Non-heme intracellular iron is critical to normal cellular function, however it is also a powerful oxidizer that creates reactive oxygen species. Aging is often associated with iron accumulation in subcortical brain structures, which disrupts cellular f...

Human T-cell lymphoma invasion and metastasis 2 (TIAM2), a member of the guanine nucleotide exchange factor (GEF) family, physiologically exists either in a long or short transcripts. The protein translated from short-TIAM2 mRNA (TIAM2S) has been noted ...

The cuprizone exposure has been used to model a wide range of pathological and behavioral deficits endpoints that recapitulate demyelinating diseases and multiple sclerosis (MS). We and others have described the behavioral, pathological and immunologica...

PICALM, a gene encoding phosphatidylinositol-binding clathrin assembly protein, is a highly-validated genetic risk factor for Alzheimer’s disease (AD). Besides its well-known role in regulating the intracellular trafficking of endocytic vesicles, studie...

The macaque brain consists of billions of neurons that can be studied across multiple spatial scales using electrical and optical techniques for recording and stimulation. Applying different techniques to study the same population of neurons offers powe...

The phonological awareness, the ability to manipulate the abstract phonological representations of oral language, is crucial for learning process of reading. The developmental dyslexia shows the deficits during both auditory and visually presented phonological awareness tasks, and manipulating phonological representation may be the core deficits of developmental dyslexia. The neuroimaging studies have revealed the contribution of the similar neural substrates to both auditory and visual tasks. The less prevalence of dyslexia in Japanese suggests that Japanese language, which has simple letter-to-syllable relation summarized in Japanese syllabary table, has some advantages for the impaired children. To derive the neural substrates for the phonological manipulation of Japanese, we used functional MRI. The same vowel exchange tasks were performed in auditory (voices) and visual (kana letters) presentation in 19 normal volunteers. Different from previous studies in alphabetic languages, the neural substrates w...

Human cognitive abilities decline with increasing chronological age, with decreased explicit memory performance being most strongly affected. However, some older adults show “successful aging,” that is, relatively preserved cognitive ability in old age. One explanation for this could be higher brain-structural integrity in these individuals. Alternatively, the brain might recruit existing resources more efficiently or employ compensatory cognitive strategies. Here, we approached this question by testing multiple candidate variables from structural and functional neuroimaging for their ability to predict chronological age and memory performance, respectively. Prediction was performed using support vector machine (SVM) classification and regression across and within two samples of young ( N  = 106) and older ( N  = 153) adults. The candidate variables were (1) behavioral response frequencies in an episodic memory test; (2) recently described functional magnetic resonance imaging (fMRI) scores reflecting pres...

Monkeys have been used widely to model human neurobiological and cognitive development. To examine early brain development a group of eight Rhesus monkeys (Macacca mulatta) were scanned repeatedly from the ages of 1 wk to 5 yrs on a GE 1.5 T Signa MR scanner. Each monkey received 8-20 (mean 14) whole brain T1-weighted structural scans in the horizontal plane using a 3-D volume SPGR pulse sequence (FOV 110 mm; slice thickness 1mm). An additional 8 adult monkeys were scanned to increase the number of cases at ages 36 and 60 months. Using the MedX image analysis program skull and extracranial structures were removed and the brain volumes calculated by two independent observers (inter-observer reliability r=0.84, p< 0.001). Total brain volumes at 1 week, 1, 2, 3, 4, 5-6, 8, 12, 18, 24, 36 and 60 months were analyzed by ANOVA with repeated measures resulting in a significant effect of age (F=50.8, p (corrected)< 0.001). Brain volumes showed a significant increase from 1 week to 2 years of 59% with no significan...

Diffuse axonal injury (DAI) is a hallmark of traumatic brain injury (TBI) pathology. Recently, the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) was developed to generate an experimental model of DAI in a mouse. The characterization of DAI using diffusion tensor magnetic resonance imaging (MRI; diffusion tensor imaging, DTI) may provide a useful set of outcome measures for preclinical and clinical studies. The objective of this study was to identify the complex neurobiological underpinnings of DTI features following DAI using a comprehensive and quantitative evaluation of DTI and histopathology in the CHIMERA mouse model. A consistent neuroanatomical pattern of pathology in specific white matter tracts was identified across ex vivo DTI maps and photomicrographs of histology. These observations were confirmed by voxelwise and regional analysis of DTI maps, demonstrating reduced fractional anisotropy (FA) in distinct regions such as the optic tract. Similar regions were identified ...

We aimed to identify brain areas involved in responding to affect communicated by expressive piano performance. Our subjects listened to two versions of Chopin’s Etude in E major, Opus 10, No. 3. The first version was an expressive performance, recorded by a highly trained musician on a computer-monitored piano. Our control was a computer-generated, mechanical performance of the same composition. Data analysis revealed differential brain activation in the two listening conditions. The expressive performance elicited greater activation in anterior cingulate, right temporal pole, right inferior frontal gyri, inferior parietal lobe and superior temporal gyri, areas that have been associated with emotion, attention and speech perception. The mechanical performance elicited greater activation in cerebellum, supplementary motor area and dorsolateral prefrontal cortex, areas primarily involved in motor and sequencing tasks. Our observations suggest that expressive music performance communicates affect beyond the ...