G. Karmos

Evoked potential correlates of stimulus deviance during wakefulness and sleep in cat — animal model of mismatch negativity

Auditory evoked potentials (EPs) elicited by standard (STs) and deviant tones (DTs) of different probabilities were studied in freely moving cats during wakefulness and sleep. A large double peaked negativity, so-called mismatch negativity (MMN), was evoked by the unattended low probability DTs. The EPs recorded from the AI and AII areas of the auditory cortex showed more dynamic changes than the vertex and association cortical responses. The amplitude of the MMN was inversely proportional to the probability of DTs. The latency of the MMN showed dependence both on the location of the recording site and on the probability of DTs. During slow wave sleep (SWS) the MMN of increased latency could be evoked only at the lowest probabilities. The cortical distribution of the MMN changed in the SWS.

Laminar analysis of slow wave activity in humans

Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/-10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity.

Steady-state responses from the cat auditory cortex

Responses to 350 ms trains of clicks with 10-100 Hz repetition rate were recorded from the auditory cortices of six cats. Click trains of 30-50 and 90-100 Hz elicited a clear steady-state response (SSR) in awake state. SSRs were small or absent below 30 Hz and in 60-70 Hz stimulus range. In slow wave sleep the optimal rate to elicit SSR shifted towards lower frequencies. 90 Hz SSR was largest in paradoxical sleep. SSRs were strongly suppressed by barbiturate anesthesia. The amplitude of the SSR from the medial geniculate body (MGB) in two cats gradually decreased from 20 to 100 Hz and was more resilient to barbiturate anesthesia than the cortical SSRs. Only low amplitude or no SSRs could be recorded from vertex, visual and association cortices and from the hippocampus in control recordings. The results suggest different generation mechanisms for SSRs recorded from cat auditory cortex and MGB. Human auditory SSRs resemble cat auditory cortical SSRs more than those recorded from cat MGB. The results imply that auditory SSRs in humans are generated in the cortex.

EFFECTS OF SIGNAL PROBABILITY ON SENSORY EVOKED POTENTIALS IN CATS

The present experiment was designed to follow the evoked potential (EP) changes recorded from the association cortex and A II area of the auditory cortex and from the vertex of the freely moving cat. The EPs elicited by clicks of different probabilities used as warning stimuli during aversive conditioning were analyzed. It was found that the EPs recorded from the auditory cortex and the vertex showed different changes during the aversive conditioning to the rare clicks of 3 and 10% probabilities. The N50 and P100 components of the auditory cortical (A II area) EPs increased significantly at both signal probabilities. On the vetex and association cortical EPs, elicited by the rare signals, a broadly distributed positivity, the P250 wave could be detected. The amplitude increase of the P250 was inversely proportional to the used probability of the signal.

Evoked Potential Correlates of Classical and Instrumental Conditioning

In our earlier study (Karmos et al., 1982) we analysed the changes of auditory cortical evoked potentials elicited by clicks which were kept indifferent by applying them as background stimuli during classical conditioning. It was shown that the modification of the late components could most probably be related to the fluctuation in the general motivational state of the animal.