Recent advancements in whole-brain imaging tools have enabled neuroscientists to investigate how coordinated brain activity processes external cues, influencing internal state changes and eliciting behavioral responses. For example, functional magnetic resonance imaging (fMRI) is a noninvasive technique that allows for the measurement of whole-brain activity in awake, behaving mice using the blood oxygenation-level-dependent (BOLD) response. However, to fully understand BOLD responses evoked by external stimuli, it is crucial that experimenters also assess behavioral responses during scans.
View Article and Find Full Text PDFIn human Alzheimer's disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI).
View Article and Find Full Text PDFMild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision.
View Article and Find Full Text PDFObjectives: Previous studies have established the role of the cortico-mesolimbic and descending pain modulation systems in chronic pain prediction. Mild traumatic brain injury (mTBI) is an acute pain model where chronic pain is prevalent and complicated for prediction. In this study, we set out to study whether functional connectivity (FC) of the nucleus accumbens (NAc) and the periaqueductal gray matter (PAG) is predictive of pain chronification in early-acute mTBI.
View Article and Find Full Text PDFCreative thinking represents a major evolutionary mechanism that greatly contributed to the rapid advancement of the human species. The ability to produce novel and useful ideas, or original thinking, is thought to correlate well with unexpected, synchronous activation of several large-scale, dispersed cortical networks, such as the default network (DN). Despite a vast amount of correlative evidence, a causal link between default network and creativity has yet to be demonstrated.
View Article and Find Full Text PDFIQSEC2 is an X-linked gene that is associated with autism spectrum disorder (ASD), intellectual disability, and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and is suggested to play a role in AMPA receptor trafficking and mediation of long-term depression. Here, we present brain-wide structural volumetric and functional connectivity characterization in a novel mouse model with a missense mutation in the IQ domain of IQSEC2 (A350V).
View Article and Find Full Text PDFIn recent years precision fMRI has emerged in human brain research, demonstrating characterization of individual differences in brain organization. However, mechanistic investigations to the sources of individual variability are limited in humans and thus require animal models. Here, we used resting-state fMRI in awake mice to quantify the contribution of individual variation to the functional architecture of the mouse cortex.
View Article and Find Full Text PDFNeurofibromin gene () mutation causes neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice, loss in adult oligodendrocytes causes myelin decompaction and increases oligodendrocyte nitric oxide (NO) levels. Nitric oxide synthase (NOS) inhibitors rescue this pathology.
View Article and Find Full Text PDFBackground MRI-guided focused US thalamotomy of ventral intermediate nucleus of the thalamus is a treatment for tremor disorders. Purpose To evaluate white matter integrity before and after thalamotomy and its correlation with clinical outcome. Materials and Methods Participants with essential tremor (ET) or Parkinson disease (PD) undergoing thalamotomy were prospectively recruited between March 2016 and October 2018.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2019
Whole brain dynamics intuitively depend upon the internal wiring of the brain; but to which extent the individual structural connectome constrains the corresponding functional connectome is unknown, even though its importance is uncontested. After acquiring structural data from individual mice, we virtualized their brain networks and simulated in silico functional MRI data. Theoretical results were validated against empirical awake functional MRI data obtained from the same mice.
View Article and Find Full Text PDFChildren with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1).
View Article and Find Full Text PDFWe have recently described an A350V mutation in IQSEC2 associated with intellectual disability, autism and epilepsy. We sought to understand the molecular pathophysiology of this mutation with the goal of developing targets for drug intervention. We demonstrate here that the A350V mutation results in interference with the binding of apocalmodulin to the IQ domain of IQSEC2.
View Article and Find Full Text PDFThe development of imaging methodologies for single cell measurements over extended timescales of up to weeks, in the intact animal, will depend on signal strength, stability, validity and specificity of labeling. Whereas light-microscopy can achieve these with genetically-encoded probes or dyes, this modality does not allow mesoscale imaging of entire intact tissues. Non-invasive imaging techniques, such as magnetic resonance imaging (MRI), outperform light microscopy in field of view and depth of imaging, but do not offer cellular resolution and specificity, suffer from low signal-to-noise ratio and, in some instances, low temporal resolution.
View Article and Find Full Text PDFMRI Segmentation of a pathological brain poses a significant challenge, as the available anatomical priors that provide top-down information to aid segmentation are inadequate in the presence of abnormalities. This problem is further complicated for longitudinal data capturing impaired brain development or neurodegenerative conditions, since the dynamic of brain atrophies has to be considered as well. For these cases, the absence of compatible annotated training examples renders the commonly used multi-atlas or machine-learning approaches impractical.
View Article and Find Full Text PDFAs the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey () visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset () primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.
View Article and Find Full Text PDFFront Aging Neurosci
January 2017
As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established.
View Article and Find Full Text PDFWhile the hippocampal memory system has been relatively conserved across mammals, the cerebral cortex has undergone massive expansion. A central question in brain evolution is how cortical development affected the nature of cortical inputs to the hippocampus. To address this question, we compared cortico-hippocampal connectivity using intrinsic functional connectivity MRI (fcMRI) in awake mice and humans.
View Article and Find Full Text PDFIn recent years, optogenetics has become a central tool in neuroscience research. Estimating the transmission of visible light through brain tissue is of crucial importance for controlling the activation levels of neurons in different depths, designing optical systems, and avoiding lesions from excessive power density. The Kubelka-Munk model and Monte Carlo simulations have previously been used to model light propagation through rodents' brain tissue, however, these prior attempts suffer from fundamental shortcomings.
View Article and Find Full Text PDFOptogenetic perturbation has become a fundamental tool in controlling activity in neurons. Used to control activity in cell cultures, slice preparations, anesthetized and awake behaving animals, optical control of cell-type specific activity enables the interrogation of complex systems. A remaining challenge in developing optical control tools is the ability to produce defined light patterns such that power-efficient, precise control of neuronal populations is obtained.
View Article and Find Full Text PDFAn important aspect of adaptive learning is the ability to flexibly use past experiences to guide new decisions. When facing a new decision, some people automatically leverage previously learned associations, while others do not. This variability in transfer of learning across individuals has been demonstrated repeatedly and has important implications for understanding adaptive behavior, yet the source of these individual differences remains poorly understood.
View Article and Find Full Text PDFTrauma-related psychopathology has been associated with an intense emotional reaction to stressful event. Emotional responses have evolved to signal the presence of risks to be avoided or of rewards to be approached in the environment. Thus, individuals' sensitivity to signals of risk and reward may affect the level of stress vulnerability.
View Article and Find Full Text PDFThe blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity.
View Article and Find Full Text PDFAsymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]).
View Article and Find Full Text PDFStudies demonstrating selective brain networks subserving motivation and mentalization (i.e. attributing states of mind to others) during social interactions have not investigated their mutual independence.
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