the information in the acoustic input, was sufficient for word recognition. The latency with which words were recognized corresponded to that of an MMN source in the left superior temporal cortex. There was a significant correlation (r = 0.7) of latency measures of word recognition in individual study participants with the latency of the activity peak of the superior temporal source. These results demonstrate a correspondence between the behaviorally determined recognition point for spoken words and the cortical activation in left posterior superior temporal areas. Both the MMN calculated in the classic manner, obtained by subtracting standard from deviant stimulus response recorded in the same experiment, and the identity MMN (iMMN), defined as the difference between the neuromagnetic responses to the same stimulus presented as standard and deviant stimulus, showed the same significant correlation with word recognition processes.     

Estimates of visually evoked cortical currents.

We have measured magnetic fields evoked by the onset of checkerboard-like sectorial patterns presented at 16 locations near the center of the visual field. Small stimuli (less than 2 degrees), which, nevertheless, gave sufficiently strong responses to enable source localization, were used to limit cortical activation to a small area, thus simplifying the analysis of the magnetic field data. We focused on optimizing the experimental design: cortical sources could be located from measurements at just one position of our 24-channel magnetometer and with as few as 15-20 repetitions of the stimulus. Minimum-norm-estimate maps calculated from even a single response showed reproducible features of the current distribution, which was, 80-100 msec after the pattern onset, retinotopically organized in the occipital lobe. Since magnetoencephalography can reveal cortical locations with a precision of 2-3 mm, our procedure appears promising for further studies of cortical retinotopy and visual field defects.     

Abstract phoneme representations in the left temporal cortex: magnetic mismatch negativity study

We investigated the brain mechanisms enabling one automatically discriminate phoneme category irrespective of the large inter-speaker variability in the acoustic features of the voices. For this purpose, subjects were presented with 450 different speech stimuli, each uttered by a different speaker, belonging to three vowel categories, while a 306-channel magnetoencephalogram (MEG) was obtained to record the magnetic counterpart of the mismatch negativity (MMNm), elicited only when sensory memory traces for repetitive sounds are formed in the auditory cortex. Despite this wide acoustic variation, category changes elicited prominent MMNm responses, which were considerably stronger in the left than in the right hemisphere in the right-handed subjects. These results implicate the presence of long-term memory traces for vowels, which can recognize the vowel-specific invariant code enabling correct vowel percept even in the presence of realistic acoustic variation.     

Interhemispheric phase synchrony and amplitude correlation of spontaneous beta oscillations in human subjects: a magnetoencephalographic study

Interhemispheric phase synchrony and amplitude correlation of beta oscillations were studied with MEG in a resting condition. The left and right hemisphere beta oscillations exhibited phase-locking with a phase-lag near zero degrees. The index of synchronization was strongest when these oscillations had large amplitude. Functionally, we interpret the phase synchrony on the basis of bilaterality of movement organization. A positive interhemispheric correlation was also found for the amplitude of spontaneous beta oscillations over long time intervals (> 1 s). The low-frequency correlation of spontaneous rhythmic activity may be the source of the low-frequency correlations of the hemodynamic responses in homologous areas that have been reported previously and have been interpreted as functional connectivity between these areas.     

A four-channel SQUID magnetometer for brain research

A 4-channel differential SQUID magnetometer has been built. Its design principles and construction are described. Proper matching of the detection coil to the SQUID input is discussed. Examples of auditory, dental pain and visual evoked response data are presented.     

Phase shift detection in thalamocortical oscillations using magnetoencephalography in humans

Magnitude and interactions of cortico-motoneuronal (CM) and Ia afferent input to spinal alpha-motoneurones (MNs) of the human hand are largely unknown. This is, however, an important question, which bears on the cortical versus peripheral-segmental 'interest' in controlling alpha-MN excitation. Alpha-MN excitation can be quantified by estimating the amplitude of alpha-MN compound excitatory post-synaptic potentials (cEPSPs) from single motor unit (SMU) recordings, if certain assumptions about the membrane trajectory are made [Exp. Brain Res. 47 (1982) 33]. Here we recorded 29 SMUs from three different hand muscles (FDI, first dorsal interosseous; ADM, abductor digiti minimi; APB, abductor pollicis brevis) of healthy subjects. Each SMU was tested for CM input by transcranial magnetic stimulation of the contralateral motor cortex, for Ia afferent input by electrical peripheral nerve stimulation, and for the interaction between inputs by paired stimulation timed to arrive coincidently at the alpha-MN. Mean cEPSP amplitude elicited by CM input was larger in the alpha-MNs of the FDI than in those of the ADM or APB, whereas mean cEPSP amplitude elicited by Ia input was larger in the alpha-MNs of the APB than in those of the FDI. Generally, cEPSP amplitude evoked by paired input closely matched the arithmetic sum of the cEPSP amplitudes evoked by the single inputs. In conclusion, alpha-MNs of the human hand can be viewed as linear integrators of CM and Ia excitatory inputs. The weights of these inputs may relate to the specific functions of the different intrinsic hand muscles in skilled finger movements.     

No evidence for dependence of early cortical auditory processing on dopamine D(2)-receptor modulation: a whole-head magnetoencephalographic study

Magnetoencephalography (MEG) was used to determine the effect of neuroleptic challenge on brain responses in healthy subjects. In a double-blind, randomized, placebo-controlled, cross-over design study, the dopamine D(2) receptor antagonist haloperidol (2 mg) was given orally to 12 healthy volunteers. The middle-latency auditory evoked magnetic fields (MAEF) were recorded 3 h after administration of haloperidol or placebo with a whole-head 122-channel MEG. Haloperidol did not significantly affect MAEF responses. The dipole moments and source locations of the responses were not significantly influenced by haloperidol. These results suggest that dopamine D(2) receptors are not involved in the early phases of auditory cortical processing.     

Memory traces for words as revealed by the mismatch negativity

Brain responses to the same spoken syllable completing a Finnish word or a pseudo-word were studied. Native Finnish-speaking subjects were instructed to ignore the sound stimuli and watch a silent movie while the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was recorded. The MMN to each syllable was larger when it completed a word than when it completed a pseudo-word. This enhancement, reaching its maximum amplitude at about 150 ms after the word's recognition point, did not occur in foreign subjects who did not know any Finnish. These results provide the first demonstration of the presence of memory traces for individual spoken words in the human brain. Using whole-head magnetoencephalography, the major intracranial source of this word-related MMN was found in the left superior temporal lobe.