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Epilepsy & Behavior : E&B Jul 2024In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a... (Review)
Review
In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a number of limbic and thalamo-cortical related structures involved in the processing of musical emotion (exposure), including the amygdala (arousal, expression of mood, fear), hippocampus (memory, regulation of HPA axis, stress), parahippocampal gyrus (recognition, memory retrieval), insula (valence), temporal poles (connectivity), ventral striatum (expectation and experience of reward), orbitofrontal cortex (valence) and cingulate cortex (autonomic regulation). One method is to audify (a form of sonification) EEG activity to find music by feedback to entrain abnormal EEG activity. We discuss various methods and our use of X-System (https://www.x-system.co.uk/) which is a computational model of the musical brain capable of predicting the neurophysiological effects of music. It models structures and pathways related to responses to music, including the cochlea, brain stem, auditory and motor cortex, as well as basal ganglia, cerebellum and limbic structures. It can predict autonomic and endocrine activity as well as the substrates of electrical activity to select music which can regularise EEG abnormalities to decrease epileptic activity and seizures, especially in those unresponsive to antiepileptic medication or invasive treatments.
Topics: Humans; Epilepsy; Music Therapy; Music; Electroencephalography; Brain; Auditory Perception; Precision Medicine
PubMed: 38761451
DOI: 10.1016/j.yebeh.2024.109829 -
Korean Circulation Journal May 2024Trigger and functional substrate are related to the tone of autonomic nervous system, and the role of the autonomic nerve is more significant in paroxysmal atrial... (Review)
Review
Trigger and functional substrate are related to the tone of autonomic nervous system, and the role of the autonomic nerve is more significant in paroxysmal atrial fibrillation (AF) compared to non-paroxysmal AF. We have several options for neuromodulation to help to manage patients with AF. Neuromodulation targets can be divided into efferent and afferent pathways. On the efferent side, block would be an intuitive approach. However, permanent block is hard to achieve due to completeness of the procedure and reinnervation issues. Temporary block such as botulinum toxin injection into ganglionated plexi would be a possible option for post-cardiac surgery AF. Low-level subthreshold stimulation could also prevent AF, but the invasiveness of the procedure is the barrier for the general use. On the afferent side, block is also an option. Various renal denervation approaches are currently under investigation. Auditory vagus nerve stimulation is one of the representative low-level afferent stimulation methods. This technique is noninvasive and easy to apply, so it has the potential to be widely utilized if its efficacy is confirmed.
PubMed: 38654454
DOI: 10.4070/kcj.2024.0050 -
Heliyon Dec 2023Presbycusis/Age-related hearing loss is a sensorineural hearing loss caused by age-related deterioration of the auditory system that poses a risk to the physical and... (Review)
Review
BACKGROUND
Presbycusis/Age-related hearing loss is a sensorineural hearing loss caused by age-related deterioration of the auditory system that poses a risk to the physical and mental health of older people, including social and cognitive decline. It is also associated with frailty, falls and depression. There are currently no specific medications for the treatment of presbycusis, and early detection and intervention are key to its prevention and management. Traditional Chinese medicine interventions may offer opportunities in the prevention and treatment of presbycusis, but there is no relevant review.
METHODS
Literature searches was conducted using PubMed, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases for review articles, research articles, clinical trials, meta-analyses, and case studies in animal models and clinical trials.
RESULTS
We summarized the pathological mechanisms associated with presbycusis, related to genetic factors, environment, lifestyle, and molecular mechanisms related to oxidative stress, mitochondrial dysfunction, and inflammatory pathways. It is suggested that traditional Chinese medicine interventions may offer opportunities in the prevention and treatment of presbycusis using active ingredients of herbs or formulas, acupuncture, and exercise such as Tai Chi Chuan or Ba Duan Jin. The active ingredients of herbs or formulas may exert ear protection through Nrf2-mediated antioxidant pathways, NF-kB and NLRP3-related anti-inflammatory signaling, and regulation of autophagy.
CONCLUSIONS
Here, we review the pathogenetic factors and pathological mechanisms involved in presbycusis, as well as traditional Chinese medicine interventions and treatments, with the aim of providing a new perspective for the prevention and treatment of hearing loss in the elderly and further improving their quality of life.
PubMed: 38076135
DOI: 10.1016/j.heliyon.2023.e22422 -
The Journal of Cell Biology Dec 2023Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains...
Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains elusive. Here, we study the impact of SCRIB-targeted gene mutations during the formation of the gut epithelium in an organ-on-chip model. We show that SCRIB KO gut-like epithelia are flatter with reduced exposed surface area. Cell differentiation on filters further shows that SCRIB plays a critical role in the control of apical cell shape, as well as in the basoapical polarization of myosin light chain localization and activity. Finally, we show that SCRIB serves as a molecular scaffold for SHROOM2/4 and ROCK1 and identify an evolutionary conserved SHROOM binding site in the SCRIB carboxy-terminal that is required for SCRIB function in the control of apical cell shape. Our results demonstrate that SCRIB plays a key role in epithelial morphogenesis by controlling the epithelial apical contractility during cell differentiation.
Topics: Animals; Binding Sites; Biological Evolution; Cell Differentiation; Cell Shape; Epithelium; Microphysiological Systems; Membrane Proteins; Morphogenesis
PubMed: 37930352
DOI: 10.1083/jcb.202211113 -
IScience Sep 2023mTOR broadly controls cell growth, but little is known about the role of mTOR complex 2 (mTORC2) in the inner ear. To investigate the role of mTORC2 in sensory hair...
mTOR broadly controls cell growth, but little is known about the role of mTOR complex 2 (mTORC2) in the inner ear. To investigate the role of mTORC2 in sensory hair cells (HCs), we generated HC-specific knockout (HC-RicKO) mice. HC-RicKO mice exhibited early-onset, progressive, and profound hearing loss. Increased DPOAE thresholds indicated outer HC dysfunction. HCs are lost, but this occurs after hearing loss. Ultrastructural analysis revealed stunted and absent stereocilia in outer HCs. In inner HCs, the number of synapses was significantly decreased and the remaining synapses displayed a disrupted actin cytoskeleton and disorganized Ca channels. Thus, the mTORC2 signaling pathway plays an important role in regulating auditory HC structure and function via regulation of the actin cytoskeleton. These results provide molecular insights on a central regulator of cochlear HCs and thus hearing.
PubMed: 37694145
DOI: 10.1016/j.isci.2023.107687 -
Frontiers in Endocrinology 2023GABA receptors are G-protein coupled receptors for the inhibitory neurotransmitter GABA. Functional GABA receptors are formed as heteromers of GABA and GABA subunits,... (Review)
Review
GABA receptors are G-protein coupled receptors for the inhibitory neurotransmitter GABA. Functional GABA receptors are formed as heteromers of GABA and GABA subunits, which further associate with various regulatory and signaling proteins to provide receptor complexes with distinct pharmacological and physiological properties. GABA receptors are widely distributed in nervous tissue, where they are involved in a number of processes and in turn are subject to a number of regulatory mechanisms. In this review, we summarize current knowledge of the cellular distribution and function of the receptors in the inner ear and auditory pathway of the mammalian brainstem and midbrain. The findings suggest that in these regions, GABA receptors are involved in processes essential for proper auditory function, such as cochlear amplifier modulation, regulation of spontaneous activity, binaural and temporal information processing, and predictive coding. Since impaired GABAergic inhibition has been found to be associated with various forms of hearing loss, GABA dysfunction could also play a role in some pathologies of the auditory system.
Topics: Animals; Receptors, GABA-B; Cell Membrane; Cognition; Deafness; Mammals; gamma-Aminobutyric Acid
PubMed: 37635966
DOI: 10.3389/fendo.2023.1195038 -
Hearing Research Oct 2023Learning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days,... (Review)
Review
Learning can induce neurophysiological plasticity in the auditory cortex at multiple timescales. Lasting changes to auditory cortical function that persist over days, weeks, or even a lifetime, require learning to induce de novo gene expression. Indeed, transcription is the molecular determinant for long-term memories to form with a lasting impact on sound-related behavior. However, auditory cortical genes that support auditory learning, memory, and acquired sound-specific behavior are largely unknown. Using an animal model of adult, male Sprague-Dawley rats, this report is the first to identify genome-wide changes in learning-induced gene expression within the auditory cortex that may underlie long-lasting discriminative memory formation of acoustic frequency cues. Auditory cortical samples were collected from animals in the initial learning phase of a two-tone discrimination sound-reward task known to induce sound-specific neurophysiological and behavioral effects. Bioinformatic analyses on gene enrichment profiles from bulk RNA sequencing identified cholinergic synapse (KEGG rno04725), extra-cellular matrix receptor interaction (KEGG rno04512), and neuroactive receptor interaction (KEGG rno04080) among the top biological pathways are likely to be important for auditory discrimination learning. The findings characterize candidate effectors underlying the early stages of changes in cortical and behavioral function to ultimately support the formation of long-term discriminative auditory memory in the adult brain. The molecules and mechanisms identified are potential therapeutic targets to facilitate experiences that induce long-lasting changes to sound-specific auditory function in adulthood and prime for future gene-targeted investigations.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Auditory Cortex; Learning; Discrimination Learning; Brain
PubMed: 37659220
DOI: 10.1016/j.heares.2023.108878 -
Nature Communications Nov 2023Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and...
Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory modalities, enabling crossmodal memory coding concurrent with modality-dependent coding. In middle age, however, crossmodal coding remarkably diminishes while modality-dependent coding persists, and both types of coding decay in advanced age. Resting-state functional connectivity, especially among memory-coding neurons, decreases already in middle age, suggesting deteriorated recurrent circuits for memory maintenance. Optogenetic inactivation reveals that the middle-aged mPFC exhibits heightened vulnerability to perturbations. These findings elucidate functional alterations of the prefrontal circuit that unfold in middle age and deteriorate further as a hallmark of cognitive aging.
Topics: Mice; Animals; Cognitive Aging; Prefrontal Cortex; Memory, Short-Term; Aging; Magnetic Resonance Imaging; Neural Pathways
PubMed: 37945561
DOI: 10.1038/s41467-023-43142-0 -
ELife Aug 2023Behavioral flexibility and timely reactions to salient stimuli are essential for survival. The subcortical thalamic-basolateral amygdala (BLA) pathway serves as a...
Behavioral flexibility and timely reactions to salient stimuli are essential for survival. The subcortical thalamic-basolateral amygdala (BLA) pathway serves as a shortcut for salient stimuli ensuring rapid processing. Here, we show that BLA neuronal and thalamic axonal activity in mice mirror the defensive behavior evoked by an innate visual threat as well as an auditory learned threat. Importantly, perturbing this pathway compromises defensive responses to both forms of threats, in that animals fail to switch from exploratory to defensive behavior. Despite the shared pathway between the two forms of threat processing, we observed noticeable differences. Blocking β-adrenergic receptors impairs the defensive response to the innate but not the learned threats. This reduced defensive response, surprisingly, is reflected in the suppression of the activity exclusively in the BLA as the thalamic input response remains intact. Our side-by-side examination highlights the similarities and differences between innate and learned threat-processing, thus providing new fundamental insights.
Topics: Mice; Animals; Fear; Amygdala; Learning; Basolateral Nuclear Complex; Thalamus
PubMed: 37526552
DOI: 10.7554/eLife.85459 -
Hearing Research Mar 2024Hearing loss affects approximately 18% of the population worldwide. Hearing difficulties in noisy environments without accompanying audiometric threshold shifts likely... (Review)
Review
Hearing loss affects approximately 18% of the population worldwide. Hearing difficulties in noisy environments without accompanying audiometric threshold shifts likely affect an even larger percentage of the global population. One of the potential causes of hidden hearing loss is cochlear synaptopathy, the loss of synapses between inner hair cells (IHC) and auditory nerve fibers (ANF). These synapses are the most vulnerable structures in the cochlea to noise exposure or aging. The loss of synapses causes auditory deafferentation, i.e., the loss of auditory afferent information, whose downstream effect is the loss of information that is sent to higher-order auditory processing stages. Understanding the physiological and perceptual effects of this early auditory deafferentation might inform interventions to prevent later, more severe hearing loss. In the past decade, a large body of work has been devoted to better understand hidden hearing loss, including the causes of hidden hearing loss, their corresponding impact on the auditory pathway, and the use of auditory physiological measures for clinical diagnosis of auditory deafferentation. This review synthesizes the findings from studies in humans and animals to answer some of the key questions in the field, and it points to gaps in knowledge that warrant more investigation. Specifically, recent studies suggest that some electrophysiological measures have the potential to function as indicators of hidden hearing loss in humans, but more research is needed for these measures to be included as part of a clinical test battery.
Topics: Animals; Humans; Hearing Loss, Noise-Induced; Noise; Auditory Threshold; Hearing Loss, Hidden; Auditory Perception; Cochlea; Synapses; Evoked Potentials, Auditory, Brain Stem
PubMed: 38335624
DOI: 10.1016/j.heares.2024.108967