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BioRxiv : the Preprint Server For... May 2024Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied...
Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas-such as primary visual cortex-but not others. Here we examine the development of network organization across diverse cortical regions in ferrets of both sexes using widefield calcium imaging of spontaneous activity. We find that all regions examined, including both primary sensory cortices (visual, auditory, and somatosensory-V1, A1, and S1, respectively) and higher order association areas (prefrontal and posterior parietal cortices) exhibit a largely similar pattern of changes over an approximately 3 week developmental period spanning eye opening and the transition to predominantly externally-driven sensory activity. We find that both a modular functional organization and millimeter-scale correlated networks remain present across all cortical areas examined. These networks weakened over development in most cortical areas, but strengthened in V1. Overall, the conserved maintenance of modular organization across different cortical areas suggests a common pathway of network refinement, and suggests that a modular organization-known to encode functional representations in visual areas-may be similarly engaged in highly diverse brain areas.
PubMed: 38853883
DOI: 10.1101/2024.05.28.595371 -
Scientific Reports Jun 2024Dementia, and in particular Alzheimer's disease (AD), can be characterized by disrupted functional connectivity in the brain caused by beta-amyloid deposition in neural...
Dementia, and in particular Alzheimer's disease (AD), can be characterized by disrupted functional connectivity in the brain caused by beta-amyloid deposition in neural links. Non-pharmaceutical treatments for dementia have recently explored interventions involving the stimulation of neuronal populations in the gamma band. These interventions aim to restore brain network functionality by synchronizing rhythmic energy through various stimulation modalities. Entrainment, a newly proposed non-invasive sensory stimulation method, has shown promise in improving cognitive functions in dementia patients. This study investigates the effectiveness of entrainment in terms of promoting neural synchrony and spatial connectivity across the cortex. EEG signals were recorded during a 40 Hz auditory entrainment session conducted with a group of elderly participants with dementia. Phase locking value (PLV) between different intraregional and interregional sites was examined as an attribute of network synchronization, and connectivity of local and distant links were compared during the stimulation and rest trials. Our findings demonstrate enhanced neural synchrony between the frontal and parietal regions, which are key components of the brain's default mode network (DMN). The DMN operation is known to be impacted by dementia's progression, leading to reduced functional connectivity across the parieto-frontal pathways. Notably, entrainment alone significantly improves synchrony between these DMN components, suggesting its potential for restoring functional connectivity.
Topics: Humans; Male; Female; Aged; Dementia; Gamma Rhythm; Electroencephalography; Default Mode Network; Acoustic Stimulation; Aged, 80 and over; Nerve Net; Alzheimer Disease; Brain
PubMed: 38849418
DOI: 10.1038/s41598-024-63727-z -
Scientific Reports Jun 2024Aberrant neuronal circuit dynamics are at the core of complex neuropsychiatric disorders, such as schizophrenia (SZ). Clinical assessment of the integrity of neuronal...
Aberrant neuronal circuit dynamics are at the core of complex neuropsychiatric disorders, such as schizophrenia (SZ). Clinical assessment of the integrity of neuronal circuits in SZ has consistently described aberrant resting-state gamma oscillatory activity, decreased auditory-evoked gamma responses, and abnormal mismatch responses. We hypothesized that corticothalamic circuit manipulation could recapitulate SZ circuit phenotypes in rodent models. In this study, we optogenetically inhibited the mediodorsal thalamus-to-prefrontal cortex (MDT-to-PFC) or the PFC-to-MDT projection in rats and assessed circuit function through electrophysiological readouts. We found that MDT-PFC perturbation could not recapitulate SZ-linked phenotypes such as broadband gamma disruption, altered evoked oscillatory activity, and diminished mismatch negativity responses. Therefore, the induced functional impairment of the MDT-PFC pathways cannot account for the oscillatory abnormalities described in SZ.
Topics: Animals; Optogenetics; Rats; Prefrontal Cortex; Evoked Potentials, Auditory; Male; Thalamus; Schizophrenia; Neural Pathways; Rats, Sprague-Dawley; Gamma Rhythm; Limbic System
PubMed: 38849374
DOI: 10.1038/s41598-024-63036-5 -
Frontiers in Molecular Neuroscience 2024Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for...
Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell numbers and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed an increase in macrophage number and increased expression of CD68, a marker of phagocytic activity and cell activation, in macrophages in the deafened ganglia. Moreover, we found an increase in MHCII expression on spiral ganglion macrophages and an increase in lymphocyte number in the deafened ganglia, suggestive of an adaptive immune response. However, C3 knockout did not affect SGN survival or increase in macrophage number/activation, implying that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.
PubMed: 38840777
DOI: 10.3389/fnmol.2024.1389816 -
Brain Structure & Function Jul 2024Connectivity maps are now available for the 360 cortical regions in the Human Connectome Project Multimodal Parcellation atlas. Here we add function to these maps by...
Selective activations and functional connectivities to the sight of faces, scenes, body parts and tools in visual and non-visual cortical regions leading to the human hippocampus.
Connectivity maps are now available for the 360 cortical regions in the Human Connectome Project Multimodal Parcellation atlas. Here we add function to these maps by measuring selective fMRI activations and functional connectivity increases to stationary visual stimuli of faces, scenes, body parts and tools from 956 HCP participants. Faces activate regions in the ventrolateral visual cortical stream (FFC), in the superior temporal sulcus (STS) visual stream for face and head motion; and inferior parietal visual (PGi) and somatosensory (PF) regions. Scenes activate ventromedial visual stream VMV and PHA regions in the parahippocampal scene area; medial (7m) and lateral parietal (PGp) regions; and the reward-related medial orbitofrontal cortex. Body parts activate the inferior temporal cortex object regions (TE1p, TE2p); but also visual motion regions (MT, MST, FST); and the inferior parietal visual (PGi, PGs) and somatosensory (PF) regions; and the unpleasant-related lateral orbitofrontal cortex. Tools activate an intermediate ventral stream area (VMV3, VVC, PHA3); visual motion regions (FST); somatosensory (1, 2); and auditory (A4, A5) cortical regions. The findings add function to cortical connectivity maps; and show how stationary visual stimuli activate other cortical regions related to their associations, including visual motion, somatosensory, auditory, semantic, and orbitofrontal cortex value-related, regions.
Topics: Humans; Magnetic Resonance Imaging; Male; Female; Adult; Brain Mapping; Hippocampus; Young Adult; Photic Stimulation; Connectome; Face; Neural Pathways; Visual Cortex; Visual Perception; Pattern Recognition, Visual
PubMed: 38839620
DOI: 10.1007/s00429-024-02811-6 -
NeuroImage Jul 2024Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different...
BACKGROUND
Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA.
METHODS
We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs.
RESULTS
Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083).
CONCLUSION
PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.
Topics: Humans; Male; Female; White Matter; Middle Aged; Aged; Diffusion Tensor Imaging; Basal Ganglia; Stroke; Aphasia; Language; Adult; Diffusion Magnetic Resonance Imaging
PubMed: 38825217
DOI: 10.1016/j.neuroimage.2024.120664 -
Hearing Research Aug 2024Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential...
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.
Topics: Animals; Superior Olivary Complex; Auditory Pathways; Sound Localization; Axons; Rats; Male; Dextrans; Biotin; Acoustic Stimulation; Efferent Pathways; Olivary Nucleus; Female; Neuroanatomical Tract-Tracing Techniques; Rats, Wistar
PubMed: 38797037
DOI: 10.1016/j.heares.2024.109036 -
Hearing Research Aug 2024Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of...
Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity.
Topics: Animals; Cats; Auditory Cortex; Deafness; Acoustic Stimulation; Gamma Rhythm; Cochlear Implants; Alpha Rhythm; Evoked Potentials, Auditory; Algorithms; Auditory Pathways; Disease Models, Animal; Theta Rhythm
PubMed: 38797035
DOI: 10.1016/j.heares.2024.109032 -
Bioengineering (Basel, Switzerland) Apr 2024Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available.... (Review)
Review
Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear's architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions.
PubMed: 38790292
DOI: 10.3390/bioengineering11050425 -
BioRxiv : the Preprint Server For... May 2024The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and has been demonstrated to play a role in behaviors that require...
The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and has been demonstrated to play a role in behaviors that require sensorimotor integration including discrimination , avoidance and defense responses. The output neurons of the striatum, the D1 and D2 striatal projection neurons (SPNs) that make up the direct and indirect pathways, respectively, are thought to play differential roles in these behavioral responses, although it remains unclear if or how these neurons display differential responsivity to sensory stimuli. Here, we used whole-cell recordings in vivo and ex vivo to examine the strength of excitatory and inhibitory synaptic inputs onto D1 and D2 SPNs following the stimulation of upstream auditory pathways. While D1 and D2 SPNs both displayed stimulus-evoked depolarizations, D1 SPN responses were stronger and faster for all stimuli tested in vivo as well as in brain slices. This difference did not arise from differences in the strength of excitatory inputs but from differences in the strength of feed forward inhibition. Indeed, fast spiking interneurons, which are readily engaged by auditory afferents exerted stronger inhibition onto D2 SPNs compared to D1 SPNs. Our results support a model in which differences in feed forward inhibition enable the preferential recruitment of the direct pathway in response to auditory stimuli, positioning this pathway to initiate sound-driven actions.
PubMed: 38766066
DOI: 10.1101/2024.05.09.592848