Biomedical subjects

Robert K Fulbright

Publications and source records attributed to Robert K Fulbright.

At least 19 recordsLinked to original sources

PubMed2006

Diffusion MRI in the early diagnosis of malignant glioma.

OBJECTIVE: A subset of patients with malignant glioma comes to medical attention before their masses show rim enhancement and central necrosis. Tumors in those cases are frequently located in eloquent areas of the brain. Tissue diagnosis is limited to stereotactic biopsy providing limited material for accurate grading. We conducted this study to determine whether imaging characteristics of early stages of malignant gliomas could aid in timely definitive diagnosis. METHODS: We retrospectively analyzed patients with newly diagnosed malignant glioma seen at the Yale Brain Tumor Center between 2002 and 2005. Patients with typical radiographic presentation were excluded. RESULTS: Of 89 patients, eight meeting the inclusion criteria were identified. In five patients, patchy or small nodular enhancing lesions without central necrosis were present within the tumor mass. Diffusion-weighted imaging (DWI) showed areas of increased signal intensity in all cases. Apparent diffusion coefficient maps (ADC) revealed low-signal intensity in corresponding areas. At the time of imaging, biopsy was performed in seven patients but diagnosis of malignant glioma could only be established prior to further tumor growth in four cases. CONCLUSIONS: The diagnosis in the early stages of malignant glioma can be challenging in a subset of cases. Information obtained through DWI should be incorporated in the clinical decision-making process. Mass lesions displaying decreased water diffusion indicating high cellularity, are suggestive of a high-grade glioma. Biopsies are recommended. However, even when biopsies are inconclusive, a strong suspicion of malignant glioma should be considered.

Aged↗

PubMed2006

The imaging appearance of Creutzfeldt-Jakob disease caused by the E200K mutation.

The E200K mutation on chromosome 20 can cause familial Creutzfeldt-Jakob disease (CJD). Patients with this mutation are clinically similar to those with sporadic CJD, but their imaging features are not well documented. We report here the quantitative and qualitative evaluation of the magnetic resonance (MR) imaging characteristics of this unique group of patients using three-dimensional spoiled gradient recalled (SPGR) echo images, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurements, MR spectroscopy and a fluid-attenuated inversion recovery (FLAIR) sequence. The SPGR and ADC data were analyzed with SPM99. ANCOVA and regression models were used for a region-of-interest (ROI) analysis of ADC and metabolic ratios. CJD patients had a decreased fraction of gray matter and an increased fraction of cerebrospinal fluid (P=.001) in the cortex and cerebellum and increased ADC values in the cortex (P<.001). Focal decreases of ADC were found in the putamen via ROI analysis (548+/-83 vs. 709+/-9 microm(2)/s, P=.02). N-acetyl aspartate (NAA) was generally reduced, with the NAA/Cho ratio lowest in the cingulate gyrus. Qualitative assessment revealed hyperintensities on FLAIR, DWI or both in the putamen (three out of four patients), caudate (three out of four patients) and thalamus. These results provide a framework for future study of patients with genetically defined familial CJD.

Brain↗

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↗

PubMed2005

Neural activity associated with stress-induced cocaine craving: a functional magnetic resonance imaging study.

OBJECTIVE: Stress is known to increase cocaine craving and relapse risk in cocaine dependence. Identifying neural activity associated with stress and stress-induced cocaine craving is important in understanding the neurobiology of cocaine craving and relapse. METHOD: Blood oxygenation level dependent (BOLD) signal changes were assessed in a functional magnetic resonance imaging (fMRI) session with healthy controls and treatment-engaged, abstinent, cocaine-dependent individuals (patients) as they participated in brief guided imagery and recall of three personal stress and three personal neutral situations. RESULTS: During stress, patients showed significantly less BOLD activation than controls in specific frontal and para-limbic regions, such as the anterior cingulate (AC) region, left hippocampal/parahippocampal region, right fusiform gyrus, and the right postcentral gyrus. On the other hand, patients had increased activity in the caudate and dorsal striatum region during stress, activation that was significantly associated with stress-induced cocaine craving ratings. CONCLUSIONS: Patients failed to activate AC and related circuits during stress, regions associated with control, and regulation of emotion and distress states. Instead, they exhibited greater craving-related activation in the dorsal striatum, a region related to reward pathways and part of the obsessive-compulsive circuitry. Such functional alterations in stress processing may underlie the stress-related vulnerability to cocaine relapse often observed in cocaine-dependent individuals in early recovery.

Adult↗

PubMed2005

Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder.

RATIONALE: Abnormal amygdala and frontocortical responses to emotional stimuli are implicated in bipolar disorder (BD) and have been proposed as potential treatment targets. OBJECTIVES: The aim of this study was to investigate amygdala and frontocortical responses to emotional face stimuli in BD and the influences of mood-stabilizing medications on these responses. METHODS: Functional magnetic resonance imaging was performed while 17 BD participants (5 unmedicated) and 17 healthy comparison (HC) participants viewed faces with happy, sad, fearful, or neutral expressions. RESULTS: The group by stimulus-condition interaction was significant (p<0.01) for amygdala activation, with the greatest effects in the happy face condition. Relative to HC, amygdala increases were greater in unmedicated BD, but lower in medicated BD. Rostral anterior cingulate (rAC) activation was decreased in unmedicated BD compared to HC; however, BD participants taking medication demonstrated rAC activation similar to HC participants. CONCLUSIONS: Although the sample sizes were small, these preliminary results suggest that BD is associated with increased amygdala and decreased rAC response to emotional faces. The findings also provide preliminary evidence that mood-stabilizing medications may reverse abnormalities in BD in the response of an amygdala-frontal neural system to emotional stimuli.

Adult↗

PubMed2005

A functional magnetic resonance imaging study of the tradeoff between semantics and phonology in reading aloud.

Using functional magnetic resonance imaging, we explored the role of semantics in mediating orthographic-to-phonological processing in reading aloud, focusing on the interaction of imageability with spelling-to-sound consistency for low-frequency words. Behaviorally, high-imageable words attenuate the standard latency and accuracy disadvantage for low-frequency inconsistent words relative to their consistent counterparts. Neurobiologically, high-imageable words reduced consistency-related activation in the inferior frontal gyrus but increased posterior activation in the angular and middle temporal gyri, representing a possible neural signature of the tradeoff between semantics and phonology in reading aloud. We discuss implications for neurobiological models of reading in terms of understanding the interplay among areas associated with component processes and suggest that the results constitute an important step toward integrating neurobiological and computational models of reading.

Brain Mapping↗

PubMed2005

Preliminary evidence for persistent abnormalities in amygdala volumes in adolescents and young adults with bipolar disorder.

OBJECTIVES: Abnormalities in volumes of the amygdala have been reported previously in adolescents and adults with bipolar disorder (BD). Several studies have reported reduced volumes in adolescents with BD; however, both decreases and increases in volumes have been reported in adults with BD. Understanding of potential developmental contributions to these disturbances in morphology of the amygdala has been limited by the absence of longitudinal data in persons with BD. Here we use a within-subject longitudinal design to investigate whether amygdala volume abnormalities persist in adolescents and young adults with BD over a time interval of approximately 2 years. METHODS: Participants included 18 adolescents and young adults: 10 participants with BD I and 8 healthy comparison participants. Amygdala volumes were measured on high-resolution magnetic resonance imaging scans acquired twice for each subject over intervals of approximately 2 years. Amygdala volumes were the dependent measures in a mixed-model statistical analysis to compare amygdala volumes between groups over time while covarying for total brain volume. RESULTS: Amygdala volumes were significantly smaller in adolescents and young adults with BD compared with healthy participants (p = 0.018). The effect of time was not significant. CONCLUSIONS: Although the sample size is modest, this study provides preliminary evidence to support the presence of decreased amygdala volumes in adolescents and young adults with BD that persist during this developmental epoch.

Adolescent↗

PubMed2004

Functional MRI changes before and after onset of reported emotions.

The social nature of emotion is evident in the importance of facial and vocal displays in emotion-related behavior. This is the first brain-imaging study to use simulated face-to-face social interactions to evoke emotional responses and to compare valence-related activations before and after subjective onset of emotional response. Videotapes were prepared with actresses who described happy or unhappy experiences. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to acquire BOLD images in 21 healthy young adults before, after, and during viewing of the happy and sad tapes. Subjects pushed buttons to indicate the onset of subjective emotional responses. Group data were analyzed by a bootstrap randomization method after anatomical normalization. Significant activation was detected in frontal and sensory regions prior to the reported onset of emotional response, and this activity showed a marked decrease after the report of conscious emotional experience. Significant differences between happy and sad conditions were evident in multiple brain regions both before and after the reported onset of emotional response, including the middle and superior temporal gyri, the middle frontal gyrus, the caudate, and the hippocampus. Socially relevant emotional stimulation is feasible and evokes robust responses. The neural correlates of the evoked emotion are multiple, widely distributed, and inclusive of areas important in many cognitive tasks. Positive and negative emotional responses include activation of common and distinctive brain regions.

Adult↗

PubMed2004

Development of left occipitotemporal systems for skilled reading in children after a phonologically- based intervention.

BACKGROUND: A range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading. METHODS: Functional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1-9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (n = 37), community intervention (n = 12), and community control subjects (n = 28). RESULTS: Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions. CONCLUSIONS: These data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading.

Child↗

PubMed2004

The neurobiology of adaptive learning in reading: a contrast of different training conditions.

fMRI was used to investigate the separate influences of orthographic, phonological, and semantic processing on the ability to learn new words and the cortical circuitry recruited to subsequently read those words. In a behavioral session, subjects acquired familiarity for three sets of pseudowords, attending to orthographic, phonological, or (learned) semantic features. Transfer effects were measured in an event-related fMRI session as the subjects named trained pseudowords, untrained pseudowords, and real words. Behaviorally, phonological and semantic training resulted in better learning than did orthographic training. Neurobiologically, orthographic training did not modulate activation in the main reading regions. Phonological and semantic training yielded equivalent behavioral facilitation but distinct functional activation patterns, suggesting that the learning resulting from these two training conditions was driven by different underlying processes. The findings indicate that the putative ventral visual word form area is sensitive to the phonological structure of words, with phonologically analytic processing contributing to the specialization of this region.

Adaptation, Psychological↗

PubMed2003

Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Adult↗

PubMed2003

Neural systems for compensation and persistence: young adult outcome of childhood reading disability.

BACKGROUND: This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes. METHODS: Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27). RESULTS: Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies. CONCLUSIONS: These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

Adult↗

PubMed2003

Gambling urges in pathological gambling: a functional magnetic resonance imaging study.

BACKGROUND: Gambling urges in pathological gambling (PG) often immediately precede engagement in self-destructive gambling behavior. An improved understanding of the neural correlates of gambling urges in PG would advance our understanding of the brain mechanisms underlying PG and would help direct research into effective treatments. METHODS: Echoplanar functional magnetic resonance imaging was used to assess brain function during viewing of videotaped scenarios with gambling, happy, or sad content. Participants rated the quality and magnitude of their emotional and motivational responses. RESULTS: Men with PG (n = 10) reported mean +/- SD greater gambling urges after viewing gambling scenarios vs control subjects (n = 11) (5.20 +/- 3.43 vs 0.32 +/- 0.60; chi21,19 = 21.71; P<.001). The groups did not differ significantly in their subjective responses to the happy (P =.56) or sad (P =.81) videotapes. The most pronounced between-group differences in neural activities were observed during the initial period of viewing of the gambling scenarios: PG subjects displayed relatively decreased activity in frontal and orbitofrontal cortex, caudate/basal ganglia, and thalamus compared with controls. Distinct patterns of regional brain activity were observed in specific temporal epochs of videotape viewing. For example, differences localized to the ventral anterior cingulate during the final period of gambling videotape viewing, corresponding to the presentation of the most provocative gambling stimuli. Although group differences in brain activity were observed during viewing of the sad and happy scenarios, they were distinct from those corresponding to the gambling scenarios. CONCLUSIONS: In men with PG, gambling cue presentation elicits gambling urges and leads to a temporally dynamic pattern of brain activity changes in frontal, paralimbic, and limbic brain structures. When viewing gambling cues, PG subjects demonstrate relatively decreased activity in brain regions implicated in impulse regulation compared with controls.

Adolescent↗

PubMed2003

Magnetic resonance spectroscopy of neurotransmitters in human brain.

Magnetic resonance spectroscopy (MRS) is a noninvasive method that permits measurement of the concentration of specific biochemical compounds in the brain and other organ systems in precisely defined regions guided by MR imaging (MRI). Recently, MRS methods have been developed to measure specific neurotransmitters in the brain. More advanced MRS methods have been developed to measure the synthesis rates and turnover of specific neurotransmitters. These turnover rates can provide measures of brain metabolism similar to radioisotope techniques. Also, investigations of the relationship of brain metabolism and specific neurotransmitter systems are now possible using MRS. Here, we review the MRS techniques and studies of neurotransmitters in the human brain. A discussion of the potential use of these techniques in the context of certain pediatric neurotransmitter disorders will be presented.

Brain Chemistry↗

PubMed2003

An FMRI Stroop task study of ventromedial prefrontal cortical function in pathological gamblers.

OBJECTIVE: Function of the ventromedial prefrontal cortex has been implicated in impulse control. The authors used the Stroop paradigm to test attention and response inhibition during the presentation of congruent and incongruent stimuli in male pathological gamblers and a group of comparison subjects. METHOD: Event-related functional magnetic resonance imaging was used to examine ventromedial prefrontal cortex function during Stroop performance. RESULTS: In response to infrequent incongruent stimuli, pathological gamblers demonstrated decreased activity in the left ventromedial prefrontal cortex relative to the comparison subjects. Both groups demonstrated similar activity changes in multiple brain regions, including activation of the dorsal anterior cingulate and dorsolateral frontal cortex. CONCLUSIONS: Pathological gamblers share many neural correlates of Stroop task performance with healthy subjects but differ in a brain region previously implicated in disorders characterized by poor impulse control.

Adolescent↗

PubMed2003

Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI.

OBJECTIVE: This study investigated whether the functional abnormalities in prefrontal systems observed in adult bipolar disorder are manifested in adolescents with this illness. METHOD: Ten adolescents with bipolar disorder and 10 healthy comparison subjects participated in a color-naming Stroop task during event-related functional magnetic resonance imaging. RESULTS: Signal increases in the left putamen and thalamus were significantly greater in the bipolar disorder group than in the healthy group. Age correlated positively with signal increases in the bilateral rostroventral prefrontal cortex and the striatum in the healthy group but not in the bipolar disorder group. In the bipolar disorder subjects, depressive symptoms correlated positively with signal increases in the ventral striatum. CONCLUSIONS: These findings suggest the presence of dysfunction in the subcortical portions of the frontostriatal circuits in adolescents with bipolar disorder. The absence of the prefrontal abnormalities that were observed previously in adults and the absence of the age-related increases in prefrontal activity observed in normal comparison subjects suggest that a developmental disturbance in prefrontal function may emerge in bipolar disorder over the course of adolescence.

Adolescent↗

PubMed2003

Quantity determination and the distance effect with letters, numbers, and shapes: a functional MR imaging study of number processing.

BACKGROUND AND PURPOSE: The ability to quantify, or to determine magnitude, is an important part of number processing, and the extent to which language and other cognitive abilities are involved with number processing is an area of interest. We compared activation patterns, reaction times, and accuracy as subjects determined stimulus magnitude by ordering letters, numbers, and shapes. A second goal was to define the brain regions involved in the distance effect (the farther apart numbers are, the faster subjects are at judging which number is larger) and whether this effect depended on stimulus type. METHODS: Functional MR images were acquired in 19 healthy subjects. The order task required the subjects to judge whether three stimuli were in order according to their position in the alphabet (letters), position in the number line (numbers), or size (shapes). In the control (identify task), subjects judged whether one of the three stimuli was a particular letter, number, or shape. Each stimulus type was divided into near trials (quantity difference of three or less) and far trials (quantity difference of at least five) to assess the distance effect. RESULTS: Subjects were less accurate and slower with letters than with numbers and shapes. A distance effect was present with shapes and numbers, as subjects ordered the near trials slower than far trials. No distance effect was detected with letters. The occipital lobes and intraparietal sulci were active with all three stimuli. Shapes required no additional areas, although analysis of the distance effect revealed that near shapes involved other brain regions, including the frontal lobes. Letters activated a large network comprising the frontal lobes, the anterior cingulate gyrus, and basal ganglia, but few additional areas were engaged by the distance effect. Numbers involved a smaller network including the inferior and middle frontal gyri. The left supramarginal gyrus and both inferior frontal gyri were active in the distance effect with numbers. CONCLUSION: Numbers and letters, which are stimuli more associated with abstract symbolism compared with shapes, resulted in slower reaction times and an increased number of active brain regions. Shapes and numbers, but not letters, elicited a distance effect, indicating access to a mental continuum of quantity. The left supramarginal gyrus and both inferior frontal gyri were involved in the distance effect with numbers. The intraparietal sulci were important in determining stimulus magnitude for all stimuli.

Adult↗

PubMed2002

Disruption of posterior brain systems for reading in children with developmental dyslexia.

BACKGROUND: Converging evidence indicates a functional disruption in the neural systems for reading in adults with dyslexia. We examined brain activation patterns in dyslexic and nonimpaired children during pseudoword and real-word reading tasks that required phonologic analysis (i.e., tapped the problems experienced by dyslexic children in sounding out words). METHODS: We used functional magnetic resonance imaging (fMRI) to study 144 right-handed children, 70 dyslexic readers, and 74 nonimpaired readers as they read pseudowords and real words. RESULTS: Children with dyslexia demonstrated a disruption in neural systems for reading involving posterior brain regions, including parietotemporal sites and sites in the occipitotemporal area. Reading skill was positively correlated with the magnitude of activation in the left occipitotemporal region. Activation in the left and right inferior frontal gyri was greater in older compared with younger dyslexic children. CONCLUSIONS: These findings provide neurobiological evidence of an underlying disruption in the neural systems for reading in children with dyslexia and indicate that it is evident at a young age. The locus of the disruption places childhood dyslexia within the same neurobiological framework as dyslexia, and acquired alexia, occurring in adults.

Adolescent↗