Alayar Kangarlu

Neural Systems Subserving Valence and Arousal During the Experience of Induced Emotions

The circumplex model of affect construes all emotions as linear combinations of 2 independent neurophysiological dimensions, valence and arousal. We used functional magnetic resonance imaging to identify the neural networks subserving valence and arousal, and we assessed, in 10 participants, the associations of the BOLD (blood oxygen level-dependent) response, an indirect index of neural activity, with ratings of valence and arousal during the emotional experiences induced by the presentation of evocative sentences. Unpleasant emotional experience was associated with increased BOLD signal intensities in the supplementary motor, anterior midcingulate, right dorsolateral prefrontal, occipito-temporal, inferior parietal, and cerebellar cortices. Highly arousing emotions were associated with increased BOLD signal intensities in the left thalamus, globus pallidus, caudate, parahippocampal gyrus, amygdala, premotor cortex, and cerebellar vermis. Separate analyses using a finite impulse response model confirmed these results and revealed that pleasant emotions engaged an additional network that included the midbrain, ventral striatum, and caudate nucleus, all portions of a reward circuit. These findings suggest the existence of distinct networks subserving the valence and arousal dimensions of emotions, with midline and medial temporal lobe structures mediating arousal and dorsal cortical areas and mesolimbic pathways mediating valence.

The Neurophysiological Bases of Emotion: An fMRI Study of the Affective Circumplex Using Emotion-Denoting Words

Objective: We aimed to study the neural processing of emotion‐denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions. Methods: Using functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion‐denoting words. Results: Valence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial prefrontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum. Conclusion: We found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect. Hum Brain Mapp, 2009.

An affective circumplex model of neural systems subserving valence, arousal, and cognitive overlay during the appraisal of emotional faces

Increasing evidence supports the existence of distinct neural systems that subserve two dimensions of affect--arousal and valence. Ten adult participants underwent functional magnetic resonance imaging during which they were presented a range of standardized faces and then asked, during the scan, to rate the emotional expressions of the faces along the dimensions of arousal and valence. Lower ratings of arousal accompanied greater activity in the amygdala complex, cerebellum, dorsal pons, and right medial prefrontal cortex (mPFC). More negative ratings of valence accompanied greater activity in the dorsal anterior cingulate (dACC) and parietal cortices. Extreme ratings of valence (highly positive and highly negative ratings) accompanied greater activity in the temporal cortex and fusiform gyrus. Building on an empirical literature which suggests that the amygdala serves as a salience and ambiguity detector, we interpret our findings as showing that a face rated as having low arousal is more ambiguous and a face rated as having extreme valence is more personally salient. This explains how both low arousal and extreme valence lead to greater activation of an ambiguity/salience system subserved by the amygdala, cerebellum, and dorsal pons. In addition, the right medial prefrontal cortex appears to down-regulate individual ratings of arousal, whereas the fusiform and related temporal cortices seem to up-regulate individual assessments of extreme valence when individual ratings are studied relative to group reference ratings for each stimulus. The simultaneous assessment of the effects of arousal and valence proved essential for the identification of neural systems contributing to the processing of emotional faces.

Correction of eddy-current distortions in diffusion tensor images using the known directions and strengths of diffusion gradients

To correct eddy‐current artifacts in diffusion tensor (DT) images without the need to obtain auxiliary scans for the sole purpose of correction.

Effects of Davunetide on N-acetylaspartate and Choline in Dorsolateral Prefrontal Cortex in Patients with Schizophrenia

Schizophrenia is associated with extensive neurocognitive and behavioral impairments. Studies indicate that N-acetylaspartate (NAA), a marker of neuronal integrity, and choline, a marker of cell membrane turnover and white matter integrity, may be altered in schizophrenia. Davunetide is a neurotrophic peptide that can enhance cognitive function in animal models of neurodegeneration. Davunetide has recently demonstrated modest functional improvement in a study of people with schizophrenia. In a subset of these subjects, proton magnetic resonance spectroscopy (1H-MRS) was conducted to explore the effects of davunetide on change in NAA/creatine (NAA/Cr) and choline/creatine (choline/Cr) over 12 weeks of treatment. Of 63 outpatients with schizophrenia who received randomized davunetide (5 and 30 mg/day) or placebo in the parent clinical trial, 18 successfully completed 1H-MRS in dorsolateral prefrontal cortex (DLPFC) at baseline and at 12 weeks. Cognition was assessed using the MATRICS Consensus Cognitive Battery (MCCB). NAA/Cr was unchanged for combined high- and low-dose davunetide groups (N=11). NAA/Cr in the high-dose davunetide group (N=8) suggested a trend increase of 8.0% (P=0.072) over placebo (N=7). Choline/Cr for combined high- and low-dose davunetide groups suggested a 6.4% increase (P=0.069), while the high-dose group showed a 7.9% increase (P=0.040) over placebo. Baseline NAA/Cr correlated with the composite MCCB score (R=0.52, P=0.033), as did individual cognitive domains of attention/vigilance, verbal learning, and social cognition; however, neither metabolite correlated with functional capacity. In this exploratory study, 12 weeks of adjunctive davunetide appeared to produce modest increases in NAA/Cr and choline/Cr in DLPFC in people with schizophrenia. This is consistent with a potential neuroprotective mechanism for davunetide. The data also support use of MRS as a useful biomarker of baseline cognitive function in schizophrenia. Future clinical and preclinical studies are needed to fully define the mechanism of action and cognitive effects of davunetide in schizophrenia.

Ultra-high-field MR imaging in multiple sclerosis

In multiple sclerosis (MS), MRI is the most important paraclinical tool used to inform diagnosis and for monitoring disease evolution, either natural or modified by treatment. The increased availability of ultra-high-field magnets (7 Tesla or higher) gives rise to questions about the main benefits of and challenges for their use in patients with MS. The main advantages of ultra-high-field MRI are the improved signal-to-noise ratio, greater chemical shift dispersion, and improved contrast due to magnetic susceptibility variations, which lead to increased sensitivity to the heterogeneous pathological substrates of the disease. At present, ultra-high-field MRI is mainly used to improve our understanding of MS pathogenesis. This review discusses the main achievements that have so far come from the use of these scanners, which are: better visualisation of white matter lesions and their morphological characteristics; an improvement in the ability to visualise grey matter lesions and their exact location; the quantification of ‘novel’ metabolites which may have a role in axonal degeneration; and greater sensitivity to iron accumulation. The application of ultra-high-field systems in standard clinical practice is still some way off since their role in the diagnostic work-up of patients at presentation with clinically isolated syndromes, or in monitoring disease progression or treatment response in patients with definite MS, needs to be established. Additional challenges remain in the development of morphological, quantitative and functional imaging methods at these field strengths, techniques which may ultimately lead to novel biomarkers for monitoring disease evolution and treatment response.

A virtual reality-based FMRI study of reward-based spatial learning

Although temporo-parietal cortices mediate spatial navigation in animals and humans, the neural correlates of reward-based spatial learning are less well known. Twenty-five healthy adults performed a virtual reality fMRI task that required learning to use extra-maze cues to navigate an 8-arm radial maze and find hidden rewards. Searching the maze in the spatial learning condition compared to the control conditions was associated with activation of temporo-parietal regions, albeit not including the hippocampus. The receipt of rewards was associated with activation of the hippocampus in a control condition when using the extra-maze cues for navigation was rendered impossible by randomizing the spatial location of cues. Our novel experimental design allowed us to assess the differential contributions of the hippocampus and other temporo-parietal areas to searching and reward processing during reward-based spatial learning. This translational research will permit parallel studies in animals and humans to establish the functional similarity of learning systems across species; cellular and molecular studies in animals may then inform the effects of manipulations on these systems in humans, and fMRI studies in humans may inform the interpretation and relevance of findings in animals.

Multimodal Magnetic Resonance Imaging: The Coordinated Use of Multiple, Mutually Informative Probes to Understand Brain Structure and Function

Differing imaging modalities provide unique channels of information to probe differing aspects of the brains structural or functional organization. In combination, differing modalities provide complementary and mutually informative data about tissue organization that is more than their sum. We acquired and spatially coregistered data in four MRI modalities—anatomical MRI, functional MRI, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS)—from 20 healthy adults to understand how interindividual variability in measures from one modality account for variability in measures from other modalities at each voxel of the brain. We detected significant correlations of local volumes with the magnitude of functional activation, suggesting that underlying variation in local volumes contributes to individual variability in functional activation. We also detected significant inverse correlations of NAA (a putative measure of neuronal density and viability) with volumes of white matter in the frontal cortex, with DTI‐based measures of tissue organization within the superior longitudinal fasciculus, and with the magnitude of functional activation and default‐mode activity during simple visual and motor tasks, indicating that substantial variance in local volumes, white matter organization, and functional activation derives from an underlying variability in the number or density of neurons in those regions. Many of these imaging measures correlated with measures of intellectual ability within differing brain tissues and differing neural systems, demonstrating that the neural determinants of intellectual capacity involve numerous and disparate features of brain tissue organization, a conclusion that could be made with confidence only when imaging the same individuals with multiple MRI modalities. Hum Brain Mapp, 2013.

Improving the spectral resolution and spectral fitting of (1) H MRSI data from human calf muscle by the SPREAD technique.

Proton magnetic resonance spectroscopic imaging (1H MRSI) has been used for the in vivo measurement of intramyocellular lipids (IMCLs) in human calf muscle for almost two decades, but the low spectral resolution between extramyocellular lipids (EMCLs) and IMCLs, partially caused by the magnetic field inhomogeneity, has hindered the accuracy of spectral fitting. The purpose of this paper was to enhance the spectral resolution of 1H MRSI data from human calf muscle using the SPREAD (spectral resolution amelioration by deconvolution) technique and to assess the influence of improved spectral resolution on the accuracy of spectral fitting and on in vivo measurement of IMCLs. We acquired MRI and 1H MRSI data from calf muscles of three healthy volunteers. We reconstructed spectral lineshapes of the 1H MRSI data based on field maps and used the lineshapes to deconvolve the measured MRS spectra, thereby eliminating the line broadening caused by field inhomogeneities and improving the spectral resolution of the 1H MRSI data. We employed Monte Carlo (MC) simulations with 200 noise realizations to measure the variations of spectral fitting parameters and used an F‐test to evaluate the significance of the differences of the variations between the spectra before SPREAD and after SPREAD. We also used Cramer–Rao lower bounds (CRLBs) to assess the improvements of spectral fitting after SPREAD. The use of SPREAD enhanced the separation between EMCL and IMCL peaks in 1H MRSI spectra from human calf muscle. MC simulations and F‐tests showed that the use of SPREAD significantly reduced the standard deviations of the estimated IMCL peak areas (p < 10−8), and the CRLBs were strongly reduced (by ~37%). Copyright

Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla

Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1-6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term approximately 185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T(1) and T(2)) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally.