Acoustic trauma-induced auditory cortex enhancement and tinnitus

There is growing evidence suggests that noise-induced cochlear damage may lead to hyperexcitability in the central auditory system(CAS)which may give rise to tinnitus.However,the correlation between the onset of the neurophysiological changes in the CAS and the onset of tinnitus has not been well studied.To investigate this relationship,chronic electrodes were implanted into the auditory cortex(AC) and sound evoked activities were measured from awake rats before and after noise exposure.The auditory brainstem response(ABR) was used to assess the degree of noise-induced hearing loss.Tinnitus was evaluated by measuring gap-induced prepulse inhibition(gap-PPI).Rats were exposed monaurally to a high-intensity narrowband noise centered at 12 kHz at a level of 120 dB SPL for 1 h.After the noise exposure,all the rats developed either permanent(>2 weeks) or temporary(<3 days) hearing loss in the exposed ear(s).The AC amplitudes increased significantly 4 h after the noise exposure.Most of the exposed rats also showed decreased gap-PPI.The post-exposure AC enhancement showed a positive correlation with the amount of hearing loss.The onset of tinnitus-like behavior was happened after the onset of AC enhancement.

BOLD-fMRI study of auditory cortex in patients with tinnitus

Objective Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was used to study activation signals in the brain cortex evoked by tone stimulation in patients with tinnitus for its potential utility as an objective indicator of tinnitus. Methods BOLD-fMRI examination was conducted in 7 patients with chronic tinnitus and 15 control subjects. The activation signal in the brain cortex was recorded. Results Significant activation was found in temporal lobe in control subjects, with greater signal volume and intensity on the contralateral than ipsilateral auditory cortex (P < 0.01). However, there was no discernable patterns in the anatomical location, volume and intensity of cortical activation signals in patients with chronic tinnitus. Conclusions Patients with chronic tinnitus may have abnormal neural activities in the auditory cortex.

Neural correlates of the Heidelberg Music Therapy: indicators for the regeneration of auditory cortex in tinnitus patients?

Tinnitus, the phenomenon of ringing or buzzing in the ears without an external sound source is one of the most commonly reported symptoms in otorhinolaryngology and affects 10 - 15% of the general population. Models have been developed to account for neural basis of tinnitus, its pathogenesis and its consequences on mental health （deRidder et al., 2013）. In most cases tinnitus onset follows a partial hearing impairment. Peripheral sensory deprivation due to cochlear damages may prompt increased neuronal activity in the central auditory system in order to adapt the neural sensitivity to the reduced sensory inputs. This central gain could over amplify the ＂neural noise＂ and thus trigger a homeostatic down-regulation of inhib- itory synapses in the auditory cortical map leading to specific reorganization of the cortical representation of the tinnitus percept. Dysfunctional feedback connections from limbic regions to auditory brain areas, interacting at the thalamic level, may account for the psychological impairment.

The thalamic-primary auditory cortex circuit: a pathway to resilience in the face of stress and a potential target for depression treatment

Major depressive disorder(MDD),characterized by anhedonia,loss of motivation,behavioral despair,and cognitive abnormalities[1],stands as the second leading cause of disability worldwide[2]owing to its heightened prevalence,suicide rates,and recurrence[3].Empirical evidence and clinical observations have substantiated the notion that patients with MDD often exhibit compromised auditory perception[4].

Regional glucose metabolic increases in left auditory cortex in tinnitus patie nts: a preliminary study with positron emission tomography

Objective To investigate the relationship between tinnitus and glucose metabolism in auditory cortex and whether positron emission tomography (PET) can be an objective tool in measuring tinnitus.Methods Eleven right-handed patients with severe tinnitus and ten right-handed control subjects participated in the 18 F-FDG/PET study. Analysis with regions of interests was used to calculate asymmetry indices according to the formula: ［(L-R)×100/［(L+R)÷2］］.Results Glucose metabolism in the auditory cortex of tinnitus patients was asymmetric between the left and right auditory cortices, with that of the left being much higher than that of the right. The asymmetry indices of tinnitus patients was significantly higher than that of the control group (unpaired t test, P<0.001). This revealed that the increased metabolic activity was present in the predominant left hemisphere with a significant focus on the superior and transverse temporal gyri (Brodmann areas 41 and 42, respectively corresponding to primary and secondary auditory cortex), and the results were independent of the subjective localization of the tinnitus sensation.Conclusion It is suggested that the increased metabolism in the left auditory cortex is related to the tinnitus sensation. PET is capable of providing objective evidence for tinnitus and may be used as a potential tool in measuring tinnitus.

Auditory cortical stimulability in non habilitated individuals-An evidence from CAEPs

Objective:The effect of long term auditory deprivation on Cortical Auditory Evoked Potentials(CAEPs)especially in human models is not well explored.Hence,the current study was aimed to investigate the effects of long-term auditory deprivation and stimulability of auditory cortex in non habilitated congenitally deaf adolescents and adults using CAEPs.Methods and Results:A total of 27 non-habilitated congenitally deaf adolescents/adults with age and gender matched normal hearing adolescents/adults participated in the study.The congenitally deaf group was fitted with high gain hearing aids(first fit).Further,the CAEPs were recorded.The obtained CAEP components were assessed for group effect,source and topographical differences.The between group analysis for CAEP responses showed a significant difference only for P2 latency and amplitude.The source analysis revealed that,in the normal hearing group for CAEPs,the sources were within the temporal regions.However,in the congenitally deaf group,along with the temporal cortex,the bilateral prefrontal cortex also was activated.Conclusion:The findings revealed that it is possible to stimulate and evoke a matured CAEP response from a long deprived auditory system with adequate acoustic stimulation.The presence of CAEP responses is indicative of the functionality of the innate auditory pathway and the crossmodal plasticity in long auditory deprived individuals.

Role of the caudate-putamen nucleus in sensory gating in induced tinnitus in rats

Tinnitus can be described as the conscious perception of sound without external stimulation,and it is often accompanied by anxiety,depression,and insomnia.Current clinical treatments for tinnitus are ineffective.Although recent studies have indicated that the caudateputamen nucleus may be a sensory gating area involved in noise elimination in tinnitus,the underlying mechanisms of this disorder are yet to be determined.To investigate the potential role of the caudate-putamen nucleus in experimentally induced tinnitus,we created a rat model of tinnitus induced by intraperitoneal administration of 350 mg/kg sodium salicylate.Our results revealed that the mean spontaneous firing rate of the caudate-putamen nucleus was increased by sodium salicylate treatment,while dopamine levels were decreased.In addition,electrical stimulation of the caudate-putamen nucleus markedly reduced the spontaneous firing rate of neurons in the primary auditory cortex.These findings suggest that the caudate-putamen nucleus plays a sensory gating role in sodium salicylate-induced tinnitus.This study was approved by the Institutional Animal Care and Use Committee of Peking University Health Science Center(approval No.A2010031)on December 6,2017.

Auditory cortical responses evoked by pure tones in healthy and sensorineural hearing loss subjects： functional MRI and magnetoencephalography

Background Blood oxygen level dependent functional magnetic resonance imaging （fMRI） and magnetoencephalography are new techniques of brain functional imaging which can provide the information of excitation of neurons by measure the changes of hemodynamics and electrophysiological data of local brain tissue. The purpose of this study was to study functional brain areas evoked by pure tones in healthy and sensorineural hearing loss subjects with these techniques and to compare the differences between the two groups. Methods Thirty healthy and 30 sensorineural hearing loss subjects were included in this study. In fMRI, block-design paradigm was used. During the active epoch the participants listened to 1000 Hz, sound pressure level 140 dB pure tones at duration 500 ms, interstimulus interval 1000 ms, which presented continuously via a magnetic resonance-compatible audio system. None stimulus was executed in control epoch. In magnetoencephalography study, every subject received stimuli of 1000 Hz tone bursts delivered to the bilateral ear at duration 8 ms, interstimulus intervals 1000 ms. Sound pressure level in healthy subjects was 30 dB; in sensorineural hearing loss subjects was 20 dB above everyone＇ s hearing threshold respectively. All subjects were examined with 306-channel whole-scalp neuromagnetometer. Results In fMRI, all subjects showed significant activations in bilateral Heschl＇s gyri, anterior pole of planum temporale, planum temporale, precentral gyri, postcentral gyri, supramarginal gyri, superior temporal gyri, inferior frontal gyri, occipital lobes and cerebellums. The healthy subjects had more intensive activation in bilateral Heschl＇s gyri, anterior pole of planum temporale, inferior frontal gyri, left superior temporal gyri and right planum temporale than the hearing loss subjects. But in precentral gyri, postcentral gyri and occipital lobes, the activation is more intensive in the hearing loss subjects. In magnetoencephalography study, both in the hearing loss and the healthy subjects, the most evident audio evoked fields activated by pure tone were N100m, which located precisely on the Heschl＇s gyrus. Compared with the hearing loss subjects, N100m of the healthy subjects was stronger and had longer latencies in right hemisphere. Conclusions Under proper pure tone stimulus the activation of auditory cortex can be elicited both in the healthy and the sensorineural hearing loss subjects. Either at objective equivalent stimuli or at subjectively perceived equivalent stimuli, the auditory responses were more intensive in healthy subjects than hearing loss subjects. The tone stimuli were processed in a network in human brain and there was an intrinsic relation between the auditory and visual cortex. Blood oxygen level dependent fMRI and magnetoencephalography could reinforce each other.

Effect of Neuronal Excitability in Hippocampal CA1 Area on Auditory Pathway in a Rat Model of Tinnitus

Background： Tinnitus is a common disorder that causes significant morbidity; however, the neurophysiological mechanism is not yet fully understood. A relationship between tinnitus and limbic system has been reported. As a significant component of the l imbic system, the hippocampus plays an important role in various pathological processes, such as emotional disturbance, decreased learning ability, and deterioration of memory. This study was aimed to explore the role of the hippocampus in the generation oftinnitus by electrophysiological technology. Methods： A tinnitus model was established in rats through intraperitoneal injection of salicylate （SA）. Subsequently, the spontaneous firing rate （SFR） of neurons in the hippocampal CAI area was recorded with in vivo multichannel recording technology to assess changes in excitability induced by SA. To investigate the effect of excitability changes ofhippocampus on the auditory pathway, the hippocampus was electrically stimulated and neural excitability in the auditory cortex （AC） was monitored. Results： Totally 65 neurons in the hippocampal CAI area were recorded, 45 from the SA group （n = 5）, and 20 from the saline group （n = 5）. Two hours after treatment, mean SFR of neurons in the hippocampal CA1 area had significantly increased from 3.06 ± 0.36 Hz to 9.18 ±1.30 Hz in the SA group （t = -4.521, P 〈 0.05）, while no significant difference was observed in the saline group （2.66 ± 0.36 Hz vs. 2.16 ± 0.36 Hz, t = 0.902, P 〉 0.05）. In the AC, 79.3% （157/198） of recorded neurons showed responses to electrical stimulation of the hippocampal CA1 area. Presumed pyramidal neurons were excited, while intermediate neurons were inhibited after electrical stimulation of the hippocampus. Conclusions： The study shows that the hippocampus is excited in SA-induced tinnitus, and stimulation of hippocampus could modulate neuronal excitability of the AC. The hippocampus is involved in tinnitus and may also have a regulatory effect on the neural center.

Developmental Exposure to Bisphenol A Degrades Auditory Cortical Processing in Rats

Developmental exposure to bisphenol A(BPA),an endocrine-disrupting contaminant,impairs cognitive function in both animals and humans.However,whether BPA affects the development of primary sensory systems,which are the first to mature in the cortex,remains largely unclear.Using the rat as a model,we aimed to record the physiological and structural changes in the primary auditory cortex(A1)following lactational BPA exposure and their possible effects on behavioral outcomes.We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test.A significant alteration in spectral and temporal processing was also recorded in their A1,manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons.These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1.Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination,particularly in the temporal domain.Thus,the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.