Frequency of gamma activity is modulated by motivation in the auditory cortex of cat.

Repetitive acoustic stimuli elicit steady-state response (SSR) in the gamma-band both in humans and in mammals. Our aim was to investigate changes of the spontaneous gamma activity and the SSR in the auditory cortex of cats in the background of an instrumental conditioning situation. Epidural electrodes were chronically implanted above the auditory neocortex. The presentation rate of the clicks varied between 20 and 65/s. Spontaneous EEG and SSR were collected in three behavioral states: in an indifferent environment, in the instrumental cage while the cat was waiting for the light CS, and when she stepped on the pedal and was waiting for the meat reward. Using different repetition rate clicks we determined which stimulus rate elicited the largest SSR in these three situations. In quiet animal the highest SSR appeared at 28-30/s. Before and during the CS the optimal stimulus rate shifted to 32-38/s. The frequency of the spontaneous gamma activity changed in parallel way depending on the situation. We conclude that both the SSR and the spontaneous gamma activity reflect resonant activity of the same neuronal circuit of the auditory cortex, and it is modulated by the motivational state of the animal.

Early discrimination of coherent versus incoherent motion by multiunit and synaptic activity in human putative MT+.

A laminar probe was chronically implanted in human putative MT+. The area was specifically responsive to globally coherent visual motion, a crucial aspect of the perception of movement through space. The probe contained 23 microcontacts spaced every 175 microm in a linear array roughly perpendicular to the cortical surface. Current-source density (CSD) and multiunit activity (MUA) were recorded while viewing initially stationary random dot patterns that either moved incoherently or dilated from the central fixation. Onset of visual motion evoked large MUA/CSD activity, with coherent motion evoking earlier and faster-rising MUA/CSD activity than incoherent, in both superficial and deep pyramidal layers. The selective response, peaking at approximately 115 ms, was especially large in deep pyramids, providing evidence that information necessary for visual flow calculations is projected from MT+ at an early latency to distant structures. The early onset of differential MUA/CSD implies that the selectivity of this area does not depend on recurrent inhibition or other intrinsic circuitry to detect coherent motion. The initially greater increase of MUA to coherent stimuli was followed by a greater decrease beginning at approximately 133 ms, apparently because of recurrent inhibition. This resulted in the total MUA being greater to incoherent than coherent stimuli, whereas total rectified CSD was overall greater to coherent than to incoherent stimuli. However, MUA distinguished stationary from moving stimuli more strongly than did CSD. Thus, while estimates of total cell firing (MUA), and of total synaptic activity (CSD) generally correspond to previously reported BOLD results, they may differ in important details.

Separation of mismatch negativity and the N1 wave in the auditory cortex of the cat: a topographic study.

OBJECTIVE: The amplitude distribution of the frequency mismatch negativity (MMN) and that of P1 and N1 components were investigated in cats to reveal their sources in the auditory areas of the neocortex. METHODS: Pure tone stimuli were given in a passive oddball paradigm with different degrees of deviance between the standard and deviant tones. Amplitude maps of event-related potential (ERP) components were generated from the responses, recorded in awake, freely moving animals by a chronically implanted epidural electrode matrix, covering both the primary and secondary auditory fields. RESULTS: The P1 and N1 components appeared with highest amplitude on the middle ectosylvian gyrus, while the amplitude maximum of the MMN was ventral and rostral to them on the AII area. Both the latency and the peak amplitude of the MMN depended on the degree of deviance. CONCLUSIONS: The MMN is generated in the rostroventral part of the secondary auditory area, well separated from the sources of the P1 and N1 components.

Multiple microelectrode-recording system for human intracortical applications.

The human brain is dominated by the neocortex, a large folded surface, whose cellular and synaptic elements are arranged in layers. Since cortical structure is relatively constant across its surface, local information processing can be inferred from multiple laminar recordings of its electrical activity along a line perpendicular to its surface. Such recordings need to be spaced at least as close together as the cortical layers, and need to be wideband in order to sample both low frequency synaptic currents as well as high-frequency action potentials. Finally, any device used in the human brain must comply with strict safety standards. The current paper presents details of a system meeting these criteria, together with sample results obtained from epileptic subjects undergoing acute or chronic intracranial monitoring for definition of the epileptogenic region.

Auditory evoked potentials reflect serotonergic neuronal activity--a study in behaving cats administered drugs acting on 5-HT1A autoreceptors in the dorsal raphe nucleus.

A valid indicator of central serotonergic neurotransmission would be useful for various diagnostic and psychopharmacological purposes in psychiatry. However, known peripheral serotonergic measures only partially reflect serotonergic function in the brain. Previous findings suggest that the intensity dependence of auditory evoked potentials (AEPs) is closely related to central serotonergic activity. The present study examines the effects of microinjection of a 5-HT1A agonist (8-OH-DPAT) and a 5-HT1A antagonist (spiperone) into the dorsal raphe nucleus (DRN) on AEP recorded epidurally from the primary and secondary auditory cortex in behaving cats. We found a stronger intensity dependence only of AEP from the primary auditory cortex after 8-OH-DPAT, which inhibits the firing rate of serotonergic DRN neurons, and a weaker intensity dependence after spiperone, which increases serotonergic cell firing, as compared to baseline measurements. These results demonstrate that the intensity dependence of AEP is inversely related to serotonergic neuronal activity and that it may be a promising tool for assessing central serotonergic function in humans (e.g., identifying patients with low serotonergic neurotransmission).

Auditory-evoked potentials as indicator of brain serotonergic activity--first evidence in behaving cats.

Due to the increasing importance of the central serotonergic neurotransmission for pathogenetic concepts and as a target of pharmacotherapeutic interventions in psychiatry, reliable indicators of this system are needed. Several findings from basic and clinical research suggest that the stimulus intensity dependence of auditory evoked potentials (AEP) may be such an indicator of behaviorally relevant aspects of serotonergic activity (Hegerl and Juckel 1993, Biol Psychiatry 33:173-187). In order to study this relationship more directly, epidural recordings over the primary and secondary auditory cortex were conducted in chronically implanted cats under intravenous (i.v.) administration of drugs influencing the serotonergic and other modulatory systems (8-OH-DPAT, m-CPP, ketanserin, DOI, apomorphine, atropine, clonidine). The intensity dependence of the cat AEP component with the highest functional similarity to this of the N1/P2-component in humans was significantly changed by influencing 5-HT1a and 5-HT2 receptors, but not 5-HT1c receptors. This serotonergic modulation of the intensity dependence was only found for the primary auditory cortex which corresponds to the known different innervation of the primary and secondary auditory cortex by serotonergic fibers. Our study supports the idea that the intensity dependence of AEP could be a valuable indicator of brain serotonergic activity; however, this indicator seems to be of relative specificity because at least cholinergic effects on the intensity dependence were also observed.

Dimensional complexity of the EEG in subcortical stroke--a case study.

The conventional electrophysiological methods used for the analysis of the functional characteristics of the nervous system are not able to grasp its non-linear and random features. Of the methods based on the application of chaos-theory the correlation dimension analysis can be used to quantify the complexity of the analyzed signal, such as the electroencephalogram (EEG). The new version (point-correlation dimension, PD2) was used in this study, which is more accurate than the other, currently used algorithms. The purpose of the present investigation was to compare the sensitivity of the methods based on chaos-theory with the traditional electrophysiological ones in a case when no apparent abnormality was present as judged on the basis of this latter methodology. The PD2 was calculated from the EEG recorded in 13 healthy control subjects and in a patient who suffered a small subcortical stroke 2 years prior to the investigation and who was free of neurological symptoms at the time of recording. Compared to that seen in the control group, in the Z-score maps of the scalp distribution of the PD2, a marked asymmetry was seen and the absolute PD2 values showed a low-dimensional area in the parietal region, ipsilateral to the stroke. A relative decrease of the gamma band was found in the frequency power spectra in the same area. It is suggested that the additional information extracted from the EEG by non-linear analysis may increase the sensitivity of electrophysiological methods for detecting brain pathology.

Adaptive modeling of the unattended acoustic environment reflected in the mismatch negativity event-related potential.

The mismatch negativity (MMN) event-related potential is elicited by changes in repetitive auditory stimuli. The present paper suggests that: (1) an acoustic model of the auditory environment is maintained even in the absence of attention focussed on auditory stimuli, preattentively detecting repetitive features of the acoustic stimulation; and (2) the MMN reflects modifications to existing parts of this model during incorporation of a new stimulus into the model. MMN responses were investigated during the period when a repetitive stimulus (standard) was replaced by a new standard sound. It was found that whereas the new standard stimulus stopped eliciting an MMN after its third presentation with respect to the old standard, a probe stimulus, differing from both standards, elicited an MMN with respect to the old standard, even when following four presentations of the new standard. The probe stimulus also elicited an MMN with respect to the new standard after four or more presentations of this new standard stimulus, thus eliciting two consecutive MMNs. The comparison (conducted on the basis of the present and some previous findings) of the present hypothesis with alternative explanations of MMN based on the presence and strength of auditory transient memory traces supported the model adjustment hypothesis.

Intensity dependence of auditory evoked potentials in behaving cats.

The intensity dependence of auditory evoked potentials (AEPs) recorded epidurally over the primary (AI) and secondary (AII) areas of the auditory cortex was studied in behaving cats during wakefulness, sleep and anesthesia. Four kHz tones of 50, 60, 70, and 80 dB SPL, presented in random order every 2 +/- 0.2 s by a bone conductor, elicited clear changes of the AEP amplitudes with increasing stimulus intensity, but individual components displayed different response curves. AEP components from the AI region showed saturation of their amplitude with stimulus intensity (P13, P34) or no amplitude increase (N19), while amplitude and intensity were linearly related in the AII area. The intensity dependence of the first positive component (P12/P13) was consistently stronger for the AEP recorded from the AI than from the AII area, while later components exhibited no difference between AI and AII. During slow wave sleep, the intensity dependence of this first positive component increased in the two areas, while that of later components decreased. Pentobarbital anesthesia abolished almost all later components and depressed the intensity dependence of the first positive component both in the AI and AII area. These results indicate that (I) clear intensity dependence of AEP exists in the cat auditory cortex and (2) this intensity dependence, especially that of the first positive AEP component, shares functional similarities to the human augmenting/reducing phenomenon in the auditory modality concerning regional differences and sleep-waking cycle.

Correlation dimension changes accompanying the occurrence of the mismatch negativity and the P3 event-related potential component.

The aim of this study was to apply recently developed mathematical tools of chaos theory to the analysis of event-related potentials (ERPs) recorded in paradigms in which the mismatch negativity (MMN) and the P3 component appeared. A new method, the point correlation dimension (PD2i), was used for data analysis, which is more accurate than other algorithms for the calculation of the correlation dimension (D2), which latter is a measure of the complexity of the generator(s) responsible for producing the analyzed time series, i.e., the EEG. ERPs were recorded from Fz, Cz and Pz in 6 subjects. With respect to baseline, the PD2i decreased significantly both during the event-related potentials in which the MMN and also in which the P3 was present, but the pattern and magnitude of this decrease was different between these two situations. The pattern of PD2i changes during the occurrence of deviant stimuli eliciting the MMN suggests the presence of a frontal MMN generator. The conspicuous PD2i decrease during the occurrence of the P3 wave may support the "context closure" hypothesis concerning its functional significance.

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.

Effect of atropine on intracortical evoked potentials during classical aversive conditioning in cats.

In this article, intracortical evoked potentials (EPs) were recorded simultaneously from six different depths of the auditory cortex of freely moving cats. The effect of (a) different states of vigilance and that of atropine, (b) classical aversive conditioning, and (c) the effect of atropine during conditioning was studied on the intracortical EP profiles. Atropine induced EP changes that were similar to those seen in slow wave sleep. During classical aversive conditioning signal stimuli elicited a middle-latency negative EP component which was localized to the superficial cortical layers. Atropine (2 mg/kg body weight) did not abolish the appearance of this component but only increased its latency. It is proposed that the cholinergic part of the ascending activating system did not play an essential role in its generation.

Intracortical auditory evoked potentials during classical aversive conditioning in cats.

Auditory evoked potentials (EPs) were recorded simultaneously from six different depths of the auditory cortex of freely moving cats. In a classical aversive learning paradigm the change of the pitch of regularly given acoustic stimuli served as warning signal. With conditioning the amplitude of a middle latency negative component increased and its latency decreased. Based on laminar analysis of EP profiles we propose that the observed EP changes were generated within the upper cortical layers and reflected a temporary aurousal reaction induced by the signal as a result of discrimination learning. For the description of this effect the term "learned aversive arousal" is suggested.

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.

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 components in the layers of the auditory cortex of the cat.

The intracortical distribution of evoked potentials was studied by seven-contact multielectrodes implanted into the primary auditory cortex of freely moving cats. The aim of the study was to compare the intracortical profiles of the responses evoked by click stimuli and by electrical stimulation of the medial geniculate body in different states of alertness and in Nembutal anesthesia. Only the early surface positive component showed phase reversal in the depth of the cortex. The middle latency components which were faithful indicators of vigilance appeared without phase reversal. Nembutal wiped out these components. A negative component of about 50 ms latency appeared in the attentive animal which had the highest amplitude close to the surface and decreased toward the depth indicating that it was generated in the most superficial layers of the cortex. The stimulation of the last nucleus of the specific auditory pathway elicited evoked potential patterns including also the middle latency components, which were closely similar to those induced by click stimuli.

Comparison of evoked potential changes during classical and instrumental conditioning in cats.

The waveform changes of cortical evoked potentials to click conditioned stimuli were analyzed by a complex computer program developed for sorting nonhomogeneous series of evoked potentials. The changes of evoked responses manifested themselves mainly in the middlelatency waves, while the first components showed only a slight fluctuation during the whole conditioning. A late negative component of 40-50 ms latency was clearly related to the attentive state of the animal. The evoked potentials with increased negative component appeared in different sequences in 'the two conditioning paradigms and in the different phases of the learning process.

Laminar analysis of intracortical auditory evoked potentials during the wakefulness-sleep cycle in the cat.

Click-elicited evoked potentials (EPs) were recorded simultaneously in six different depths of the auditory cortex of freely moving cats during the wakefulness-sleep cycle. Chronically implanted multielectrodes designed especially for this purpose were used. The clicks were given through a bone conductor and middle ear muscles were cut to keep the acoustic input constant. The EPs recorded in different cortical depths changed in different ways during the wakefulness-sleep cycle as evidenced by both the early and middle latency components. The amplitude of the middle latency components was the largest in slow wave sleep (SWS) in all cortical depths. The early deep negative wave was the smallest in paradoxical sleep (PS) probably indicating a reduced sensory input. In the aroused state a negative component of approximately 60 ms appeared localized to the superficial layers. The lack of a true phase reversal of the early components, their independently changing amplitudes and the homogeneous polarity of the later waves in the different cortical depths do not support the idea of simple dipole processes that could explain their generation.