• Translating Time
• diffusion
• human
• mouse
• pathways
• time

• Animals
• Humans
• Mice
• Male
• Female
• Brain/growth & development
• Brain/diagnostic imaging
• Adolescent
• Adult
• Diffusion Tensor Imaging/methods
• Young Adult
• Mice, Inbred C57BL
• Aging/physiology
• Child
• Middle Aged
• Neuroimaging/methods
• Rats
• Aged
• Child, Preschool
• Neural Pathways/growth & development
• Neural Pathways/diagnostic imaging
• Infant
• Longevity/physiology
• White Matter/growth & development
• White Matter/diagnostic imaging

• P20 GM103446 NIGMS NIH HHS
• NIH

• fMRI
• impulsivity
• negative mood
• reward
• self‐regulation
• working memory

• Humans
• Female
• Adult
• Inhibition, Psychological
• Male
• Motivation/physiology
• Emotions/physiology
• Young Adult
• Magnetic Resonance Imaging
• Memory, Short-Term/physiology
• Brain Mapping
• Executive Function/physiology
• Cerebral Cortex/physiology
• Cerebral Cortex/diagnostic imaging
• Impulsive Behavior/physiology
• Cognition/physiology

• F31 MH120936 NIMH NIH HHS
• F31MH135695-01A1 NIMH NIH HHS
• P30 GM145765 NIGMS NIH HHS
• 1R01MH116228 NIMH NIH HHS
• P20 GM103653 NIGMS NIH HHS
• R01 MH116228 NIMH NIH HHS
• F31 MH135695 NIMH NIH HHS
• P30GM145765 NIGMS NIH HHS
• 2P20GM103653 NIGMS NIH HHS
• 1F31MH120936 NIMH NIH HHS
• National Institute of General Medical Sciences
• National Institute of Mental Health

• T32 GM144895 NIGMS NIH HHS
• P30 GM145765 NIGMS NIH HHS
• R21 HD101964 NICHD NIH HHS
• P20 GM103446 NIGMS NIH HHS
• P20 GM103653 NIGMS NIH HHS
• R25 GM122722 NIGMS NIH HHS

• neural circuits
• social behaviour
• stress and resilience

• Mice
• Animals
• Social Interaction
• Social Behavior
• Prefrontal Cortex/physiology
• Social Dominance
• Nucleus Accumbens

• R01 DA050454 NIDA NIH HHS
• R01 DA047851 NIDA NIH HHS
• TL1 TR002386 NCATS NIH HHS
• R01 MH125006 NIMH NIH HHS
• T32 DA039080 NIDA NIH HHS
• R01 MH109685 NIMH NIH HHS
• R01 DA054368 NIDA NIH HHS
• R01 MH123154 NIMH NIH HHS
• T32 GM007739 NIGMS NIH HHS
• R01 MH118451 NIMH NIH HHS
• R01 MH118934 NIMH NIH HHS
• R01 DA029122 NIDA NIH HHS
• F30 MH115622 NIMH NIH HHS
• R01 DA053261 NIDA NIH HHS
• U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)

• Basal ganglia
• Caudate
• Coyote
• Diffusion tensor imaging
• Putamen
• Sea lion

• Animals
• Caudate Nucleus
• Sea Lions
• Coyotes
• Putamen
• Primates

Cerebral small vessel disease (CSVD) is a leading cause of age-related microvascular cognitive decline, resulting in significant morbidity and decreased quality of life. Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging (MRI), key questions on CSVD remain elusive. Enhanced relationships and reliable lesion studies, such as white matter tractography using diffusion-based MRI (dMRI) are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD. Diffusion tensor imaging (DTI) and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage. However, due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting, interpreting the findings remain contentious, especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use. In this minireview, we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD, even for subclinical CSVD in at-risk individuals.

• Diffusion tensor imaging
• White matter
• Cerebral small vessel disease
• Pipeline processing
• Tractography

• T1-weighted imaging, tract-tracing
• brain-wide activity mapping
• computational image analysis
• longitudinal imaging
• magnetic resonance imaging
• manganese
• rodent brain imaging

• Animals
• Brain/metabolism
• Calcium Channels/pharmacology
• Contrast Media
• Image Enhancement/methods
• Magnetic Resonance Imaging/methods
• Manganese/metabolism
• Retrospective Studies

• UF1 NS100598 NINDS NIH HHS
• P20 GM121176 NIGMS NIH HHS
• R01 MH096093 NIMH NIH HHS
• R01 DA018184 NIDA NIH HHS
• R01 NS046810 NINDS NIH HHS
• UL1 TR001449 NCATS NIH HHS
• R01 NS062184 NINDS NIH HHS
• P20 AG068077 NIA NIH HHS

Connectivity data of the nervous system and subdivisions, such as the brainstem, cerebral cortex and subcortical nuclei, are necessary to understand connectional structures, predict effects of connectional disorders and simulate network dynamics. For that purpose, a database was built and analyzed which comprises all known directed and weighted connections within the rat brainstem. A longterm metastudy of original research publications describing tract tracing results form the foundation of the brainstem connectome (BC) database which can be analyzed directly in the framework neuroVIISAS. The BC database can be accessed directly by connectivity tables, a web-based tool and the framework. Analysis of global and local network properties, a motif analysis, and a community analysis of the brainstem connectome provides insight into its network organization. For example, we found that BC is a scale-free network with a small-world connectivity. The Louvain modularity and weighted stochastic block matching resulted in partially matching of functions and connectivity. BC modeling was performed to demonstrate signal propagation through the somatosensory pathway which is affected in Multiple sclerosis.

• Amygdala
• Animals
• Conditioning, Classical
• Extinction, Psychological
• Fear
• Humans
• Prefrontal Cortex

• Deutsche Forschungsgemeinschaft
• National Natural Science Foundation of China
• Beijing Municipal Science and Technology Commission
• National Key Research and Development Program of China
• Strategic Priority Research Program of Chinese Academy of Science
• CAS Interdisciplinary Innovation Team

• dielectric resonators
• electromagnetic coupling
• magnetic resonance microscopy
• signal-to-noise ratio
• solenoid

• Ceramics/chemistry
• Electromagnetic Fields
• Magnetic Resonance Imaging/instrumentation
• Microscopy/instrumentation
• Numerical Analysis, Computer-Assisted
• Plant Leaves/anatomy & histology
• Signal-To-Noise Ratio

• Horizon 2020 Framework Programme
• Russian Foundation for Basic Research
• President of the Russian Federation

The understanding of human and non-human microstructural brain alterations in the course of neurodegenerative diseases has substantially improved by the non-invasive magnetic resonance imaging (MRI) technique of diffusion tensor imaging (DTI). Animal models (including disease or knockout models) allow for a variety of experimental manipulations, which are not applicable to humans. Thus, the DTI approach provides a promising tool for cross-species cross-sectional and longitudinal investigations of the neurobiological targets and mechanisms of neurodegeneration. This overview with a systematic review focuses on the principles of DTI analysis as used in studies at the group level in living preclinical models of neurodegeneration. The translational aspect from in-vivo animal models toward (clinical) applications in humans is covered as well as the DTI-based research of the non-human brains' microstructure, the methodological aspects in data processing and analysis, and data interpretation at different abstraction levels. The aim of integrating DTI in multiparametric or multimodal imaging protocols will allow the interrogation of DTI data in terms of directional flow of information and may identify the microstructural underpinnings of neurodegeneration-related patterns.

• DTI
• group studies
• in vivo animal model
• magnetic resonance imaging
• neurodegeneration
• translational

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear.

In order to determine the MRI-derived correlates of myelin dynamics and to test if brain network characteristics derived from diffusion tensor imaging reflect microstructural tissue reorganization, we took advantage of the cuprizone model of general demyelination in mice and performed longitudinal histological and imaging analyses with behavioral tests. By introducing cuprizone into the diet, we induced targeted and consistent demyelination of oligodendrocytes, over a period of 5 weeks. Subsequent myelin synthesis was enabled by reintroduction of normal food.

Using specific immune-histological markers, we demonstrated that 2 weeks of cuprizone diet induced a 52% reduction of myelin content in the corpus callosum (CC) and a 35% reduction in the neocortex. An extended cuprizone diet increased myelin loss in the CC, while remyelination commenced in the neocortex. These histologically determined dynamics were reflected by MRI measurements from diffusion tensor imaging. Demyelination was associated with decreased fractional anisotropy (FA) values and increased modularity and clustering at the network level. MRI-derived modularization of the brain network and FA reduction in key anatomical regions, including the hippocampus, thalamus, and analyzed cortical areas, were closely related to impaired memory function and anxiety-like behavior.

Network-specific remyelination, shown by histology and MRI metrics, determined amelioration of functional performance and neuropsychiatric symptoms. Taken together, we illustrate the histological basis for the MRI-driven network responses to demyelination, where increased modularity leads to evolving damage and abnormal behavior in MS. Quantitative information about in vivo myelination processes is mirrored by diffusion-based imaging of microstructural integrity and network characteristics.

• Demyelination
• MRI
• Modularity
• Network Dynamics
• Remyelination

• GABAergic signaling
• anterior cingulate cortex
• cholinergic synapse
• depression
• infralimbic cortex
• mental comorbidities
• neuropathic pain
• prelimbic cortex

• Animals
• Chronic Pain/complications
• Chronic Pain/drug therapy
• Chronic Pain/physiopathology
• Cognition Disorders/complications
• Cognition Disorders/drug therapy
• Cognition Disorders/physiopathology
• Depressive Disorder/complications
• Depressive Disorder/drug therapy
• Depressive Disorder/physiopathology
• Gray Matter/drug effects
• Gyrus Cinguli/drug effects
• Gyrus Cinguli/physiopathology
• Humans
• Neural Pathways/pathology
• Neurons/drug effects
• Neurons/pathology
• Prefrontal Cortex/drug effects
• Prefrontal Cortex/physiopathology
• Synaptic Transmission/drug effects

• P 30809 Austrian Science Fund FWF
• P30809 Austrian Science Fund
• W1206-06 Austrian Science Fund
• P253450 Austrian Science Fund

• cingulate cortex
• comparative neuroscience
• cross-species research
• humans
• primates
• rodents

• Connectome
• Differential connectomics
• Graph analysis
• Multidimensional connectomes
• Nervous system
• Neuronal networks
• Rat
• Visualization

• Diffusion MRI
• High field
• Post mortem
• Segmented echo planar imaging
• T1 and T2 parametric maps
• Tractography

• Anxiety
• circuit
• negative bias
• prefrontal cortex

• Wellcome Trust
• 206459/Z/17/Z Wellcome Trust
• MR/K024280/1 Medical Research Council
• MR/R020817/1 Medical Research Council

Adult pair bonding involves dramatic changes in the perception and valuation of another individual¹. One key change is that partners come to reliably activate the brain's reward system^2-6, though the precise neural mechanisms by which partners become rewarding during sociosexual interactions leading to a bond remain unclear. Using a prairie vole model of social bonding⁷, we show how a functional circuit from medial prefrontal cortex (mPFC) to nucleus accumbens (NAcc) is dynamically modulated to enhance females' affiliative behavior towards a partner. Individual variation in the strength of this functional connectivity, particularly after the first mating encounter, predicts how quickly animals begin affiliative huddling with their partner. Rhythmically activating this circuit in a social context without mating biases later preference towards a partner, indicating that this circuit's activity is not just correlated with how quickly animals become affiliative but causally accelerates it. These results provide the first dynamic view of corticostriatal activity during bond formation, revealing how social interactions can recruit brain reward systems to drive changes in affiliative behavior.

• auditory
• diffusion tensor imaging
• dolphin

Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD). As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) regulate the expression and suppression of fear in rodents, respectively. Here, we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

• extinction
• fear
• freezing
• infralimbic
• prelimbic

• connectome
• diffusion tensor imaging
• maturation
• mouse

• Age Factors
• Animals
• Animals, Newborn
• Brain/anatomy & histology
• Brain/growth & development
• Connectome
• Diffusion Tensor Imaging
• Image Processing, Computer-Assisted
• Mice
• Mice, Inbred C57BL
• Neural Pathways/anatomy & histology
• Neural Pathways/growth & development

• R01 MH070365 NIMH NIH HHS

Neuroimaging has provided compelling data about the brain. Yet the underlying mechanisms of many neuroimaging techniques have not been elucidated. Here we report a voxel-based morphometry (VBM) study of Thy1-YFP mice following auditory fear conditioning complemented by confocal microscopy analysis of cortical thickness, neuronal morphometric features and nuclei size/density. Significant VBM results included the nuclei of the amygdala, the insula and the auditory cortex. There were no significant VBM changes in a control brain area. Focusing on the auditory cortex, confocal analysis showed that fear conditioning led to a significantly increased density of shorter and wider dendritic spines, while there were no spine differences in the control area. Of all the morphology metrics studied, the spine density was the only one to show significant correlation with the VBM signal. These data demonstrate that learning-induced structural changes detected by VBM may be partially explained by increases in dendritic spine density.

Voxel-based morphometry (VBM) involves comparisons of high resolution structural images of the brain between groups, but what causes changes in the VBM signal is unclear. Here the authors perform a VBM study of Thy1-YFP mice following auditory fear conditioning and propose that the signal changes can be partially explained by increases in dendritic spine density.

Interest in structural brain connectivity has grown with the understanding that abnormal neural connections may play a role in neurologic and psychiatric diseases. Small animal connectivity mapping techniques are particularly important for identifying aberrant connectivity in disease models. Diffusion magnetic resonance imaging tractography can provide nondestructive, 3D, brain-wide connectivity maps, but has historically been limited by low spatial resolution, low signal-to-noise ratio, and the difficulty in estimating multiple fiber orientations within a single image voxel. Small animal diffusion tractography can be substantially improved through the combination of ex vivo MRI with exogenous contrast agents, advanced diffusion acquisition and reconstruction techniques, and probabilistic fiber tracking. Here, we present a comprehensive, probabilistic tractography connectome of the mouse brain at microscopic resolution, and a comparison of these data with a neuronal tracer-based connectivity data from the Allen Brain Atlas. This work serves as a reference database for future tractography studies in the mouse brain, and demonstrates the fundamental differences between tractography and neuronal tracer data.

• connectome
• magnetic resonance imaging
• mouse
• neuroanatomy
• tractography

• Connectome
• Diffusion tensor imaging
• Diffusion weighted imaging
• Magnetic resonance imaging
• Medial geniculate nucleus
• Tractography

Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1) and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs) which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET) and wild-type (WT) mice using [³H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV) and the dentate gyrus (DG) of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL) subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However, in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.

• NMDA
• adolescence
• hippocampus
• lateral septum
• medial prefrontal cortex
• neuregulin 1
• schizophrenia
• stress

Microvascular disease leads to alterations of cerebral vasculature including the formation of microembolic (ME) strokes. Though ME are associated with changes in mood and the severity and progression of cognitive decline, the effect of ME strokes on cerebral microstructure and its relationship to behavioral endpoints is unknown. Here, we used adult and aged male rats to test the hypotheses that ME lesions result in subtle changes to white and gray matter integrity as detected by high-throughput diffusion tensor imaging (DTI) and that these structural disruptions correspond to behavioral deficits. Two weeks post-surgery, aged animals showed depressive-like behaviors in the sucrose consumption test in the absence of altered cerebral diffusivity as assessed by ex-vivo DTI. Furthermore, DTI indices did not correlate with the degree of behavioral disruption in aged animals or in a subset of animals with observed tissue cavitation and subtle DTI alterations. Together, data suggest that behavioral deficits are not the result of damage to brain regions or white matter tracts, rather the activity of other systems may underlie functional disruption and recovery.

• Aging/pathology
• Anhedonia
• Animals
• Cerebral Infarction/complications
• Depression/etiology
• Diffusion Tensor Imaging
• Embolism/complications
• Embolism/pathology
• Gray Matter/pathology
• Male
• Microspheres
• Microvessels/pathology
• Rats
• White Matter/pathology

• T32 GM008605 NIGMS NIH HHS

• Amygdala/physiology
• Animals
• Auditory Cortex/physiology
• Conditioning, Psychological/physiology
• Excitatory Postsynaptic Potentials/physiology
• Extinction, Psychological/physiology
• Fear/physiology
• Fear/psychology
• Inhibitory Postsynaptic Potentials/physiology
• Interneurons/physiology
• Male
• Mice
• Neural Inhibition/physiology
• Neural Pathways/physiology
• Optogenetics
• Prefrontal Cortex/physiology
• Synaptic Transmission/physiology

• R01 MH090464 NIMH NIH HHS
• R21 MH083011 NIMH NIH HHS
• MH090464 NIMH NIH HHS
• MH083011 NIMH NIH HHS

• diffusion tensor imaging
• emotional behavior
• nonhuman primates
• prepuberty
• social stress

• Amyloid beta-Protein Precursor/genetics
• Amyloid beta-Protein Precursor/metabolism
• Animals
• Anisotropy
• Brain/metabolism
• Brain Mapping/methods
• Cohort Studies
• Diffusion Magnetic Resonance Imaging/methods
• Diffusion Tensor Imaging/methods
• Mice
• Mice, Transgenic

• Animals
• Anisotropy
• Brain/anatomy & histology
• Brain/diagnostic imaging
• Cohort Studies
• Diffusion Tensor Imaging/methods
• Image Enhancement/methods
• Image Processing, Computer-Assisted/methods
• Mice
• Mice, Inbred C57BL
• Radiography
• Time Factors