Nallakkandi Rajeevan

Testing Predictions From Personality Neuroscience Brain Structure and the Big Five

We used a new theory of the biological basis of the Big Five personality traits to generate hypotheses about the association of each trait with the volume of different brain regions. Controlling for age, sex, and whole-brain volume, results from structural magnetic resonance imaging of 116 healthy adults supported our hypotheses for four of the five traits: Extraversion, Neuroticism, Agreeableness, and Conscientiousness. Extraversion covaried with volume of medial orbitofrontal cortex, a brain region involved in processing reward information. Neuroticism covaried with volume of brain regions associated with threat, punishment, and negative affect. Agreeableness covaried with volume in regions that process information about the intentions and mental states of other individuals. Conscientiousness covaried with volume in lateral prefrontal cortex, a region involved in planning and the voluntary control of behavior. These findings support our biologically based, explanatory model of the Big Five and demonstrate the potential of personality neuroscience (i.e., the systematic study of individual differences in personality using neuroscience methods) as a discipline.

More accurate Talairach coordinates for neuroimaging using non-linear registration

While the Talairach atlas remains the most commonly used system for reporting coordinates in neuroimaging studies, the absence of an actual 3-D image of the original brain used in its construction has severely limited the ability of researchers to automatically map locations from 3-D anatomical MRI images to the atlas. Previous work in this area attempted to circumvent this problem by constructing approximate linear and piecewise-linear mappings between standard brain templates (e.g. the MNI template) and Talairach space. These methods are limited in that they can only account for differences in overall brain size and orientation but cannot correct for the actual shape differences between the MNI template and the Talairach brain. In this paper we describe our work to digitize the Talairach atlas and generate a non-linear mapping between the Talairach atlas and the MNI template that attempts to compensate for the actual differences in shape between the two, resulting in more accurate coordinate transformations. We present examples in this paper and note that the method is available freely online as a Java applet.

Functional connectivity and alterations in baseline brain state in humans

This work examines the influence of changes in baseline activity on the intrinsic functional connectivity fMRI (fc-fMRI) in humans. Baseline brain activity was altered by inducing anesthesia (sevoflurane end-tidal concentration 1%) in human volunteers and fc-fMRI maps between the pre-anesthetized and anesthetized conditions were compared across different brain networks. We particularly focused on low-level sensory areas (primary somatosensory, visual, and auditory cortices), the thalamus, and pain (insula), memory (hippocampus) circuits, and the default mode network (DMN), the latter three to examine higher-order brain regions. The results indicate that, while fc-fMRI patterns did not significantly differ (p<0.005; 20-voxel cluster threshold) in sensory cortex and in the DMN between the pre- and anesthetized conditions, fc-fMRI in high-order cognitive regions (i.e. memory and pain circuits) was significantly altered by anesthesia. These findings provide further evidence that fc-fMRI reflects intrinsic brain properties, while also demonstrating that 0.5 MAC sevoflurane anesthesia preferentially modulates higher-order connections.

Alterations in neural connectivity in preterm children at school age.

Converging data suggest recovery from injury in the preterm brain. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernickes area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600-1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children - III (WISC-III), the Peabody Individual Achievement Test - Revised (PIAT-R) and the Peabody Picture Vocabulary Test - Revised (PPVT-R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found that PT subjects scored significantly lower on all components of the WISC-III (p<0.009), the PIAT-R Reading Comprehension test (p=0.013), and the PPVT-R (p=0.001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernickes area and the right inferior frontal gyrus (R IFG, Brocas area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p</=0.02 for all). We conclude that PT subjects employ neural systems for auditory language function at school age differently than T controls; these alterations may represent a delay in maturation of neural networks or the engagement of alternate circuits for language processing.

Diffusion Tensor Imaging in Autism Spectrum Disorders: Preliminary Evidence of Abnormal Neural Connectivity

Objective: This study indirectly tested the hypothesis that individuals with autism spectrum disorders (ASDs) have impaired neural connections between the amygdala, fusiform face area, and superior temporal sulcus, key processing nodes of the ‘social brain’. This would be evidenced by abnormalities in the major fibre tracts known to connect these structures, including the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. Method: Magnetic resonance diffusion tensor imaging was performed on 20 right-handed males (ASD = 10, controls = 10) with a mean age 13.5 ± 4.0 years. Subjects were group-matched according to age, full-scale IQ, handedness, and ethnicity. Fractional anisotropy was used to assess structural integrity of major fibre tracts. Voxel-wise comparison of white matter fractional anisotropy was conducted between groups using ANCOVA adjusting for age, full-scale IQ, and brain volume. Volumes of interest were identified using predetermined probability and cluster thresholds. Follow-up tractography was performed to confirm the anatomic location of all volumes of interest which were observed primarily in peri-callosal regions and the temporal lobes. Results: The regions of lower fractional anisotropy, as confirmed by tractography, involved the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and corpus callosum/cingulum. Notably, some volumes of interest were adjacent to the fusiform face area, bilaterally, corresponding to involvement of the inferior longitudinal fasciculus. The largest effect sizes were noted for volumes of interest in the right anterior radiation of the corpus callosum/cingulum and right fusiform face area (inferior longitudinal fasciculus). Conclusions: This study provides preliminary evidence of impaired neural connectivity in the corpus callosum/cingulum and temporal lobes involving the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus and superior longitudinal fasciculus in ASDs. These findings provide preliminary support for aberrant neural connectivity between the amygdala, fusiform face area, and superior temporal sulcus–temporal lobe structures critical for normal social perception and cognition.

Variation in orbitofrontal cortex volume: relation to sex, emotion regulation and affect

Sex differences in brain structure have been examined extensively but are not completely understood, especially in relation to possible functional correlates. Our two aims in this study were to investigate sex differences in brain structure, and to investigate a possible relation between orbitofrontal cortex subregions and affective individual differences. We used tensor-based morphometry to estimate local brain volume from MPRAGE images in 117 healthy right-handed adults (58 female), age 18-40 years. We entered estimates of local brain volume as the dependent variable in a GLM, controlling for age, intelligence and whole-brain volume. Men had larger left planum temporale. Women had larger ventromedial prefrontal cortex (vmPFC), right lateral orbitofrontal (rlOFC), cerebellum, and bilateral basal ganglia and nearby white matter. vmPFC but not rlOFC volume covaried with self-reported emotion regulation strategies (reappraisal, suppression), expressivity of positive emotions (but not of negative), strength of emotional impulses, and cognitive but not somatic anxiety. vmPFC volume statistically mediated sex differences in emotion suppression. The results confirm prior reports of sex differences in orbitofrontal cortex structure, and are the first to show that normal variation in vmPFC volume is systematically related to emotion regulation and affective individual differences.

Vector-extrapolated fast maximum likelihood estimation algorithms for emission tomography

A new class of fast maximum-likelihood estimation (MLE) algorithms for emission computed tomography (ECT) is developed. In these cyclic iterative algorithms, vector extrapolation techniques are integrated with the iterations in gradient-based MLE algorithms, with the objective of accelerating the convergence of the base iterations. This results in a substantial reduction in the effective number of base iterations required for obtaining an emission density estimate of specified quality. The mathematical theory behind the minimal polynomial and reduced rank vector extrapolation techniques, in the context of emission tomography, is presented. These extrapolation techniques are implemented in a positron emission tomography system. The new algorithms are evaluated using computer experiments, with measurements taken from simulated phantoms. It is shown that, with minimal additional computations, the proposed approach results in substantial improvement in reconstruction.

Kinetic and equilibrium analyses of [123I]epidepride binding to striatal and extrastriatal dopamine D2 receptors

Quantitative SPECT measures of dopamine D2 like receptors with [123I]epidepride is complicated by its high affinity and lipophilic metabolites. The purpose of this study was to use both parent (P) and lipophilic metabolites (M) as input functions in a kinetic paradigm and in comparison to the results of equilibrium studies. Kinetic studies on eleven healthy human subjects, ages 32 ± 10 were performed following i.v. injection of ∼370 MBq of [123I]epidepride. Images were acquired for 13.5 ± 1.0 hours. Equilibrium studies were done on seven of eleven subjects with a bolus injection of ∼140 MBq, bolus/infusion ratio of 10 hours, and infusion for 30–32 hours. High (striatum) and low (temporal cortex) density regions were studied. Two (P and M) and one (P) input function models were applied in the kinetic studies. In receptor‐rich regions, the distribution volumes in nondisplaceable compartments were fixed to those in cerebellum. In addition, in the two input function model, K  1P /K  1M was fixed to the values in the cerebellum. The one input function model provided V′3 values (=f1•B′max/KD) which were consistent with those obtained in equilibrium studies in both receptor‐rich regions, while the two input function model provided consistent values only in striatum. Poor identifiability of the rate constants of metabolites seemed to be the source of errors in the two input function model. These results suggest that correct V′3 values can be obtained with the one input function model both in high‐ and low‐density regions. Synapse 34:290–304, 1999.

Arterial transit time effects in pulsed arterial spin labeling CBF mapping: insight from a PET and MR study in normal human subjects.

Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per‐voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 ± 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 ± 30 to 1220 ± 30 ms for the first slice, with an increase of 610 ± 20 ms over a four‐slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm. When the per‐slice ATTs were employed in ASL cerebral blood flow quantification and the in‐slice ATT variations ignored, regional cerebral blood flow could be significantly different from the positron emission tomography measures. ATT also decreased with focal activation by the same amount for both visual and motor tasks (∼80 ms). These results provide a quantitative relationship between ATT and the ASL imaging geometry and yield an assessment of the assumptions commonly used in ASL imaging. These findings should be considered in the interpretation of, and comparisons between, different ASL‐based cerebral blood flow studies. The results also provide spatially specific ATT data that may aid in optimizing the ASL imaging parameters. Magn Reson Med, 2010.

Changes of benzodiazepine receptors during chronic benzodiazepine administration in humans

Changes of central type GABA(A)/benzodiazepine receptors during 24-day per-oral administration of alprazolam (2 mg/day) were measured with single photon emission computed tomography (SPECT) in nine healthy human subjects. Receptor densities were measured on days -4 (baseline), 3, 10, 17 and 24. Comparison of baseline and day 3 SPECT images was used to assess receptor occupancy; comparisons of the four scans on medication were used to assess alterations in receptor levels. Clinical effects were evaluated by subjective ratings of mood and the Hopkins verbal learning test. Alprazolam induced sedation associated with a 16% receptor occupancy. Unoccupied receptor levels decreased 10% from day 3 to day 10 but then normalized to baseline values by day 17. Clinical effects showed corresponding changes 1-2 weeks after the changes in the receptor. Thus, the decrease of benzodiazepine receptor densities may be one of the major mechanisms for tolerance development in humans.