Hippocampus responds to auditory change in rabbits.

Any change or novelty in the auditory environment is potentially important for survival. The cortex has been implicated in the detection of auditory change whereas the hippocampus has been associated with the detection of auditory novelty. Local field potentials (LFPs) were recorded from the CA1 area of the hippocampus in waking rabbits. In the oddball condition, a rare tone of one frequency (deviant) randomly replaced a repeated tone of another frequency (standard). In the equal-probability condition, the standard was replaced by a set of tones of nine different frequencies in order to remove the repetitive auditory background of the deviant (now labelled as control-deviant) while preserving its temporal probability. In the oddball condition, evoked potentials at 36-80 ms post-stimulus were found to have greater amplitude towards negative polarity for the deviant relative to the standard. No significant differences in response amplitudes were observed between the control-deviant and the standard. These findings suggest that the hippocampus plays a role in auditory change detection.

Dose-related effects of memantine on a mismatch negativity-like response in anesthetized rats.

Memantine is a low-affinity NMDA receptor antagonist that is used in the treatment of Alzheimer's disease to alleviate the cognitive symptoms of the disease. In humans, memantine has been shown to facilitate auditory change detection as reflected in the mismatch negativity (MMN) response recorded in the frontal cortex. In the present study we investigated the effects of memantine on the auditory MMN-like responses recorded in anesthetized rats. Saline, a low (3 mg/kg) or a high (10 mg/kg) dose of memantine was i.p. injected into the animals. Auditory MMN-like responses were recorded during the presentation of a repeated tone of one frequency (standard, P=0.956) that was rarely replaced by a tone of another frequency (deviant, P=0.044). The low dose of memantine did not observably affect the amplitude of the auditory MMN-like response, but it prolonged the duration of the response relative to saline. The high dose of memantine, in contrast, blocked the generation of the auditory MMN-like response. The findings suggest that memantine may, with appropriate doses, facilitate already this early stage of auditory processing.

Mismatch negativity for item rather than serial-order information in a 150-ms tone series that is not repeated as a melodic pattern.

Speech, for example, consists of fast-paced (>5/s) sounds in specific spectrotemporal patterns. Humans are generally held to be able to represent not only such sounds themselves (item information) but also their serial order (order-information) as a repeated melody with ease, as suggested by studies on the mismatch negativity (MMN) of event-related potentials (ERPs). The present study tested whether this ability tolerates the absence of the support of melodic repetitiveness. ERPs were recorded from adult humans presented with rare 150-ms series of three 50-ms tones ('deviants') interspersed with frequently repeated ones ('standards'). The frequency of each tone was pseudorandomly one of four alternative frequencies. The series were of type 'AAB' (two tones of one frequency followed by a tone of another frequency), 'ABB' (two tones of one frequency preceded by a tone of another frequency), or 'AAA' (three tones of one frequency). The MMN was robustly elicited by AAA deviants against AAB standards. It was, however, less distinct for ABB deviants against AAB standards and even statistically non-significant for AAB deviants against ABB standards. MMN generation in the human brain thus seems to be based on item rather than serial-order information in a rapid spectro-temporal pattern of acoustic signals that is not repeated frequently in the short term.

The fast detection of rare auditory feature conjunctions in the human brain as revealed by cortical gamma-band electroencephalogram.

Natural environments typically contain temporal scatters of sounds emitted from multiple sources. The sounds may often physically stand out from one another in their conjoined rather than simple features. This poses a particular challenge for the brain to detect which of these sounds are rare and, therefore, potentially important for survival. We recorded gamma-band (32-40 Hz) electroencephalographic (EEG) oscillations from the scalp of adult humans who passively listened to a repeated tone carrying frequent and rare conjunctions of its frequency and intensity. EEG oscillations that this tone induced, rather than evoked, differed in amplitude between the two conjunction types within the 56-ms analysis window from tone onset. Our finding suggests that, perhaps with the support of its non-phase-locked synchrony in the gamma band, the human brain is able to detect rare sounds as feature conjunctions very rapidly.

Differences in pitch between tones affect behaviour even when incorrectly identified in direction.

The ability to detect differences between simultaneously presented contra- and ipsilesional stimuli but not to identify the former on neurological patients with the symptom termed 'extinction' has given rise to the hypothesis that extinguished stimuli have impaired access to attentive processing but are detected pre-attentively. Such a dissociation found in normal participants with experimentally degraded sensory information, and its absence in equivalent tasks in terms of the amount of information required has, however, led to an alternative hypothesis that the lesser amount of information required to perform same/different judgements is sufficient to explain this dissociation. In the present paper, the correctness and reaction time (RT) of normal participants' forced-choice decisions about whether the second (comparison) tone of a pair of tones is higher/lower in pitch than the first (standard) tone were measured. It was found that even when participants' decisions were incorrect, the RT of these decisions varied as a function of the magnitude of the difference in pitch between the two tones. The first hypothesis was supported in the sense that stimulus differences might affect behaviour even without their successful attentive processing in normal participants.

Somatosensory event-related potentials in the rabbit cerebral and cerebellar cortices: a correspondence with mismatch responses in humans.

Somatosensory event-related potentials (ERPs) were recorded from the cerebellar (CerCx), somatosensory (SomCx) and visual (VCx) cortices in rabbits in two stimulus conditions. In the oddball condition, airpuffs to two different locations in the rabbit's muzzle corresponded to infrequently presented deviant stimuli (oddball-deviants) interspersed with frequently presented standard stimuli. In the deviant-alone condition, deviants (alone-deviants) were presented without standards. ERPs to oddball-deviants differed significantly from those to standards in CerCx and SomCx, but not in VCx. Furthermore, some of these differences were not found between ERPs to alone-deviants and those to standards. Thus, ERPs to oddball-deviants contributing these differences were dependent on the presence of preceding standards. The results are in line with the elicitation of mismatch negativity-like ERPs to somatosensory changes in humans.

ERP and EOG responses elicited by deviant tones when presented with and without standard tones to reading subjects.

Event-related potentials (ERPs) and horizontal electro-oculograms (HEOGs) were recorded in 11 subjects to infrequently presented spatially deviant tones (oddball-deviants) embedded in a series of frequently presented standard tones and also to these deviant tones when presented without the standard tones (alone-deviants). Subjects were instructed to read a self-selected book during the stimulus presentation. The mismatch negativity (MMN), a component of the ERP, was elicited by the oddball-deviants, whereas ERPs to the alone-deviants were characterized by a prominent N1. In an additional counting condition (subjects counting the oddball-deviants), the MMN to the oddball-deviants was followed by the P3b. Although the effects of pre-attentive and attentive processing of the oddball-deviants were evident in the ERPs, HEOGs were affected by these stimuli in neither reading nor counting condition. In contrast, robust HEOG responses were elicited by the alone-deviants in the reading condition. The results suggest that reading is a sufficiently demanding task to enable the subject to effectively ignore the oddball-deviants but not the alone-deviants.

Proactive interference of a sequence of tones in a two-tone pitch comparison task.

Subjects compared pitches of a standard tone and a comparison tone separated by 1,300-3,000 msec and responded according to whether the comparison tone sounded higher or lower in pitch than the standard tone. Three interfering tones at 300-msec intervals were presented before each pair of tones. Their pitch range varied, being either below or above the pitch of the standard tone; in some of the trials, their pitches were identical to the pitch of the standard tone (no interference). The highest error rate in performance was found when the interfering tones and the comparison tone deviated in the same direction in pitch from the standard tone. In turn, their deviations in the opposite directions resulted in the lowest error rate. This effect was not found to be dependent on whether the interfering tones were randomly ordered or monotonically ordered, together with the standard tone, into melodically ascending/descending sequences. An intermediate error rate in performance was found when the interfering tones and the standard tone were identical. The results support earlier hypotheses, presented in the context of retroactive interference, by demonstrating proactive interference of a tone sequence at the level of representations of individual tones.

Cortical and subcortical visual event-related potentials to oddball stimuli in rabbits.

Event-related potentials (ERPs) to changes in the visual environment were recorded in rabbits. In the oddball condition, infrequently presented (deviant) stimuli occurred in a series of frequently presented (standard) stimuli. In the deviant-alone condition, standards were omitted. ERPs to oddball-deviants differed from those to standards in all recording sites (cerebellar cortex, visual cortex, dentate gyrus). No corresponding differences were found between ERPs to deviants in the oddball condition and those in the deviant-alone condition. However, because ERPs to deviants in the deviant-alone condition and those to standards did not differ either, ERPs to stimulus changes in the oddball condition seemed to be dependent on the presence of standards, thus representing an analogue to mismatch negativity (MMN) in humans.

From spatial acoustic changes to attentive behavioral responses within 200 ms in humans.

Human event-related potentials (ERPs) and electro-oculograms (EOGs) were recorded in 14 subjects presented with spatially deviant tones in a series of standard tones. In separate sessions, they were instructed to read a book, to count the deviant tones, and to respond to the deviant tones by shifting the eyes towards them from the standard tone source. When reading a book, the mismatch negativity (MMN) of ERP, reflecting pre-attentive detection of acoustic changes, was elicited to the deviant tones at approximately 105-180 ms. No deviance related EOGs were observed in the reading or counting conditions. When the subjects responded behaviorally to the deviant tones, EOGs revealed that the eye movements in their direction took place from approximately 185 ms latency. Thus, all stages of processing required for overt attention to the acoustic changes were completed very rapidly, especially when taking into account the latency of MMN. The results are discussed in the context of endogenous ERPs and of attentive processes across sensory modalities.

Auditory cortical event-related potentials to pitch deviances in rats.

We recorded epidural event-related potentials (ERPs) from the auditory cortex in anesthetized rats when pitch-deviant tones were presented in a homogeneous series of standard tones (oddball condition). Additionally, deviant tones were presented without standard tones (deviant-alone condition). ERPs to deviant tones in the oddball condition differed significantly from ERPs to standard tones at the latency range of 63-243 ms. On the other hand, ERPs to deviant tones in the deviant-alone condition did not differ from ERPs to standard tones until 196 ms from stimulus onset. The results suggest that oddball stimuli can be neurophysiologically discriminated in anesthetized rats. Furthermore, as the difference between ERPs to deviant tones and those to standard tones at the 63-196 ms latency range could be detected only when standard tones precede deviant tones it shows concordance with mismatch negativity in humans.

Effects of rewarding electrical stimulation of lateral hypothalamus on classical conditioning of the nictitating membrane response.

1. Adult New Zealand albino rabbits were prepared with chronic hypothalamic stimulating electrodes and hippocampal recording electrodes. 2. Rabbits were restrained and classically conditioned by a tone CS and an airpuff US either followed or preceded by a hypothalamic stimulation (HS). Control rabbits were conditioned without the HS. 3. It was found that HS following the CS facilitated both behavioral and hippocampal responses, while HS preceding the CS inhibited them. 4. Enhanced hippocampal learning-related unit firing to the CS may represent an early indication of conditioning before the behavioral activity produces any observable change.

Evidence of the origin of specific spontaneous head turns during intertrial intervals.

Direction and the frequency of spontaneous head movements during the ITIs following forward and backward paired trials were compared to an acquisition of a conditioned orienting (alpha) response directed to the side of the tone source. The head movements were analyzed from video recordings using classification of head turns to preferred and to nonpreferred directions. The results showed a significant increase in the alpha responses during the forward paired conditioning to the preferred direction and rapid extinction during the subsequent backward conditioning sessions. Spontaneous head movements during the ITIs increased to the same preferred direction as the conditioned alpha responses. The results of this experiment suggest that the response initially elicited by the CS can later appear as "spontaneous," instrumental behavior, the form and the nature of which is determined by the characteristics of the conditioned alpha response developing as a result of classical conditioning.

Multiple-unit responses to pitch changes in rabbits.

Multiple-unit activity (MUA) was recorded from the hippocampus (Hc), the visual cortex (VCx) and the cerebellar cortex (CerCx) in rabbits when pitch deviant tones were presented in a series of standard tones (oddball situation) and when standard tones were absent (deviant-alone situation). Significant MMN-like responses (deviant responses minus standard responses in the oddball situation) occurred in Hc, reflecting a MUA increase to the standards and its decrease to the deviants. In accordance with parallel ERPs reported earlier, the MMN-like responses reflected responses only to different presentation frequencies of stimuli. Non-selectivity in the pitch of such responses in VCx and a lack of an effect of the different stimulus repetition frequencies on responses in CerCx resulted in absent MMN-like responses in both of these locations.

ERPs to pitch changes: a result of reduced responses to standard tones in rabbits.

Event-related potentials (ERPs) were recorded in rabbits when pitch deviant tones occurred in a series of standard tones (oddball situation). In control recordings, the deviant tones were presented without the standard tones (deviant-alone situation). In the oddball situation, significant difference ERPs (deviant ERPs-standard ERPs) could be found in the hippocampal and cerebellar recordings but not in the visual cortex. All the ERPs to the deviant stimuli observed in the oddball situation were also present in the deviant-alone situation. The difference ERPs were therefore based on reduced responses to the standards. The results are discussed in the context of a mismatch negativity (MMN) in humans.

Hippocampal event-related potentials to pitch deviances in an auditory oddball situation in the cat: experiment I.

Hippocampal event-related potentials (ERP) in the areas CA1, CA3, and dentate fascia (Df) were recorded in cats during an oddball situation when pitch deviant tones occurred in a series of standard tones. When difference waves were calculated by subtracting ERPs to the standard tones from those to the deviant tones, no clear N40d, corresponding to a cat analogue of the human mismatch negativity (MMN) observed in earlier studies, could be detected. Instead, a prominent later negativity (N130d) was observed. A possible extra-hippocampal source of the process reflected by the MMN-like negativity, and a relation between an orienting response (OR) and the N130d are discussed.

Behavioral and hippocampal evoked responses in an auditory oddball situation when an unconditioned stimulus is paired with deviant tones in the cat: experiment II.

Event-related potentials (ERP) in the areas CA1, CA3 and dentate fascia (Df) of the hippocampal formation were recorded during an oddball situation in the cat. A rewarding electrical stimulation of the lateral hypothalamus (US) was paired with deviant tones (2500 Hz) that occurred randomly in a series of the standard tones (2000 Hz) given to the left ear. In addition to developing orienting head movements to the side of the deviant tones, an increase in the amplitude of parallel hippocampal ERPs was observed. Both the behavioral and neural responses appeared not until a 50 ms latency range. Furthermore, time-amplitude characteristics of the ERPs corresponded to time-acceleration characteristics of the conditioned orienting head movements. The results are discussed in the context of a cat analogue of the human mismatch negativity (MMN) and a role of the hippocampal formation to model and predict the conditioned behavioral orienting responses.

Hippocampal evoked potentials to pitch deviances in an auditory oddball situation in the rabbit: no human mismatch-like dependence on standard stimuli.

Hippocampal auditory evoked potentials (AEP) were recorded in 10 rabbits when pitch deviant tones occurred in a series of standard tones (oddball situation). In control recordings, deviant tones were presented without intervening standard tones (deviant-alone situation). All AEP deflections observed in the oddball situation were found also in the deviant-alone situation. Thus, it appeared that none of the AEP deflections to deviant tones in the oddball situation was specific to a memory trace of preceding standard tones. This observation was in contradiction to such a specificity of the mismatch negativity (MMN) found in humans. Instead, a connection to a neuronal orienting reaction interpretation was shown to be apparent. A need for additional control procedures revealing a contribution of neural orienting responses in animal MMN experiments is discussed.

Bilaterally recorded multiple-unit activity of the cingulate cortex during head turning conditioning with unilateral medial forebrain bundle stimulation.

Cats were conditioned to turn their heads using a tone conditioned stimulus (CS) and medial forebrain bundle stimulation (MFB) unconditioned stimulus (US). The CS+ was delivered to one ear at a time, in random order, followed by the US. A tone of a different frequency was used as a CS-. The cats learned to respond differentially to the CSs showing head movements of greater acceleration to the CS+ than CS- over sessions. Bilateral recordings of cingulate cortex multiple-unit activity showed increased response amplitudes over sessions and larger responses in the hemisphere ipsilateral to the US. Since ipsilateral multiple-unit responses did not differ for the CSs, the asymmetry was probably due to the sensitizing effect of the unilateral US. Although increases in cingulate cortex neural activity coincided with increases in conditioned head movements, larger activation of the cingulate cortex ipsilateral to the US suggests that the neural changes were independent of these movements.