MRI-based methodology to monitor the impact of positional changes on the airway caliber in obstructive sleep apnea patients.

PURPOSE: To develop a non-invasive MRI-based methodology to visually and quantitatively assess the impact of head and chest rotations on the airway caliber. METHODS: An MRI table set-up was developed for independent rotations of the head and chest along B0 field and tested for feasibility using phantom scans. The accuracy of the head and chest rotations was validated with ten volunteer scans. A 3T MRI protocol was optimized to image the regions of interest (ROIs) that were the retropalatal (RP) and retroglossal (RG) sections of the upper airway. A workflow for data analysis was developed to assess the changes of the airway caliber following the independent head and chest rotations. RESULTS: A prototype MRI table setup was established with two separate plates each supporting and rotating the head or chest independently. Subject positioning and image acquisition were finished within seven minutes for each position. Thus, each subject MRI was set up with seven positions and completed for less than one hour. The implemented angles were within 0.3-degree deviation from the targeted angles. The data analysis workflow provided 2D and 3D visualization and quantification with the measurements of cross-sectional area, lateral and anterior-posterior distances of the ROIs. Sharp contrast of the airway and its surrounding tissues facilitated an automatic approach to ROI placement to minimize subjectivity. CONCLUSIONS: The 3T MRI data acquisition and analysis methodology could reliably assess the impact of head and chest rotations on the upper airway caliber to identify the optimal position for obstructive sleep apnea patients.

Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of Cortical Connectivity With Therapeutic SCS.

INTRODUCTION: The neurophysiological basis of pain relief due to spinal cord stimulation (SCS) and the related cortical processing of sensory information are not completely understood. The aim of this study was to use resting state functional magnetic resonance imaging (rs-fMRI) to detect changes in cortical networks and cortical processing related to the stimulator-induced pain relief. METHODS: Ten patients with complex regional pain syndrome (CRPS) or neuropathic leg pain underwent thoracic epidural spinal cord stimulator implantation. Stimulation parameters associated with "optimal" pain reduction were evaluated prior to imaging studies. Rs-fMRI was obtained on a 3 Tesla, Philips Achieva MRI. Rs-fMRI was performed with stimulator off (300TRs) and stimulator at optimum (Opt, 300 TRs) pain relief settings. Seed-based analysis of the resting state functional connectivity was conducted using seeds in regions established as participating in pain networks or in the default mode network (DMN) in addition to the network analysis. NCUT (normalized cut) parcellation was used to generate 98 cortical and subcortical regions of interest in order to expand our analysis of changes in functional connections to the entire brain. We corrected for multiple comparisons by limiting the false discovery rate to 5%. RESULTS: Significant differences in resting state connectivity between SCS off and optimal state were seen between several regions related to pain perception, including the left frontal insula, right primary and secondary somatosensory cortices, as well as in regions involved in the DMN, such as the precuneus. In examining changes in connectivity across the entire brain, we found decreased connection strength between somatosensory and limbic areas and increased connection strength between somatosensory and DMN with optimal SCS resulting in pain relief. This suggests that pain relief from SCS may be reducing negative emotional processing associated with pain, allowing somatosensory areas to become more integrated into default mode activity. CONCLUSION: SCS reduces the affective component of pain resulting in optimal pain relief. Study shows a decreased connectivity between somatosensory and limbic areas associated with optimal pain relief due to SCS.

Subclinical albuminuria is linked to gray matter atrophy in type 2 diabetes mellitus.

OBJECTIVE: Microalbuminuria (MA), a marker of renal microvascular disease, is associated with brain atrophy and neurovascular changes in older adults with type 2 diabetes mellitus (DM). We evaluated the relationship between urine albumin-to-creatinine ratio (UACR) and regional brain volumes to determine whether subclinical albuminuria may indicate early structural brain changes in type 2 DM. MATERIALS/METHODS: We studied UACR and brain volumes in 85 type 2 DM patients (64.8±8.3years) and 40 age-matched controls using 3D magnetization prepared rapid acquisition with gradient echo (MP-RAGE) MRI (magnetic resonance imaging) at 3 Tesla. The relationship between UACR and brain volumes was analyzed using the least square models. RESULTS: In DM patients, UACR ≥5mg/g, UACR ≥10mg/g and clinically significant MA (UACR ≥17mg/g [males] and 25mg/g [females]) were associated with lower gray matter (GM) volume in the frontal lobe (r(2)adj=0.2-0.4, P=0.01-0.05) and UACR ≥5mg/g was also related to global GM atrophy (r(2)adj=0.1, P=0.04), independent of DM duration, glucose levels, HbA1c and hypertension. For UACR ≥5mg/g, a lower global GM volume was related to worse executive function (P=0.04) in the DM group. No associations were found for UACR (<5mg/g) and controls. CONCLUSIONS: Subclinical albuminuria (UACR ≥5mg/g) is associated with lower GM volume that has clinical impact on cognitive function in older diabetic patients, and these relationships are independent of DM control and hypertension. Therefore, UACR levels may serve as an additional marker of DM-related brain structural changes.

Multi-scale glycemic variability: a link to gray matter atrophy and cognitive decline in type 2 diabetes.

OBJECTIVE: Type 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM. RESEARCH DESIGN AND METHODS: Forty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC1-5) that modulate serum glucose with periods ranging from 0.5-12 hrs. RESULTS: Type 2 DM subjects demonstrated greater variability in GVC3-5 (period 2.0-12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC1-3; 0.5-2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC2-3 was associated with worse learning and memory scores. Greater variability in GVC5 was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes. CONCLUSIONS: Type 2 DM is associated with dysregulation of glycemic variability over multiple scales of time. These time-scale-dependent glycemic fluctuations might contribute to brain atrophy and cognitive outcomes within this vulnerable population.

Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes.

OBJECTIVE: To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: This was a proof-of-concept, randomized, double-blind, placebo-controlled intervention evaluating the effects of a single 40-IU dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control subjects. Measurements included regional perfusion, vasodilatation to hypercapnia with 3-Tesla MRI, and neuropsychological evaluation. RESULTS: Intranasal insulin administration was well tolerated and did not affect systemic glucose levels. No serious adverse events were reported. Across all subjects, intranasal insulin improved visuospatial memory (P ≤ 0.05). In the DM group, an increase of perfusion after insulin administration was greater in the insular cortex compared with the control group (P = 0.0003). Cognitive performance after insulin administration was related to regional vasoreactivity. Improvements of visuospatial memory after insulin administration in the DM group (R(2)adjusted = 0.44, P = 0.0098) and in the verbal fluency test in the control group (R(2)adjusted = 0.64, P = 0.0087) were correlated with vasodilatation in the middle cerebral artery territory. CONCLUSIONS: Intranasal insulin administration appears safe, does not affect systemic glucose control, and may provide acute improvements of cognitive function in patients with type 2 DM, potentially through vasoreactivity mechanisms. Intranasal insulin-induced changes in cognitive function may be related to vasodilatation in the anterior brain regions, such as insular cortex that regulates attention-related task performance. Larger studies are warranted to identify long-term effects and predictors of positive cognitive response to intranasal insulin therapy.

Resting-state functional connectivity in multiple sclerosis: an examination of group differences and individual differences.

Multiple sclerosis (MS) is a neurodegenerative, inflammatory disease of the central nervous system, resulting in physical and cognitive disturbances. The goal of the current study was to examine the association between network integrity and composite measures of cognition and disease severity in individuals with relapsing-remitting MS (RRMS), relative to healthy controls. All participants underwent a neuropsychological and neuroimaging session, where resting-state data was collected. Independent component analysis and dual regression were employed to examine network integrity in individuals with MS, relative to healthy controls. The MS sample exhibited less connectivity in the motor and visual networks, relative to healthy controls, after controlling for group differences in gray matter volume. However, no alterations were observed in the frontoparietal, executive control, or default-mode networks, despite previous evidence of altered neuronal patterns during tasks of exogenous processing. Whole-brain, voxel-wise regression analyses with disease severity and processing speed composites were also performed to elucidate the brain-behavior relationship with neuronal network integrity. Individuals with higher levels of disease severity demonstrated reduced intra-network connectivity of the motor network, and the executive control network, while higher disease burden was associated with greater inter-network connectivity between the medial visual network and areas involved in visuomotor learning. Our findings underscore the importance of examining resting-state oscillations in this population, both as a biomarker of disease progression and a potential target for therapeutic intervention.

Treatment of multiple system atrophy using intravenous immunoglobulin.

BACKGROUND: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA. METHODS: This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment. RESULTS: Nine subjects were enrolled, and seven (2 women and 5 men, age range 55-64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment. CONCLUSIONS: Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.

The relationship between brain volume and walking outcomes in older adults with and without diabetic peripheral neuropathy.

OBJECTIVE: Diabetic peripheral neuropathy (DPN) alters walking. Yet, the compensatory role of central locomotor circuits remains unclear. We hypothesized that walking outcomes would be more closely related to regional gray matter volumes in older adults with DPN as compared with nonneuropathic diabetic patients and nondiabetic control subjects. RESEARCH DESIGN AND METHODS: Clinically important outcomes of walking (i.e., speed, stride duration variability, and double support time) were measured in 29 patients with DPN (type 2 diabetes with foot-sole somatosensory impairment), 68 diabetic (DM) patients (type 2 diabetes with intact foot-sole sensation), and 89 control subjects. Global and regional gray matter volumes were calculated from 3 Tesla magnetic resonance imaging. RESULTS: DPN subjects walked more slowly (P = 0.005) with greater stride duration variability (P < 0.001) and longer double support (P < 0.001) as compared with DM and control subjects. Diabetes was associated with less cerebellar gray matter volume (P < 0.001), but global gray matter volume was similar between groups. DPN subjects with lower gray matter volume globally (P < 0.004) and regionally (i.e., cerebellum, right-hemisphere dorsolateral prefrontal cortex, basal ganglia, P < 0.005) walked more slowly with greater stride duration variability and/or longer double support. Each relationship was stronger in DPN than DM subjects. In control subjects, brain volumes did not relate to walking patterns. CONCLUSIONS: Strong relationships between brain volumes and walking outcomes were observed in the DPN group and to a lesser extent the DM group, but not in control subjects. Individuals with DPN may be more dependent upon supraspinal elements of the motor control system to regulate several walking outcomes linked to poor health in elderly adults.

"Tumoral pseudoblush" identified within gliomas at high-spatial-resolution ultrahigh-field-strength gradient-echo MR imaging corresponds to microvascularity at stereotactic biopsy.

PURPOSE: To use directed biopsy sampling to determine whether microvascular assessment within gliomas, by means of ultrahigh-field-strength high-spatial-resolution gradient-echo (GRE) magnetic resonance (MR) imaging at 8 T, correlates with histopathologic assessment of microvascularity. MATERIALS AND METHODS: The study was institutional review board approved and HIPAA compliant. Informed consent was obtained. Thirty-five subjects with gliomas underwent 8-T and 80-cm MR imaging by using a GRE sequence (repetition time, 600-750 msec; echo time, 10 msec; in-plane resolution, 196 mm). Haphazardly arranged serpentine low-signal-intensity structures, often associated with areas of low signal intensity within the tumor bed ("tumoral pseudoblush") at MR imaging, were presumed to be related to tumoral microvascularity. Microvessel density (MVD) and microvessel size (MVS) ranked with a semiquantitative three-tier scale (high, medium, and low) relative to cortical penetrating veins were assessed from regions of interest identified at MR imaging and were compared with a similar assessment of stereotactic biopsy specimens by using Kendall τb. Tumor grade (high vs low) was compared with ultrahigh-field-strength high-resolution GRE MR analysis by using Pearson χ2. Discrepancies between 8-T and histopathologic assessment were identified and analyzed. RESULTS: Ultrahigh-field-strength high-resolution GRE MR imaging and histopathologic assessment concurred for MVS (P<.0001) and MVD (P<.0001). World Health Organization classification tumor grade was associated with number (P<.0005) and size (P<.0005) of foci of microvascularity within the tumor bed at 8-T MR imaging. Radiation-induced microvessel hyalinosis mimicked tumor microvascularity at 8-T MR imaging. Potential confounders could result from radiofrequency inhomogeneity and displaced normal microvasculature. CONCLUSION: Microvascularity identified as a tumoral pseudoblush at ultrahigh-field-strength high-resolution GRE MR imaging without contrast material shows promise as a marker for increased tumoral microvascularity.

Functional connectivity during language processing in acute cocaine withdrawal: a pilot study.

Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal. Eight subjects in acute cocaine withdrawal were compared to controls for connectivity in language areas while performing a task involving categorization of words according to semantic and phonological relatedness. Acute withdrawal subjects had significantly less overall connectivity during semantic relatedness, and a trend towards less connectivity during phonological relatedness. Of potential future interest is whether this might serve as an imaging marker for treatment in patients.

Physical activity associated with increased resting-state functional connectivity in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates.

The value of success: acquiring gains, avoiding losses, and simply being successful.

A large network of spatially contiguous, yet anatomically distinct regions in medial frontal cortex is involved in reward processing. Although it is clear these regions play a role in critical aspects of reward-related learning and decision-making, the individual contributions of each component remains unclear. We explored dissociations in reward processing throughout several key regions in the reward system and aimed to clarify the nature of previously observed outcome-related activity in a portion of anterior medial orbitofrontal cortex (mOFC). Specifically, we tested whether activity in anterior mOFC was related to processing successful actions, such that this region would respond similarly to rewards with and without tangible benefits, or whether this region instead encoded only quantifiable outcome values (e.g., money). Participants performed a task where they encountered monetary gains and losses (and non-gains and non-losses) during fMRI scanning. Critically, in addition to the outcomes with monetary consequences, the task included trials that provided outcomes without tangible benefits (participants were simply told that they were correct or incorrect). We found that anterior mOFC responded to all successful outcomes regardless of whether they carried tangible benefits (monetary gains and non-losses) or not (controls). These results support the hypothesis that anterior mOFC processes rewards in terms of a common currency and is capable of providing reward-based signals for everything we value, whether it be primary or secondary rewards or simply a successful experience without objectively quantifiable benefits.

Adhesion molecules, altered vasoreactivity, and brain atrophy in type 2 diabetes.

OBJECTIVE: To investigate the effects of inflammation on perfusion regulation and brain volumes in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 147 subjects (71 diabetic and 76 nondiabetic, aged 65.2 ± 8 years) were studied using 3T anatomical and continuous arterial spin labeling magnetic resonance imaging. Analysis focused on the relationship between serum soluble vascular and intercellular adhesion molecules (sVCAM and sICAM, respectively, both markers of endothelial integrity), regional vasoreactivity, and tissue volumes. RESULTS: Diabetic subjects had greater vasoconstriction reactivity, more atrophy, depression, and slower walking. Adhesion molecules were specifically related to gray matter atrophy (P = 0.04) and altered vasoreactivity (P = 0.03) in the diabetic and control groups. Regionally, sVCAM and sICAM were linked to exaggerated vasoconstriction, blunted vasodilatation, and increased cortical atrophy in the frontal, temporal, and parietal lobes (P = 0.04-0.003). sICAM correlated with worse functionality. CONCLUSIONS: Diabetes is associated with cortical atrophy, vasoconstriction, and worse performance. Adhesion molecules, as markers of vascular health, have been indicated to contribute to altered vasoregulation and atrophy.

Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke.

Reprint of: Aspects of neuroticism and the amygdala: chronic tuning from motivational styles.

Recent research and theory has highlighted the dynamic nature of amygdala activation. Rather than simply being sensitive to a few limited stimulus categories, amygdala activation appears to be dependent on the goals of the perceiver. In this study, we extend this line of work by demonstrating that the means by which a person seeks to accomplish a goal also modulates the amygdala response. Specifically, we examine the modulatory effects of the aspects of neuroticism (volatility/withdrawal), a personality variable that has been linked to both generalized anxiety and differences in amygdala sensitivity. Whereas Neuroticism-Volatility is proposed to be associated with the fight-flight-freeze system (FFFS) and a sensitivity for any cues of negativity, Neuroticism-Withdrawal is proposed to be associated with the behavioral inhibition system (BIS) and a generalized tendency toward passive avoidance. During fMRI scanning, participants were presented with positive, negative, and neutral images and were required to approach (move perceptually closer) or avoid (move perceptually farther away) stimuli in different blocks of trials. Consistent with hypotheses proposing a dissociation between these two aspects of neuroticism, participants higher in Neuroticism-Volatility had increased amygdala activation to negative stimuli (regardless of whether they were approached or avoided), whereas participants higher in Neuroticism-Withdrawal had increased amygdala activation to all approached stimuli (regardless of stimulus valence). These data provide further support for the motivational salience hypothesis of amygdala function, and demonstrate that both the ends and means of goal pursuit are important for shaping a response.

An endovascular canine middle cerebral artery occlusion model for the study of leptomeningeal collateral recruitment.

OBJECTIVES: This work aimed to refine a large animal in minimally invasive reversible middle cerebral artery (MCA) occlusion (MCAO) model to account for leptomeningeal collateral formation. MATERIALS AND METHODS: An angiographically based methodology allowed for transient MCA and carotid terminus occlusion in 12 mongrel dogs and assessment of pial collateral recruitment. Outcome measures included 1- and 24-hour magnetic resonance imaging-based infarct volume calculation, a behavioral scale and histopathologic sections. RESULTS: MCAO succeeded in 8 of 12 dogs (67% efficiency). One-hour postreperfusion infarct volume predicted 24-hour postreperfusion infarct volume (r = 0.997, P < 0.0001). Pial collateral recruitment varied with time and reproducibly assessed predicted infarct volume on 1-hour postreperfusion mean diffusivity maps (P < 0.0001; r = 0.946) and 24-hour fluid-attenuated inversion recovery FLAIR magnetic resonance imaging (P = 0.0033; r = 0.961). The canine stroke scale score correlated with infarct volumes and pial collateral score. CONCLUSION: This canine MCAO model produces defined cerebral infarct lesions whose volumes correlate with leptomeningeal collateral formation and canine behavior.

Aspects of neuroticism and the amygdala: chronic tuning from motivational styles.

Recent research and theory has highlighted the dynamic nature of amygdala activation. Rather than simply being sensitive to a few limited stimulus categories, amygdala activation appears to be dependent on the goals of the perceiver. In this study, we extend this line of work by demonstrating that the means by which a person seeks to accomplish a goal also modulates the amygdala response. Specifically, we examine the modulatory effects of the aspects of neuroticism (volatility/withdrawal), a personality variable that has been linked to both generalized anxiety and differences in amygdala sensitivity. Whereas Neuroticism-Volatility is proposed to be associated with the fight-flight-freeze system (FFFS) and a sensitivity for any cues of negativity, Neuroticism-Withdrawal is proposed to be associated with the behavioral inhibition system (BIS) and a generalized tendency toward passive avoidance. During fMRI scanning, participants were presented with positive, negative, and neutral images and were required to approach (move perceptually closer) or avoid (move perceptually farther away) stimuli in different blocks of trials. Consistent with hypotheses proposing a dissociation between these two aspects of neuroticism, participants higher in Neuroticism-Volatility had increased amygdala activation to negative stimuli (regardless of whether they were approached or avoided), whereas participants higher in Neuroticism-Withdrawal had increased amygdala activation to all approached stimuli (regardless of stimulus valence). These data provide further support for the motivational salience hypothesis of amygdala function, and demonstrate that both the ends and means of goal pursuit are important for shaping a response.

Effect of propranolol on functional connectivity in autism spectrum disorder--a pilot study.

A decrease in interaction between brain regions is observed in individuals with autism spectrum disorder (ASD), which is believed to be related to restricted neural network access in ASD. Propranolol, a beta-adrenergic antagonist, has revealed benefit during performance of tasks involving flexibility of access to networks, a benefit also seen in ASD. Our goal was to determine the effect of propranolol on functional connectivity in ASD during a verbal decision making task as compared to nadolol, thereby accounting for the potential spurious fMRI effects due to peripheral hemodynamic effects of propranolol. Ten ASD subjects underwent fMRI scans after administration of placebo, propranolol or nadolol, while performing a phonological decision making task. Comparison of functional connectivity between pre-defined ROI-pairs revealed a significant increase with propranolol compared to nadolol, suggesting a potential imaging marker for the cognitive effects of propranolol in ASD.

Association of blood pressure elevation and nocturnal dipping with brain atrophy, perfusion and functional measures in stroke and nonstroke individuals.

BACKGROUND: Although both blood pressure elevation and lower nocturnal dipping increase vascular risk, it is not known whether either or both are also associated with brain atrophy, cerebral perfusion, and functional status. METHODS: We investigated the association of elevated blood pressure and nocturnal dipping based on 24-h ambulatory recordings with brain atrophy and perfusion and functional status in 80 older adults with and without stroke (age 66.4 +/- 0.8 years, 51% women, 16% nonwhite, 46% prior ischemic stroke, 55% hypertension). Anatomical and three-dimensional continuous arterial spin labeling (CASL) brain magnetic resonance imaging (MRI) measuring volumes and perfusion and 24-h ambulatory blood pressure readings were completed. RESULTS: Nocturnal dipping of lesser magnitude in systolic (nonstroke: P = 0.03; stroke: P = 0.005) and pulse pressure (PP; nonstroke: P = 0.002; stroke: P = 0.01) was associated with greater brain atrophy, affecting preferentially the fronto-parietal regions. Dipping of lesser magnitude in systolic blood pressure (SBP; nonstroke: P = 0.01; stroke: P = 0.03) and greater brain atrophy (nonstroke: P = 0.04; stroke: P = 0.05) were also associated with slower gait speed and worse functional outcome after stroke. Higher 24-h blood pressure averages were associated with lower cerebral perfusion but not atrophy in those with and without stroke. CONCLUSIONS: In those with and without stroke, dipping of lesser magnitude in systolic and PP is associated with brain atrophy and worse functional status. Nocturnal dipping, in addition to elevated blood pressure, should be considered as an additional important target in the clinical evaluation of those at risk for cerebrovascular disease or functional loss.

7 Tesla MR imaging of the human eye in vivo.

PURPOSE: To develop a protocol which optimizes contrast, resolution and scan time for three-dimensional (3D) imaging of the human eye in vivo using a 7 Tesla (T) scanner and custom radio frequency (RF) coil. MATERIALS AND METHODS: Initial testing was conducted to reduce motion and susceptibility artifacts. Three-dimensional FFE and IR-TFE images were obtained with variable flip angles and TI times. T(1) measurements were made and numerical simulations were performed to determine the ideal contrast of certain ocular structures. Studies were performed to optimize resolution and signal-to-noise ratio (SNR) with scan times from 20 s to 5 min. RESULTS: Motion and susceptibility artifacts were reduced through careful subject preparation. T(1) values of the ocular structures are in line with previous work at 1.5T. A voxel size of 0.15 x 0.25 x 1.0 mm(3) was obtained with a scan time of approximately 35 s for both 3D FFE and IR-TFE sequences. Multiple images were registered in 3D to produce final SNRs over 40. CONCLUSION: Optimization of pulse sequences and avoidance of susceptibility and motion artifacts led to high quality images with spatial resolution and SNR exceeding prior work. Ocular imaging at 7T with a dedicated coil improves the ability to make measurements of the fine structures of the eye.