Feel the beat: multimodal rhythm perception in cochlear implant users
Alberte Seeberg, Department of Clinical Medicine, Center for Music in the Brain
B. Petersen, Center for Music in the Brain, Department of Clinical Medicine; P. Vuust, Center for Music in the Brain, Department of Clinical Medicine; A. Højlund, Department of
Linguistics, Cognitive Science and Semiotics
Cochlear implants (CIs) are optimized for speech perception but poor in conveying music.
Rhythm, however, is repeatedly reported as the most successfully conveyed property of music, with CI users often performing on par with normal hearing (NH) controls in rhythmic tasks. These are often based on rhythmic stimuli presented in single streams, being at variance with real-world music, where multiple streams of rhythmic patterns occur
simultaneously. However, being able to perceive real-world musical rhythms is important for groove, i.e. the pleasurable desire to move to music.
NH listeners prefer moving to music of medium rhythmic complexity compared to high and low complexity. This relationship follows an inverted U-shape, implying that there is a
“sweet spot” at which a maximum pleasurable sensation of wanting to move is experienced. However, groove perception in CI users remains largely unexplored.
For a more complete experience of rhythm and groove, it is necessary to enhance CI users’
sensory input so they can distinguish and integrate sound of rhythmic instruments occurring simultaneously. Findings suggest that electro-haptic stimulation (EHS) enhances
perception of various sound properties in CI users. If optimized for rhythm perception, EHS may enhance perception of more complex rhythmic patterns in CI users.
This project studies rhythm and groove perception in CI users and the potential effect of rhythm-specific EHS. CI users’ perception of rhythm and groove will be mapped out with and without EHS. This will be done through behavioral testing and using
electroencephalography, enabling elucidation of the neural correlates of rhythm and groove perception in CI users.
Keywords: Basic neuroscience, Medical technology and diagnostic techniques, Ear, nose and throat (ENT)
Nano- and microstructural organization of OFC top-down connectivity and its optogenetic functional role in wild type and Slitrk5 knockout mice.
Ole Borup Svendsen, Department of Clinical Medicine, Core Center for Molecular Morphology, Sektion for Stereology and Microscopy
Jens Randel Nyengaard, Department of Clinical Medicine, Core Center for Molecular Morphology, Sektion for Stereology and Microscopy
The orbitofrontal cortex (OFC) and Striatum are two intensively studied brain areas, which both play essential roles in a wide range of cognitive functions. Both brain areas have been associated with obsessive-compulsive disorder (OCD), same as an impaired cortico- striatal circuit, in which both the OFC and Striatum are included. We propose to study the functional and structural role of OFC connectivity to subcortical regions (striatum) in wild- type and transgenic mice to understand and identify molecular and circuit events leading to OCD behavior. The transgenic mice, Slitrk5 KO-/-, have already shown overactivation in the OFC, structural irregularities in the striatum, such as reduced volume of the striatum, decrease in dendritic complexity of striatal neurons, and downregulation of glutamate receptors. All these dysfunctionalities and irregularities might contribute to deficient cortico-striatal neurotransmission, which is one of the primary hypotheses in developing obsessive-compulsive disorder. It is highly challenging to identify the structure and
functional role of OFC to Striatum, which is why various methods are implemented in this project. We will use optogenetics to manipulate mice pathways from OFC to striatum during behavioral assessments, to identify the functional role of this pathway during a simple decision-making. Three-dimensional electron microscopy is implemented to explore and compare the physical properties of the neural connectivity from OFC to the striatum at nanometer resolution. Lastly, tissue clearing with light sheet microscopy is incorporated to provide fine structural and molecular analysis of the OFC pathways within the whole mouse brain.
Keywords: Basic neuroscience, Animal models/disease models, Cell biology
Understanding cerebral alpha-synuclein pathology in Parkinson’s Disease – Histological studies of brains from the Danish Brain Collection
Mie Kristine Just Pedersen, Department of Clinical Medicine
P. Borghammer, Department of Clinical Medicine, AU; N. V. D. Berge, Department of Clinical Medicine, AU; T. Steiniche, Department of Pathology, AUH; M. W. Nielsen,
Department of Pathology, OUH; L. Parkkinen, Nuffield Department of Clinical Neuroscience, Oxford University
Parkinson’s Disease (PD) is by definition an asymmetrical disease according to the diagnostic criteria. The most influential neuropathological staging system of PD (Braak staging) cannot explain the asymmetrical onset in many PD patients. A competing system (Unified Staging System for Lewy Body Disorders) also cannot explain the asymmetry. Both these systems are based on neuropathological examination of single hemispheres at post mortem.
We have hypothesized that Lewy pathology in PD can originate in two different locations, the enteric nervous system and the brain, leading to two distinct disease courses i.e., body- first and brain-first PD. During early disease stages patients show different clinical profiles, but all cases end up in widespread pathology and clinically similar profiles during end stages.
Here, we investigate the spreading of Lewy pathology in both hemispheres of PD and incidental Lewy Body Disease post mortem brains from the Danish Brain Collection. We expect two distinctive patterns; a symmetrical pattern compatible with gut-first PD subtype and an asymmetrical pattern compatible with brain-first PD subtype.
Tissue samples obtained from 12 bihemispheric regions are immunohistochemically stained against α-synuclein, a major component of Lewy pathology, and the pathological burden in each region will be assessed quantificationally by artificial intelligence software trained to detect Lewy pathology.
An estimated 250 brains will be screened to include cases of varying degrees of Lewy pathology to assess the temporal aspect of spreading. This may elucidate the sites of the initial pathology within the CNS supporting the body- vs. brain-first hypothesis.
Keywords: Basic neuroscience, Other, Other
The role of single-chain SorCS2 in cerebellar connectivity: implications for cerebellar dysfunction and memory impairment
Pia Boxy, Department of Biomedicine
L. Kisiswa, Department of Biomedicine; A. Nykjær, Department of Biomedicine
Emerging research has indicated that the cerebellum is involved in higher-order cognitive functioning including spatial learning, attention, and memory, through extensive
interconnections between the deep cerebellar nuclei and several limbic structures.
Furthermore, aberrant cerebellar functionality is implicated in several neurodevelopmental diseases (NDDs) such as autism spectrum disorder as well as neuropsychiatric diseases. We focus on SorCS2, a member of the sortilin receptor family, known for their involvement in sorting and signaling, which is abundantly expressed during cerebellar development as well as in the adult Purkinje neurons. Additionally, SorCS2 is involved in various types of memory and a risk factor for several NDDs, including autism. The receptor undergoes proteolytic cleavage resulting in a single-chain receptor which can be further processed into a double-chain isoform, each with distinct expression patterns and biological
functions. Whilst both isoforms are highly expressed at early cerebellar postnatal stages, the expression shifts to predominantly the double-chain form from postnatal day 3 and onwards. By utilizing a transgenic mouse model which solely expresses the single-chain isoform, we wish to elucidate the role of SorCS2 in cerebellar maturation, synapse formation and circuit wiring. We hypothesize that correct expression of the different isoforms in a spatiotemporal manner is critical for proper cerebellar patterning as well as circuit assembly. And that ablation of SorCS2 contributes to cognitive and affective processing impairments as well as memory deficits.
Keywords: Basic neuroscience, Cell biology, Animal models/disease models
Learning complex music: Brain mechanisms underlying the encoding of auditory patterns
Gemma Fernández Rubio, Department of Clinical Medicine, Center for Music in the Brain (MIB)
E. Brattico, Department of Clinical Medicine - Center for Music in the Brain; P. Vuust, Department of Clinical Medicine - Center for Music in the Brain; L. Bonetti, Department of Clinical Medicine - Center for Music in the Brain
Memory is one of the most complex and crucial cognitive processes of the human mind.
Research on the neural mechanisms of memory encoding and recognition is largely based on the processing of static stimuli, such as pictures or words. However, to broaden our knowledge about memory processing and understand its fast dynamics of brain activity and connectivity, we must incorporate the temporal properties of dynamic stimuli, such as speech or music. Recently, we investigated the brain mechanisms underlying the
recognition of musical patterns in 71 participants using magnetoencephalography (MEG) and magnetic resonance imaging (MRI). Results showed that music recognition was strongly supported by brain areas typically linked to memory processing, such as the hippocampus, parahippocampal cortex, and cingulate and paracingulate gyri. We aim to expand our work by studying the neural mechanisms underlying the encoding of musical patterns and explore how previously acquired information (priors) influences this process.
We will investigate this in a healthy population with MEG and MRI using a wide range of musical patterns of varying complexity (i.e., tonal versus atonal music). We expect that the brain mechanisms will differ between encoded and forgotten musical patterns and that encoding will be supported by memory-related brain areas such as the hippocampus and dorsolateral prefrontal cortex, as shown in previous studies of static stimuli. Furthermore, we expect that providing cognitive priors will aid the encoding and subsequent recognition of complex musical patterns. We hope that our research will shed light on the intricate
spatiotemporal dynamics underlying memory encoding.
Keywords: Basic neuroscience, Psychiatry, psychology and mental health, Other
Locus coeruleus: The master switch for brain health?
Rasmus West Knopper, Department of Clinical Medicine, Center of Functionally Integrative Neuroscience
B. Hansen, Center of Functionally Integrative Neuroscience
Locus coeruleus (LC) is a pontine nucleus consisting of noradrenaline (NA) producing neurons. NA is central for brain blood flow and capillary permeability regulation. Evidence shows dysfunctional brain microvasculature to contribute significantly to the development of neurodegenerative diseases. Furthermore, LC neurons degenerate earlier than other brain regions in the course of Alzheimer’s disease (AD). LC also seems to be involved in the sleep-waking cycle through LC-NA projections to the cortex and by preventing an
inhibition of wake-promoting histamine release from the hypothalamus. Sleep is thought to drive the clearance of neurotoxic proteins which are accumulated in AD. All this leads to the hypothesis that LC is a significant contributor to the development of
neurodegenerative diseases and may constitute a therapeutic target. We aim to investigate LC’s control over brain capillary function.
An initial pilot study will employ an alpha 2 adrenergic autoreceptor agonist, clonidine, to inhibit the release of NA. Using fluorescein labelled dextrans, the study will use two-photon microscopy line scans to visualize the effect of LC ablation on red blood cell velocity.
Observed microvascular effects will then aid design of improved techniques for MRI
detection of subtle alterations in capillary flow. One potential window into this is via default mode network (DMN) MRI. This has direct translational value as the human DMN is known to be altered in AD patients. The cause of this, however, is not clear but may be elucidated by our study. With refinement subtle DMN changes may be detected as an earlier marker of AD thus widening the therapeutic window of the disease.
Keywords: Basic neuroscience, Clinical neuroscience, Cardiovascular system
Is the omega-6 to omega-3 ratio associated with late-onset multiple sclerosis? – A Danish Cohort Study
Hani Ahmed Sheik, Department of Public Health, Epidemiology
U. Pommerich, Department of Clinical Medicine; C. Dahm, Department of Public Health
Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The prevalence of MS in Denmark was estimated to 16,500 persons in 2020; one of the highest prevalence worldwide. The aetiology of MS is not fully understood, however, environmental factors and genetic predisposition are known risk factors. The dietary intake may have an impact on MS risk, too. Omega 3 fatty acids decrease inflammatory processes, through various mechanisms. Nonetheless, the functions of omega-3 fatty acids interact competitively with those of omega-6 fatty acids, which are known to have pro-inflammatory properties. The ratio between omega-6/omega-3 (n6:n3) intake has been shown to be associated with the incidence of other inflammatory diseases. Nevertheless, there is a scarcity in studies on the n6:n3 ratio and its association with MS. Hence, the aim of this study was to investigate the association between the n6:n3- ratio and the hazards of developing late-onset MS.
Method: The present prospective cohort study is based on participants from the Danish
‘Diet, Cancer and Health’-study, including middle-aged Danes (age 50-64 years). Cox proportional hazard models were used to estimate the association between tertiles of omega-3 intake and hazards of late-onset MS diagnosis. The Danish National Patient Registry was used to extract information on the diagnosis of MS during follow-up.
Results: The cohort contained 56,867 participants. A total number of 124 persons were diagnosed with late-onset MS during the follow-up. The statistical analysis is ongoing;
preliminary results will be presented at PhD day.
Keywords: Multiple Sclerosis, Omega-3, Omega-6, inflammation
Keywords: Public health, Inflammation, Epidemiology and biostatistics