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Abstract: Across species, the brain evolved to respond to natural rewards such as food and sex. These physiological responses are important for survival, reproduction and evolutionary processes. It is no surprise, therefore, that many of the neural circuits and signaling pathways supporting reward processes are conserved from Caenorhabditis elegans to Drosophilae, to rats, monkeys and humans. The central role of dopamine (DA) in encoding reward and in attaching salience to external environmental cues is well recognized. Less widely recognized is the role of reporters of the “internal environment”, particularly insulin, in the modulation of reward. Insulin has traditionally been considered an important signaling molecule in regulating energy homeostasis and feeding behavior rather than a major component of neural reward circuits. However, research over recent decades has revealed that DA and insulin systems do not operate in isolation from each other, but instead, work together to orchestrate both the motivation to engage in consummatory behavior and to calibrate the associated level of reward. Insulin signaling has been found to regulate DA neurotransmission and to affect the ability of drugs that target the DA system to exert their neurochemical and behavioral effects. Given that many abused drugs target the DA system, the elucidation of how dopaminergic, as well as other brain reward systems, are regulated by insulin will create opportunities to develop therapies for drug and potentially food addiction. Moreover, a more complete understanding of the relationship between DA neurotransmission and insulin may help to uncover etiological bases for “food addiction” and the growing epidemic of obesity. This review focuses on the role of insulin signaling in regulating DA homeostasis and DA signaling, and the potential impact of impaired insulin signaling in obesity and psychostimulant abuse. This article is part of a Special Issue entitled ‘Synaptic Plasticity and Addiction’. [Copyright &y& Elsevier]

Abstract: We report studies of the nonlinear nature of blood oxygen level-dependent (BOLD) responses to short transient deactivations in human visual cortex. Both functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) have been used to compare and contrast the hemodynamic response functions (HRFs) associated with transient activation and deactivation in primary visual cortex. We show that signal decreases for short duration deactivations are smaller than corresponding signal increases in activation studies. Moreover, the standard balloon model of BOLD effects may be modified to account for the observed nonlinear nature of deactivations by appropriate changes to simple hemodynamic parameters without recourse to new assumptions about the nature of the coupling between activity and oxygen use. [Copyright &y& Elsevier]

Abstract: Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs). [Copyright &y& Elsevier]

Abstract: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in human brain and has been implicated in several neuropsychiatric disorders. In vivo human brain GABA concentrations are near the detection limit for magnetic resonance spectroscopy (∼1 mM), and because of overlap with more abundant compounds, spectral editing is generally necessary to detect GABA. In previous reports, GABA spectra edited by J-difference spectroscopy vary considerably in appearance. We have evaluated the factors that affect GABA spectra and the conditions necessary for robust acquisition of J-difference spectra from arbitrary brain regions. In particular, we demonstrate that variations in spectral quality can be explained in part by the incoherent addition of transients that results from shot to shot frequency and phase variations. An automated time-domain spectral alignment strategy that enables reproducible acquisition of high-quality GABA spectra at 3 T with a standard 30-cm T/R volume coil is presented. Representative GABA spectra from human frontal lobe, an area where susceptibility-induced frequency and phase variations are especially troublesome, that demonstrate the robustness of the acquisition and data handling strategy used in this study are presented. [Copyright &y& Elsevier]

Investigates the role of magnetic resonance in understanding the pathogenesis and treatment of HIV dementia. Mechanisms of HIV neurotoxicity; Contribution of inflammatory and non-inflammatory pathways to the central nervous system toxicity of HIV; Insight into the variable host CNS response to HIV infection and therapy from magnetic resonance.

This work presents a robust and comprehensive approach for the in vivo automated segmentation and quantitative tissue volume measurement of normal brain composition from multispectral magnetic resonance imaging (MRI) data. Statistical pattern recognition methods based on a finite mixture model are used to partition the intracranial volume into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) spaces. A masking algorithm initially extracts the brain volume from surrounding extrameningeal tissue. Radio frequency (RF) field inhomogeneity effects in the images are then removed using a recursive method that adapts to the intrinsic local tissue contrast. Our technique supports heterogeneous data with multispectral MR images of different contrast and intensity weighting acquired at varying spatial resolution and orientation. The proposed image segmentation methods have been tested using multispectral T1-, proton density-, and T2-weighted MRI data from young and aged non-human primates as well as from human subjects. [Copyright &y& Elsevier]

Abstract: Functional magnetic resonance imaging (fMRI) at high magnetic field strength can suffer from serious degradation of image quality because of motion and physiological noise, as well as spatial distortions and signal losses due to susceptibility effects. Overcoming such limitations is essential for sensitive detection and reliable interpretation of fMRI data. These issues are particularly problematic in studies of awake animals. As part of our initial efforts to study functional brain activations in awake, behaving monkeys using fMRI at 4.7 T, we have developed acquisition and analysis procedures to improve image quality with encouraging results. We evaluated the influence of two main variables on image quality. First, we show how important the level of behavioral training is for obtaining good data stability and high temporal signal-to-noise ratios. In initial sessions, our typical scan session lasted 1.5 h, partitioned into short (<10 min) runs. During reward periods and breaks between runs, the monkey exhibited movements resulting in considerable image misregistrations. After a few months of extensive behavioral training, we were able to increase the length of individual runs and the total length of each session. The monkey learned to wait until the end of a block for fluid reward, resulting in longer periods of continuous acquisition. Each additional 60 training sessions extended the duration of each session by 60 min, culminating, after about 140 training sessions, in sessions that last about 4 h. As a result, the average translational movement decreased from over 500 μm to less than 80 μm, a displacement close to that observed in anesthetized monkeys scanned in a 7-T horizontal scanner. Another major source of distortion at high fields arises from susceptibility variations. To reduce such artifacts, we used segmented gradient-echo echo-planar imaging (EPI) sequences. Increasing the number of segments significantly decreased susceptibility artifacts and image distortion. Comparisons of images from functional runs using four segments with those using a single-shot EPI sequence revealed a roughly twofold improvement in functional signal-to-noise-ratio and 50% decrease in distortion. These methods enabled reliable detection of neural activation and permitted blood-oxygenation-level-dependent-based mapping of early visual areas in monkeys using a volume coil. In summary, both extensive behavioral training of monkeys and application of segmented gradient-echo EPI sequence improved signal-to-noise ratio and image quality. Understanding the effects these factors have is important for the application of high field imaging methods to the detection of submillimeter functional structures in the awake monkey brain. [Copyright &y& Elsevier]

Abstract: Accurate anatomic co-registration is a prerequisite for identifying structural and functional changes in longitudinal studies of brain plasticity. Current MRI methods permit collection of brain images across multiple scales, ranging from whole brain at relatively low resolution (≥1mm), to local brain areas at the level of cortical layers and columns (∼100μm) in the same session, allowing detection of subtle structural changes on a similar spatial scale. To measure these changes reliably, high resolution structural and functional images of local brain regions must be registered accurately across imaging sessions. The present study describes a robust fully automated strategy for the registration of high resolution structural images of brain sub-volumes to lower resolution whole brain images collected within a session, and the registration of partially overlapping high resolution MRI sub-volumes (“slabs”) across imaging sessions. In high field (9.4T) reduced field-of-view high resolution structural imaging studies using a surface coil in an anesthetized non-human primate model, this fully automated coregistration pipeline was robust in the face of significant inhomogeneities in image intensity and tissue contrast arising from the spatially inhomogeneous transmit and receive properties of the surface coil, achieving a registration accuracy of 30±15μm between sessions. [Copyright &y& Elsevier]

Abstract: Dynamic slice-wise shimming improves B 0 field homogeneity by updating shim coil currents for every slice in a multislice acquisition, producing better field homogeneity over a volume than can be obtained by a single static global shim. The first aim of this work was to evaluate the performance of slice-wise field-map-based second-order dynamic shimming in a human high-field 7 T clinical scanner vis-à-vis image based second order static global shimming. Another goal was to characterize eddy currents induced by second and third order shim switching. A final aim was to compare global and dynamic shimming through shim orders to elucidate the relative benefits of going to higher orders and to dynamic shim updating from a static shimming regime. An external hardware module was used to store and dynamically update slice-optimized shim values during multislice data acquisition. High-bandwidth multislice gradient echo scans with B 0 field mapping and low-bandwidth single-shot echo planar scans were performed on phantoms and humans using second-order dynamic and static global shims. For the measurement of second and third order shim induced eddy currents, step response temporal phase changes of individual shims were measured and fit to shim harmonics spatially and to multiexponential decay functions temporally. Finally, an order-wise field-map-based comparison was performed with first, second and third order global static shimming, first and second order dynamic shimming, as well as combined second or third order global and first order dynamic shim. Dynamic shimming considerably improved B 0 homogeneity compared to static global shimming both in phantoms and in human subjects, reducing image distortion and signal dropout. The unshielded second and third order shims generated strong B 0 and self and cross-term eddy fields, with multiple time constants ranging from milliseconds to seconds. Field homogeneity improved with increasing order of shim, with dynamic shimming performing better than global shimming. Hybrid global and dynamic shimming approach yielded field homogeneity better than global static shims but worse than dynamic shims. [Copyright &y& Elsevier]

Abstract: Gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, normalized to total creatine (tCr), were measured in the anterior cingulate and cerebellar vermis in healthy adults (n=19, age=24.6±6.4 years) using 1H MRS at 3 T, and metabolite correlations across regions and subjects were determined. Mean anterior cingulate and cerebellar GABA/tCr ratios were 0.31 (0.08) and 0.23 (0.06), respectively, while corresponding Glu levels were 1.16 (0.10) and 0.70 (0.07), respectively. Anterior cingulate and cerebellar glutamate levels were correlated (r=0.6103, P=.0140), although it is noted that when adjusted for multiple comparisons, all correlations reported here cluster to a P value of .0583. It is unlikely that this correlation is driven by correlations in tCr, since interregional correlations were not observed for other metabolites referenced to tCr. Correlations were also observed among metabolites in both the anterior cingulate and cerebellar vermis. In the former, N-acetylasparate was linearly dependent on glutamate (r=0.6577, P=.0063) and, at or below this significance threshold, four metabolites were correlated in the cerebellar vermis (Ins/tCh: r=0.6261, P=.0109. NAA/tCh: r=0.6426, P=.0082. NAA/Glu: r=0.6412, P=.0085. tCh/Glu: r=0.6193, P=0.0122). [ABSTRACT FROM AUTHOR]

Abstract: Recently, we have demonstrated that the fine-digit topography (millimeter sized) previously identified in the primary somatosensory cortex (SI), using electrophysiology and intrinsic signal optical imaging, can also be mapped with submillimeter resolution using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging at high field. In the present study, we have examined the dependence of BOLD signal response on stimulus intensity in two subregions of SI, Areas 3b and 1. In a region(s)-of-interest (ROI) analysis of Area 3b, BOLD signal amplitude increased linearly with increasing amplitude of an 8-Hz vibrotactile stimulus, and BOLD signal was sustained throughout the stimulation period. In contrast, in Area 1, a significant BOLD signal response was only observed with more intense stimuli, and ROI analysis of the dependence of BOLD response showed no significant dependence on stimulus intensity. In addition, activation was not sustained throughout the period of stimulation. Differing responses of Areas 3b and 1 suggest potentially divergent roles for subregions of SI cortices in vibrotactile intensity encoding. Moreover, this study underscores the importance of imaging at small spatial scales. In this case, such high-resolution imaging allows differentiation between area-specific roles in intensity encoding and identifies anatomic targets for detailed electrophysiological studies of somatosensory neuronal populations with different coding properties. These experiments illustrate the value of nonhuman primates for characterizing the dependence of the BOLD signal response on stimulus parameters and on underlying neural response properties. [Copyright &y& Elsevier]

The extent to which the brain regions associated with face processing are selective for that specific function remains controversial. In addition, little is known regarding the extent to which face-responsive brain regions are selective for human faces. To study regional selectivity of face processing, we used functional magnetic resonance imaging to examine whole brain activation in response to human faces, dog faces, and houses. Fourteen healthy right-handed volunteers participated in a passive viewing, blocked experiment. Results indicate that the lateral fusiform gyrus (Brodmann''s area 37) responds maximally to both dog and human faces when compared with other sites, followed by the middle/inferior occipital gyrus (BA 18/19). Sites that were activated by houses versus dog and human faces included the medial fusiform gyrus (BA 19/37), the posterior cingulate (BA 30), and the superior occipital gyrus (BA 19). The only site that displayed significant differences in activation between dog and human faces was the lingual/medial fusiform gyrus. In this site, houses elicited the strongest activation, followed by dog faces, while the response to human faces was negligible and did not differ from fixation. The parahippocampal gyrus/amygdala was the sole site that displayed significant activation to human faces, but not to dog faces or houses. [Copyright &y& Elsevier]