Faculty Bibliography

Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). The mechanisms underlying these properties are not completely understood, although the amplitude of neural signal oscillations (Vogel and Machizawa, 2004) and brain activation in specific cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM performance may also reflect variability in white matter structural properties. However, data based primarily on diffusion tensor imaging approaches remain inconclusive. Here, we investigate the relationship between white matter and VWM capacity in human subjects using an advanced diffusion imaging technique, diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel quantitative white mater metrics, among them the axonal water fraction (faxon), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in faxon within a widely distributed network of white matter tracts. Increased faxon associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition.

Microstructural white matter deficits in Autism Spectrum Disorders (ASD) have been suggested by both histological findings and Diffusion Tensor Imaging (DTI) studies, which show reduced fractional anisotropy (FA) and increased mean diffusivity (MD). However, imaging reports are generally not consistent across studies and the underlying physiological causes of the reported differences in FA and MD remain poorly understood. In this study, we sought to further characterize white matter deficits in ASD by employing an advanced diffusion imaging method, the Diffusional Kurtosis Imaging (DKI), and a two-compartment diffusion model of white matter. This model differentially describes intra- and extra-axonal white matter compartments using Axonal Water Fraction (faxon ) a measure reflecting axonal caliber and density, and compartment-specific diffusivity measures. Diagnostic utility of these measures and associations with processing speed performance were also examined. Comparative studies were conducted in 16 young male adults with High Functioning Autism (HFA) and 17 typically developing control participants (TDC). Significantly decreased faxon was observed in HFA compared to the control group in most of the major white matter tracts, including the corpus callosum, cortico-spinal tracts, and superior longitudinal, inferior longitudinal and inferior fronto-occipital fasciculi. Intra-axonal diffusivity (Daxon ) was also found to be reduced in some of these regions. Decreased axial extra-axonal diffusivity (ADextra ) was noted in the genu of the corpus callosum. Reduced processing speed significantly correlated with decreased faxon and Daxon in several tracts. faxon of the left cortico-spinal tract and superior longitudinal fasciculi showed good accuracy in discriminating the HFA and TDC groups. In conclusion, these findings suggest altered axonal microstructure in young adults with HFA which is associated with reduced processing speed. Compartment-specific diffusion metrics appear to improve specificity and sensitivity to white matter deficits in this population.

Purpose: To investigate the integrity of the default-mode network (DMN) by using independent component analysis (ICA) methods in patients shortly after mild traumatic brain injury (MTBI) and healthy control subjects, and to correlate DMN connectivity changes with neurocognitive tests and clinical symptoms. Materials and Methods: This study was approved by the institutional review board and complied with HIPAA regulations. Twenty-three patients with MTBI who had posttraumatic symptoms shortly after injury (<2 months) and 18 age-matched healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging was performed at 3 T to characterize the DMN by using ICA methods, including a single-participant ICA on the basis of a comprehensive template from core seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) nodes. ICA z images of DMN components were compared between the two groups and correlated with neurocognitive tests and clinical performance in patients by using Pearson and Spearman rank correlation. Results: When compared with the control subjects, there was significantly reduced connectivity in the PCC and parietal regions and increased frontal connectivity around the MPFC in patients with MTBI (P < .01). These frontoposterior opposing changes within the DMN were significantly correlated (r = -0.44, P = .03). The reduced posterior connectivity correlated positively with neurocognitive dysfunction (eg, cognitive flexibility), while the increased frontal connectivity correlated negatively with posttraumatic symptoms (ie, depression, anxiety, fatigue, and postconcussion syndrome). Conclusion: These results showed abnormal DMN connectivity patterns in patients with MTBI, which may provide insight into how neuronal communication and information integration are disrupted among DMN key structures after mild head injury. (c) RSNA, 2012.

Purpose: To explore the neural correlates of the thalamus by using resting-state functional magnetic resonance (MR) imaging and to investigate whether thalamic resting-state networks (RSNs) are disrupted in patients with mild traumatic brain injury (MTBI). Materials and Methods: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained from 24 patients with MTBI and 17 healthy control subjects. The patients had varying degrees of symptoms, with a mean disease duration of 22 days. The resting-state functional MR imaging data were analyzed by using a standard seed-based whole-brain correlation method to characterize thalamic RSNs. Student t tests were used to perform comparisons. The association between thalamic RSNs and performance on neuropsychologic and neurobehavioral measures was also investigated in patients with MTBI by using Spearman rank correlation. Results: A normal pattern of thalamic RSNs was demonstrated in healthy subjects. This pattern was characterized as representing relatively symmetric and restrictive functional thalamocortical connectivity, suggesting an inhibitory property of the thalamic neurons during the resting state. This pattern was disrupted, with significantly increased thalamic RSNs (P </= .005) and decreased symmetry (P = .03) in patients with MTBI compared with healthy control subjects. Increased functional thalamocortical redistributive connectivity was correlated with diminished neurocognitive functions and clinical symptoms in patients with MTBI. Conclusion: These findings of abnormal thalamic RSNs lend further support to the presumed subtle thalamic injury in patients with MTBI. Resting-state functional MR imaging can be used as an additional imaging modality for detection of thalamocortical connectivity abnormalities and for better understanding of the complex persistent postconcussive syndrome. (c) RSNA, 2011

OBJECTIVE: To assess cerebral blood flow (CBF) changes in patients with mild traumatic brain injury (MTBI) using an arterial spin labelling (ASL) perfusion MRI and to investigate the severity of neuropsychological functional impairment with respect to haemodynamic changes. MATERIALS AND METHODS: Twenty-one patients with MTBI and 20 healthy controls were studied at 3T MR. The median time since the onset of brain injury in patients was 24.6 months. Both patients and controls underwent a traditional consensus battery of neurocognitive tests. ASL was performed using true fast imaging with steady state precession and a flow-sensitive alternating inversion recovery preparation. Regional CBF were measured in both deep and cortical gray matter as well as white matter at the level of basal ganglia. RESULTS: The mean regional CBF was significantly lower in patients with MTBI (45.9 +/- 9.8 ml/100 g min(-1)) as compared to normal controls (57.1 +/- 8.1 ml/100 g min(-1); p = 0.002) in both sides of thalamus. The decrease of thalamic CBF was significantly correlated with several neurocognitive measures including processing and response speed, memory/learning, verbal fluency and executive function in patients. CONCLUSIONS: Haemodynamic impairment can occur and persist in patients with MTBI, the extent of which is more severe in thalamic regions and correlate with neurocognitive dysfunction during the extended course of disease

Many studies cite infertility as highly stressful, yet women's responses to infertility are quite variable. Lazarus and Folkman's cognitive phenomenological theory of stress, coping, and appraisal may explain this variability. Gender role identity, career role salience, and societal pressure for motherhood are variables hypothesized to affect a woman's cognitive appraisal of infertility, thus influencing distress level. Female participants (N = 119) were recruited through the NYU Fertility Clinic and Resolve, a support organization for individuals faced with infertility. Participants completed questionnaires assessing gender characteristics, career role salience, social pressure for motherhood, cognitive appraisal, and distress. Many respondents (42%) reported clinically significant levels of distress. A path analysis assessed the effects of gender-role identity, career role salience, social pressure for motherhood, and cognitive appraisal on distress. The model accounted for 32% of the variance in distress. Women experiencing social pressure for motherhood viewed infertility as more stressful, women identifying with more positively valued instrumental gender role traits reported less distress, and women who endorsed more negatively valued instrumental gender role traits and cognitively appraised infertility as stressful reported greater distress.

PRIMARY OBJECTIVE: To explore whether baseline diffusion tensor imaging (DTI) metrics are predictive of cognitive functioning 6 months post-injury in patients with mild traumatic brain injury (MTBI). RESEARCH DESIGN: Seventeen patients with MTBI and 29 sex- and age-matched healthy controls were studied. METHODS AND PROCEDURES: Participants underwent an MRI protocol including DTI, at an average of 4.0 (range: 1-10) days post-injury. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the following white matter (WM) regions: centra semiovale, the genu and the splenium of the corpus callosum and the posterior limb of the internal capsule. Participants underwent neuropsychological (NP) testing at baseline and at 6-month follow-up. Least squares regression analysis was used to evaluate the association of MD and FA with each NP test score at baseline and follow-up. MAIN OUTCOMES AND RESULTS: Compared to controls, average MD was significantly higher (p = 0.02) and average FA significantly lower (p = 0.0001) in MTBI patients. At the follow-up, there was a trend toward a significant association between baseline MD and response speed (r = -0.53, p = 0.087) and a positive correlation between baseline FA and Prioritization form B (r = 0.72, p = 0.003). CONCLUSIONS: DTI may provide short-term non-invasive predictive markers of cognitive functioning in patients with MTBI

Although cognitive impairment is common in multiple sclerosis (MS), its pathophysiology is still poorly understood. Abnormalities of cerebral blood flow (CBF) have long been acknowledged in MS and advances in perfusion magnetic resonance imaging (MRI) allow for their assessment in vivo. We investigated the relationship between regional perfusion changes and neuropsychological (NP) dysfunctions in patients with relapsing-remitting and primary-progressive MS. Absolute CBF, cerebral blood volume (CBV) and mean transit time were measured in 32 MS patients and 11 healthy controls using dynamic susceptibility contrast-enhanced T2(*)-weighted MRI. A comprehensive NP test battery was administered to all patients. A mixed model analysis of covariance was performed for group comparisons in terms of perfusion measures in normal-appearing white matter (NAWM) and deep gray matter (GM). Pearson's correlations were used to describe the association of perfusion metrics with NP Z-scores. CBF and CBV values were significantly decreased in both NAWM and deep GM in MS patients compared with controls (P=0.01). In all patients, deep GM CBF was significantly associated with Rey Complex Figure Test (RCFT)-Copy (r=0.5; P=0.001) and deep GM CBV and NAWM CBV were significantly associated with Color-Word Interference Inhibition Switching test (D-KEFSIS) (r=0.4; P=0.008 and r=0.4; P=0.02). However, the only associations that remained significant after Bonferroni correction were between deep GM CBF and RCFT-Copy (P=0.006), and deep GM CBV and D-KEFSIS (P=0.04). Our results suggest a role for tissue perfusion impairment in NP dysfunction in MS. Large-scale studies are needed to characterize better this association.Journal of Cerebral Blood Flow & Metabolism advance online publication, 2 May 2007; doi:10.1038/sj.jcbfm.9600504

BACKGROUND AND PURPOSE: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging. MATERIALS AND METHODS: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients. RESULTS: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found. CONCLUSION: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS

OBJECTIVES: To assess the presence of perfusion abnormalities in the deep gray matter of patients with relapsing-remitting and primary progressive multiple sclerosis (MS) in comparison with healthy controls and to investigate the impact of perfusion impairment on clinical disability and fatigue. DESIGN: Survey. SETTING: Research-oriented hospital. Patients Twenty-two patients with MS and 11 age- and sex-matched healthy volunteers. Intervention Absolute cerebral blood flow, cerebral blood volume, and mean transit time were measured in the thalamus, putamen, and caudate nuclei. MAIN OUTCOME MEASURES: Decrease of cerebral blood flow in the deep gray matter of patients with MS and correlation between perfusion impairment and the severity of fatigue. RESULTS: The cerebral blood flow value averaged over the thalamus, putamen, and caudate nuclei was significantly lower in patients with primary progressive MS (P<.001) and in patients with relapsing-remitting MS (P = .01) compared with controls, and there was a trend for patients with primary progressive MS to have lower average cerebral blood flow than patients with relapsing-remitting MS (P = .06). With respect to cerebral blood volume, there was a significant difference between patients with primary progressive MS and controls (P<.001) and between the 2 groups of patients (P = .03) but not between patients with relapsing-remitting MS and controls (P>.30). The fatigue score was significantly correlated with cerebral blood flow (r = 0.4; P<.001) and cerebral blood volume (r = 0.5; P = .004). CONCLUSION: The decrease of tissue perfusion in the deep gray matter of patients with MS is associated with the severity of fatigue