Biomedical subjects

R Todd Constable

Publications and source records attributed to R Todd Constable.

At least 19 recordsLinked to original sources

PubMed2006

Brain connectivity related to working memory performance.

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Adult↗

PubMed2006

Neural correlates of epigenesis.

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.

Adult↗

PubMed2006

Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat.

BACKGROUND: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established. METHODS: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging. FINDINGS: Elevated ALT (> 35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18-35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver. INTERPRETATION: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.

Adiponectin↗

PubMed2006

T1 measurements incorporating flip angle calibration and correction in vivo.

In this work, we propose a variable FA method that combines in vivo flip angle (FA) calibration and correction with a short TR variable FA approach for a fast and accurate T(1) mapping. The precision T(1)s measured across a uniform milk phantom is estimated to be 2.65% using the conventional (slow) inversion recovery (IR) method and 28.5% for the variable FA method without FA correction, and 2.2% when FA correction is included. These results demonstrate that the sensitivity of the variable FA method to RF nonuniformities can be dramatically reduced when these nonuniformities are directly measured and corrected. The acquisition time for this approach decreases to 10 min from 85 min for the conventional IR method. In addition, we report that the averaged T(1)s measured from five normal subjects are 900 +/- 3 ms, 1337 +/- 8 ms and 2180 +/- 25 ms in white matter (WM), gray matter (GM) and cerebral spinal fluid (CSF) using the variable flip angle method with FA correction at 3 T, respectively. These results are consistent with previously reported values obtained with much longer acquisition times. The method reduces the total scan time for whole brain T(1) mapping, including FA measurement and calibration, to approximately 6 min. The novelty of this method lies in the in vivo calibration and the correction of the FAs, thereby allowing a rapid and accurate T(1) mapping at high field for many applications.

Adult↗

PubMed2006

Hemodynamic retrieval intensity in hippocampus is decreased by pre-exposure to autobiographic test items.

The purpose of this experiment was to assess the effects of probe familiarity, the consequences of having recently retrieved an autobiographic memory (AM), on subsequent recall. This was accomplished by replicating an earlier imaging experiment, using the same participants and memory probes. Subtractions between sessions showed significant pre-exposure effects (i.e., drop in BOLD signal intensity) in the prefrontal cortex, thalamus, cerebellum and other brain structures. Further, region of interest (ROI) analysis illustrated a significant decrease in neural activity in the hippocampus in both conditions. The results are discussed in terms of the pre-scan interview technique, a method applied in AM research to procure personal information. Although invaluable, we emphasize it must be used with caution as it can result in a loss of power. The widespread use of this method in AM research may explain why studies often fail to find evidence of significant responding in the hippocampus in response to memory probes. Alternatively, when activity in the hippocampus is reported, it often fails to differentiate between recent and remote memories. This point is of particular importance to the on-going consolidation debate, as it often centers on a failure to detect an effect in the hippocampus in one or both conditions.

Adult↗

PubMed2006

Gender differences in the neural correlates of response inhibition during a stop signal task.

We used functional magnetic resonance imaging to examine gender differences in the neural correlates of response inhibition during a stop signal task. The task has a frequent "go" signal to set up a pre-potent response tendency and a less frequent "stop" signal for subjects to withhold their response. A contrast in brain activation was made between successful and failed inhibitions for individual subjects. We compared 20 men and 20 women matched in age and years of education and in stop signal performance, with stop success rate, post-error slowing and task-related frustration ratings as covariates. The results showed greater activation in men, compared to women, in a wide array of cortical and subcortical areas, including the globus pallidus and motor thalamus during stop signal inhibition. In contrast, no brain regions demonstrated greater activation in women, even at a lower statistical threshold. Moreover, while men activated the medial superior frontal and anterior cingulate cortices, women activated the caudate tail to mediate response inhibition. These results extended gender differences in regional brain activation to response inhibition during a cognitive motor task. Men activated the motor circuitry while women appeared to involve visual association or habit learning during stop signal performance.

Adult↗

PubMed2006

Effects of estrogen variation on neural correlates of emotional response inhibition.

Despite behavioral evidence that variation in ovarian hormones is associated with changes in affect, the neural basis of these processes is poorly understood. We combined functional magnetic resonance imaging (fMRI) with quantitative analysis of ovarian hormones in a within-subject design to investigate brain activation patterns during affective response inhibition, comparing activation between the early follicular (low estrogen and progesterone) and mid-luteal (high estrogen and progesterone) phases of the menstrual cycle in healthy women. There was significantly increased activation in the anterior cingulate and dorsolateral prefrontal cortex (DLPFC) while inhibiting response to positive words during the luteal, compared to the follicular phase. Furthermore, luteal phase estradiol level positively correlated with DLPFC activation while inhibiting response to positive words and negatively correlated with activation in several structures while inhibiting response to negative words, supporting estrogen's modulation of affective processing.

Adult↗

PubMed2006

Connectivity-behavior analysis reveals that functional connectivity between left BA39 and Broca's area varies with reading ability.

Correlations between temporal fluctuations in MRI signals may reveal functional connectivity between brain regions within individual subjects. Such correlations would be especially useful indices of functional connectivity if they covary with behavioral performance or other subject variables. This study investigated whether such a relationship could be demonstrated in the context of the reading circuit in the brain. The method proved sufficiently powerful to reveal significant correlations between the reading abilities of subjects and the strength of their functional connection between left Brodmann's area 39 and Broca's area during reading. This suggests that the disconnection of the angular gyrus previously reported for dyslexic readers is part of a larger continuum in which poor (but nonimpaired readers) also show reduced connectivity to the region. In addition, it illustrates the potential power of paradigms that examine correlations between behavior and functional brain connections.

Adult↗

PubMed2006

Imaging response inhibition in a stop-signal task: neural correlates independent of signal monitoring and post-response processing.

Execution of higher cortical functions requires inhibitory control to restrain habitual responses and meet changing task demands. We used functional magnetic resonance imaging to show the neural correlates of response inhibition during a stop-signal task. The task has a frequent "go" stimulus to set up a pre-potent response tendency and a less frequent "stop" signal for subjects to withhold their response. We contrasted brain activation between successful and failed inhibition for individual subjects and compared groups of subjects with short and long stop-signal reaction times. The two groups of subjects did not differ in their inhibition failure rates or the extent of signal monitoring, error monitoring, or task-associated frustration ratings. The results showed that short stop-signal reaction time or more efficient response inhibition was associated with greater activation in the superior medial and precentral frontal cortices. Moreover, activation of these inhibitory motor areas correlated negatively with stop-signal reaction time. These brain regions may represent the neural substrata of response inhibition independent of other cognitive and affective functions.

Adult↗

PubMed2006

Factors influencing flip angle mapping in MRI: RF pulse shape, slice-select gradients, off-resonance excitation, and B0 inhomogeneities.

To understand the various effects that influence actual flip angles, and correct for these effects, it is important to precisely quantify the MRI parameters (such as T1, T2, and perfusion). In this paper actual flip angle maps are calculated using a conventional gradient-echo (GRE) sequence with different radiofrequency (RF) pulse shapes (Gaussian, sinc, and truncated-sinc), slice-selection gradients, off-resonance excitations, and B0 field inhomogeneities. The experimental results demonstrate that RF pulse shapes significantly affect the flip angle distribution and calibration factors. Off-resonance RF excitations, B0 nonuniformities, and slice-selection gradients can lead to degradations in the signal intensities of the images used to map the flip angle, and potentially introduce a bias and increased variance in the measured flip angles.

Algorithms↗

PubMed2006

Cortical recruitment patterns in children born prematurely compared with control subjects during a passive listening functional magnetic resonance imaging task.

OBJECTIVES: To use functional magnetic resonance imaging (fMRI) to test the hypothesis that subjects who were born prematurely develop alternative systems for processing language. STUDY DESIGN: Subjects who were born prematurely (n = 14; 600-1250 g birthweight) without neonatal brain injury and 10 matched term control subjects were examined with a fMRI passive listening task of language, the Clinical Evaluation of Language Fundamentals (CELF) and portions of the Comprehensive Test of Phonological Processing (CTOPP). The fMRI task was evaluated for both phonologic and semantic processing. RESULTS: Although there were differences in CELF scores between the subjects born prematurely and control subjects, there were no significant differences in the CTOPP measures in the 2 groups. fMRI studies demonstrated that the groups differentially engaged neural systems known to process language. Children born at term were significantly more likely to activate systems for the semantic processing of language, whereas subjects born prematurely preferentially engaged regions that subserve phonology. CONCLUSIONS: At 12 years of age, children born prematurely and children born at term activate neural systems for the auditory processing of language differently. Subjects born prematurely engage different networks for phonologic processing; this strategy is associated with phonologic language scores that are similar to those of control subjects. These biologically based developmental strategies may provide the substrate for the improving language skills noted in children who are born prematurely.

Auditory Perception↗

PubMed2006

Differentiation of speech and nonspeech processing within primary auditory cortex.

Primary auditory cortex (PAC), located in Heschl's gyrus (HG), is the earliest cortical level at which sounds are processed. Standard theories of speech perception assume that signal components are given a representation in PAC which are then matched to speech templates in auditory association cortex. An alternative holds that speech activates a specialized system in cortex that does not use the primitives of PAC. Functional magnetic resonance imaging revealed different brain activation patterns in listening to speech and nonspeech sounds across different levels of complexity. Sensitivity to speech was observed in association cortex, as expected. Further, activation in HG increased with increasing levels of complexity with added fundamentals for both nonspeech and speech stimuli, but only for nonspeech when separate sources (release bursts/fricative noises or their nonspeech analogs) were added. These results are consistent with the existence of a specialized speech system which bypasses more typical processes at the earliest cortical level.

Acoustic Stimulation↗

PubMed2006

A functional magnetic resonance imaging study of the long-term influences of early indomethacin exposure on language processing in the brains of prematurely born children.

BACKGROUND: Previous studies have demonstrated that indomethacin lowers the incidence and decreases the severity of intraventricular hemorrhage, as well as improves the cognitive outcome, in prematurely born male infants. OBJECTIVE: The purpose of this work was to use functional magnetic resonance imaging to test the hypothesis that neonatal indomethacin treatment would differentially affect brain activation across genders in school-aged, prematurely born children during performance of a language task. METHODS: Forty-seven prematurely born children (600-1250-g birth weight) and 24 matched term control subjects were evaluated using a functional magnetic resonance imaging passive language task and neurodevelopmental assessments that included the Wechsler Intelligence Scale for Children-III and the Peabody Picture Vocabulary Test-Revised. Neural activity was assessed during both phonologic and semantic processing in the functional magnetic resonance imaging protocol. RESULTS: Neurodevelopmental assessments demonstrated significant differences in full-scale, verbal, and performance intelligence quotient, as well as Peabody Picture Vocabulary Test scores, between the preterm and term control subjects. Rates of perinatal complications did not differ significantly across preterm treatment groups, but male preterm subjects randomly assigned to saline tended to have lower Peabody Picture Vocabulary Test-Revised scores than did all of the other preterm groups. During phonological processing, a significant treatment-by-gender effect was demonstrated in 3 brain regions: the left inferior parietal lobule, the left inferior frontal gyrus (Broca's area), and the right dorsolateral prefrontal cortex. CONCLUSIONS: These data demonstrate a differential effect of indomethacin administration early in postnatal life on the subsequent development of neural systems that subserve language functioning in these male and female preterm infants.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Interference produced by emotional conflict associated with anterior cingulate activation.

The anterior cingulate cortex (ACC) is involved in cognition and emotion. In the classic Stroop task, presentation of stimuli that are in response conflict with one another produces activation in the caudal ACC. In the emotional Stroop task, presentation of emotionally salient stimuli produces activation in the rostral ACC. Presentation of stimuli that are emotionally conflicting should activate the caudal ACC; stimuli that are emotionally salient should activate the rostral ACC. We tested this prediction using functional magnetic resonance imaging while subjects made emotional valence judgments of words overlaid on emotional faces (word-face Stroop task). Emotionally incongruent pairs were responded to more slowly than emotionally congruent pairs. Emotionally incongruent trials were associated with increased activation within the caudal ACC, whereas no ACC activation was found in response to emotional saliency. These results support the conflict-monitoring model of caudal ACC and extend this function to conflict within the domain of emotional stimuli.

Adolescent↗

PubMed2005

Amygdala gray matter concentration is associated with extraversion and neuroticism.

Using high-resolution magnetic resonance imaging and voxel-based morphometry in 41 healthy individuals, this study evaluated the association between the personality traits of extraversion and neuroticism, on the one hand, and individual differences in localized brain volume and gray matter concentration, on the other, with a special focus on the amygdala. Extraversion was positively correlated with gray matter concentration in the left amygdala, whereas neuroticism was negatively correlated with gray matter concentration in the right amygdala. Given that neuroticism is a risk factor for depression, our finding offers one explanation as to why prior structural imaging studies of depressed patients (which did not control for personality) produced conflicting findings. Furthermore, our data are consistent with the view that amygdala reduction seen in depressed patients precedes the onset of the disease, rather than being a consequence of the illness.

Adult↗

PubMed2005

Recent cannabis abuse decreased stress-induced BOLD signals in the frontal and cingulate cortices of cocaine dependent individuals.

Previous neuroimaging studies showed that use of marijuana can alter patterns of cortical activation during rest or a task challenge. We used functional magnetic resonance imaging to examine whether recent cannabis abuse contributed to stress-induced blood-oxygen-level-dependent (BOLD) contrast in a group of cocaine-dependent individuals. Emotional stress was induced using the script-guided imagery paradigm, in which subjects imagined being in a real-life stressful situation and, as a control, in a neutral situation, while BOLD signals of their brain were acquired with a 1.5 T scanner. Abstinent cocaine-dependent subjects with recent marijuana abuse (n=8) were compared with abstinent cocaine-dependent subjects who had not abused marijuana recently (n=18). The two groups were otherwise matched in their demographic characteristics and drug use history. All subjects were abstinent for at least 15 days and drug free as confirmed by urine drug screening before the imaging session. Recent cannabis abusers demonstrated hypo-activation in frontal cortical areas including the perigenual anterior cingulate during increased emotional stress. In contrast, at the same statistical threshold, no brain regions showed increased activation in recent cannabis abusers compared with non-abusers. The group difference in the perigenual anterior cingulate remained even when lifetime cocaine and alcohol consumption was accounted for in covariance analysis. These results provide evidence that recent cannabis abuse is associated with decreased activation in the frontal cortex during an emotional stress task. The results suggest an abnormal cognitive control mechanism during affective processing in association with heavy cannabis use.

Adult↗

PubMed2005

Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task.

Prior work has highlighted the role of genetic variation within the repetitive sequence in the transcriptional control region of the serotonin (5-HT) transporter gene (5-HTT, SLC6A4) in modulating amygdala and prefrontal activation to negative emotional stimuli. However, these studies have not explicitly tested the assumption that the control condition (neutral baseline) does not itself produce changes in activation as a function of 5-HTT genotype. Using a fixation baseline condition, we show that variation in 5-HTT genotype is associated with differential activation to negative, positive, and neutral stimuli in limbic, striatal, and cortical regions. We replicate earlier reports of increased amygdala activation to negative, relative to neutral, stimuli, but then show that these differences are driven by decreased activation to neutral stimuli, rather than increased activation to negative stimuli, in carriers of the 5-HTT short allele. Using high-resolution structural images and automated processes to test for brain volume and gray matter density, we further report significant differences, as a function of 5-HTT genotype, in frontal cortical regions, anterior cingulate, and cerebellum. These functional and structural differences suggest a much broader role for 5-HT transport efficiency in brain processes than previously thought. 5-HTT genotype affects neural systems controlling affective, cognitive, and motor processes.

Analysis of Variance↗

PubMed2005

Measurement and correction of transmitter and receiver induced nonuniformities in vivo.

Signal intensity nonuniformities in high field MR imaging limit the ability of MRI to provide quantitative information and can negatively impact diagnostic scan quality. In this paper, a simple method is described for correcting these effects based on in vivo measurement of the transmission field B1+ and reception sensitivity maps. These maps can be obtained in vivo with either gradient echo (GE) or spin echo (SE) imaging sequences, but the SE approach exhibits an advantage over the GE approach for correcting images over a range of flip angles. In a uniform phantom, this approach reduced the ratio of the signal SD to its mean from around 30% before correction to approximately 6% for the SE approach and 9% for the GE approach after correction. The application of the SE approach for correcting intensity nonuniformities is demonstrated in vivo with human brain images obtained using a conventional spin echo sequence at 3.0 T. Furthermore, it is also shown that this in vivo B1+ and reception sensitivity mapping can be performed using segmented echo planar imaging sequences providing acquisition times of less than 2 min. Although the correction presented here is demonstrated with a simultaneous transmit and receive volume coil, it can be extended to the case of separate transmission and reception coils, including surface and phase array coils.

Algorithms↗