Classical Auditory Pathway Research Articles

Unexpected Consequences of Noise-Induced Hearing Loss: Impaired Hippocampal Neurogenesis, Memory, and Stress.

Noise-induced hearing loss (NIHL), caused by direct damage to the cochlea, reduces the flow of auditory information to the central nervous system, depriving higher order structures, such as the hippocampus with vital sensory information needed to carry out complex, higher order functions. Although the hippocampus lies outside the classical auditory pathway, it nevertheless receives acoustic information that influence its activity. Here we review recent results that illustrate how NIHL and other types of cochlear hearing loss disrupt hippocampal function. The hippocampus, which continues to generate new neurons (neurogenesis) in adulthood, plays an important role in spatial navigation, memory, and emotion. The hippocampus, which contains place cells that respond when a subject enters a specific location in the environment, integrates information from multiple sensory systems, including the auditory system, to develop cognitive spatial maps to aid in navigation. Acute exposure to intense noise disrupts the place-specific firing patterns of hippocampal neurons, “spatially disorienting” the cells for days. More traumatic sound exposures that result in permanent NIHL chronically suppresses cell proliferation and neurogenesis in the hippocampus; these structural changes are associated with long-term spatial memory deficits. Hippocampal neurons, which contain numerous glucocorticoid hormone receptors, are part of a complex feedback network connected to the hypothalamic-pituitary (HPA) axis. Chronic exposure to intense intermittent noise results in prolonged stress which can cause a persistent increase in corticosterone, a rodent stress hormone known to suppress neurogenesis. In contrast, a single intense noise exposure sufficient to cause permanent hearing loss produces only a transient increase in corticosterone hormone. Although basal corticosterone levels return to normal after the noise exposure, glucocorticoid receptors (GRs) in the hippocampus remain chronically elevated. Thus, NIHL disrupts negative feedback from the hippocampus to the HPA axis which regulates the release of corticosterone. Preclinical studies suggest that the noise-induced changes in hippocampal place cells, neurogenesis, spatial memory, and glucocorticoid receptors may be ameliorated by therapeutic interventions that reduce oxidative stress and inflammation. These experimental results may provide new insights on why hearing loss is a risk factor for cognitive decline and suggest methods for preventing this decline.

Investigating the Effect of Noise Exposure on Hippocampal‐Dependent Spatial Learning and Memory in a Rat Model

Hearing loss is one of the most prevalent chronic health conditions worldwide, with excessive exposure to loud noise as a leading cause of hearing loss. Beyond the devastating effects of hearing impairment itself, epidemiological studies have identified hearing loss as a major risk factor for cognitive decline. Furthermore, preclinical studies on rodents have identified that the hippocampus—a brain region outside of the classical auditory pathway which subserves spatial navigation—appears to be vulnerable to noise exposure. For example, two hours of exposure to very loud noise (e.g., 123 dB sound pressure level, SPL) has been shown to cause long-term impairment in spatial learning and memory, as well as suppress hippocampal neurogenesis (i.e., the processes by which new neurons are generated from neural stem cells in the adult brain). That said, because these past studies used noise levels that far exceed those frequently experienced by humans who work in noisy environments, it remains uncertain whether a more modest degree of hearing loss, consistent with that caused by daily, occupational noise exposure, is also problematic for normal hippocampal function. In the present study, we are using a rat model to study the effect of daily noise exposure on spatial learning, memory and hippocampal neurogenesis. Following baseline hearing testing using the auditory brainstem response (i.e., an electrophysiologically-measured evoked potential from the brain in response to sound), 6-month old Fischer 344 rats were exposed to 100 dB SPL white noise (or silence) for 4 hours/day for 30 days. Separate cohorts of noise- and sham-exposed rats then underwent behavioral testing at 7, 10, or 13 months old using a Morris water maze (MWM) protocol to assess hippocampal-dependent spatial acquisition learning and reference memory. After completion of the behavioral testing and post-exposure hearing assessments, the rats were sacrificed, and their brains harvested for tissue processing. As predicted, the noise-exposed rats had a mild degree of high-frequency hearing loss, evidenced by a ~25 dB increase in the rats’ hearing threshold to a 20 kHz acoustic stimulus. Overall, both treatment groups demonstrated spatial acquisition learning over the 5 training days on the MWM hidden platform task; however, the noise-exposed rats performed slightly, albeit significantly worse than the shams at 10 months of age. Moreover, in contrast to past studies that used very loud noise exposures, none of the cohorts of noise-exposed rats in the present study were impaired during the MWM probe task; findings which identify that deficits in spatial reference memory are not an inevitable consequence of repeated exposure to sounds that cause a mild degree of hearing loss. Histological analysis of hippocampal neurogenesis is ongoing. Ultimately, given that not all individuals exposed to occupational noise suffer the same degree of hearing loss, it will be important that we correlate each rat's hearing sensitivity with its’ cognitive-behavioral performance and extent of hippocampal neurogenesis, so as to better understand the complex relationship between noise-induced hearing loss, cognitive impairment and neuropathology.

Behavioral and neuroanatomical effects on exposure to White noise in rats

Noise pollution is a severe public health problem as continuous exposure to even moderate noise levels between 55−65 dB can lead to various pathologies, including neurological states. In the present study, we assessed the ultrastructural alterations in selective auditory pathways of the rat brain following high intensity white noise exposure. In addition, learning, anxiety-like behavior and locomotor activity were assessed. Adult male rats were exposed to 100 dB noise, one hour daily, for 10 consecutive days. The evaluations were performed on day 11. Exposure to noise did not affect learning or the components of locomotor activity. However, it induced anxiety-like behavior as evidenced by time spent in the closed arm of elevated-plus maze. Concomitantly, ultrastructural changes in medial geniculate body, considered an integral component of classical auditory pathway, as well as in the hippocampus and basolateral amygdala, considered important structures of non-classical auditory pathway were noted. Specifically, noise resulted in neuronal apoptosis, chromatolysis, cytoplasmic organelle destruction, and glial activation in medial geniculate body and hippocampus, as well as mild alterations in amygdala. These results provide further evidence of detrimental consequences following exposure to loud noise.

Plasticity in Limbic Regions at Early Time Points in Experimental Models of Tinnitus.

Tinnitus is one of the most prevalent auditory disorders worldwide, manifesting in both chronic and acute forms. The pathology of tinnitus has been mechanistically linked to induction of harmful neural plasticity stemming from traumatic noise exposure, exposure to ototoxic medications, input deprivation from age-related hearing loss, and in response to injuries or disorders damaging the conductive apparatus of the ears, the cochlear hair cells, the ganglionic cells of the VIIIth cranial nerve, or neurons of the classical auditory pathway which link the cochlear nuclei through the inferior colliculi and medial geniculate nuclei to auditory cortices. Research attempting to more specifically characterize the neural plasticity occurring in tinnitus have used a wide range of techniques, experimental paradigms, and sampled at different windows of time to reach different conclusions about why and which specific brain regions are crucial in the induction or ongoing maintenance of tinnitus-related plasticity. Despite differences in experimental methodologies, evidence reveals similar findings that strongly suggest that immediate and prolonged activation of non-classical auditory structures (i.e., amygdala, hippocampus, and cingulate cortex) may contribute to the initiation and development of tinnitus in addition to the ongoing maintenance of this devastating condition. The overarching focus of this review, therefore, is to highlight findings from the field supporting the hypothesis that abnormal early activation of non-classical sensory limbic regions are involved in tinnitus induction, with activation of these regions continuing to occur at different temporal stages. Since initial/early stages of tinnitus are difficult to control and to quantify in human clinical populations, a number of different animal paradigms have been developed and assessed in experimental investigations. Reviews of traumatic noise exposure and ototoxic doses of sodium salicylate, the most prevalently used animal models to induce experimental tinnitus, indicate early limbic system plasticity (within hours, minutes, or days after initial insult), supports subsequent plasticity in other auditory regions, and contributes to the pathophysiology of tinnitus. Understanding this early plasticity presents additional opportunities for intervention to reduce or eliminate tinnitus from the human condition.

Dissociation between Cerebellar and Cerebral Neural Activities in Humans with Long-Term Bilateral Sensorineural Hearing Loss.

Abnormal neural activity in the cerebellum has been implicated in hearing impairments, but the effects of long-term hearing loss on cerebellar function are poorly understood. To further explore the role of long-term bilateral sensorineural hearing loss on cerebellar function, we investigated hearing loss-induced changes among neural networks within cerebellar subregions and the changes in cerebellar-cerebral connectivity patterns using resting-state functional MRI. Twenty-one subjects with long-term bilateral moderate-to-severe sensorineural hearing loss and 21 matched controls with clinically normal hearing underwent MRI scanning and a series of neuropsychological tests targeting cognition and emotion. Voxel-wise functional connectivity (FC) analysis demonstrated decreased couplings between the cerebellum and other cerebral areas, including the temporal pole (TP), insula, supramarginal gyrus, inferior frontal gyrus (IFG), medial frontal gyrus, and thalamus, in long-term bilateral sensorineural hearing loss patients. An ROI-wise FC analysis found weakened interregional connections within cerebellar subdivisions. Moreover, there was a negative correlation between anxiety and FC between the left cerebellar lobe VI and left insula. Hearing ability and anxiety scores were also correlated with FC between the left cerebellar lobe VI and left TP, as well as the right cerebellar lobule VI and left IFG. Our results suggest that sensorineural hearing loss disrupts cerebellar-cerebral circuits, some potentially linked to anxiety, and interregional cerebellar connectivity. The findings contribute to a growing body showing that auditory deprivation caused by cochlear hearing loss disrupts not only activity with the classical auditory pathway but also portions of the cerebellum that communicates with other cortical networks.

Altered Spatial and Temporal Brain Connectivity in the Salience Network of Sensorineural Hearing Loss and Tinnitus.

Sensorineural hearing loss (SNHL), sometimes accompanied with tinnitus, is associated with dysfunctions within and outside the classical auditory pathway. The salience network, which is anchored in bilateral anterior insula and dorsal anterior cingulate cortex, has been implicated in sensory integration. Partial auditory deprivation could alter the characteristics of the salience network and other related brain areas, thereby contributing to hearing impairments-induced neuropsychiatric symptoms. To test this hypothesis, we performed fMRI scanning and neuropsychological tests on 32 subjects with long-term bilateral hearing impairment and 30 well-matched Controls. Non-directional functional connectivity and directional Granger causality analysis were used to identify aberrant spatial and temporal patterns of connections targeting bilateral anterior insula and dorsal anterior cingulate cortex. We found that the left anterior insula showed decreased connectivity with right precentral gyrus and superior frontal gyrus. The connections between the dorsal anterior cingulate cortex and middle frontal gyrus, superior parietal gyrus and supplementary motor area (SMA) were also reduced. Relative to Controls, SNHL patients showed abnormal effective connectivity of the salience network, including inferior temporal gyrus, cerebellum lobule VI, lobule VIII, precentral gyrus, middle frontal gyrus and SMA. Furthermore, correlation analysis demonstrated that some of these atypical connectivity measures were correlated with performance of neuropsychiatric tests. These findings suggest that the inefficient modulation of the salience network might contribute to the neural basis of SNHL and tinnitus, as well as associated cognition and emotion deficits.

Serotonergic Modulation of Sensory Representation in a Central Multisensory Circuit Is Pathway Specific

SUMMARYMany studies have explored how neuromodulators affect synaptic function, yet little is known about how they modify computations at the microcircuit level. In the dorsal cochlear nucleus (DCN), a region that integrates auditory and multisensory inputs from two distinct pathways, serotonin (5-HT) enhances excitability of principal cells, predicting a generalized reduction in sensory thresholds. Surprisingly, we found that when looked at from the circuit level, 5-HT enhances signaling only from the multisensory input, while decreasing input from auditory fibers. This effect is only partially explained by an action on auditory nerve terminals. Rather, 5-HT biases processing for one input pathway by simultaneously enhancing excitability in the principal cell and in a pathway-specific feed-forward inhibitory interneuron. Thus, by acting on multiple targets, 5-HT orchestrates a fundamental shift in representation of convergent auditory and multisensory pathways, enhancing the potency of non-auditory signals in a classical auditory pathway.

Noise trauma induced plastic changes in brain regions outside the classical auditory pathway

The effects of intense noise exposure on the classical auditory pathway have been extensively investigated; however, little is known about the effects of noise-induced hearing loss on non-classical auditory areas in the brain such as the lateral amygdala (LA) and striatum (Str). To address this issue, we compared the noise-induced changes in spontaneous and tone-evoked responses from multiunit clusters (MUC) in the LA and Str with those seen in auditory cortex (AC) in rats. High-frequency octave band noise (10–20kHz) and narrow band noise (16–20kHz) induced permanent threshold shifts at high-frequencies within and above the noise band but not at low frequencies. While the noise trauma significantly elevated spontaneous discharge rate (SR) in the AC, SRs in the LA and Str were only slightly increased across all frequencies. The high-frequency noise trauma affected tone-evoked firing rates in frequency and time-dependent manner and the changes appeared to be related to the severity of noise trauma. In the LA, tone-evoked firing rates were reduced at the high-frequencies (trauma area) whereas firing rates were enhanced at the low-frequencies or at the edge-frequency dependent on severity of hearing loss at the high frequencies. The firing rate temporal profile changed from a broad plateau to one sharp, delayed peak. In the AC, tone-evoked firing rates were depressed at high frequencies and enhanced at the low frequencies while the firing rate temporal profiles became substantially broader. In contrast, firing rates in the Str were generally decreased and firing rate temporal profiles become more phasic and less prolonged. The altered firing rate and pattern at low frequencies induced by high-frequency hearing loss could have perceptual consequences. The tone-evoked hyperactivity in low-frequency MUC could manifest as hyperacusis whereas the discharge pattern changes could affect temporal resolution and integration.

Hearing Without Listening: Functional Connectivity Reveals the Engagement of Multiple Nonauditory Networks During Basic Sound Processing

The present functional magnetic resonance imaging (fMRI) study presents data challenging the traditional view that sound is processed almost exclusively in the classical auditory pathway unless imbued with behavioral significance. In a first experiment, subjects were presented with broadband noise in on/off fashion as they performed an unrelated visual task. A conventional analysis assuming predictable sound-evoked responses demonstrated a typical activation pattern that was confined to classical auditory centers. In contrast, spatial independent component analysis (sICA) disclosed multiple networks of acoustically responsive brain centers. One network comprised classical auditory centers, but four others included nominally "nonauditory" areas: cingulo-insular cortex, mediotemporal limbic lobe, basal ganglia, and posterior orbitofrontal cortex, respectively. Functional connectivity analyses confirmed the sICA results by demonstrating coordinated activity between the involved brain structures. In a second experiment, fMRI data obtained from unstimulated (i.e., resting) subjects revealed largely similar networks. Together, these two experiments suggest the existence of a coordinated system of multiple acoustically responsive intrinsic brain networks, comprising classical auditory centers but also other brain areas. Our results suggest that nonauditory centers play a role in sound processing at a very basic level, even when the sound is not intertwined with behaviors requiring the well-known functionality of these regions.

Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC)

Tinnitus is an auditory disorder characterized by perception of internally generated phantom auditory sensations without corresponding mechanical stimuli arising from the body or external environment. Current auditory based treatment approaches, sometimes in conjunction with nonauditory based strategies, such as Tinnitus Retraining Therapy and Cognitive Behavioral Therapy, have been helpful in mitigating symptoms for the majority of patients. Yet there are over 1 million tinnitus sufferers who still endure troublesome chronic, continuous head noises that are debilitating and interfere with activities of daily living. Here we show that application of deep brain stimulation (DBS) therapy to a locus of caudate neurons (area LC) in the body of the nucleus, a subsite of the striatum that is not part of the classical auditory pathway, can decrease or increase tinnitus loudness perception. The DBS lead traversed through or was adjacent to area LC in six Parkinson's disease and essential tremor subjects with concomitant tinnitus who underwent implantation of the subthalamic or ventral intermediate nucleus. In five subjects where the DBS lead tip traversed area LC, tinnitus loudness in both ears was suppressed to a nadir of level 2 or lower on a 0–10 rating scale. In one subject where the DBS lead was outside area LC, tinnitus was not modulated. In three subjects with preoperative and postoperative audiograms, hearing thresholds were unchanged by area LC stimulation. Neuromodulation of area LC may be interrupting perceptual integration of phantom sensations generated in the central auditory system. This new, basal ganglia based approach to tinnitus modulation warrants further investigation and may be ultimately refined to treat patients with refractory symptoms.

Representation of Binaural Spatial Cues in Field L of the Barn Owl Forebrain

This study examined the representation of spatial information in the barn owl Field L, the first telencephalic processing stage of the classical auditory pathway. Field L units were recorded extracellularly, and their responses to dichotically presented interaural time differences (ITD) and interaural level differences (ILD) were tested. We observed a variety of tuning profiles in Field L. Some sites were not sensitive to ITD or ILD. Other sites, especially those in the high-frequency region, were highly selective for values of ITD and ILD. These sites had multipeaked (commonly called "phase ambiguous") ITD tuning profiles and were tuned for a single value of ILD. The tuning properties of these sites are similar to those seen in the lateral shell of the central nucleus of the inferior colliculus. Although the tuning properties of Field L sites were similar to those observed in the inferior colliculus, the functional organization of this spatial information was fundamentally different. Whereas in the inferior colliculus spatial information is organized into global topographics maps, in Field L spatial information is organized into local clusters, with sites having similar binaural tuning properties grouped together. The representation of binaural cues in Field L suggests that it is involved in auditory space processing but at a lower level of information processing than the auditory archistriatum, a forebrain area that is specialized for processing spatial information, and that the levels of information processing in the forebrain space processing pathway are remarkably similar to those in the well-known midbrain space processing pathway.

Representation of frequency in the primary auditory field of the barn owl forebrain.

1. The primary auditory field (PAF) constitutes the first telencephalic stage of auditory information processing in the classical auditory pathway. In this study we investigated the frequency representation in the PAF of the barn owl, a species with a broad frequency range of hearing and a highly advanced auditory system. 2. Single- and multiunit sites were recorded extracellularly in ketamine-anesthetized owls. The frequency response properties of PAF sites were assessed with the use of digitally synthesized dichotic stimuli. PAF sites (n = 442) either were unresponsive to tonal stimulation (but responsive to noise stimuli), were tuned for frequency, or had multipeaked frequency response profiles. Tuned sites responded best to frequencies between 0.2 and 8.8 kHz, a range that encompasses nearly the entire hearing range of the barn owl. Most sites responding best to frequencies < 4 kHz had relatively broad frequency tuning, whereas sites responding best to higher frequencies had either broad or narrow frequency tuning. Sites with multipeaked frequency response profiles typically had two response peaks. The first peak was usually between 1 and 3 kHz and the second was usually between 5 and 8 kHz; there was no systematic relationship between the two peak frequencies. 3. In dorsoventral electrode penetrations that contained sites with tuned and/or multipeaked response profiles, a "common frequency" was identified that elicited a maximal response from all of the sites in the penetration. 4. The PAF contains a single tonotopic field. Units tuned to low frequencies are located caudomedially, whereas units tuned to high frequencies are located rostrolaterally. Compared with the frequency representation along the basilar papilla and in other auditory structures, the PAF overrepresents low frequencies (< 4 kHz) that are important for barn owl vocalizations. Conversely, high frequencies (> or = 4 kHz), which are necessary for precise sound localization, are underrepresented relative to these more peripheral auditory structures. 5. There was considerable interindividual variability both in the relative magnification of different frequency ranges and in the orientation of the tonotopic map in the brain. 6. These results suggest that the barn owl PAF, like the mammalian primary auditory cortex, is a general processor of auditory information that is involved in the analysis of both the meaning (such as species-specific vocalizations) and the location of auditory stimuli. In addition, the high degree of interindividual variability in the representation of frequency information suggests that the barn owl PAF, like the mammalian auditory cortex, is subject to modification by sensory experience.

Auditory projections from the cochlear nucleus to pontine and mesencephalic reticular nuclei in the rat

We investigated projections from the cochlear nucleus in the rat using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. We focused on nuclei in the brainstem which are not considered to be part of the classical auditory pathway. In addition to labeling in auditory nuclei, we found presumed terminal fibers in 4 pontine and mesencephalic areas: (1) the pontine nucleus (PN), which receives bilateral projections from the antero- and posteroventral cochlear nuclei; (2) the ventrolateral tegmental nucleus (VLTg), which receives a contralateral projection from the rostral portion of the anteroventral cochlear nucleus; (3) the caudal pontine reticular nucleus (PnC), which receives bilateral input originating predominantly in the dorsal cochlear nucleus; and (4) the lateral paragigantocellular nucleus (LPGi), which receives projections from all subdivisions of the cochlear nuclei. In the VLTg and PnC, anterogradely labeled varicose axons were often found in close apposition to the primary dendrites and somata of large reticular neurons. Injections of the retrograde fluorescent tracer Fluoro-Gold into the VLTg demonstrated that the neurons of origin are mainly located contralaterally in the rostral anteroventral cochlear nucleus and in the cochlear root nucleus. The relevance of these auditory projections for short-latency audio-motor behaviors and acoustically elicited autonomic responses is discussed.

聴覚誘発眼輪筋反射に関する電気生理学的研究第2編-中枢神経系の破壊および切断実験-

The pathway of the blink reflex elicited by auditory stimulation was investigated by means of destructions and transections in some parts of the central nervous system. The reflex was recorded as microvibrations of the eyelid (auditory-evoked eyelid microvibration, AMV).1) Bilateral electric lesions in the midbrain reticular formation resulted in a marked re duction or a disappearance of AMV.2) Lesions in the inferior colliculus reduced the amplitude of AMV, while lesions in the medial geniculate body had no effect.3) Temporal suppression of the cerebral cortex by KCI solution did not reduce the amplitude of AMV, but sometimes increased it. The same result was obtained after mechanical destruction including the hippocampus.4) The transecti ons of the brainstem at both the intercollicular and upper medullary level did not affect AMV. On the other hand, AMV disappeared after the transection at the postcollicular level.5) The se results suggest that the reflex pathway of AMV exists between lower midbrain and upper medulla, including the classical auditory pathway, peripheral to the inferior colliculus. AMV has a close relation to the function of the midbrain reticular formation, but does not have a direct relation to the cerebral cortex.6) AMV will be useful in evalua ting the function of the brainstem. Furthermore, MV (photo-evoked eyelid microvibration) is preferable to record in combination, to certify the localization of the lesion in the brainstem.

Progressive changes in auditory response patterns to repeated tone during normal wakefulness and paralysis

1. In a series of 8 cats, electrodes were implanted in the cochlear nucleus, inferior colliculus, and medial geniculate body, pars principalis and pars magnocellularis. Subsequent studies of auditory habituation were carried out in the normal, waking cat and in the same animal during complete neuromuscular paralysis. During each session 200 presentations of a 1.5 sec duration tone were made at 5 sec intervals. Following a brief rest period, 10 additional tones were presented to test for dishabituation. 2. At each site characteristic tone response patterns of multiple unit fast activity were quantitated with frequency integration. Both onset and sustained response components were analyzed for changes during tone repetitions. 3. During acoustic habituation in the normal, walking cat, the cochlear nucleus generally showed a gradual disappearance of the sharp inhibition 70 msec after tone onset and a progressively more accelerated sustained response. Coincidentally, the inferior colliculus and medial geniculate body, pars principalis and magnocellularis, showed increasing inhibition of both onset and sustained response components. These changes were most prominent during the first 50 trials and are believed to reflect, primarily, habituation of acoustic reflex pathways with gradual disappearance of ear muscle contractions and resultant increases in tone intensity. 4. Acoustic habituation of the same cats during reversible neuromuscular paralysis induced a slight decrease or, less frequently, no progressive change in the cochlear nucleus response; concurrently, the inferior colliculus and medial geniculate body, pars principalis and magnocellularis, showed progressively intense inhibition of both onset and sustained response components. These response alterations, which developed at a rather steady rate for the first 100–150 trials, are believed to reflect central mechanisms of decreasing excitation or increasing inhibition. 5. Habituation sessions repeated on consecutive days resulted in progressive auditory response alterations which often became increasingly enhanced from one day to the next. 6. Background fast activity showed no progressive change at any site during the course of a single habituation session or from one session to the next. 7. Prior conclusions that acoustic habituation does not affect sites peripheral to the medial geniculate body may largely reflect the insensitivity of the stimulation and recording procedures utilized, e.g., clicks or tone bursts and evoked potentials. Although increasingly prominent from the peripheral to central nuclei, the progressive changes recorded in this study during acoustic habituation indicate that modulation of auditory input is possible at all subcortical levels of the classical auditory pathway.

Modification of the cortical click-evoked response during eye movement in cats

1. 1. Optokinetic nystagmus was induced in four cats by moving vertical black and white stripes before their eyes. The response to click stimuli triggered by the eye movements was recorded from electrodes chronically implanted along the classical auditory pathway. 2. 2. Computer-averaged click-evoked responses from the cortex declined linearly in amplitude as a function of eye movement velocity; no such relationship existed at subcortical auditory nuclei. 3. 3. Within 15 msec after the onset of eye movement the amplitude of cortical evoked responses was substantially reduced, and at 100 msec, when the velocity of movement was beginning to decline, the depression was at its maximum (50% of control amplitude). 4. 4. Despite their disparate time courses, eye movements and depression of the cortical auditory evoked response are clearly interrelated. Some properties of a central mechanism that could be responsible for this are described.

Effect of attention on evoked responses in the classical auditory pathway.

Hernandez-Peon, Scherrer and Jouvet1 have reported marked decrements in the amplitude of click-evoked responses in the cochlear nucleus in cats attending to stimuli of other sensory modalities. It was argued that this reduction was brought about by efferent inhibition from the brain-stem reticular formation. In a later investigation, Jane, Smirnov and Jasper2 were unable to demonstrate any reduction in evoked potential amplitudes in the medial genicu-late body and the auditory cortex during ‘attention’. In view of these conflicting results, it was decided to examine the effect of the act of ‘attention’ on evoked potentials recorded simultaneously from three levels in the primary auditory pathway of unanaesthetized cats.

Extralemniscal activation of auditory cortex in cats

Unanesthetized cats exhibit a complex pattern of evoked activity at the cortex lasting up to a second or longer following click stimulation to the ear. Transection of the classical auditory pathway at the level of the brachium of the inferior colliculus does not in any significant way alter this pattern of response. Most important, the onset of the response, if affected at all by the section, is delayed only up to 2 or 3 msec. A more medial pathway of prime importance paralleling the classical auditory projection must therefore be postulated. Conduction in this extralemniscal system is completely blocked by deep barbiturate anesthesia while it is left intact by chloralose anesthesia.