Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCK_B antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCK_B antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.     

Dynamics of evoked potentials in the auditory zone of the dog cerebral cortex following extirpation of the medial geniculate bodies during formation of goal-directed behavior]

Integrative processes in the auditory cortical zone were studied in three dogs by EEG and EP parameters during the formation of a defensive reaction to clicks (four clicks, two per second) after the extirpation of the medial geniculate bodies. In the operated animals information is transmitted to the cortical end of the auditory analyser by compensatory paths with a larger number of relays. In the auditory cortex EPs are recorded with a longer latency (12 to 16 msec), and the duration of the negative EP component is increased (up to 40 msec). It is split mainly on the ascending front. The cortical end of the analyser participates in the formation of processes of afferent synthesis. In the active period of reflex elaboration the inflow of information increases: the EP amplitude and the duration of its main negative component become greater (up to 45-55 msec), as well as the splits on its fronts. In the course of preparing for a decision, before the achievement of the conditioned reaction, a "double EP" appears, which is due to enhanced reverberation of excitations in the compensatory paths.     

Cortical motion deafness

The extent to which the auditory system, like the visual system, processes spatial stimulus characteristics such as location and motion in separate specialized neuronal modules or in one homogeneously distributed network is unresolved. Here we present a patient with a selective deficit for the perception and discrimination of auditory motion following resection of the right anterior temporal lobe and the right posterior superior temporal gyrus (STG). Analysis of stimulus identity and location within the auditory scene remained intact. In addition, intracranial auditory evoked potentials, recorded preoperatively, revealed motion-specific responses selectively over the resected right posterior STG, and electrical cortical stimulation of this region was experienced by the patient as incoming moving sounds. Collectively, these data present a patient with cortical motion deafness, providing evidence that cortical processing of auditory motion is performed in a specialized module within the posterior STG.     

Effects of pentobarbital and ketamine-xylazine anaesthesia on somatosensory, brainstem auditory and peripheral sensory-motor responses in the rat.

Somatosensory, brainstem auditory evoked and peripheral sensory-motor responses were recorded in rats anaesthetized with either pentobarbital or a ketamine-xylazine combination. This was carried out in order to assess which of these agents degraded responses to a lesser extent and thus would be more suitable for monitoring experimental effects. Neither of the anaesthetic agents affected peripheral sensory or motor conduction, nor were there any interpeak latency changes of the early components of the brainstem auditory response. However, pentobarbital anaesthesia resulted in an increase in latency of the initial positive component of the somatosensory cortical evoked potential and attenuation of the following negative component. During the recovery stages of ketamine-xylazine anaesthesia the longer latency evoked potential components were observed to emerge.     

Foetal and neonatal development of evoked responses in guinea-pig auditory cortex.

Development of the response of the auditory cortex to unilateral acoustic stimulation by a chick was studied in guinea-pig foetuses from the 50th day to the end of gestation and in newborn animals. The first cortical response appeared on the 52nd to 53rd day of gestation. The maximum responses were concentrated in the temporal cortex, between the somatosensory (parietal) and optic (occipital) area. The progressive development of the latent period of the cortical response and of its various components distinctly slowed down on the last days of gestation. At the same time, the amplitude of the cortical response was temporarily augmented. The cortical response developed from a simple negative wave in the youngest embryos into an intricate complex with an initial positive component in newborn guinea-pigs. The basic components of this complex were already discernible on the 64th to 65th day of gestation. The ability to react to repeated peripheral stimulation of 0.1-2 c/s frequency increased with foetal age, with temporary deterioration on the last days of gestation. Resistance of the cortical auditory response to cerebral anoxia rose up to term, with a temporary drop from the 64th day of gestation. After the initiation of independent respiration, cerebral hypoxia and bilateral vagotomy chiefly influenced the stability of the more recent components of the cortical auditory response in mature foetuses.     

Functional Changes in the Human Auditory Cortex in Ageing

Hearing loss, presbycusis, is one of the most common sensory declines in the ageing population. Presbycusis is characterised by a deterioration in the processing of temporal sound features as well as a decline in speech perception, thus indicating a possible central component. With the aim to explore the central component of presbycusis, we studied the function of the auditory cortex by functional MRI in two groups of elderly subjects (>65 years) and compared the results with young subjects (<lt;30 years). The elderly group with expressed presbycusis (EP) differed from the elderly group with mild presbycusis (MP) in hearing thresholds measured by pure tone audiometry, presence and amplitudes of transient otoacoustic emissions (TEOAE) and distortion-product oto-acoustic emissions (DPOAE), as well as in speech-understanding under noisy conditions. Acoustically evoked activity (pink noise centered around 350 Hz, 700 Hz, 1.5 kHz, 3 kHz, 8 kHz), recorded by BOLD fMRI from an area centered on Heschl’s gyrus, was used to determine age-related changes at the level of the auditory cortex. The fMRI showed only minimal activation in response to the 8 kHz stimulation, despite the fact that all subjects heard the stimulus. Both elderly groups showed greater activation in response to acoustical stimuli in the temporal lobes in comparison with young subjects. In addition, activation in the right temporal lobe was more expressed than in the left temporal lobe in both elderly groups, whereas in the young control subjects (YC) leftward lateralization was present. No statistically significant differences in activation of the auditory cortex were found between the MP and EP groups. The greater extent of cortical activation in elderly subjects in comparison with young subjects, with an asymmetry towards the right side, may serve as a compensatory mechanism for the impaired processing of auditory information appearing as a consequence of ageing.     

The combined activities of the temporal cortical area and hippocampus in man during the localization of a moving sound image

In patients with epileptic lesions in the cortex and mediobasal structures of the brain, studies have been made on the perception of spatial position of sound images during dichotic stimulation. It was established that the extreme interval which is necessary for formation of sensation of the moving sound image increases during right-side lesions of the temporal cortex. During left-side lesion of the temporal lobe, more diffuse disturbances in the trajectory of image movement (from the right and left) are observed, whereas right-side lesions result in disturbances of movement only at the opposite side of the latter. Cortical lesions and those in the mediobasal parts of the temporal lobe are accompanied by identical gradient of disturbances in the trajectory of sound image movement and short-term imprinting of succession of signals which differ with respect to their spatial position. Maximum disturbances are observed during lesions in the cortical and mediobasal parts of the temporal lobe, whereas only cortical lesions or only hippocampal lesions result in less significant disturbances. It is suggested that combined activity of the auditory cortex and hippocamp is necessary for localization of a sound source.     

Using Auditory Steady State Responses to Outline the Functional Connectivity in the Tinnitus Brain

Background

Tinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions.

Methods and Findings

Using whole-head magnetoencephalography we investigated cortical connectivity by means of phase synchronization in tinnitus subjects and healthy controls. We found evidence for a deviating pattern of long-range functional connectivity in tinnitus that was strongly correlated with individual ratings of the tinnitus percept. Phase couplings between the anterior cingulum and the right frontal lobe and phase couplings between the anterior cingulum and the right parietal lobe showed significant condition x group interactions and were correlated with the individual tinnitus distress ratings only in the tinnitus condition and not in the control conditions.

Conclusions

To the best of our knowledge this is the first study that demonstrates existence of a global tinnitus network of long-range cortical connections outside the central auditory system. This result extends the current knowledge of how tinnitus is generated in the brain. We propose that this global extend of the tinnitus network is crucial for the continuos perception of the tinnitus tone and a therapeutical intervention that is able to change this network should result in relief of tinnitus.     

The neurochemical basis of human cortical auditory processing: combining proton magnetic resonance spectroscopy and magnetoencephalography

Background  

A combination of magnetoencephalography and proton magnetic resonance spectroscopy was used to correlate the electrophysiology of rapid auditory processing and the neurochemistry of the auditory cortex in 15 healthy adults. To assess rapid auditory processing in the left auditory cortex, the amplitude and decrement of the N1m peak, the major component of the late auditory evoked response, were measured during rapidly successive presentation of acoustic stimuli. We tested the hypothesis that: (i) the amplitude of the N1m response and (ii) its decrement during rapid stimulation are associated with the cortical neurochemistry as determined by proton magnetic resonance spectroscopy.     

Auditory evoked potentials to abrupt pitch and timbre change of complex tones: electrophysiological evidence of `streaming'?

Examination of the cortical auditory evoked potentials to complex tones changing in pitch and timbre suggests a useful new method for investigating higher auditory processes, in particular those concerned with `streaming' and auditory object formation. The main conclusions were: (i) the N1 evoked by a sudden change in pitch or timbre was more posteriorly distributed than the N1 at the onset of the tone, indicating at least partial segregation of the neuronal populations responsive to sound onset and spectral change; (ii) the T-complex was consistently larger over the right hemisphere, consistent with clinical and PET evidence for particular involvement of the right temporal lobe in the processing of timbral and musical material; (iii) responses to timbral change were relatively unaffected by increasing the rate of interspersed changes in pitch, suggesting a mechanism for detecting the onset of a new voice in a constantly modulated sound stream; (iv) responses to onset, offset and pitch change of complex tones were relatively unaffected by interfering tones when the latter were of a different timbre, suggesting these responses must be generated subsequent to auditory stream segregation.     

Changes in characteristics of sensory evoked potentials in dynamics of monotonous activity

Visual and auditory evoked potentials were recorded in 19 volunteers during their monotonous activity. Three groups of subjects different in performance quality were set aside. Characteristics of evoked potential components were subjected to analysis of variance. The latency of P1 component of visual and auditory evoked potentials recorded in respective projection cortical areas significantly increased over the course of the long-term monotonous activity. These changes were associated with performance deterioration. The observed changes in performance quality and brain functional state were determined by individual features of subjects.     

Intracranial and extracranial recordings of the auditory middle latency response

Simultaneous epidural and cortical depth recordings of the auditory middle latency reponse (MLR) were obtained from 18 anesthetized guinea pigs. Microelectrodes were advanced at a right angle to the cortical surface at sites shown to be optimal for recording surface MLRs.Transcortical polarity reversals of waves A (14 msec) and B (24 msec) of the MLR were recorded in depth penetrations initiated at sites on the temporal lobe with large amplitude surface potentials. In 6 of 18 penetrations yielding phase inversions, wave polarities changed abruptly as microelectrodes were advanced into the cortex. In the remaining penetrations, the reversals were preceded by gradual decreases in wave latencies at progressively deep sites. As electrodes were advanced beyond the depth at which polarity reversals were encountered, decreases in amplitude and only minor changes in latency were observed.Surface and depth MLR activity were temporarily eliminated immediately after electrolytic lesions were made at polarity reversal sites. Recovery of responses occurred within 30–60 min. Lesions produced in penetrations initiated at sites with no surface MLR activity had no effect. Histologic examination confirmed the location of the phase reversal sites as being within grey matter of the temporal lobe.These results are consistent with previous investigations in experimental animals which demonstrated transcortical polarity reversals, and provide evidence for dipolar generating systems of the early components of the MLR at the cortical level.     

Role of corticofugal feedback in hearing

The auditory system consists of the ascending and descending (corticofugal) systems. The corticofugal system forms multiple feedback loops. Repetitive acoustic or auditory cortical electric stimulation activates the cortical neural net and the corticofugal system and evokes cortical plastic changes as well as subcortical plastic changes. These changes are short-term and are specific to the properties of the acoustic stimulus or electrically stimulated cortical neurons. These plastic changes are modulated by the neuromodulatory system. When the acoustic stimulus becomes behaviorally relevant to the animal through auditory fear conditioning or when the cortical electric stimulation is paired with an electric stimulation of the cholinergic basal forebrain, the cortical plastic changes become larger and long-term, whereas the subcortical changes stay short-term, although they also become larger. Acetylcholine plays an essential role in augmenting the plastic changes and in producing long-term cortical changes. The corticofugal system has multiple functions. One of the most important functions is the improvement and adjustment (reorganization) of subcortical auditory signal processing for cortical signal processing.     

Thalamic activation modulates the responses of neurons in rat primary auditory cortex: an in vivo intracellular recording study

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing.     

Temporal integration in auditory sensory memory: neuromagnetic evidence

The cortical mechanisms of auditory sensory memory were investigated by analysis of neuromagnetic evoked responses. The major deflection of the auditory evoked field (N100m) appears to comprise an early posterior component (N100m^P) and a late anterior component (N100m^A) which is sensitive to temporal factors. When pairs of identical sounds are presented at intervals less than about 250 msec, the second sound evokes N100m^A with enhanced amplitude at a latency of about 150 msec. We suggest that N100m^A may index the activity of two distinct processes in auditory sensory memory. Its recovery cycle may reflect the activity of a memory trace which, according to previous studies, can retain processed information about an auditory sequence for about 10 sec. The enhancement effect may reflect the activity of a temporal integration process, whose time constant is such that sensation persists for 200–300 msec after stimulus offset, and so serves as a short memory store. Sound sequences falling within this window of integration seem to be coded holistically as unitary events.     

Dynamics of evoked potentials in cortical projection structures during a retarded instrumental defense reflex in dogs]

Evoked potentials (EP) in the somatosensory and auditory cortical areas were studied in four dogs against the background of a retarded defensive instrumental conditioned reflex to clicks. Four phases of the reflex were singled out by the changes in the structure of EP late components (LC) in the two projection zones. The most complex LC changes in the form of intensified negative components and the appearance of additional negative LC are recorded in response to the first click of the series and to the one followed by the conditioned motor reaction (CMR). Against the background of CMR delay, the EPs increased, while during the CMR, they decreased, owing to the diminished negative components, while the positive components were preserved and sometimes intensified. An assumption has been made that cortical projection structures of paired stimuli function in one and the same regime.     

Spatiotemporal Segregation of Neural Response to Auditory Stimulation: An fMRI Study Using Independent Component Analysis and Frequency-Domain Analysis

Although auditory processing has been widely studied with conventional parametric methods, there have been a limited number of independent component analysis (ICA) applications in this area. The purpose of this study was to examine spatiotemporal behavior of brain networks in response to passive auditory stimulation using ICA. Continuous broadband noise was presented binaurally to 19 subjects with normal hearing. ICA was performed to segregate spatial networks, which were subsequently classified according to their temporal relation to the stimulus using power spectrum analysis. Classification of separated networks resulted in 3 stimulus-activated, 9 stimulus-deactivated, 2 stimulus-neutral (stimulus-dependent but not correlated with the stimulation timing), and 2 stimulus-unrelated (fluctuations that did not follow the stimulus cycles) components. As a result of such classification, spatiotemporal subdivisions were observed in a number of cortical structures, namely auditory, cingulate, and sensorimotor cortices, where parts of the same cortical network responded to the stimulus with different temporal patterns. The majority of the classified networks seemed to comprise subparts of the known resting-state networks (RSNs); however, they displayed different temporal behavior in response to the auditory stimulus, indicating stimulus-dependent temporal segregation of RSNs. Only one of nine deactivated networks coincided with the “classic” default-mode network, suggesting the existence of a stimulus-dependent default-mode network, different from that commonly accepted.     

Subjective Acoustic Field of Patients with Cortical Temporal Lobe Epilepsy as Revealed Using Signals Simulating Various Directions of Sound Movement

Perception of signals simulating directional movement of a sound source was studied in two groups of patients with cortical temporal lobe epilepsy and epileptic activity foci in the right or left temporal area of the cortex. On dichotic stimulation, the character and length of the trajectories of subjective auditory images (SAIs) were determined as dependent on the direction of SAI movement and the initial interaural delay (700, 400, and 200 s). For any delay or direction examined, SAI trajectories were shorter in the patients of both groups than in healthy subjects. Regardless of the side of an epileptic focus, the shortest trajectories were detected in the hemisphere where SAI movement ended, especially at an interaural delay of 200 s. The narrowest subjective acoustic field was observed in patients with epileptic foci in the right temporal cortex. Possible mechanisms of the changes in spatial hearing are discussed. The changes in SAI perception are assumed to result from distorted binaural interactions, which manifest themselves in functional asymmetry of the two auditory centers and may be caused by a convulsive activity focus present in one temporal lobe.     

Spatio-temporal source modeling of evoked potentials to acoustic and cochlear implant stimulation

Spatio-temporal source modeling (STSM) of event-related potentials was used to estimate the loci and characteristics of cortical activity evoked by acoustic stimulation in normal hearing subjects and by electrical stimulation in cochlear implant (CI) subjects. In both groups of subjects, source solutions obtained for the N₁/P₂ complex were located in the superior half of the temporal lobe in the head model. Results indicate that it may be possible to determine whether stimulation of different implant channels activates different regions of cochleotopically organized auditory cortex. Auditory system activation can be assessed further by examining the characteristics of the source wave forms. For example, subjects whose cochlear implants provided auditory sensations and normal hearing subjects had similar source activity. In contrast, a subject in whom implant activation evoked eyelid movements exhibited different source wave forms. STSM analysis may provide an electrophysiological technique for guiding rehabilitation programs based on the capabilities of the individual implant user and for disentangling the complex response patterns to electrical stimulation of the brain.     

Event-related potentials recorded from the scalp and nasopharynx. I. N1 and P2

Event-related potentials were recorded from the scalp and nasopharynx during a signal-detection task. These responses were evaluated with respect to the effects of interstimulus interval, intensity, frequency, attention and modality. Our results indicate the existence of at least 4 distinct processes occurring in the 75–150 msec latency range following auditory stimuli. The first process is indexed in the vertex-N1b/temporal-N1a component. This component does not reverse in polarity below the sylvian fissure and is not seen in nasopharyngeal recordings. The location of its generator is not known. Probably there are two or more sources active at this latency. The second process finds reflection in the N1c/PgP120 component. This component is recorded with maximum amplitude on the side contralateral to the ear of delivery. A source in the lateral surface of the temporal lobe is a likely generator. The third process corresponds to Wolpaw and Penry's (1975) Ta positivity. How much of this represents the underside of a vertically oriented dipole and how much a surface positivity is unknown. Finally, during attention, a lateralized processing negativity seems to overlap these components at the scalp, but not at the nasopharynx. The auditory vertex N1 peak is quite distinct from the visual N1 which is more posteriorly recorded on the scalp and which is associated with a definite nasopharyngeal positive wave. The P2 peak is quite similar across auditory and visual modalities. In both modalities it is maximally recorded from the vertex and has no nasopharyngeal concomitant.