Evolution of aberrant brain-wide spatiotemporal dynamics of resting-state networks in a Huntington's disease mouse model.

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.

Adult auditory brain responses to nestling begging calls in seasonal songbirds: an fMRI study in non-parenting male and female starlings ().

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 (). 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.

Auditory cortical regions show resting-state functional connectivity with the default mode-like network in echolocating bats.

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.

Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington's disease.

Background: Huntington's disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF).

Diffusion MRI marks progressive alterations in fiber integrity in the zQ175DN mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disease affecting motor and cognitive abilities. Multiple studies have found white matter anomalies in HD-affected humans and animal models of HD. The identification of sensitive white-matter-based biomarkers in HD animal models will be important in understanding disease mechanisms and testing the efficacy of therapeutic interventions.

Longitudinal investigation of changes in resting-state co-activation patterns and their predictive ability in the zQ175 DN mouse model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by expanded (≥ 40) glutamine-encoding CAG repeats in the huntingtin gene, which leads to dysfunction and death of predominantly striatal and cortical neurons. While the genetic profile and clinical signs and symptoms of the disease are better known, changes in the functional architecture of the brain, especially before the clinical expression becomes apparent, are not fully and consistently characterized. In this study, we sought to uncover functional changes in the brain in the heterozygous (HET) zQ175 delta-neo (DN) mouse model at 3, 6, and 10 months of age, using resting-state functional magnetic resonance imaging (RS-fMRI).

Resting-state fMRI reveals longitudinal alterations in brain network connectivity in the zQ175DN mouse model of Huntington's disease.

Huntington's disease is an autosomal, dominantly inherited neurodegenerative disease caused by an expansion of the CAG repeats in exon 1 of the huntingtin gene. Neuronal degeneration and dysfunction that precedes regional atrophy result in the impairment of striatal and cortical circuits that affect the brain's large-scale network functionality. However, the evolution of these disease-driven, large-scale connectivity alterations is still poorly understood.

Altered dynamics of glymphatic flow in a mature-onset Tet-off APP mouse model of amyloidosis.

Background: Alzheimer's disease (AD) is an incurable neurodegenerative disorder characterised by the progressive buildup of toxic amyloid-beta (Aβ) and tau protein aggregates eventually leading to cognitive decline. Recent lines of evidence suggest that an impairment of the glymphatic system (GS), a brain waste clearance pathway, plays a key role in the pathology of AD. Moreover, a relationship between GS function and neuronal network integrity has been strongly implicated.

Altered basal forebrain function during whole-brain network activity at pre- and early-plaque stages of Alzheimer's disease in TgF344-AD rats.

Background: Imbalanced synaptic transmission appears to be an early driver in Alzheimer's disease (AD) leading to brain network alterations. Early detection of altered synaptic transmission and insight into mechanisms causing early synaptic alterations would be valuable treatment strategies. This study aimed to investigate how whole-brain networks are influenced at pre- and early-plague stages of AD and if these manifestations are associated with concomitant cellular and synaptic deficits.

A brain for all seasons: An in vivo MRI perspective on songbirds.

Seasonality in songbirds includes not only reproduction but also seasonal changes in singing behavior and its neural substrate, the song control system (SCS). Prior research mainly focused on the role of sex steroids on this seasonal SCS neuroplasticity in males. In this review, we summarize the advances made in the field of seasonal neuroplasticity by applying in vivo magnetic resonance imaging (MRI) in male and female starlings, analyzing the entire brain, monitoring birds longitudinally and determining the neuronal correlates of seasonal variations in plasma hormone levels and song behavior.

Striatal Injury Induces Overall Brain Alteration at the Pallial, Thalamic, and Cerebellar Levels.

The striatal region Area X plays an important role during song learning, sequencing, and variability in songbirds. A previous study revealed that neurotoxic damage within Area X results in micro and macrostructural changes across the entire brain, including the downstream dorsal thalamus and both the upstream pallial nucleus HVC (proper name) and the deep cerebellar nuclei (DCN). Here, we specify these changes on cellular and gene expression levels.

Development of a ligand for in vivo imaging of mutant huntingtin in Huntington's disease.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin () gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (polyQ) tract. Whereas several therapeutic programs targeting mHTT expression have advanced to clinical evaluation, methods to visualize mHTT protein species in the living brain are lacking. Here, we demonstrate the development and characterization of a positron emission tomography (PET) imaging radioligand with high affinity and selectivity for mHTT aggregates.

Monitoring Neuronal Network Disturbances of Brain Diseases: A Preclinical MRI Approach in the Rodent Brain.

Functional and structural neuronal networks, as recorded by resting-state functional MRI and diffusion MRI-based tractography, gain increasing attention as data driven whole brain imaging methods not limited to the foci of the primary pathology or the known key affected regions but permitting to characterize the entire network response of the brain after disease or injury. Their connectome contents thus provide information on distal brain areas, directly or indirectly affected by and interacting with the primary pathological event or affected regions. From such information, a better understanding of the dynamics of disease progression is expected.

Uncovering a 'sensitive window' of multisensory and motor neuroplasticity in the cerebrum and cerebellum of male and female starlings.

Traditionally, research unraveling seasonal neuroplasticity in songbirds has focused on the male song control system and testosterone. We longitudinally monitored the song behavior and neuroplasticity in male and female starlings during multiple photoperiods using Diffusion Tensor and Fixel-Based techniques. These exploratory data-driven whole-brain methods resulted in a population-based tractogram confirming microstructural sexual dimorphisms in the song control system.

TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy.

Neuroinflammation is a key component of epileptogenesis, the process leading to acquired epilepsy. In recent years, with the development of non-invasive in vivo positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO), a marker of neuroinflammation, it has become possible to perform longitudinal studies to characterize neuroinflammation at different disease stages in animal models of epileptogenesis. This study aimed to utilize the prognostic capability of TSPO PET imaging at disease onset (2 weeks post-SE) to categorize epileptic rats with distinct seizure burden based on TSPO levels at disease onset and investigate their association to TSPO expression at the chronic epilepsy stage.

DNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression Dynamics in Zebra Finch Telencephalon.

Song learning in zebra finches () is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development.

Resting-State Co-activation Patterns as Promising Candidates for Prediction of Alzheimer's Disease in Aged Mice.

Alzheimer's disease (AD), a neurodegenerative disorder marked by accumulation of extracellular amyloid-β (Aβ) plaques leads to progressive loss of memory and cognitive function. Resting-state fMRI (RS-fMRI) studies have provided links between these two observations in terms of disruption of default mode and task-positive resting-state networks (RSNs). Important insights underlying these disruptions were recently obtained by investigating dynamic fluctuations in RS-fMRI signals in old TG2576 mice (a mouse model of amyloidosis) using a set of quasi-periodic patterns (QPP).

Resting Brain Fluctuations Are Intrinsically Coupled to Visual Response Dynamics.

How do intrinsic brain dynamics interact with processing of external sensory stimuli? We sought new insights using functional magnetic resonance imaging to track spatiotemporal activity patterns at the whole brain level in lightly anesthetized mice, during both resting conditions and visual stimulation trials. Our results provide evidence that quasiperiodic patterns (QPPs) are the most prominent component of mouse resting brain dynamics. These QPPs captured the temporal alignment of anticorrelation between the default mode (DMN)- and task-positive (TPN)-like networks, with global brain fluctuations, and activity in neuromodulatory nuclei of the reticular formation.

Progressive tau aggregation does not alter functional brain network connectivity in seeded hTau.P301L mice.

Progressive accumulation of hyperphosphorylated tau is a hallmark of various neurodegenerative disorders including Alzheimer's disease. However, to date, the functional effects of tau pathology on brain network connectivity remain poorly understood. To directly interrogate the impact of tau pathology on functional brain connectivity, we conducted a longitudinal experiment in which we monitored a fibril-seeded hTau.

Chemogenetic silencing of neurons in the mouse anterior cingulate area modulates neuronal activity and functional connectivity.

The anterior cingulate area (ACC) is an integral part of the prefrontal cortex in mice and supports cognitive functions, including attentional processes, motion planning and execution as well as remote memory, fear and pain. Previous anatomical and functional imaging studies demonstrated that the ACC is interconnected with numerous brain regions, such as motor and sensory cortices, amygdala and limbic areas, suggesting it serves as a hub in functional networks. However, the exact role of the ACC in regulating functional network activity and connectivity remains to be elucidated.