Task-dependent field potentials in human hippocampal formation

Task-dependent field potentials were recorded from implanted electrodes located in the hippocampus and other medial temporal lobe (MTL) structures of epileptic patients undergoing evaluation for possible surgery. In 2-alternative categorization tasks, low-probability auditory, somatic, and visual stimuli elicited potentials with large amplitudes and sharp spatial gradients having the following characteristic spatial distribution: positive posterior to the hippocampus, negative within the hippocampus, and positive anterior to the hippocampus. The sharp spatial gradients within the MTL suggest that these potentials were locally generated, probably by hippocampal pyramidal cells. The MTL potentials were also reliably elicited by exemplars of semantic categories and by stimulus omissions and were sensitive to the sequence of preceding stimuli. However, they were not elicited by the same stimulus sequences when the patient's attention was directed elsewhere and categorization was not required. These results indicate that the MTL potentials reflect endogenous as opposed to obligatory processes. The time course and task dependence of the MTL potentials suggest that MTL structures could contribute to P300 and related event-related potentials on the scalp.     

Two P300 generators in the hippocampal formation

The presentation of rare target stimuli results in P300 scalp event‐related potentials (ERPs). Generators of this ERP component were found in various brain areas, indicating that multiple cortical and subcortical areas subserve target detection. One of these structures is the mediotemporal lobe (MTL). In the hippocampus, large negative MTL‐P300 potentials are usually observed, whereas reports concerning the rhinal cortex and subiculum are inconsistent. The aim of the present study was to investigate the topography of the mediotemporal P300. ERPs were recorded in epilepsy patients from multicontact depth electrodes, implanted along the longitudinal axis of MTL. Patients had to respond to rare visual target stimuli by a button press. ERP data from the nonfocal hemisphere of 53 patients were included in the analysis. Target detection resulted in large MTL‐P300 potentials in the hippocampus and subiculum. Their latencies did not differ. The hippocampal P300 amplitude increased linearly from anterior to posterior hippocampal body (HB). In contrast, an inverse gradient with larger mean amplitudes in anterior parts was observed for the subiculum. Our results indicate two separate generators of the MTL‐P300, one in the anterior subiculum and one in the posterior HB. Since latencies did not differ, a parallel activation via the entorhinal cortex might have initiated the simultaneous MTL‐P300. Hippocampus and subiculum are essential parts of the MTL‐memory system. Their function within target detection might be to maintain a template of previous stimuli for a comparison with incoming sensory stimuli. © 2009 Wiley‐Liss, Inc.     

Intracranial potentials correlated with an event-related potential, P300, in the cat

Intracranial recordings of long-latency, event-related potentials were obtained from paralyzed, artificially respirated cats. A modified oddball paradigm was employed in which cats were presented with a randomized series of two tones, a 'frequent' 4 kHz stimulus and a 'rare' 1 kHz stimulus. A tail shock was administered 700 ms after onset of the rare tone. Under these circumstances the stimulus elicited a positive component at the vertex similar to the human P300. Intracranial potentials associated with the rare tone usually manifested components of greater amplitude than did potentials associated with the frequent tone. A positive component occurring in latency between 200 and 350 ms only accompanied the presentation of the rare stimulus. The P300 component, which was positive at the dura, appeared as a negative component within a few millimeters of the surface over a wide area of the marginal and suprasylvian gyri. Changing the probability of the rare stimulus resulted in a reduction in the amplitudes of both the intracranial negative component and the P300 recorded at the skull. Components of large amplitude associated with the rare stimulus were obtained from the region of the hippocampus. These components reversed polarity, sometimes more than once, as the electrode was advanced. Substantial latency differences were often observed between the P300 recorded at the skull and P300-like intracranial components associated with the rare stimulus. These results suggest that the cortices of the marginal and suprasylvian gyri and the hippocampal region contribute to the generation of the cat P300.     

The habituation of event-related potentials to speech sounds and tones

We examined the short- and long-term habituation of auditory event-related potentials (ERPs) elicited by tones, complex tones and digitized speech sounds (vowels and consonant-vowel-consonant syllables). Twelve different stimuli equated in loudness and duration (300 msec) were studied. To examine short-term habituation stimuli were presented in trains of 6 with interstimulus intervals of 0.5 or 1.0 sec. The first 4 stimuli in a train were identical standards. On 50% of the trains the standard in the 5th position was replaced by a deviant probe stimulus, and on 20% of the trains the standard in the 6th position was replaced by a target, a truncated standard that required a speeded button press response. Short-term habituation (STH) was complete by the third stimulus in the train and resulted in amplitude decrements of 50-75% for the N1 component. STH was partially stimulus specific in that amplitudes were larger following deviant stimuli in the 5th position than following standards. STH of the N1 was more marked for speech sounds than for loudness-matched tones or complex tones at short ISI. In addition, standard and deviant stimuli that differed in phonetic structure showed more cross-habituation than did tones or complex tones that differed in frequency. This pattern of results suggests that STH is a function of the acoustic resemblance of successive stimuli. The long-term habituation (LTH) of the ERP was studied by comparing amplitudes across balanced 5.25 m stimulus blocks over the course of the experiment. Two types of LTH were observed. The N1 showed stimulus-specific LTH in that N1 amplitudes declined during the presentation of a stimulus, but returned to control levels when a different stimulus was presented in the subsequent condition. In contrast, the P3 elicited by the deviant stimuli showed non-specific LTH, being reduced across successive blocks containing different stimuli. P3s elicited by target stimuli remained stable in amplitude.     

Hippocampal function during behaviorally silent associative learning: dissociation of memory storage and expression

In laboratory studies, the assessment of memory is typically associated with overt behavioral responses. Thus, it has been difficult to determine whether the enhancement of hippocampal sensory-evoked potentials that often accompany memory formation are the neurophysiological manifestation of a memory "trace" or are a secondary product of the behavioral expression of the memory. We addressed this issue by examining changes in evoked hippocampal field potentials during sensory preconditioning, a form of behaviorally silent relational learning that requires an intact hippocampus for execution. Rats were exposed to presentations of a white noise (S1) that terminated with a tone (S2). These pairings of ostensibly "neutral" stimuli supported no change in the behavior elicited by the noise. However, if the tone was subsequently paired with mild footshock (US), suppression of ongoing licking behavior (indicative of fear) was elicited by the noise, indicating that the animal had associated the noise with tone (S1-S2), and had represented the noise-tone-shock (S1-S2-US) relationship. Pre-training neurotoxic lesions of the hippocampus had no effect on conditioned suppression to tone after tone-shock (S2-US) pairings, but disrupted the expression of continued suppression to noise (S1) after tone-shock pairings. In a second experiment, sensory-evoked field potentials in the dorsal hippocampus were recorded with extracellular electrodes. No changes in the hippocampal response evoked by white noise were observed after pairings of noise and tone, i.e., no evidence for a memory trace could be detected. In contrast, after tone was paired with footshock, two short-latency negative potentials within the noise-evoked field response increased in amplitude, a response often presumed to reflect a neurophysiological correlate of memory storage. In total, these results suggest that although the hippocampus critically contributes to the processing of a behaviorally silent associative memory, there may be no role for changes in the amplitude of hippocampal sensory-evoked field potentials in storing representations of the relationships between sensory experiences.     

Auditory event-related potentials in the squirrel monkey: Parallels to human late wave responses

Event-related potentials (ERPs) were recorded from the brain surface in squirrel monkeys during the presentation of two auditory stimulus paradigms which have previously been utilized to elicit scalp-recorded ERPs in humans. In the first paradigm, inter-stimulus interval (ISI) was systematically varied during the presentation of a series of tone pips. The tones produced a negative (70 ms)-positive (130 ms) sequence of components similar in morphology to the human scalp-recorded N1-P2 'vertex' potential. The amplitude of the N70 and P130 components recorded from midline electrodes decreased with decreasing ISI, as previously shown for the human vertex potential. However, this amplitude change with ISI was not observed in ERPs recorded from lateral frontal and temporal electrodes. These results agree with previous studies of monkeys and humans which suggest at least two different sources contribute to N1-P2 components recorded in response to tones. The effects of stimulus probability and novelty on ERP morphology and amplitude were studied in the second paradigm. ERPs elicited by frequent (P = 0.92) and infrequent (P = 0.08) tone pips presented in an unpredictable order were compared. N70 - P130 components were produced by both stimuli, and the infrequent stimuli also elicited a broad, long latency (300 ms) positive complex that decreased in amplitude with repeated presentations. In humans the same infrequent auditory stimuli produce a frontally distributed late positive component that has been interpreted as indicating the activation of orientation mechanisms or of a 'mismatch detector'. These data suggest that in these paradigms squirrel monkeys exhibit ERPs which are similar in several respects to ERPs recorded to identical stimuli in humans.     

Electrophysiological evidence for vestibular activation of the guinea pig hippocampus

Vestibular information modulates hippocampal activity for spatial processing and place cell firing. However, evidence of a purely vestibular stimulus modulating hippocampal activity is confounded as most studies use stimuli containing somatosensory and visual components. In the present study, high-frequency electrical stimulation of specific vestibular sensory regions of the right labyrinth in anaesthetized guinea pigs induced an evoked field potential in the hippocampal formation bilaterally with a latency of about 40 ms following stimulation onset. Field potentials localized in the hippocampal formation occurred with stimulus current parameters that were too small to produce eye movements. This provides direct electrophysiological evidence of vestibular input to the hippocampus.     

Auditory evoked transient and sustained potentials in the human EEG: I. Effects of expectation of stimuli

The characteristics of auditory evoked transient and sustained potentials were recorded using trains of four-tone stimuli of 1-second duration (interstimulus interval = 1 second) presented once every minute. The subject either attentively expected the stimuli or ignored them while reading. The electroencephalogram was recorded from derivations Cz-Al and Fz-Al. Expectation of the stimuli was associated with increased amplitudes of the transient responses both at the first stimulus of the train and during stimulus repetition. In contrast, the sustained potential at the first stimulus of the train was unchanged or smaller when the subject expected the stimuli. During stimulus repetition, however, the amplitude of the potential was enhanced by expectation of the stimuli. The results support the hypothesis of two sustained potential components and stress the importance of stimulus repetition rate when sustained potentials are studied.     

Auditory evoked transient and sustained potentials in the human EGG: II. Effects of small doses of ethanol

The effect of small doses of ethanol (0.4 ) on auditory evoked transient and sustained potentials was studied. Tones of 1-second duration were presented in trains of four stimuli (interstimulus interval = 1 second; intertrain interval = 1 minute). The electroencephalogram was recorded from derivation Cz-Al. Ethanol depressed the transient responses both at the first stimulus of the train and during repeated stimuli. The sustained potentials elicited by the first stimuli of the train were not affected by ethanol, whereas the sustained potentials elicited by repeated stimuli were larger in amplitude under the influence of ethanol than during control experiments. It is suggested that the decrease of the transient responses under the influence of ethanol is mainly due to depression of the reticular formation, whereas the increase of sustained potentials reflects ethanol-induced release of intracortical inhibition.     

An electrophysiologic indication of defective information storage in childhood autism.

We used a combined behavioral and electrophysiological technique to test the hypothesis that storage of information is impaired in childhood autism. Endogenous event-related potentials associated with the random deletion of stimuli within a regular train of auditory or visual stimuli were examined in three autistic and three normal children. We found that all subjects were able to detect the stimulus deletions, but cortical potentials associated with stimulus omissions were smaller or absent in the autistic subjects. These results are consistent with dysfunction within the system that includes posterior parietal cortex and its connections with the mesolimbic temporal cortex and hippocampus.     

Effects of physostigmine on septo-hippocampal averaged evoked field potentials

Field potentials were elicited in the CA3 field of freely-moving animals by paired-pulse stimulation of the ventral portion of the medial septum before and after exposure to physotigmine. Physostigmine had no effect on response components elicited by a single stimulus or by the first stimulus of a pulse pair. However, the amplitude of a late positive component elicited by the second stimulus of a pair was increased significantly following physostigmine. These results suggest that activity in a cholinergic portion of the septo-hippocampal pathway may serve to modulate the responsiveness of neurons in the CA3 field to subsequent stimulation.     

Auditory evoked transient and sustained potentials in the human EEG: II. Effects of small doses of ethanol.

The effect of small doses of ethanol (0.4 g/kg) on auditory evoked transient and sustained potentials was studied. Tones of 1-second duration were presented in trains of four stimuli (interstimulus interval = 1 second; intertrain interval = 1 minute). The electroencephalogram was recorded from derivation Cz-Al. Ethanol depressed the transient responses both at the first stimulus of the train and during repeated stimuli. The sustained potentials elicited by the first stimuli of the train were not affected by ethanol, whereas the sustained potentials elicited by repeated stimuli were larger in amplitude under the influence of ethanol than during control experiments. It is suggested that the decrease of the transient responses under the influence of ethanol is mainly due to depression of the reticular formation, whereas the increase of sustained potentials reflects ethanol-induced release of intracortical inhibition.     

Relationship between vertex potentials and magnitude of pre-pain and pain sensations evoked by electrical skin stimuli.

Vertex potentials evoked by painful and non-painful electrical skin stimuli were recorded in 10 healthy male volunteers. Peak-to-peak amplitudes of the major vertex potential components were compared with subjective rating of the stimuli. While a significant correlation was observed between peak-to-peak amplitudes and stimulus rating following non-painful stimuli, generally no such correlation was present following stimulations above the pain threshold. These findings suggest that vertex potentials elicited by electrical skin stimuli may reflect central processing of non-noxious afferent information rather than of pain-related information.     

Increased responsivity of dentate granule cells during nictitating membrane response conditioning in rabbit

We examined the responsivity of dentate gyrus granule cells to perforant path stimulation during classical conditioning of the rabbit nictitating membrane response. Dentate field potentials elicited by perforant path stimulation were recorded during training to test for changes in granule cell responsivity. Results showed above-baseline increases in dentate population spike amplitudes over the course of training in paired but not unpaired animals. In addition, population spike amplitudes were smaller when elicited during tone presentations in both paired and unpaired animals than between trials when no conditioning stimuli were present. While alternative interpretations remain, these results provide preliminary evidence that processes similar to long-term potentiation may occur in the hippocampus during behavioral conditioning.     

Efects of corticosterone on the electrophysiology of hippocampal CA1 pyramidal Cells in vitro

Modulation of CA1 field potential amplitudes by normal and stress concentrations of corticosterone (CT) was observed in hippocampal slice preparations from adrenalectomized rats. Slices exposed to CT levels characteristic of a morning (4 nM) or evening (7 nM) resting state showed increased population spike amplitudes in the CA1 pyramidal cell field within 10 min. A stress concentration (15 nM) also increased spike amplitudes, but only at the higher stimulus intensities. The effects of these doses were essentially the same 10 and 60 min after administration. The hormone facilitated responding more in morning resting concentrations than in concentrations characteristic of the evening resting state. This occurred, however, only for relatively low intensity stimuli. The data provide some support for the suggestion that circadian fluctuations in magnitude of long-term potentiation result from corresponding changes in CT level. The rapid onset of the observed changes is difficult to account for in terms of generally accepted mechanisms of receptor binding.     

Conditioning of hippocampal cells: its acceleration and long-term facilitation by post-trial reticular stimulation

Neuronal activity, recorded in the dorsal hippocampus (CA3) during classical conditioning, was studied in rats receiving mild post-trial stimulation of the mesencephalic reticular formation. Hippocampal multi-unit activity increased in response to an auditory signal (conditioned stimulus) after pairing of the signal with a footshock (unconditioned stimulus), while the auditory signal alone, presented before conditioning, did not change the rate of hippocampal cell discharges. Trial-by-trial analysis of hippocampal multi-unit responses to the conditioned stimulus, both during acquisition and during a test of long-term retention, indicated that post-trial mesencephalic reticular stimulation hastened the onset of cellular conditioning and facilitated conversion to long-term storage. A study of evoked potentials recorded in the hippocampal formation to stimulation of the perforant path in awake rats, suggested that these effects could be mediated through a modulation of synaptic efficiency within hippocampal neuronal networks. These data are discussed in relation to the concept of neural perseveration in memory consolidation.     

Visual mismatch negativity is sensitive to symmetry as a perceptual category

We investigated the sensitivity of visual mismatch negativity (vMMN) to an abstract and non‐semantic category, vertical mirror symmetry. Event‐related potentials (ERPs) elicited by random and symmetric square patterns, delivered in passive oddball paradigm (participants played a video game), were recorded. In one of the conditions, symmetric patterns were frequent (standard) stimuli and the random patterns were infrequent (deviant) stimuli; in the other condition, the probabilities were reversed. We compared the ERPs elicited by symmetric stimuli as deviants and as standards, and, similarly, the ERPs elicited by the random deviants and random standards. As the difference between the ERPs elicited by random deviant and random standard stimuli, a posterior negativity emerged in two latency ranges (112–120 and 284–292 ms). These negativities were considered to be vMMN components. We suggest that the two vMMN components are organised in cascade error signals. However, there was no significant difference between the ERPs elicited by symmetric deviants and those elicited by symmetric standards. The emergence of vMMN in response to the deviant random stimuli is considered to be a deviation of a perceptual category (in the symmetric standard sequence presented). Accordingly, random stimuli acquired no perceptual category; for this reason, the symmetric deviant (in the random standard sequence presented) elicited no vMMN. The results show that the memory system underlying vMMN is capable of coding perceptual categories such as bilateral symmetry, even if the stimulus patterns are unrelated to the ongoing behavior.     

Kindling-induced neuronal plasticity in the dorsal hippocampus CA1 in acutely prepared rabbits: unit activity analysis.

To elucidate kindling-induced neuronal plasticity single cell discharge analysis, responses consisting of action potentials orthodromically elicited in the dorsal hippocampus CA1 by a single electric shock to the neighboring region were serially observed before, during and after kindling i.e. the repetition of stimulus trains applied to the same hippocampal region in acutely prepared rabbits. Eventually, the orthodromic unit response with identical amplitudes, which were regarded as a single cell origin, gradually increased in the firing rate at the interictal stages during and after the kindling. Further, an inhibitory period following the unit responses, during which no spontaneous unit activity appeared, was remarkably prolonged during and after the kindling. Both the increase of the unit responses and the prolongation of the inhibitory period irreversibly lasted for hours once they occurred. Such unit activity analysis confirms kindling-induced excitatory and inhibitory synaptic plasticity.     

Auditory event-related potentials in patients with psychotic illness: A 5-year follow-up

The auditory processing is diversely impaired in patients with the first-episode psychosis. During acute phase we previously reported reduced amplitudes in attention-dependent auditory evoked electrical brain potentials but not in those of early automatic components. Here seven first-episode patients at the disease onset and 5 years later were studied and compared to control subjects. At follow-up, also the unattended auditory stimuli elicited reduced amplitudes both in primary sensory component (N100, p = .043) and in automatic deviance detection (N200, p = .013) as compared to acute phase. Patients' psychopathology had improved, however they still showed alterations in components detecting automatic stimulus classification which may convey persisting tendency for misinterpretation in auditory perception.     

Stereotactic recordings of median nerve somatosensory-evoked potentials in the human pre-supplementary motor area

Median nerve somatosensory-evoked potentials (SEPs) have been recorded using intracortical electrodes stereotactically implanted in the frontal lobe of eight epileptic patients in order to assess the waveforms, latencies and surface-to-depth distributions of somatosensory responses generated in the anterior subdivision of supplementary motor areas (SMAs), the so-called pre-SMA. Intracortical responses were analysed in two latency ranges: 0--50 ms and 50--150 ms after stimulus. In all patients, we recorded in the first 50 ms after stimulus two positive P14 and P20 potentials followed by a N30 negativity. In the hemisphere contralateral to stimulation, the P20--N30 potentials showed a clear amplitude decrease from the outer to the inner aspect of the frontal lobe with minimal amplitudes in the pre-SMA. In the hemisphere ipsilateral to stimulus, P20 and N30 amplitudes were decreasing from mesial to lateral frontal cortex. In the 50--150 ms latency range, contacts implanted in the pre-SMA recorded a negative potential in the 60--70 ms latency range which, in five patients, was followed by a positive response peaking 80--110 ms after stimulus. These potentials were not picked up by more superficial contacts. We conclude that no early SEP is generated in pre-SMA in the first 50 ms after stimulation, while some potentials peaking in the 60--100 ms after stimulus are likely to originate from this cortical area. The latency of the pre-SMA responses recorded in our patients supports the hypothesis that the pre-SMA does not receive short-latency somatosensory inputs via direct thalamocortical projections. More probably the pre-SMA receives somatosensory inputs mediated by a polysynaptic transcortical transmission through functionally secondary motor and somatosensory areas.