Marked clozapine-induced slowing of EEG background over frontal, central, and parietal scalp areas in schizophrenic patients.

The authors studied how clozapine treatment of patients with chronic schizophrenia affects the scalp topographic distribution of different frequency bands on EEG. Twenty-one patients treated with clozapine, in addition to zero to two typical neuroleptics (13 patients were treated with clozapine as the only neuroleptic), were compared with two control groups: one of healthy subjects and another of patients with schizophrenia receiving one to three typical neuroleptics and no clozapine. Significant differences in the EEG topography were seen between the groups: The theta and delta powers and were increased in the clozapine group compared with the two other groups (P < 0.001). Changes were observed over all electrodes, and were most prominent at the frontal, central, and parietal electrode locations. The nonclozapine-treated group of patients and the healthy control group did not differ significantly from each other. These results suggest that the topographic EEG features caused by clozapine are quite specific to it and can be differentiated from those of other neuroleptics.

The mismatch negativity for duration decrement of auditory stimuli in healthy subjects.

The amplitude and latency of the mismatch negativity (MMN) elicited by occasional shorter-duration tones (25 and 50 ms) in a sequence of 75 ms standard tones were studied in 40 healthy subjects (9-84 years). The replicability and age dependence of the MMN-responses were determined. The 25 ms deviant tone evoked a clear response in 39 of the subjects, while the 50 ms deviant tone evoked an observable MMN only in 32 of the subjects. The MMN peak amplitude for the 25 ms deviants was significantly larger than for the 50 ms deviants. There was no significant difference in the peak latencies (measured from stimulus offset). For the 25 ms deviant, the amplitude diminished with increasing age. The MMN curves for the 25 ms deviant, measured on separate days in 14 subjects, looked very replicable. As a result of noise and filtering effect, the product-moment correlations were poor. The results indicate that the signal-to-noise ratio for the MMN to 25 ms deviants, obtained even in a 25 min recording session, is large enough for clinical use and individual diagnostics when undetectable (or very low amplitude) MMN is used as a sign of pathology. However, judged from the low correlation coefficients, despite the good replicability in visual evaluation, better methods for MMN quantification have to be used for clinical follow-up.

Self-organizing map in recognition of topographic patterns of EEG spectra.

The self-organizing map, a neural network algorithm, was applied to the recognition of topographic patterns in clinical 22-channel EEG. Inputs to the map were extracted from short-time power spectra of all channels. Each location on a self-organized map entails a model for a cluster of similar input patterns; the best-matching model determines the location of a sample on the map. Thus, an instantaneous topographic EEG pattern corresponds to the location of the sample, and changes with time correspond to the trajectories of consecutive samples. EEG segments of "alpha," "alpha attenuation," "theta of drowsiness," "eye movements," "EMG artifact," and "electrode artifacts" were selected and labeled by visual inspection of the original records. The map locations of the labeled segments were different; the map thus distinguished between them. The locations of individual EEG's on the "alpha-area" of the map were also different. The clustering and easily understandable visualization of topographic EEG patterns are obtainable on a self-organized map in real time.

Locomotor activity and melatonin rhythms in rats under non-24-h lighting cycles.

The adjustment of pineal melatonin and locomotor activity rhythms to 10:10-h light:dark (LD) or 14:14-h LD cycles was studied in male Wistar rats. Both lighting conditions were thought to be outside the limits of entrainment of the rest-activity rhythm in this species. We assumed that the rhythm of pineal melatonin synthesis might be more adaptable. As expected, the locomotor activity rhythm was not adjusted to the 10:10-h LD cycles. Under these conditions, a free-running component (25 h) became dominant. Under the 14:14-h LD cycles, however, an unexpected adaptation occurred within 10 days. The profiles of the pineal melatonin contents measured on days 5 and 30 under the 10:10-h LD and on day 7 under the 14:14-h LD schedule were in line with the estimated free-running oscillations, but the profile on day 21 under the 14:14-h LD schedule was not. This melatonin pattern fitted the LD-adjusted activity rhythm. Thus, the melatonin rhythm did not adapt better than the activity rhythm to the exotic LD cycles. Instead, parallel changes were found.

Hormonal and locomotor activity rhythms in rats under 90-min dark-pulse conditions.

The ability of a short dark pulse to entrain the circadian rhythms in rats was investigated. Pineal melatonin contents and serum levels of corticosterone and thyrotropin, a thyroid-stimulating hormone (TSH), were measured and locomotor activity was recorded under 12:12-h light-dark cycles (LD; darkness from 1800 to 0600 h) and under a 22.5:1.5 h LD lighting schedule (darkness from 1800 to 1930 h). The 90-min dark pulse was enough to trigger the rise of melatonin synthesis, but a free-running component was detected in the locomotor activity. Corticosterone levels showed diurnal variations under both conditions. The decrease of corticosterone and the increase of melatonin were phase locked, but the corticosterone pattern was distorted under the dark-pulse conditions. The 24-h rhythm of TSH was detectable in the control but not in the dark-pulse schedule. The results suggest that the circadian rhythm of pineal melatonin and the decrease of serum corticosterone levels were entrainable by the dark pulses, whereas the increase of corticosterone, the variations of TSH, and the rhythm of locomotor activity were not.

Pineal melatonin and locomotor activity of rats under gradual illuminance transitions.

The locomotor activity and pineal melatonin patterns of adult male rats were compared under two different lighting regimes. The animals were kept 8 days under 12/12 h light/dark cycles with abrupt or slowly decreasing and increasing transitions (twilight periods about 2 h). The onsets of high activity and melatonin rise were phase-locked in the two conditions and related to about half-maximal illuminance level of the gradual dusk. The high activity of the control rats stopped 30-60 min before the abrupt light onset and the rats under the gradual lighting transitions ceased the locomotor activity at about 1 hour before the half-maximal illuminance. The melatonin peak levels were found 4 h before the abrupt lights-on time. Under the slow illuminance transitions the average melatonin peak was related to the illuminance level between maximum and minimum in the morning. Thus, both the melatonin rhythm and the rest-activity rhythm under the gradual dawn and dusk were adjusted according to about half-maximal illuminances in the present conditions.

Generator sites of spontaneous MEG activity during sleep.

We have recorded spontaneous magnetoencephalographic (MEG) activity during overnight natural sleep in 4 healthy adults with a 24-channel SQUID gradiometer, mainly over the sides of the head. All sleep stages were obtained. The MEG wave forms resembled the EEG phenomena recorded simultaneously from the scalp midline, but the electric and magnetic signals did not always coincide. The source locations of different signals were studied by using a current dipole model. The equivalent sources of magnetic transients, resembling and often coinciding with the electric vertex waves and K-complexes, as well as the transients during REM sleep, were concentrated within a volume of 4 x 4 x 3 cm3 in the inferior parietal lobe. For spindles and slow waves, no such focal generators were found.

Continuous recording of locomotor activity in groups of rats: postweaning maturation.

A method was developed for continuous recording of locomotor activity in ten groups of rats housed in standard plastic cages under controlled lighting conditions. An inexpensive pressure transducer detected movements in the cage, and a light resistor monitored the lighting. The output voltages from the sensors were digitized, integrated for 5 s, and stored for off-line analysis. The data from separate cages were averaged for the detection of statistical differences between the experimental groups. The method was applied to study maturational changes after weaning. Wistar rats were recorded from 21 to 62 days of age under 12/12 h light/dark cycle. The cumulative activity distributions of the pups of 4 and 5 weeks of age differed significantly from those of 7-9 weeks, or older. Differences between the rats aged 8 or 9 weeks and the older adults were less consistent, but still detectable. The cumulative activity distributions of the males and females did not differ significantly from each other.

Neuromagnetic steady-state responses to auditory stimuli.

Steady-state magnetic responses to clicks presented at rates between 10 and 70 Hz have been recorded in healthy humans. The responses were highest in amplitude around 40 Hz. This amplitude enhancement is satisfactorily explained by summation of responses evoked by single clicks. The field maps suggest activation of the auditory cortex at all stimulus frequencies. Similar responses were obtained with gated noise bursts and by pauses in a series of clicks. The mean "apparent latency," determined from the phase lag at rates 30-70 Hz, was 54 ms. The physiological relevance of this quantity is shown to be questionable.

Omissions of Auditory Stimuli May Activate Frontal Cortex.

We measured, with a 7 channel SQUID gradiometer, cerebral magnetic responses, time-locked to unpredictable and infrequent stimulus omissions (10% of stimuli) in an otherwise regular sequence of short tones, repeated once every 510 ms. In 10 out of 12 subjects broad responses with multiple peaks and with wide interindividual variability were detected. Attention clearly increased the observed signals. The magnetic field patterns evoked by stimulus omissions could be explained by single current dipoles, whose locations agree with activation of the posterolateral frontal cortex.

Neuromagnetic responses of human auditory cortex to interruptions in a steady rhythm.

We have recorded, with a 7-channel SQUID gradiometer, evoked magnetic responses of 6 healthy humans to interruptions of a steady rhythm of 50 ms 'standard' tone bursts repeated once every 610 ms. Ten percent of the tones occurred 'too early', 410 ms after the preceding stimulus. The response to standards peaked, on average, at 90 ms and that to the early tones at 148 ms. Field patterns were dipolar during both responses and the equivalent sources agreed with activation of the supratemporal auditory cortex, at slightly different locations. The dipole moments were more than twice as strong for the early tones as for the standards. The results emphasize the importance of temporal stimulation patterns in activating the human auditory cortex.

Auditory evoked potentials and magnetic fields in patients with lesions of the auditory cortex.

Auditory evoked potentials and magnetic fields of 40-200 ms latencies were measured from 4 patients with temporal lobe infarcts and compared with results from healthy subjects. Magnetic fields over the diseased hemisphere were abnormal in all 4; the responses were missing in 2. In one patient the responses were of abnormally high amplitude, and in one parts of the response sequence were missing. Evoked potentials were also abnormal in all 4 patients and the results were in accordance with the findings in the magnetic field measurements.

Multichannel detection of magnetic compound action fields of median and ulnar nerves.

We have recorded magnetic compound action fields, evoked by median and ulnar nerve stimulation at the wrist, with a 7-channel 1st-order SQUID gradiometer. Responses at cubita, elbow and brachial plexus were usually monophasic, with polarities and field patterns corresponding to the intracellular current flow in the leading edge of the action potential volley.

Cerebral magnetic responses to noise bursts and pauses of different durations.

We compared magnetic-evoked responses of human auditory cortex to short (5, 10, 20, 40, 80 and 160 ms) noise bursts and to pauses of identical durations in continuous noise. Onsets of both stimuli evoked responses with the most prominent deflection (N100m) peaking at about 100 ms. Both field maps could be explained by current dipoles, which agree with activity at the supratemporal cortex at slightly different locations. At the shortest 5-ms duration the noise bursts evoked a clear N100m whereas pauses elicited very low-amplitude responses or no response at all. For both stimuli, N100m increased in amplitude when the stimulus duration was increased from 5 up to 20-40 ms. The latencies were 10-20 ms longer for pauses than noise bursts with the longest latencies at the shortest stimulus durations. The differences in amplitudes and latencies as a function of stimulus duration and the slightly different source areas indicate that the generators of the on- and off-responses are not identical.

Selective listening modifies activity of the human auditory cortex.

We have studied the effect of selective listening on the neuromagnetic evoked activity of the human auditory cortex. In the word categorization experiment the stimuli were 5-letter words, each beginning with (k). Half of them were targets, i.e., names of animals or plants, and half other meaningful Finnish words. In the duration discrimination experiment equiprobable tones of 425 ms (targets) or 600 ms duration were presented. In both experiments the interstimulus interval (ISI) was 2.3 s and the stimuli of the two classes were presented randomly. Subjects either ignored the stimuli (reading condition) or counted the number of targets (listening condition). The magnetic field over the head was measured with a 7-channel 1st-order SQUID-gradiometer. The stimuli evoked a transient response followed by a sustained field. The transient response did not differ between the two conditions but the sustained field was significantly larger in the listening than reading condition; the increase began 120-200 ms after stimulus onset and continued for several hundred milliseconds. The equivalent source locations of both transient and sustained responses agreed with activation of the supratemporal auditory cortex. In the dichotic listening experiment 25-ms square-wave stimuli were presented randomly and equiprobably either to the left or to the right ear at an ISI of 0.8-1 s, either alone or in presence of a speech masker. Counting the stimuli of either ear resulted in differences between responses to relevant and irrelevant sounds. The difference began 140-150 ms after stimulus onset and peaked at 200-240 ms. During monaural speech masking, N100m was larger for attended than ignored stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison between electric evoked potentials, source dipole components and magnetic evoked fields elicited by noise/square-wave stimuli.

The aim of this study was to compare auditory evoked electric potentials (AEPs), source dipole components calculated from AEPs, and auditory evoked magnetic fields (AEFs). Noise/square-wave stimuli were presented either to the left or to the right ear. AEPs were measured from scalp electrodes on a coronal plane and AEFs were recorded over frontotemporal regions of both hemispheres. An increase of the ISI from 2 to 4-6 s did not change the scalp topography of AEPs nor the ratio of the tangential and radial source components. The 100-ms deflections of AEFs were higher in amplitude and shorter in latency to contra- than ipsilateral stimuli; a similar behaviour was seen in the tangential source components of AEPs. The similarity of the tangential components and the magnetic responses suggests that the method to calculate source dipole components can be useful in differentiating between the hemispheric differences in the activation of the auditory cortices and in discerning the tangential and the radial sources.

Spatial resolution of neuromagnetic records: theoretical calculations in a spherical model.

Spatial resolution of magnetoencephalography (MEG) was studied by computer simulations using a spherical conductor model for the head. The accuracy obtainable in the absolute location of a dipole was found by calculating the confidence limits for source location in 3 dimensions. The accuracy in determining the relative locations of two sources was estimated by calculating the smallest shift in source location that could be detected with statistical significance. The results were used to illustrate the dependence of spatial resolution on several factors including noise, source depth, source strength, flux transformer configuration and the choice of the measurement locations. Under optimal conditions, separations of a couple of millimeters in superficial non-simultaneous sources can be detected, whereas for deeper sources the resolution is worse.