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Alterations in myelin integrity are involved in many neurological disorders and demyelinating diseases, such as multiple sclerosis (MS). Although magnetic resonance imaging (MRI) is the gold standard method to diagnose and monitor MS patients, clinically available MRI protocols show limited specificity for myelin detection, notably in cerebral grey matter areas. Ultrashort echo time (UTE) MRI has shown great promise for direct imaging of lipids and myelin sheaths, and thus holds potential to improve lesion detection. In this study, we used a sequence combining magnetization transfer (MT) with UTE ("UTE-MT", TE ​= ​76 ​μs) and with short TE ("STE-MT", TE ​= ​3000 ​μs) to evaluate spatial and temporal changes in brain myelin content in the cuprizone mouse model for MS on a clinical 7 ​T scanner. During demyelination, UTE-MT ratio (UTE-MTR) and STE-MT ratio (STE-MTR) values were significantly decreased in most white matter and grey matter regions. However, only UTE-MTR detected cortical changes. After remyelination in subcortical and cortical areas, UTE-MTR values remained lower than baseline values, indicating that UTE-MT, but not STE-MT, imaging detected long-lasting changes following a demyelinating event. Next, we evaluated the potential correlations between imaging values and underlying histopathological markers. The strongest correlation was observed between UTE-MTR and percent coverage of myelin basic protein (MBP) immunostaining (r2 ​= ​0.71). A significant, although lower, correlation was observed between STE-MTR and MBP (r2 ​= ​0.48), and no correlation was found between UTE-MTR or STE-MTR and gliosis immunostaining. Interestingly, correlations varied across brain substructures. Altogether, our results demonstrate that UTE-MTR values significantly correlate with myelin content as measured by histopathology, not only in white matter, but also in subcortical and cortical grey matter regions in the cuprizone mouse model for MS. Readily implemented on a clinical 7 ​T system, this approach thus holds great potential for detecting demyelinating/remyelinating events in both white and grey matter areas in humans. When applied to patients with neurological disorders, including MS patient populations, UTE-MT methods may improve the non-invasive longitudinal monitoring of brain lesions, not only during disease progression but also in response to next generation remyelinating therapies.

Background: Huntington's disease (HD) is marked by irreversible loss of neuronal function for which currently no availability for disease‐modifying treatment exists. Advances in the understanding of disease progression can aid biomarker development, which in turn can accelerate therapeutic discovery. Methods: We characterised the progression of altered dynamics of whole‐brain network states in the zQ175DN mouse model of HD using a dynamic functional connectivity (FC) approach to resting‐state fMRI and identified quasi‐periodic patterns (QPPs) of brain activity constituting the most prominent resting‐state networks. Results: The occurrence of the normative QPPs, as observed in healthy controls, was reduced in the HD model as the phenotype progressed. This uncovered progressive cessation of synchronous brain activity with phenotypic progression, which is not observed with the conventional static FC approaches. To better understand the potential underlying cause of the observed changes in these brain states, we further assessed how mutant huntingtin (mHTT) protein deposition affects astrocytes and pericytes – one of the most important effectors of neurovascular coupling, along phenotypic progression. Increased cell‐type dependent mHTT deposition was observed at the age of onset of motor anomalies, in the caudate putamen, somatosensory and motor cortex, regions that are prominently involved in HD pathology as seen in humans. Conclusion: Our findings provide meaningful insights into the development and progression of altered functional brain dynamics in this HD model and open new avenues in assessing the dynamics of whole brain states, through QPPs, in clinical HD research. Highlights: Hyperactivity in the LCN‐linked regions within short QPPs observed before motor impairment onset.DMLN QPP presents a progressive decrease in DMLN activity and occurrence along HD‐like phenotype development.Breakdown of the LCN DMLN state flux at motor onset leads to a subsequent absence of the LCN DMLN QPP at an advanced HD‐like stage. [ABSTRACT FROM AUTHOR]

The present study aims to investigate whether begging calls elicit specific auditory responses in non-parenting birds, whether these responses are influenced by the hormonal status of the bird, and whether they reflect biparental care for offspring in the European starling (Sturnus vulgaris). An fMRI experiment was conducted to expose non-parenting male and female European starlings to recordings of conspecific nestling begging calls during both artificially induced breeding and non-breeding seasons. This response was compared with their reaction to conspecific individual warbling song motifs and artificial pure tones, serving as social species-specific and artificial control stimuli, respectively. Our findings reveal that begging calls evoke a response in non-parenting male and female starlings, with significantly higher responsiveness observed in the right Field L and the Caudomedial Nidopallium (NCM), regardless of season or sex. Moreover, a significant seasonal variation in auditory brain responses was elicited in both sexes exclusively by begging calls, not by the applied control stimuli, within a ventral midsagittal region of NCM. This heightened response to begging calls, even in nonparenting birds, in the right primary auditory system (Field L), and the photoperiod induced hormonal neuromodulation of auditory responses to offspring's begging calls in the secondary auditory system (NCM), bears resemblance to mammalian responses to hunger calls. This suggests a convergent evolution aimed at facilitating swift adult responses to such calls crucial for offspring survival. [ABSTRACT FROM AUTHOR]

Proinflammatory mononuclear phagocytes (MPs) play a crucial role in the progression of multiple sclerosis (MS) and other neurodegenerative diseases. Despite advances in neuroimaging, there are currently limited available methods enabling noninvasive detection of MPs in vivo. Interestingly, upon activation and subsequent differentiation toward a proinflammatory phenotype MPs undergo metabolic reprogramming that results in increased glycolysis and production of lactate. Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) is a clinically translatable imaging method that allows noninvasive monitoring of metabolic pathways in real time. This method has proven highly useful to monitor the Warburg effect in cancer, through MR detection of increased HP [1-13C]pyruvate-to-lactate conversion. However, to date, this method has never been applied to the study of neuroinflammation. Here, we questioned the potential of 13C MRSI of HP [1-13C]pyruvate to monitor the presence of neuroinflammatory lesions in vivo in the cuprizone mouse model of MS. First, we demonstrated that 13C MRSI could detect a significant increase in HP [1-13C]pyruvate-to-lactate conversion, which was associated with a high density of proinflammatory MPs. We further demonstrated that the increase in HP [1-13C]lactate was likely mediated by pyruvate dehydrogenase kinase 1 up-regulation in activated MPs, resulting in regional pyruvate dehydrogenase inhibition. Altogether, our results demonstrate a potential for 13C MRSI of HP [1-13C]pyruvate as a neuroimaging method for assessment of inflammatory lesions. This approach could prove useful not only in MS but also in other neurological diseases presenting inflammatory components.

Echolocating bats are among the most social and vocal of all mammals. These animals are ideal subjects for functional MRI (fMRI) studies of auditory social communication given their relatively hypertrophic limbic and auditory neural structures and their reduced ability to hear MRI gradient noise. Yet, no resting-state networks relevant to social cognition (e.g., default mode-like networks or DMLNs) have been identified in bats since there are few, if any, fMRI studies in the chiropteran order. Here, we acquired fMRI data at 7 Tesla from nine lightly anesthetized pale spear-nosed bats (Phyllostomus discolor). We applied independent components analysis (ICA) to reveal resting-state networks and measured neural activity elicited by noise ripples (on: 10 ms; off: 10 ms) that span this species' ultrasonic hearing range (20 to 130 kHz). Resting-state networks pervaded auditory, parietal, and occipital cortices, along with the hippocampus, cerebellum, basal ganglia, and auditory brainstem. Two midline networks formed an apparent DMLN. Additionally, we found four predominantly auditory/parietal cortical networks, of which two were left-lateralized and two right-lateralized. Regions within four auditory/parietal cortical networks are known to respond to social calls. Along with the auditory brainstem, regions within these four cortical networks responded to ultrasonic noise ripples. Iterative analyses revealed consistent, significant functional connectivity between the left, but not right, auditory/parietal cortical networks and DMLN nodes, especially the anterior-most cingulate cortex. Thus, a resting-state network implicated in social cognition displays more distributed functional connectivity across left, relative to right, hemispheric cortical substrates of audition and communication in this highly social and vocal species. [ABSTRACT FROM AUTHOR]

BackgroundMale songbirds learn their songs from an adult tutor when they are young. A network of brain nuclei known as the 'song system' is the likely neural substrate for sensorimotor learning and production of song, but the neural networks involved in processing the auditory feedback signals necessary for song learning and maintenance remain unknown. Determining which regions show preferential responsiveness to the bird's own song (BOS) is of great importance because neurons sensitive to self-generated vocalisations could mediate this auditory feedback process. Neurons in the song nuclei and in a secondary auditory area, the caudal medial mesopallium (CMM), show selective responses to the BOS. The aim of the present study is to investigate the emergence of BOS selectivity within the network of primary auditory sub-regions in the avian pallium.Methods and findingsUsing blood oxygen level-dependent (BOLD) fMRI, we investigated neural responsiveness to natural and manipulated self-generated vocalisations and compared the selectivity for BOS and conspecific song in different sub-regions of the thalamo-recipient area Field L. Zebra finch males were exposed to conspecific song, BOS and to synthetic variations on BOS that differed in spectro-temporal and/or modulation phase structure. We found significant differences in the strength of BOLD responses between regions L2a, L2b and CMM, but no inter-stimuli differences within regions. In particular, we have shown that the overall signal strength to song and synthetic variations thereof was different within two sub-regions of Field L2: zone L2a was significantly more activated compared to the adjacent sub-region L2b.ConclusionsBased on our results we suggest that unlike nuclei in the song system, sub-regions in the primary auditory pallium do not show selectivity for the BOS, but appear to show different levels of activity with exposure to any sound according to their place in the auditory processing stream.

Song perception in songbirds, just as music and speech perception in humans, requires processing the spectral and temporal structure found in the succession of song-syllables. Using functional magnetic resonance imaging and synthetic songs that preserved exclusively either the temporal or the spectral structure of natural song, we investigated how vocalizations are processed in the avian forebrain. We found bilateral and equal activation of the primary auditory region, field L. The more ventral regions of field L showed depressed responses to the synthetic songs that lacked spectral structure. These ventral regions included subarea L3, medial-ventral subarea L and potentially the secondary auditory region caudal medial nidopallium. In addition, field L as a whole showed unexpected increased responses to the temporally filtered songs and this increase was the largest in the dorsal regions. These dorsal regions included L1 and the dorsal subareas L and L2b. Therefore, the ventral region of field L appears to be more sensitive to the preservation of both spectral and temporal information in the context of song processing. We did not find any differences in responses to playback of the bird's own song vs other familiar conspecific songs. We also investigated the effect of three commonly used anaesthetics on the blood oxygen level-dependent response: medetomidine, urethane and isoflurane. The extent of the area activated and the stimulus selectivity depended on the type of anaesthetic. We discuss these results in the context of what is known about the locus of action of the anaesthetics, and reports of neural activity measured in electrophysiological experiments.