The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion–behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucl...

Plexiform neurofibromas in patients with neurofibromatosis type I (NF1) typically involve deep or named nerves, can become very large, may cause serious functional impairment and have a risk of malignant progression. In developing an animal model to study plexiform neurofibromas, we have shown that human NF1 neurofibrosarcoma-derived Schwann cells (SC) can be successfully xenografted into the sciatic nerves of scid mice. The histogenesis of engrafted neurofibrosarcoma SC was consistent with that of established human plexiform neurofibromas. The tumors invaded and degenerated the host nerve structure and proliferated in a slow, sustained manner without apparent malignancy. In addition, we observed angiogenic markers in xenografted nerves. We performed MRI to study the formation and progression of these tumors in our model. Using a 17.6 tesla, 89mm bore magnet we performed H-1 MRI at 750MHz on excised, fixed xenografted mouse sciatic nerves. We then compared the T1 weighted images to immunostaining of the sa...

High spatial and temporal resolution is critical to most research utilizing brain imaging techniques. Electroencephalography (EEG) offers high temporal resolution, but poor spatial information whereas functional magnetic resonance imaging (fMRI) yields little temporal information, but has a high spatial and true 3d-volume resolution. Therefore, many researchers utilize both techniques (sometimes even simultaneously) when conducting brain imaging experiments. The fact that fMRI scanners produce a loud pulsing noise during data acquisition is an obvious problem in studies that involve auditory stimuli. This sound cannot be completely shielded from the subjects and necessarily leads to different brain activation as compared to a silent environment hence contaminating the fMRI signal. The problem has been worked around by the development of the sparse sampling technique in which single volumes are acquired with long pauses between them before and after stimulus presentation. This technique is thought to minimi...

Lithium (Li) robustly upregulates the cytoprotective protein bcl-2 in rodent brain, and exerts potent neurotrophic/neuroprotective effects in several preclinical models. Utilizing high resolution 3-D MRI and validated quantitative brain tissue segmentation methodology, Li’s potential neurotrophic effects were investigated in Bipolar Disorder (BD) patients (n=10). MRI scans were conducted at baseline (medication free), and after 4 weeks of Li. Chronic Li significantly increased total gray matter content, with 8/10 patients showing an increase; the mean change was ~ 3%, representing an ~ 24cc increase in total brain gray matter. No changes were observed in brain white matter volume or in quantitative measures of regional cerebral water content (measured using MR spectroscopy). This provides strong evidence that the observed increases in gray matter content are due to neurotrophic effects, rather than cell swelling, osmotic effects, or changes in MRI contrast associated with Li. A finer grained sub-regional a...

Functional MRI studies in individuals with substance use disorder commonly show functional connectivity impairments across cortico-striatal circuits that underlie executive control, reward processing and salience attribution. However, substantially few ...

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...

The ability to discriminate between stimuli relies on a chain of neural operations associated with perception, memory and decision-making. Accumulating studies show learning-dependent plasticity in perception or decision-making, yet whether perceptual learning modifies mnemonic processing remains unclear. Here, we trained human participants of both sexes in an orientation discrimination task, while using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to separately examine training-induced changes in working memory (WM) representation. fMRI decoding revealed orientation-specific neural patterns during the delay period in primary visual cortex (V1) before, but not after, training, whereas neurodisruption of V1 during the delay period led to behavioral deficits in both phases. In contrast, both fMRI decoding and disruptive effect of TMS showed that intraparietal sulcus (IPS) represented WM content after, but not before, training. These results suggest that training do...

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...

Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, deficits in verbal and nonverbal communication, and a restricted repertoire of activities or interests. We performed a magnetic resonance imaging study to better define the neuropathology of autistic spectrum disorders. Here we report findings on the amygdala and the hippocampal formation. Borders of the amygdala, hippocampus, and cerebrum were defined, and their volumes were measured in male children (7.5-18.5 years of age) in four diagnostic groups: autism with mental retardation, autism without mental retardation, Asperger syndrome, and age-matched typically developing controls. Although there were no differences between groups in terms of total cerebral volume, children with autism (7.5-12.5 years of age) had larger right and left amygdala volumes than control children. There were no differences in amygdala volume between the adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in ...

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...