Lateral Lemniscus Research Articles

Diffusion Tensor Imaging of the Auditory Pathway in Prelingual Deaf Children in Comparison to Normal Hearing Children in the 1 to 7 Years of Age Group

Abstract Objective This article aims to determine the microstructural alterations in the auditory pathway in prelingual deaf children using diffusion tensor imaging (DTI)-derived parameters—fractional anisotropy (FA) and apparent diffusion coefficient (ADC), and secondarily to evaluate these changes in rubella and cytomegalovirus (CMV) positive cases. Method A consecutive series of consenting deaf and normal children between 1 and 7 years of age, forming the case and control groups, respectively, underwent DTI, audiological tests, and testing for rubella, CMV, and toxoplasma infections. FA and ADC were measured at four locations bilaterally: lateral lemniscus (LL), inferior colliculus, medial geniculate body, and auditory cortex (AC). Result The mean ADC values were higher and the mean FA values were lower in cases (19 males, 21 females, mean age 2.65 years) than the controls (21 males, 19 females, mean age 4.63 years) at all eight sites. Sixteen (40%), 17 (42.5%), and 7 (17.5%) cases had severe, severe to profound, and profound hearing loss, respectively, the FA and ADC values being significantly different for LL. For rubella and CMV immunoglobulin G, 20/40and 17/40 cases were positive, respectively, 11 for both, and none for toxoplasma. Significant decrease in FA was seen at LL and AC in rubella/CMV positive cases. Conclusion Microstructural changes are seen throughout the auditory pathway in prelingual deaf children, especially with rubella and/or CMV positive status. Further studies may pave the path to segregate out patient groups potentially more responsive to cochlear implant.

Ototoxicity-related changes in GABA immunolabeling within the rat inferior colliculus

Several studies suggest that hearing loss results in changes in the balance between inhibition and excitation in the inferior colliculus (IC). The IC is an integral nucleus within the auditory brainstem. The majority of ascending pathways from the lateral lemniscus (LL), superior olivary complex (SOC), and cochlear nucleus (CN) synapse in the IC before projecting to the thalamus and cortex. Many of these ascending projections provide inhibitory innervation to neurons within the IC. However, the nature and the distribution of this inhibitory input have only been partially elucidated in the rat. The inhibitory neurotransmitter, gamma aminobutyric acid (GABA), from the ventral nucleus of the lateral lemniscus (VNLL), provides the primary inhibitory input to the IC of the rat with GABA from other lemniscal and SOC nuclei providing lesser, but prominent innervation.There is evidence that hearing related conditions can result in dysfunction of IC neurons. These changes may be mediated in part by changes in GABA inputs to IC neurons. We have previously used gene micro-arrays in a study of deafness-related changes in gene expression in the IC and found significant changes in GAD as well as the GABA transporters and GABA receptors (Holt 2005). This is consistent with reports of age and trauma related changes in GABA (Bledsoe et al., 1995; Mossop et al., 2000; Salvi et al., 2000). Ototoxic lesions of the cochlea produced a permanent threshold shift. The number, intensity, and density of GABA positive axon terminals in the IC were compared in normal hearing and deafened rats. While the number of GABA immunolabeled puncta was only minimally different between groups, the intensity of labeling was significantly reduced. The ultrastructural localization and distribution of labeling was also examined. In deafened animals, the number of immuno gold particles was reduced by 78 % in axodendritic and 82 % in axosomatic GABAergic puncta. The affected puncta were primarily associated with small IC neurons. These results suggest that reduced inhibition to IC neurons contribute to the increased neuronal excitability observed in the IC following noise or drug induced hearing loss. Whether these deafness diminished inhibitory inputs originate from intrinsic or extrinsic CNIC sources awaits further study.

Anatomy of superior olivary complex and lateral lemniscus in Etruscan shrew

Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this insectivore has not been investigated. Using labelling techniques, we assessed the structures of their superior olivary complex (SOC) and the nuclei of the lateral lemniscus (NLL). There, we identified the position of the major nuclei, their input pattern, transmitter content, expression of calcium binding proteins (CaBPs) and two voltage-gated ion channels. The most prominent SOC structures were the medial nucleus of the trapezoid body (MNTB), the lateral nucleus of the trapezoid body (LNTB), the lateral superior olive (LSO) and the superior paraolivary nucleus (SPN). In the NLL, the ventral (VNLL), a specific ventrolateral VNLL (VNLLvl) cell population, the intermediate (INLL) and dorsal (DNLL) nucleus, as well as the inferior colliculus’s central aspect were discerned. INLL and VNLL were clearly separated by the differential distribution of various marker proteins. Most labelled proteins showed expression patterns comparable to rodents. However, SPN neurons were glycinergic and not GABAergic and the overall CaBPs expression was low. Next to the characterisation of the Etruscan shrew’s auditory brainstem, our work identifies conserved nuclei and indicates variable structures in a species that approximates ancestral conditions.

The value of synthetic MRI in detecting the brain changes and hearing impairment of children with sensorineural hearing loss.

Sensorineural hearing loss (SNHL) can arise from a diverse range of congenital and acquired factors. Detecting it early is pivotal for nurturing speech, language, and cognitive development in children with SNHL. In our study, we utilized synthetic magnetic resonance imaging (SyMRI) to assess alterations in both gray and white matter within the brains of children affected by SNHL. The study encompassed both children diagnosed with SNHL and a control group of children with normal hearing {1.5-month-olds (n = 52) and 3-month-olds (n = 78)}. Participants were categorized based on their auditory brainstem response (ABR) threshold, delineated into normal, mild, moderate, and severe subgroups.Clinical parameters were included and assessed the correlation with SNHL. Quantitative analysis of brain morphology was conducted using SyMRI scans, yielding data on brain segmentation and relaxation time.Through both univariate and multivariate analyses, independent factors predictive of SNHL were identified. The efficacy of the prediction model was evaluated using receiver operating characteristic (ROC) curves, with visualization facilitated through the utilization of a nomogram. It's important to note that due to the constraints of our research, we worked with a relatively small sample size. Neonatal hyperbilirubinemia (NH) and children with inner ear malformation (IEM) were associated with the onset of SNHL both at 1.5 and 3-month groups. At 3-month group, the moderate and severe subgroups exhibited elevated quantitative T1 values in the inferior colliculus (IC), lateral lemniscus (LL), and middle cerebellar peduncle (MCP) compared to the normal group. Additionally, WMV, WMF, MYF, and MYV were significantly reduced relative to the normal group. Additionally, SNHL-children with IEM had high T1 values in IC, and LL and reduced WMV, WMF, MYV and MYF values as compared with SNHL-children without IEM at 3-month group. LL-T1 and WMF were independent risk factors associated with SNHL. Consequently, a prediction model was devised based on LL-T1 and WMF. ROC for training set, validation set and external set were 0.865, 0.806, and 0.736, respectively. The integration of T1 quantitative values and brain volume segmentation offers a valuable tool for tracking brain development in children affected by SNHL and assessing the progression of the condition's severity.

Presence of Auditory Pathway Abnormalities in Children With Neurofibromatosis Type 1 With Brainstem Focal Areas of Abnormal Signal Intensity: Diffusion Tensor Imaging Features.

Background: To investigate whether there is a difference in mean diffusivity (MD) and fractional anisotropy (FA) values in the auditory pathways of neurofibromatosis type 1 patients with and without focal areas of abnormal signal intensity (FASI) compared to healthy controls by using diffusion tensor imaging (DTI). Methods: Patients were classified as group 1 with focal areas of abnormal signal intensity in the brainstem, group 2 without focal areas of abnormal signal intensity, and healthy control group 3 according to the MRI findings. Mean diffusivity and fractional anisotropy values of lateral lemniscus, inferior colliculus, corpus geniculatum mediale, Heschl gyrus, and brainstem were compared between groups. The correlation between mean diffusivity and fractional anisotropy values of auditory pathways and age was investigated. Results: There was a significant difference between group 1 and group 2 in terms of mean diffusivity and fractional anisotropy values at lateral lemniscus, inferior colliculus, corpus geniculatum mediale, and Heschl gyrus. Increased mean diffusivity and decreased fractional anisotropy values at brainstem were found in group 1. There was a significant difference between group 1 and group 3 in terms of mean diffusivity values at all auditory pathways. Fractional anisotropy values obtained from lateral lemniscus, inferior colliculus, and Heschl gyrus decreased in group 1 compared with group 3. There was a negative correlation between mean diffusivity values and positive correlation between fractional anisotropy values at lateral lemniscus, inferior colliculus, Heschl gyrus, and age. Conclusions: Our diffusion tensor imaging findings show that the neuronal integrity of the auditory pathways is affected in neurofibromatosis type 1 patients with brainstem focal areas of abnormal signal intensity. We think that the disappearance of brainstem focal areas of abnormal signal intensity associated with myelin repair and the regression of diffusion tensor imaging changes in the auditory pathways occur simultaneously with advancing age in patients with neurofibromatosis type 1.

Efferent projections of Nps-expressing neurons in the parabrachial region.

In the brain, connectivity determines function. Neurons in the parabrachial nucleus (PB) relay diverse information to widespread brain regions, but the connections and functions of PB neurons that express Nps (neuropeptide S, NPS) remain mysterious. Here, we use Cre-dependent anterograde tracing and whole-brain analysis to map their output connections. While many other PB neurons project ascending axons through the central tegmental tract, NPS axons reach the forebrain via distinct periventricular and ventral pathways. Along the periventricular pathway, NPS axons target the tectal longitudinal column and periaqueductal gray, then continue rostrally to target the paraventricular nucleus of the thalamus. Along the ventral pathway, NPS axons blanket much of the hypothalamus but avoid the ventromedial and mammillary nuclei. They also project prominently to the ventral bed nucleus of the stria terminalis, A13 cell group, and magnocellular subparafasciular nucleus. In the hindbrain, NPS axons have fewer descending projections, targeting primarily the superior salivatory nucleus, nucleus of the lateral lemniscus, and periolivary region. Combined with what is known already about NPS and its receptor, the output pattern of Nps-expressing neurons in the PB region predicts roles in threat response and circadian behavior.

Medial superior olive in the rat: Anatomy, sources of input and axonal projections

Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus.The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research.

Comparison of the connectivity of the posterior intralaminar thalamic nucleus and peripeduncular nucleus in rats and mice.

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.

Reduced white matter maturation in the central auditory system of children living with HIV.

School-aged children experience crucial developmental changes in white matter (WM) in adolescence. The human immunodeficiency virus (HIV) affects neurodevelopment. Children living with perinatally acquired HIV (CPHIVs) demonstrate hearing and neurocognitive impairments when compared to their uninfected peers (CHUUs), but investigations into the central auditory system (CAS) WM integrity are lacking. The integration of the CAS and other brain areas is facilitated by WM fibers whose integrity may be affected in the presence of HIV, contributing to neurocognitive impairments. We used diffusion tensor imaging (DTI) tractography to map the microstructural integrity of WM between CAS regions, including the lateral lemniscus and acoustic radiation, as well as between CAS regions and non-auditory regions of 11-year-old CPHIVs. We further employed a DTI-based graph theoretical framework to investigate the nodal strength and efficiency of the CAS and other brain regions in the structural brain network of the same population. Finally, we investigated associations between WM microstructural integrity outcomes and neurocognitive outcomes related to auditory and language processing. We hypothesized that compared to the CHUU group, the CPHIV group would have lower microstructural in the CAS and related regions. Our analyses showed higher mean diffusivity (MD), a marker of axonal maturation, in the lateral lemniscus and acoustic radiations, as well as WM between the CAS and non-auditory regions predominantly in frontotemporal areas. Most affected WM connections also showed higher axial and radial diffusivity (AD and RD, respectively). There were no differences in the nodal properties of the CAS regions between groups. The MD of frontotemporal and subcortical WM-connected CAS regions, including the inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and internal capsule showed negative associations with sequential processing in the CPHIV group but not in the CHUU group. The current results point to reduced axonal maturation in WM, marked by higher MD, AD, and RD, within and from the CAS. Furthermore, alterations in WM integrity were associated with sequential processing, a neurocognitive marker of auditory working memory. Our results provide insights into the microstructural integrity of the CAS and related WM in the presence of HIV and link these alterations to auditory working memory.

Harmony in the Molecular Orchestra of Hearing: Developmental Mechanisms from the Ear to the Brain.

Auditory processing in mammals begins in the peripheral inner ear and extends to the auditory cortex. Sound is transduced from mechanical stimuli into electrochemical signals of hair cells, which relay auditory information via the primary auditory neurons to cochlear nuclei. Information is subsequently processed in the superior olivary complex, lateral lemniscus, and inferior colliculus and projects to the auditory cortex via the medial geniculate body in the thalamus. Recent advances have provided valuable insights into the development and functioning of auditory structures, complementing our understanding of the physiological mechanisms underlying auditory processing. This comprehensive review explores the genetic mechanisms required for auditory system development from the peripheral cochlea to the auditory cortex. We highlight transcription factors and other genes with key recurring and interacting roles in guiding auditory system development and organization. Understanding these gene regulatory networks holds promise for developing novel therapeutic strategies for hearing disorders, benefiting millions globally.

GABAB receptor-mediated modulation in the developing dorsal nucleus of the lateral lemniscus.

The dorsal nucleus of the lateral lemniscus (DNLL) is a GABAergic, reciprocally connected auditory brainstem structure that continues to develop postnatally in rodents. One key feature of the DNLL is the generation of a strong, prolonged, ionotropic, GABAA receptor-mediated inhibition. Possible GABAB receptor-mediated signalling is unexplored in the DNLL. Here, we used Mongolian gerbils of either sex to describe GABAB receptor-mediated modulation of postsynaptic potassium currents and synaptic inputs in postnatal (P) animals of days 10/11 and 23-28. Throughout development, we observed the presence of a Baclofen-activated GABAB receptor-enhanced potassium outward conductance that is capable of suppressing action potential generation. In P10/11, old gerbils GABAB receptor activation enhances glutamatergic and suppresses ionotropic GABAergic synaptic transmission. During development, this differential modulation becomes less distinct, because in P22-28, old animals Baclofen-activated GABAB receptors rather enhance ionotropic GABAergic synaptic transmission, whereas glutamatergic transmission is both enhanced and suppressed. Blocking GABAB receptors causes an increase in ionotropic GABAergic transmission in P10/11 old gerbils that was independent on stimulation frequency but depended on the type of short-term plasticity. Together with the lack of Baclofen-induced changes in the synaptic paired-pulse ratio of either input type, we suggest that GABAB receptor-mediated modulation is predominantly postsynaptic and activates different signalling cascades. Thus, we argue that in DNLL neurons, the GABAB receptor is a post-synaptically located signalling hub that alters signalling cascades during development for distinct targets.

Auditory central pathways in children and adolescents with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease. Auditory evoked potential studies have demonstrated conduction and neural processing deficits in adults with MS, but little is known about the electrophysiological responses in children and adolescents. to evaluate the central auditory pathway with brainstem auditory evoked potentials (BAEP) and long-latency auditory evoked potentials (LLAEP) in children and adolescents with MS. The study comprised 17 individuals with MS, of both sexes, aged 9 to 18 years, and 17 healthy volunteers, matched for age and sex. All individuals had normal hearing and no middle ear impairments. They were assessed with click-BAEP and LLAEP through oddball paradigm and tone-burst stimuli. Abnormal responses were observed in 60% of electrophysiologic assessments of individuals with MS. In BAEP, 58.82% of MS patients had abnormal responses, with longer wave V latency and therefore longer III-V and I-V interpeak latencies than healthy volunteers. In LLAEP, 52.94% of MS patients had abnormal responses. Although statistical differences were found only in P2-N2 amplitude, MS patients had longer latencies and smaller amplitudes than healthy volunteers in all components. Children and adolescents with MS had abnormal BAEP responses, with delayed neural conduction between the cochlear nucleus and the lateral lemniscus. Also, abnormal LLAEP results suggest a decrease in neural processing speed and auditory sensory discrimination response.

Neuronal morphology and synaptic input patterns of neurons in the intermediate nucleus of the lateral lemniscus of gerbils

The lateral lemniscus encompasses processing stages for binaural hearing, suppressing spurious frequencies and frequency integration. Within the lemniscal fibres three nuclei can be identified, termed after their location as dorsal, intermediate and ventral nucleus of the lateral lemniscus (DNLL, INLL and VNLL). While the DNLL and VNLL have been functionally and anatomically characterized, less is known about INLL neurons. Here, we quantitatively describe the morphology, the cellular orientation and distribution of synaptic contact sites along dendrites in mature Mongolian gerbils. INLL neurons are largely non-inhibitory and morphologically heterogeneous with an overall perpendicular orientation regarding the lemniscal fibers. Dendritic ranges are heterogeneous and can extend beyond the nucleus border. INLL neurons receive VGluT1/2 containing glutamatergic and a mix of GABA- and glycinergic inputs distributed over the entire dendrite. Input counts suggest that numbers of excitatory exceed the inhibitory contact sites. Axonal projections indicate connectivity to ascending and descending auditory structures. Our data show that INLL neurons form a morphologically heterogeneous continuum and incoming auditory information is processed on thin dendrites of various length and biased to perpendicular orientation. Together with the different axonal projection patterns, this indicates that the INLL is a highly complex structure that might hold many unexplored auditory functions.

The nuclei of the lateral lemniscus: unexpected players in the descending auditory pathway.

In the mammalian auditory pathway, the nuclei of the lateral lemniscus (NLL) are thought to be exclusively involved in the bottom-up transmission of auditory information. However, our repeated observation of numerous NLL neurons labeled after injection of retrograde tracers into the superior olivary complex (SOC) led us to systematically investigate with retrograde tracers the descending projections from the NLL to the SOC of the rat. We performed large injections of FluoroGold into the SOC to determine NLL contributions to descending projections, and focal injections of biotinylated dextran amine (BDA) to pinpoint the specific nuclei of the SOC innervated by each NLL. The SOC is innervated by thousands of neurons distributed across four nuclei or regions associated with the lateral lemniscus: the ipsilateral ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL); the medial paralemniscal region (PL) of both sides; and the ipsilateral semilunar nucleus (SLN), a previously unrecognized nucleus that wraps around the INLL dorsally, medially, and caudally and consists of small, flat neurons. In some experiments, at least 30% of neurons in the VNLL and INLL were retrogradely labeled. All nuclei of the SOC, except the medial and lateral superior olives, are innervated by abundant lemniscal neurons, and each SOC nucleus receives a unique combination of lemniscal inputs. The primary target of the projections from the VNLL is the ventral nucleus of the trapezoid body (VNTB), followed by the superior paraolivary nucleus (SPON), and the medial nucleus of the trapezoid body (MNTB). The INLL selectively innervates the VNTB. The PL innervates dorsal periolivary regions bilaterally. The SLN preferentially innervates the MNTB and may provide the first identified non-calyceal excitatory input to MNTB neurons. Our novel findings have strong implications for understanding acoustic information processing in the initial stages of the auditory pathway. Based on the proportion of lemniscal neurons involved in all the projections described, the NLL should be considered major players in the descending auditory pathway.

Use of reverse noise to measure ongoing delay.

Counts of spike coincidences provide a powerful means to compare responses to different stimuli or of different neurons, particularly regarding temporal factors. A drawback is that these methods do not provide an absolute measure of latency, i.e., the temporal interval between stimulus features and response. It is desirable to have such a measure within the analysis framework of coincidence counting. Single neuron responses were obtained, from 130 fibers in several tracts (auditory nerve, trapezoid body, lateral lemniscus), to a broadband noise and its polarity-inverted version. The spike trains in response to these stimuli are the "forward noise" responses. The same stimuli were also played time-reversed. The resulting spike trains were then again time-reversed: These are the "reverse-noise" responses. The forward and reverse responses were then analyzed with the coincidence count methods we have introduced earlier. Correlograms between forward- and reverse-noise responses show maxima at values consistent with latencies measured with other methods; the pattern of latencies with characteristic frequency, sound pressure level, and recording location was also consistent. At low characteristic frequencies, correlograms were well-predicted by reverse-correlation functions. We conclude that reverse noise provides an easy and reliable means to estimate latency of auditory nerve and brainstem neurons.

Quantitative analysis of white matter brain changes in tinnitus patients with normal hearing: a case-controlled study with diffusion tensor imaging

BackgroundThis research aimed at assessing the white matter microstructural (WM) brain changes in tinnitus patients with bilateral normal peripheral hearing using diffuse tensor imaging to test whether, tinnitus alone without hearing loss can cause WM brain changes or not.Patients and materialsTwenty-eight patients were enrolled in this research, 14 patients with bilateral tinnitus without hearing loss (audiometrically proven) and 14 normal hearing controls. All subjects underwent a full basic audiological evaluation, tinnitus matching, and were asked to fill the Tinnitus Handicap Inventory (THI) questionnaire. They underwent diffusion tensor brain imaging, mean diffusivity (MD) and fractional anisotropy (FA) values were measured at special parts of central auditory pathway, and parts of limbic system. A comparison between study and control groups was held as regards MD and FA at different brain sites using an independent sample Student t-test or Mann–Whitney U test. Furthermore, the relationship between THI scores and the MD/FA measures was examined by correlation tests.ResultsAs regards FA values, some regions as [lateral lemniscus (LL), inferior colliculus (IC), frontal arcuate fasciculi (AF) and parahippocampus] showed statistically significant decreased FA values in the tinnitus group compared to Normal Hearing (NH) group (p < 0.05). As regards MD values, tinnitus patients showed significantly higher MD values at (auditory cortex, amygdala, and AF) compared to control group (p < 0.05). As regards correlations, THI scores showed statistically significant positive correlation with MD values measured at Rt Amygdala (r = 0.55, p = 0.04).ConclusionsThe central auditory pathway affection is proved in tinnitus patients with normal hearing (as least as evidenced by conventional audiological examinations) and the auditory-limbic association is proved so far. The involvement of IC confirms the subcortical auditory centres involvement in the generation of the tinnitus. Auditory associations are also significantly impacted by the effect of tinnitus.

Molecular identity of the lateral lemniscus nuclei in the adult mouse brain.

The dorsal (DLL), intermediate (ILL), and ventral (VLL) lateral lemniscus nuclei are relay centers in the central auditory pathway of the brainstem, commonly referred to as the lateral lemniscus nuclei (LLN). The LLN are situated in the prepontine and pontine hindbrain, from rhombomeres 1 to 4, extending from the more rostral DLL to the caudal VLL, with the ILL lying in between. These nuclei can be distinguished morphologically and by topological and connectivity criteria, and here, we set out to further characterize the molecular nature of each LLN. We searched in situ hybridization studies in the Allen Mouse Brain Atlas for genes differentially expressed along the rostrocaudal axis of the brainstem, identifying 36 genes from diverse functional families expressed in the LLN. Available information in the databases indicated that 7 of these 36 genes are either associated with or potentially related to hearing disorders. In conclusion, the LLN are characterized by specific molecular profiles that reflect their rostrocaudal organization into the three constituent nuclei. This molecular regionalization may be involved in the etiology of some hearing disorders, in accordance with previous functional studies of these genes.

The brainstem connections of the supplementary motor area and its relations to the corticospinal tract: Experimental rat and human 3-tesla tractography study

Although the supplementary motor area (SMA) is a large region on the medial surface of the frontal lobe of the brain, little is known about its function. The current study uses 3-tesla high-resolution diffusion tensor tractography (DTI) in healthy individuals and biotinylated dextran amine (BDA) and fluoro-gold (FG) tracer in rats to demonstrate the afferent and efferent connections of the SMA with brainstem structures. It also aims to clarify how SMA fibers relate to the corticospinal tract (CST). The BDA (n = 6) and FG (n = 8) tracers were pressure-injected into the SMA of 14 Wistar albino rats. Light and fluorescence microscopy was used to capture images of the FG and BDA-labeled cells and axons. High-resolution 3-tesla DTI data were acquired from the Human Connectome Project database. Tracts between the SMA and brainstem structures were analyzed using diffusion spectrum imaging (DSI) studio software. The FG injections into the SMA showed afferent projections from mesencephalic (periaqueductal gray matter, substantia nigra pars reticulata, ventral tegmental area, inferior colliculus, mesencephalic reticular, tegmental, and raphe nuclei), pontine (locus coeruleus, pontine reticular and vestibular nuclei), and medullary (area postrema, parabrachial, and medullary reticular nuclei) structures. The anterograde tracer BDA injections into the SMA showed efferent connections with mesencephalic (periaqueductal gray, substantia nigra pars compacta, dorsal raphe, trigeminal motor mesencephalic, and mesencephalic reticular nuclei), pontine (locus coeruleus, nucleus of the lateral lemniscus, vestibular, cochlear, and pontine reticular nuclei), and medullary (area postrema, medullary reticular, olivary, and parabrachial nuclei) structures. The SMA had efferent but no afferent connections with the cerebellar nuclei. The DTI results in healthy human subjects highly corresponded with the experimental results. Further, the DTI results showed a distinct bundle that descended to spinal levels closely related to the CST. Understanding SMA’s afferent and efferent connections will enrich our knowledge of its contribution to various brainstem networks and may provide new perspectives for understanding its motor and non-motor functions.

Auditory-limbic-cerebellum interactions and cognitive impairments in noise-induced hearing loss.

This study aimed to explore the neural substrate of hearing loss-related central nervous system in rats and its correlation with cognition. We identified the neural mechanism for these debilitating abnormalities by inducing a bilateral hearing loss animal model using intense broadband noise (122 dB of broadband noise for 2h) and used the Morris water maze test to characterize the behavioral changes at 6months post-noise exposure. Functional magnetic resonance imaging (fMRI) was conducted to clarify disrupted functional network using bilateral auditory cortex (ACx) as a seed. Structural diffusion tensor imaging (DTI) was applied to illustrate characteristics of fibers in ACx and hippocampus. Pearson correlation was computed behavioral tests and other features. A deficit in spatial learning/memory, body weight, and negative correlation between them was observed. Functional connectivity revealed weakened coupling within the ACx and inferior colliculus, lateral lemniscus, the primary motor cortex, the olfactory tubercle, hippocampus, and the paraflocculus lobe of the cerebellum. The fiber number and mean length of ACx and different hippocampal subregions were also damaged in hearing loss rats. A new model of auditory-limbic-cerebellum interactions accounting for noise-induced hearing loss and cognitive impairments is proposed.

Neurotransmitter phenotype and axonal projection patterns of VIP-expressing neurons in the inferior colliculus

Neurons in the inferior colliculus (IC), the midbrain hub of the central auditory pathway, send ascending and descending projections to other auditory brain regions, as well as projections to other sensory and non-sensory brain regions. However, the axonal projection patterns of individual classes of IC neurons remain largely unknown. Vasoactive intestinal polypeptide (VIP) is a neuropeptide expressed by subsets of neurons in many brain regions. We recently identified a class of IC stellate neurons that we called VIP neurons because they are labeled by tdTomato (tdT) expression in VIP-IRES-Cre x Ai14 mice. Here, using fluorescence in situ hybridization, we found that tdT+ neurons in VIP-IRES-Cre x Ai14 mice express Vglut2, a marker of glutamatergic neurons, and VIP, suggesting that VIP neurons use both glutamatergic and VIPergic signaling to influence their postsynaptic targets. Next, using viral transfections with a Cre-dependent eGFP construct, we labeled the axonal projections of VIP neurons. As a group, VIP neurons project intrinsically, within the ipsilateral and contralateral IC, and extrinsically to all the major targets of the IC. Within the auditory system, VIP neurons sent axons and formed axonal boutons in higher centers, including the medial geniculate nucleus and the nucleus of the brachium of the IC. Less dense projections terminated in lower centers, including the nuclei of the lateral lemniscus, superior olivary complex, and dorsal cochlear nucleus. VIP neurons also project to several non-auditory brain regions, including the superior colliculus, periaqueductal gray, and cuneiform nucleus. The diversity of VIP projections compared to the homogeneity of VIP neuron intrinsic properties suggests that VIP neurons play a conserved role at the microcircuit level, likely involving neuromodulation through glutamatergic and VIPergic signaling, but support diverse functions at the systems level through their participation in different projection pathways.