The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI to assess the effect of hypertension on glymphatic transport kinetics in male young and adult spontaneously hypertensive (SHR) rats compared with age-matched normotensive Wistar-Kyoto rats (WKY). We anesthetized the rats with dexmedetomidine/isoflurane and infused paramagnetic contrast (Gd-DOTA) into the cisterna magna during dynamic contrast-enhanced MRI to quantify glymphatic transport kinetics. Structural MRI analysis showed that cerebroventricular volumes are larger and brain volumes significantly smaller in SHR compared with WKY rats, regardless of age. We observed ventricular reflux of Gd-DOTA in SHR rats only, indicating abnormal CSF flow dynamics secondar...

Deactivation of the human brain's default mode network (DMN) is regarded as suppression of endogenous activity to support exogenous task-related processes. This phenomenon has important functional relevance and insufficient DMN deactivation has been implicated in several neuropsychiatric disorders. However, the neurochemical mechanism of the DMN′s deactivation remains largely unknown. In the present study, we test the hypothesis that the major excitatory and inhibitory neurotransmitters, glutamate and GABA, respectively, are associated with DMN deactivation. We used magnetic resonance spectroscopy to measure neurotransmitter concentrations in the posterior cingulate cortex/precuneus (PCC/PCu), a key component of the DMN, and functional magnetic resonance imaging to evaluate DMN deactivation induced by an n-back working memory task. Our results demonstrate significant associations of glutamate and GABA with DMN deactivation. Specifically, high regional GABA concentration in the PCC/PCu area is associated wi...

Multiple Sclerosis (MS) results in visual cortex (VC) dysfunction, even in the absence of ophthalmic pathologies. The precise mechanism of this dysfunction remains elusive. Our previous studies have shown an association between white-matter microstructu...

Does a conflict between inborn motor preferences and educational standards during childhood impact the structure of the adult human brain? To examine this issue, we acquired high-resolution T1-weighted magnetic resonance scans of the whole brain in adult “converted” left-handers who had been forced as children to become dextral writers. Analysis of sulcal surfaces revealed that consistent right- and left-handers showed an interhemispheric asymmetry in the surface area of the central sulcus with a greater surface contralateral to the dominant hand. This pattern was reversed in the converted group who showed a larger surface of the central sulcus in their left, nondominant hemisphere, indicating plasticity of the primary sensorimotor cortex caused by forced use of the nondominant hand. Voxel-based morphometry showed a reduction of gray matter volume in the middle part of the left putamen in converted left-handers relative to both consistently handed groups. A similar trend was found in the right putamen. Con...

Background: While hippocampal atrophy is a well-known biomarker of Alzheimer Disease (AD), its use in a clinical setting is limited because atrophy begins years before clinical onset. This preclinical (amyloid positive) stage of AD is undetectable witho...

Intracranial neurophysiological recordings require chronic implants to provide transcranial access to the brain. Especially in larger animals, which participate in experiments over extended periods of time, implants should match the skull curvature to promote osseointegration and avoid tissue and bacterial ingress over time. Proposed CAD methods for designing implants to date have focused on naive animals with continuous and even skull surfaces and calculate Boolean differences between implant and skull surface to fit the implant to the skull curvature. However, custom-fitting by calculating the difference fails, if a discontinuous skull surface needs to be matched. Also, the difference method does not allow designs with constant material thickness along the skull curvature, e.g., to allow fixed screw lengths. We present a universal step-by-step guide for custom-fitting implants which overcomes these limitations. It is suited for unusual skull conditions, like surface discontinuities or irregularities and ...

Previous research from our laboratory demonstrated that volumes of mesial temporal lobe structures such as the entorhinal cortex and hippocampus are sensitive markers of incident Alzheimer’s disease (AD). In addition, older people with amnestic mild cog...

Functional magnetic resonance imaging (fMRI) of the hand representation in primary somatosensory cortex (area 3b) of macaque monkeys revealed an ipsilateral hand input undetected by most previous studies. Ipsilateral responses had a hemodynamic signature indistinguishable from that of contralateral hand responses. We explored the neural mechanisms of the fMRI effects using a second derivative analysis of field potentials [current source density (CSD) analysis] combined with action potential profiles, sampled from area 3b using linear array multielectrodes. In contrast to the predominantly excitatory contralateral response, the colocated ipsilateral response appeared dominated by inhibition, suggesting that ipsilateral inputs may have modulatory effects on contralateral input processing. Our findings confirm bimanual convergence at the earliest stage of cortical somatosensory processing in primates. They also illustrate the value of combined CSD and fMRI analyses in monkeys for defining hidden aspects of se...

Major sequelae of mild traumatic brain injury (mTBI) in adolescence include attention deficit hyperactivity disorder (ADHD) symptoms and cognitive deficits. As cognitive deficits are linked to abnormal dopamine (DA) function in the brain, we aimed to ex...

A core property of human semantic processing is the rapid, facilitatory influence of prior input on extracting the meaning of what comes next, even under conditions of minimal awareness. Previous work has shown a number of neurophysiological indices of this facilitation, but the mapping between time course and localization—critical for separating automatic semantic facilitation from other mechanisms—has thus far been unclear. In the current study, we used a multimodal imaging approach to isolate early, bottom-up effects of context on semantic memory, acquiring a combination of electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) measurements in the same individuals with a masked semantic priming paradigm. Across techniques, the results provide a strikingly convergent picture of early automatic semantic facilitation. Event-related potentials demonstrated early sensitivity to semantic association between 300 and 500 ms; MEG localized the differential ne...