Contralateral Auditory Cortex Research Articles

Dorsal dentate gyrus mediated enriched environment-induced anxiolytic and antidepressant effects in cortical infarcted mice

Anxiety and depression are the most common mental health disorders worldwide, each affecting around 30% stroke survivors. These complications not only affect the functional recovery and quality of life in stroke patients, but also are distressing for caregivers. However, effective treatments are still lacking. Enriched environment (EE), characterized with novel and multi-dimensional stimulation, has been reported to exert therapeutic effects on physical and cognitive function. In addition, EE also had potential positive effects on emotional disorders after ischemic stroke; however, the underling mechanisms have not been well elucidated. This study aimed to explore the effectiveness of EE on emotional disorders after cerebral ischemia and its underling mechanism. Sensorimotor cortical infarction was induced by photothrombosis with stable infarct location and volume, resulting in motor dysfunction, anxiety and depression-like behaviors in mice, with decreased ALFF and ReHo values and decreased c-fos expression in the infarction area and adjacent regions. Seven days' EE treatment significantly improved motor function of contralateral forelimb and exhibited anxiolytic and antidepressant effects in infarcted mice. Compared to the mice housing in a standard environment, those subjected to acute EE stimulation had significantly increased ALFF and ReHo values in the bilateral somatosensory cortex (S1, S2), dorsal dentate gyrus (dDG), dorsal CA1 of hippocampus (dCA1), lateral habenular nucleus (LHb), periaqueductal gray (PAG), ipsilateral primary motor cortex (M1), retrosplenial cortex (RSC), parietal association cortex (PtA), dorsal CA3 of hippocampus (dCA3), claustrum (Cl), ventral pallidum (VP), amygdala (Amy), and contralateral auditory cortex (Au). Some of, but not all, the ipsilateral brain regions mentioned above showed accompanying increases in c-fos expression with the most significant changes in the dDG. The number of FosB positive cells in the dDG, decreased in infarcted mice, was significantly increased after chronic EE treatment. Chemogenetic activation of dDG neurons reduced anxiety and depressive-like behaviors in infarcted mice, while neuronal inhibition resulted in void of the anxiolytic and antidepressant effects of EE. Altogether, these findings indicated that dDG neurons may mediate EE-triggered anxiolytic and antidepressant effects in cortical infarcted mice.

Asymmetry in Cortical Thickness of the Heschl's Gyrus in Unilateral Ear Canal Atresia.

Unilateral congenital conductive hearing impairment in ear canal atresia leads to atrophy of the gray matter of the contralateral primary auditory cortex or changes in asymmetry pattern if left untreated in childhood. Unilateral ear canal atresia with associated severe conductive hearing loss results in deteriorated sound localization and difficulties in understanding of speech in a noisy environment. Cortical atrophy in the Heschl's gyrus has been reported in acquired sensorineural hearing loss but has not been studied in unilateral conductive hearing loss. We obtained T1w and T2w FLAIR MRI data from 17 subjects with unilateral congenital ear canal atresia and 17 matched controls. Gray matter volume and thickness were measured in the Heschl's gyrus using Freesurfer. In unilateral congenital ear canal atresia, Heschl's gyrus exhibited cortical thickness asymmetry (right thicker than left, corrected p = 0.0012, mean difference 0.25 mm), while controls had symmetric findings. Gray matter volume and total thickness did not differ from controls with normal hearing. We observed cortical thickness asymmetry in congenital unilateral ear canal atresia but no evidence of contralateral cortex atrophy. Further research is needed to understand the implications of this asymmetry on central auditory processing deficits.

Emotional sounds in space: asymmetrical representation within early-stage auditory areas.

Evidence from behavioral studies suggests that the spatial origin of sounds may influence the perception of emotional valence. Using 7T fMRI we have investigated the impact of the categories of sound (vocalizations; non-vocalizations), emotional valence (positive, neutral, negative) and spatial origin (left, center, right) on the encoding in early-stage auditory areas and in the voice area. The combination of these different characteristics resulted in a total of 18 conditions (2 categories x 3 valences x 3 lateralizations), which were presented in a pseudo-randomized order in blocks of 11 different sounds (of the same condition) in 12 distinct runs of 6 min. In addition, two localizers, i.e., tonotopy mapping; human vocalizations, were used to define regions of interest. A three-way repeated measure ANOVA on the BOLD responses revealed bilateral significant effects and interactions in the primary auditory cortex, the lateral early-stage auditory areas, and the voice area. Positive vocalizations presented on the left side yielded greater activity in the ipsilateral and contralateral primary auditory cortex than did neutral or negative vocalizations or any other stimuli at any of the three positions. Right, but not left area L3 responded more strongly to (i) positive vocalizations presented ipsi- or contralaterally than to neutral or negative vocalizations presented at the same positions; and (ii) to neutral than positive or negative non-vocalizations presented contralaterally. Furthermore, comparison with a previous study indicates that spatial cues may render emotional valence more salient within the early-stage auditory areas.

Ipsilateral auditory cortex responses to the intact ear after unilateral noise trauma in juvenile rats

BackgroundWhile ear stimulation produces a robust response in the contralateral auditory cortex (AC), it produces only a weak response in the ipsilateral AC, known as interhemispheric asymmetry. Unilateral deafness can lead to AC plastic changes, resulting in reduced interhemispheric asymmetry and auditory perceptual consequences. However, the unilateral hearing loss-associated plastic changes are far from fully understood. The purpose of this study was to investigate AC responses to the ipsilateral unimpaired ear after noise injury to the contralateral ear in juvenile rats. MethodsRats (50 days) were monaurally exposed to an intense noise (10.0-12.5 kHz, 126 dB SPL) for 2 hours. The unexposed ear-induced ipsilateral AC responses were recorded 2 days and 4 months after exposure and compared between groups. ResultsThe noise exposure resulted in complete hearing loss in the exposed ear, but normal function in the other. Two days after exposure, the ipsilateral AC response induced by the intact ear was significantly enhanced and the threshold decreased (the early-onset effect). Four months after noise exposure, in addition to the increased response amplitude, the “slow-increasing” firing pattern of the neurons in the ipsilateral AC turned into the contralateral-AC-response-like “sharp-increasing” pattern (the late-onset effect) with shortened response latency. DiscussionThe early-onset effect can result from release of inhibition due to decreased contralateral input, while the late-onset effect may imply the formation of direct connections in the ipsilateral auditory pathway. The enhanced AC response may help maintain loudness perception and monaural sound localization after unilateral deafness.

Corticofugal VIP Gabaergic Projection Neurons in the Mouse Auditory and Motor Cortex.

Anatomical and physiological studies have described the cortex as a six-layer structure that receives, elaborates, and sends out information exclusively as excitatory output to cortical and subcortical regions. This concept has increasingly been challenged by several anatomical and functional studies that showed that direct inhibitory cortical outputs are also a common feature of the sensory and motor cortices. Similar to their excitatory counterparts, subsets of Somatostatin- and Parvalbumin-expressing neurons have been shown to innervate distal targets like the sensory and motor striatum and the contralateral cortex. However, no evidence of long-range VIP-expressing neurons, the third major class of GABAergic cortical inhibitory neurons, has been shown in such cortical regions. Here, using anatomical anterograde and retrograde viral tracing, we tested the hypothesis that VIP-expressing neurons of the mouse auditory and motor cortices can also send long-range projections to cortical and subcortical areas. We were able to demonstrate, for the first time, that VIP-expressing neurons of the auditory cortex can reach not only the contralateral auditory cortex and the ipsilateral striatum and amygdala, as shown for Somatostatin- and Parvalbumin-expressing long-range neurons, but also the medial geniculate body and both superior and inferior colliculus. We also demonstrate that VIP-expressing neurons of the motor cortex send long-range GABAergic projections to the dorsal striatum and contralateral cortex. Because of its presence in two such disparate cortical areas, this would suggest that the long-range VIP projection is likely a general feature of the cortex’s network.

Local versus long-range connectivity patterns of auditory disturbance in schizophrenia

Auditory hallucinations are a debilitating symptom of schizophrenia. Effective treatment is limited because the underlying neural mechanisms remain unknown. Our study investigates how local and long-range functional connectivity is associated with auditory perceptual disturbances (APD) in schizophrenia. APD was assessed using the Auditory Perceptual Trait and State Scale. Resting state fMRI data were collected for N=99 patients with schizophrenia. Local functional connectivity was estimated using regional homogeneity (ReHo) analysis; long-range connectivity was estimated using resting state functional connectivity (rsFC) analysis. Mediation analyses tested whether local (ReHo) connectivity significantly mediated associations between long-distance rsFC and APD. Severity of APD was significantly associated with reduced ReHo in left and right putamen, left temporoparietal junction (TPJ), and right hippocampus-pallidum. Higher APD was also associated with reduced rsFC between the right putamen and the contralateral putamen and auditory cortex. Local and long-distance connectivity measures together explained 40.3% of variance in APD (P < 0.001), with the strongest predictor being the left TPJ ReHo (P < 0.001). Additionally, TPJ ReHo significantly mediated the relationship between right putamen – left putamen rsFC and APD (Sobel test, P = 0.001). Our findings suggest that both local and long-range functional connectivity deficits contribute to APD, emphasizing the role of striatum and auditory cortex. Considering the translational impact of these circuit-based findings within the context of prior clinical trials to treat auditory hallucinations, we propose a model in which correction of both local and long-distance functional connectivity deficits may be necessary to treat auditory hallucinations.

Consistent and chronic cochlear implant use partially reverses cortical effects of single sided deafness in children

Potentially neuroprotective effects of CI use were studied in 22 children with single sided deafness (SSD). Auditory-evoked EEG confirmed strengthened representation of the intact ear in the ipsilateral auditory cortex at initial CI activation in children with early-onset SSD (n = 15) and late-onset SSD occurring suddenly in later childhood/adolescence (n = 7). In early-onset SSD, representation of the hearing ear decreased with chronic CI experience and expected lateralization to the contralateral auditory cortex from the CI increased with longer daily CI use. In late-onset SSD, abnormally high activity from the intact ear in the ipsilateral cortex reduced, but responses from the deaf ear weakened despite CI use. Results suggest that: (1) cortical reorganization driven by unilateral hearing can occur throughout childhood; (2) chronic and consistent CI use can partially reverse these effects; and (3) CI use may not protect children with late-onset SSD from ongoing deterioration of pathways from the deaf ear.

Irrelevant Predictions: Distractor Rhythmicity Modulates Neural Encoding in Auditory Cortex.

Dynamic attending theory suggests that predicting the timing of upcoming sounds can assist in focusing attention toward them. However, whether similar predictive processes are also applied to background noises and assist in guiding attention "away" from potential distractors, remains an open question. Here we address this question by manipulating the temporal predictability of distractor sounds in a dichotic listening selective attention task. We tested the influence of distractors' temporal predictability on performance and on the neural encoding of sounds, by comparing the effects of Rhythmic versus Nonrhythmic distractors. Using magnetoencephalography we found that, indeed, the neural responses to both attended and distractor sounds were affected by distractors' rhythmicity. Baseline activity preceding the onset of Rhythmic distractor sounds was enhanced relative to nonrhythmic distractor sounds, and sensory response to them was suppressed. Moreover, detection of nonmasked targets improved when distractors were Rhythmic, an effect accompanied by stronger lateralization of the neural responses to attended sounds to contralateral auditory cortex. These combined behavioral and neural results suggest that not only are temporal predictions formed for task-irrelevant sounds, but that these predictions bear functional significance for promoting selective attention and reducing distractibility.

O2.1. LOCAL AND LONG-RANGE CONNECTIVITY PATTERNS OF AUDITORY PERCEPTUAL DISTURBANCE IN SCHIZOPHRENIA

BackgroundAuditory hallucinations are a prevalent, debilitating symptom of schizophrenia (Sz). Lack of detailed phenomenological assessments of perceptual disturbances in large psychiatric imaging datasets limits our ability to disentangle the underlying neural mechanisms of hallucinations. Our study investigates how changes in local functional communication dynamics may be associated with wide-ranging auditory disturbances in Sz.MethodsLocal functional connectivity was estimated using regional homogeneity (ReHo) analysis of resting fMRI data, which quantifies synchronization of fMRI activity of a voxel to its neighboring voxels. Resting fMRI data of 99 Sz patients was analyzed (mean age=36.2±13.3 y, sex=71/28 m/f); Auditory perceptual disturbance in the past week was estimated using the auditory perception state (APS) subscale score of the recently validated Auditory Perceptual Trait and State Scale (http://www.mdbrain.org/APTS.pdf). Voxelwise regression analysis of ReHo was performed including APS score as a regressor of interest. Significant results were thresholded using AFNI’s 3dClustSim with autocorrelation function option to yield corrected p<0.05, corresponding to cluster-size threshold of 49 voxels at voxelwise p=0.001.ResultsHigher APS scores were associated with reduced ReHo in clusters in left putamen, right putamen, left temporoparietal junction, and right hippocampus. In a follow-up analysis using these clusters as seeds in whole-brain resting-state functional connectivity analysis (rsFC) analysis, higher APS scores were significantly associated with reduced rsFC between the right putamen seed and clusters in the contralateral putamen and auditory cortex.DiscussionOur findings are consistent with those of a prior study that reported abnormal ReHo in left and right putamen of a unmedicated first-episode Sz patients (Cui et al. 2016). However, in that small sample (n=32), striatal ReHo was elevated relative to controls, and AH severity was not significantly correlated with striatal ReHo measures. Our study investigated ReHo in a large sample of chronic, medicated patients (all except 4 were taking antipsychotic medication at time of study). While it is widely accepted that striatal signaling is disrupted in Sz, future work is needed to better understand how striatal signaling deficits may change over the course of illness and how this relates to particular symptoms such as hallucinations. Implications for development of novel therapies that account for these nuanced findings will be discussed.

T159. Hemispheric difference in temporal perception between 40- and 80-Hz auditory steady-state responses: MEG and ECoG studies

Auditory steady-state responses (ASSRs) underlie the temporal integration of the auditory cortex (AC). However, the hemispheric asymmetry of the temporal integration has not yet been systematically studied because most of studies adopted binaural stimulation to record ASSRs. Although 40-Hz ASSRs are considered as a potential biomarker for various psychiatric diseases, physiological implications of 80-Hz ASSRs have not been well understood due to their weak EEG responses. Currently, 80-Hz oscillations are reported to be brain stem origin. Thus, we studied the functional difference between 40-Hz and 80-Hz ASSRs with monaural presentation measured by MEG and ECoG in order to clarify the hemispheric lateralization of temporal integration. MEGs were recorded from 14 healthy subjects (aged 20–46 years). The trains of clicks for 40 Hz or 80 Hz with 500 ms duration were presented 200 times monaurally with inter-train interval of 500 ms. ASSRs consisted of transient onset and offset responses intermixed with induced oscillations. The amplitudes and peak latencies of transient responses were analyzed after applying 5 to 30 Hz bandpass filter. In contrast, the induced oscillations were time-frequency analyzed in the frequency range of 40 Hz (35–45 Hz) and 80 Hz (75–85 Hz). Then, they were evaluated by the phase locking factor. In four patients with localization-related epilepsy who underwent ECoG, ASSRs were recorded to elucidate the neural sources of 80-Hz oscillations. Both the onset and offset responses were well delineated in the 80-Hz condition compared with those of 40 Hz. The onset responses were recorded in the bilateral ACs without asymmetry while the offset responses were significantly larger in the right AC by left ear stimulation. 40-Hz oscillations were induced mainly in the contralateral AC in the 40-Hz condition, while 80 Hz oscillations showed right hemispheric predominance in the 80-Hz condition irrespective of the stimulated ear. In ECoG recordings, the 80-Hz stimulation revealed clear 80 Hz oscillations in the bilateral ACs. The offset responses by 80-Hz stimulation were clearly obtained in the right AC. The 80-Hz oscillations showed the right hemispheric predominance while those of 40-Hz were recorded mainly in the contralateral AC. The discrimination among single sounds is an important part of the perceptual process. The auditory perception to 80-Hz (12.5 ms) stimulation is considered as “continuous sound”, while that to 40-Hz (25 ms) stimulation as “periodic sound”. Our findings suggest that the former is processed in the right AC whereas the latter in the contralateral AC. Our results are consistent with behavioral studies that separation time of 20–30 ms is required to distinguish sequences of auditory events and that the inflection point of amplitude modulation detection is about 50 Hz. Our findings also endorse use of 80-Hz ASSRs for the basic and clinical researches in temporal perception.

The role of auditory cortex in the spatial ventriloquism aftereffect

Cross-modal recalibration allows the brain to maintain coherent sensory representations of the world. Using functional magnetic resonance imaging (fMRI), the present study aimed at identifying the neural mechanisms underlying recalibration in an audiovisual ventriloquism aftereffect paradigm. Participants performed a unimodal sound localization task, before and after they were exposed to adaptation blocks, in which sounds were paired with spatially disparate visual stimuli offset by 14° to the right. Behavioral results showed a significant rightward shift in sound localization following adaptation, indicating a ventriloquism aftereffect. Regarding fMRI results, left and right planum temporale (lPT/rPT) were found to respond more to contralateral sounds than to central sounds at pretest. Contrasting posttest with pretest blocks revealed significantly enhanced fMRI-signals in space-sensitive lPT after adaptation, matching the behavioral rightward shift in sound localization. Moreover, a region-of-interest analysis in lPT/rPT revealed that the lPT activity correlated positively with the localization shift for right-side sounds, whereas rPT activity correlated negatively with the localization shift for left-side and central sounds. Finally, using functional connectivity analysis, we observed enhanced coupling of the lPT with left and right inferior parietal areas as well as left motor regions following adaptation and a decoupling of lPT/rPT with contralateral auditory cortex, which scaled with participants’ degree of adaptation. Together, the fMRI results suggest that cross-modal spatial recalibration is accomplished by an adjustment of unisensory representations in low-level auditory cortex. Such persistent adjustments of low-level sensory representations seem to be mediated by the interplay with higher-level spatial representations in parietal cortex.

Simultaneous bilateral cochlear implants: Developmental advances do not yet achieve normal cortical processing.

BackgroundSimultaneous bilateral cochlear implantation promotes symmetric development of bilateral auditory pathways but binaural hearing remains abnormal. To evaluate whether bilateral cortical processing remains impaired in such children, cortical activity to unilateral and bilateral stimuli was assessed in a unique cohort of 16 children who received bilateral cochlear implants (CIs) simultaneously at 1.97 ± 0.86 years of age and had ~4 years of CI experience, providing the first opportunity to assess electrically driven cortical development in the absence of reorganized asymmetries from sequential implantation.MethodsCortical activity to unilateral and bilateral stimuli was measured using multichannel electro‐encephalography. Cortical processing in children with bilateral CIs was compared with click‐elicited activity in 13 normal hearing children matched for time‐in‐sound. Source activity was localized using the Time Restricted, Artefact and Coherence source Suppression (TRACS) beamformer method.ResultsConsistent with dominant crossed auditory pathways, normal P1 activity (~100 ms) was weaker to ipsilateral stimuli relative to contralateral and bilateral stimuli and both auditory cortices preferentially responded to the contralateral ear. Right hemisphere dominance was evident overall. Children with bilateral CIs maintained the expected right dominance but differences from normal included: (i) minimal changes between ipsilateral, contralateral and bilateral stimuli, (ii) weaker than normal contralateral stimulus preference, (iii) symmetric activity to bilateral stimuli, and (iv) increased occipital lobe recruitment during bilateral relative to unilateral stimulation. Between‐group contrasts demonstrated lower than normal activity in the inferior parieto‐occipital lobe (suggesting deficits in sensory integration) and greater than normal left frontal lobe activity (suggesting increased attention), even during passive listening.ConclusionsTogether, findings suggest that early simultaneous bilateral cochlear implantation promotes normal‐like auditory symmetry but that abnormalities in cortical processing consequent to deafness and/or electrical stimulation through two independent speech processors persist.

Temporal Cortical Plasticity in Single-Sided Deafness: A Functional Imaging Study.

To refine and extend the knowledge on cortical plasticity in single-sided deafness (SSD) by assessing magnetoencephalographic imaging in a well-defined group of subjects. SSD causes difficulties with directional hearing, signal extraction in noise, and multispeaker identification and separation. In SSD, the ipsilateral auditory cortex is never powerfully driven by sound, which may lead to plastic change and contribute to higher-order psychoacoustic dysfunction beyond loss of a peripheral sound sensor. A cross-sectional study on 12 subjects with long-term, adult-onset, nontraumatic SSD and 12 normal-hearing controls was conducted using magnetoencephalographic imaging, magnetic resonance imaging, and validated hearing instruments. Pure-tone stimuli at five frequencies were presented to each hearing ear individually. M100 activation peak times of the ipsilateral and contralateral auditory cortices were analyzed. Controls showed an M100 interhemispheric mean latency difference of 6.6 milliseconds. In contrast, subjects with SSD exhibited a mean of 1.7 milliseconds. This loss of interhemispheric latency difference was statistically significant (p < 0.05, analysis of variance with repeated measures). SSD subjects confirmed degraded hearing function on both Hearing Handicap Inventory for Adults (p < 0.001) and Speech, Spatial, and Qualities of Hearing Scale instruments (p < 0.001). SSD disrupts M100 latency difference between the two hemispheres to sound stimulation. This finding may represent maladaptive temporal cortical plasticity because of loss of a peripheral sensor. Based on this premise, a new generation of neurophysiologically inspired auditory treatments to correct or mitigate central consequences of SSD may be considered to optimize hearing in individuals with only one functional ear.

Cell-Specific Activity-Dependent Fractionation of Layer 2/3→5B Excitatory Signaling in Mouse Auditory Cortex

Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input-output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3→corticocollicular and L2/3→corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3→corticocollicular connections, but substantial depression in L2/3→corticocallosal connections. Synaptic potentials in L2/3→corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3→corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input-output functions.

Stimulus dependence of contralateral dominance in human auditory cortex.

The auditory system is often considered to show little contralateral dominance but physiological reports on the contralateral dominance of activity evoked by monaural sound vary widely. Here, we show that part of this variation is stimulus-dependent: blood oxygen level dependent (BOLD) responses to 32 s of monaurally presented unmodulated noise (UN) showed activation in contralateral auditory cortex (AC) and deactivation in ipsilateral AC compared to nonstimulus baseline. Slow amplitude-modulated (AM) noise evoked strong contralateral activation and minimal ipsilateral activation. The contrast of AM-versus-UN was used to separate fMRI activity related to the slow amplitude modulation per se. This difference activation was bilateral although still stronger in contralateral AC. In magnetoencephalography (MEG), the response was dominated by the steady-state activity phase locked to the amplitude modulation. This MEG activity showed no consistent contralateral dominance across listeners. Subcortical BOLD activation was strongly contralateral subsequent to the superior olivary complex (SOC) and showed no significant difference between modulated and UN. An acallosal participant showed similar fMRI activation as the group, ruling transcallosal transmission an unlikely source of ipsilateral enhancement or ipsilateral deactivation. These results suggest that ascending activity subsequent to the SOC is strongly dominant contralateral to the stimulus ear. In contrast, the part of BOLD and MEG activity related to slow amplitude modulation is more bilateral and only observed in AC. Ipsilateral deactivation can potentially bias measures of contralateral BOLD dominance and should be considered in future studies.

Sensory cortex lesion triggers compensatory neuronal plasticity

BackgroundLesions to the human brain often cause dramatic impairments in the life of patients because of the very limited capacity of the mammalian nervous system to regenerate. On the other hand, neuronal tissue has a high capacity to reorganize itself so that loss of function due to brain damage may be compensated through neuroplastic reorganization of undamaged tissue in brain regions adjacent or contralateral to the lesion site. In this study we investigated the effect of serial lesions of the auditory cortices (AC) in both hemispheres of Mongolian gerbils on discrimination performance for fast amplitude modulated tones (AM). Healthy animals were trained to discriminate two fast AM, an ability that has previously been shown to critically depend on cortical processing. Their ability to maintain significant discrimination performance was retested after unilateral AC lesion, and again after lesion of the contralateral AC, with 15 days of continuing training in between the two lesions.ResultsAfter bilateral cortical ablation of both AC and 45 days of training the animals show no change in pure tone detection threshold as measured with modulation of the acoustic startle reflex which has been shown to rely on subcortical structures. In contrast to simultaneous bilateral ablation of AC that results in complete loss of AM discrimination ability in this paradigm we found compensatory plasticity that seems to be triggered by unilateral cortical ablation with subsequent training and that is able to almost fully compensate for the lost cortical functions.ConclusionsOur results demonstrate that AM discrimination ability that normally depends on AC may be transferred to other brain regions when the brain has time to activate compensatory plasticity between the lesions of the two AC hemispheres. For this process to take place obviously one intact AC hemisphere is needed. This finding may open perspectives for new therapeutic strategies that may alleviate the impairments after multiple ischemic strokes.

Measuring auditory selective attention using frequency tagging

Frequency tagging of sensory inputs (presenting stimuli that fluctuate periodically at rates to which the cortex can phase lock) has been used to study attentional modulation of neural responses to inputs in different sensory modalities. For visual inputs, the visual steady-state response (VSSR) at the frequency modulating an attended object is enhanced, while the VSSR to a distracting object is suppressed. In contrast, the effect of attention on the auditory steady-state response (ASSR) is inconsistent across studies. However, most auditory studies analyzed results at the sensor level or used only a small number of equivalent current dipoles to fit cortical responses. In addition, most studies of auditory spatial attention used dichotic stimuli (independent signals at the ears) rather than more natural, binaural stimuli. Here, we asked whether these methodological choices help explain discrepant results. Listeners attended to one of two competing speech streams, one simulated from the left and one from the right, that were modulated at different frequencies. Using distributed source modeling of magnetoencephalography results, we estimate how spatially directed attention modulates the ASSR in neural regions across the whole brain. Attention enhances the ASSR power at the frequency of the attended stream in contralateral auditory cortex. The attended-stream modulation frequency also drives phase-locked responses in the left (but not right) precentral sulcus (lPCS), a region implicated in control of eye gaze and visual spatial attention. Importantly, this region shows no phase locking to the distracting stream. Results suggest that the lPCS in engaged in an attention-specific manner. Modeling results that take account of the geometry and phases of the cortical sources phase locked to the two streams (including hemispheric asymmetry of lPCS activity) help to explain why past ASSR studies of auditory spatial attention yield seemingly contradictory results.

Effects of Core Auditory Cortex Deactivation on Neuronal Response to Simple and Complex Acoustic Signals in the Contralateral Anterior Auditory Field

Interhemispheric communication has been implicated in various functions of sensory signal processing and perception. Despite ample evidence demonstrating this phenomenon in the visual and somatosensory systems, to date, limited functional assessment of transcallosal transmission during periods of acoustic signal exposure has hindered our understanding of the role of interhemispheric connections between auditory cortical fields. Consequently, the present investigation examines the impact of core auditory cortical field deactivation on response properties of contralateral anterior auditory field (AAF) neurons in the felis catus. Single-unit responses to simple and complex acoustic signals were measured across AAF before, during, and after individual and combined cooling deactivation of contralateral primary auditory cortex (A1) and AAF neurons. Data analyses revealed that on average: 1) interhemispheric projections from core auditory areas to contralateral AAF neurons are predominantly excitatory, 2) changes in response strength vary based on acoustic features, 3) A1 and AAF projections can modulate AAF activity differently, 4) decreases in response strength are not specific to particular cortical laminae, and 5) contralateral inputs modulate AAF neuronal response thresholds. Collectively, these observations demonstrate that A1 and AAF neurons predominantly modulate AAF response properties via excitatory projections.

Comparison of the outcomes of repetitive transcranial magnetic stimulation to the ipsilateral and contralateral auditory cortex in unilateral tinnitus

Transcranial magnetic stimulation (TMS) is a noninvasive method of activating or deactivating focal areas of the human brain. Repetitive TMS (rTMS) applied over the temporoparietal cortex has been reported to show therapeutic effects on tinnitus. We compared the effects of 1 Hz rTMS delivered either contralaterally or ipsilaterally to the symptomatic ear in patients with unilateral tinnitus. Forty patients with asymmetric hearing loss and non-pulsatile tinnitus localized to poorer ear of 6 months in duration or greater who were refractory to medication were enrolled in this study. Patients were assigned randomly to one of two treatment groups: with 1 Hz stimulation applied the temporoparietal junction either ipsilaterally (n = 21) or contralaterally (n = 19) to the symptomatic ear. The patients were given 600 pulses per session daily for 5 d. Changes in the tinnitus handicap inventory (THI) and self-rating visual analog scores (VAS) for loudness, awareness and annoyance were analyzed before, immediately after and 1 month after treatment. There was no significant difference in the rate of patients with marked improvement between ipsilateral and contralateral stimulation groups. In addition, there were no significant differences in the amount of decreases in THI scores and VAS between the two groups immediately or 1 month after rTMS. Finally, significant decreases in THI scores and most VAS were observed 1 month after rTMS in both groups compared to pretreatment. Daily treatment with 1 Hz rTMS ipsilaterally and contralaterally to the side of tinnitus both had significant beneficial effects. The laterality of stimulation with 1 Hz rTMS is not the decisive factor in relieving symptoms.

Mapping interhemispheric connectivity using functional MRI after transcranial magnetic stimulation on the human auditory cortex

Interhemispheric interactions can be important in transcranial magnetic stimulation (TMS) studies investigating motor or cognitive brain functions, but their role in predicting the outcome of TMS is not clear. Previously, we showed that individual differences in interhemispheric functional connectivity of auditory cortices influenced the behavioral effect of repetitive TMS (rTMS) applied over auditory cortex in a melody discrimination task. Here, functional magnetic resonance imaging (fMRI) scanning with the same task was carried out before and after rTMS applied over auditory cortex to determine how rTMS affects both behavior and neural function. After rTMS applied over the right auditory cortex, we found mean increases in activation in the contralateral auditory cortex. The degree and direction of modulation of the fMRI response were correlated with behavior: the higher the contralateral increase after stimulation, the faster the response times, whereas individuals with reduced contralateral activity showed no behavioral facilitation. We also found that higher interhemispheric connectivity between auditory cortices before TMS was associated with faster response times. This study shows directly the role of functional connectivity in the auditory network on TMS-induced modulation, which could explain its often variable effects on behavior. Combined TMS and fMRI is particularly useful to promote plastic reorganization in the auditory network and has implications for research on auditory-related disorders.