Biomedical subjects

Scott K Holland

Publications and source records attributed to Scott K Holland.

At least 19 recordsLinked to original sources

PubMed2006

Functional MRI evidence for disparate developmental processes underlying intelligence in boys and girls.

Previous research has shown evidence for sex differences in the neuroanatomical bases for intelligence in adults. Possible differences in the neuroanatomical correlates of intelligence and their developmental trajectories between boys and girls were investigated using functional MRI (fMRI). A large cohort of over 300 children, ages 5-18, performed the semantic processing task of silent verb generation. Regions were found in the left hemisphere exhibiting positive correlations of blood-oxygenation-level-dependent (BOLD) activation with IQ, including the middle temporal gyrus, prefrontal cortex (Broca's area), medial frontal gyrus, precuneus, and cingulate gyrus, while the superior temporal gyrus in the right hemisphere displayed a negative correlation of BOLD activation with IQ. Significant sex-X-IQ and sex-X-IQ-X-age interaction effects were also seen in the left middle temporal gyrus and left inferior frontal gyrus. Using a data-driven analysis procedure, a sex-X-IQ-X-age interaction was also demonstrated in the functional connectivity between regions in the left hemisphere, parameterized as a weighted sum of pairwise covariances between fMRI time courses. While young girls (<13 years) exhibited no correlation of connectivity with intelligence, older girls (>13 years) demonstrated a positive association of functional connectivity with intelligence. Boys, however, demonstrated the opposite developmental trajectory, from a positive association of connectivity with intelligence in young boys (ages <9 years), to a negative association in older boys (ages >13 years). Our results provide evidence for disparate neuroanatomical trajectories underlying intelligence in boys and girls.

Adolescent↗

PubMed2006

Prosodic processing by children: an fMRI study.

Prosodic information in the speech signal carries information about linguistic structure as well as emotional content. Although children are known to use prosodic information from infancy onward to assist linguistic decoding, the brain correlates of this skill in childhood have not yet been the subject of study. Brain activation associated with processing of linguistic prosody was examined in a study of 284 normally developing children between the ages of 5 and 18 years. Children listened to low-pass filtered sentences and were asked to detect those that matched a target sentence. fMRI scanning revealed multiple regions of activation that predicted behavioral performance, independent of age-related changes in activation. Likewise, age-related changes in task activation were found that were independent of differences in task accuracy. The overall pattern of activation is interpreted in light of task demands and factors that may underlie age-related changes in task performance.

Adolescent↗

PubMed2006

A longitudinal functional magnetic resonance imaging study of language development in children 5 to 11 years old.

OBJECTIVE: Language skills continue to develop rapidly in children during the school-age years, and the "snapshot" view of the neural substrates of language provided by current neuroimaging studies cannot capture the dynamic changes associated with brain development. The aim of this study was to conduct a 5-year longitudinal investigation of language development using functional magnetic resonance imaging in healthy children. METHODS: Thirty subjects enrolled at ages 5, 6, or 7 were examined annually for 5 years using a 3-Tesla magnetic resonance imaging scanner and a verb generation task. Data analysis was conducted based on a general linear model that was modified to investigate developmental changes whereas minimizing the potential for missing data. RESULTS: With increasing age, there is progressive participation in language processing by the inferior/middle frontal, middle temporal, and angular gyri of the left hemisphere and the lingual and inferior temporal gyri of the right hemisphere and regression of participation of the left posterior insula/extrastriate cortex, left superior frontal and right anterior cingulate gyri, and left thalamus. CONCLUSION: The age-related changes observed in this study provide evidence of increased neuroplasticity of language in this age group and may have implications for further investigations of normal and aberrant language development.

Algorithms↗

PubMed2006

fMRI study of language lateralization in children and adults.

Language lateralization in the brain is dependent on family history of handedness, personal handedness, pathology, and other factors. The influence of age on language lateralization is not completely understood. Increasing left lateralization of language with age has been observed in children, while the reverse has been noted in healthy young adults. It is not known whether the trend of decreasing language lateralization with age continues in the late decades of life and at what age the inflection in language lateralization trend as a function of age occurs. In this study, we examined the effect of age on language lateralization in 170 healthy right-handed children and adults ages 5-67 using functional MRI (fMRI) and a verb generation task. Our findings indicate that language lateralization to the dominant hemisphere increases between the ages 5 and 20 years, plateaus between 20 and 25 years, and slowly decreases between 25 and 70 years.

Adolescent↗

PubMed2006

fMRI shows atypical language lateralization in pediatric epilepsy patients.

PURPOSE: The goal of this study was to compare language lateralization between pediatric epilepsy patients and healthy children. METHODS: Two groups of subjects were evaluated with functional magnetic resonance imaging (fMRI) by using a silent verb-generation task. The first group included 18 pediatric epilepsy patients, whereas the control group consisted of 18 age/gender/handedness-matched healthy subjects. RESULTS: A significant difference in hemispheric lateralization index (LI) was found between children with epilepsy (mean LI =-0.038) and the age/gender/handedness-matched healthy control subjects (mean LI=0.257; t=6.490, p<0.0001). A dramatic difference also was observed in the percentage of children with epilepsy (77.78%) who had atypical LI (right-hemispheric or bilateral, LI<0.1) when compared with the age/gender/handedness-matched group (11.11%; chi(2)=16.02, p<0.001). A linear regression analysis showed a trend toward increasing language lateralization with age in healthy controls (R(2)=0.152; p=0.108). This association was not observed in pediatric epilepsy subjects (R(2)=0.004, p=0.80). A significant association between language LI and epilepsy duration also was found (R(2)=0.234, p<0.05). CONCLUSIONS: This study shows that epilepsy during childhood is associated with neuroplasticity and reorganization of language function.

Adolescent↗

PubMed2006

Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study.

OBJECTIVE: Previous diffusion tensor imaging findings have supported suggestions that bipolar disorder is characterized by subtle white matter changes. The chronic nature of the study population, however, has limited interpretation of these findings. In this study the authors utilized diffusion tensor imaging to study white matter tracts of adolescents in their first episode of mania to address whether abnormalities are present in early bipolar disorder. METHOD: Eleven medication-naive adolescents in their first episode of mania and 17 healthy subjects underwent diffusion tensor imaging scans. Fractional anisotropy and trace apparent diffusion coefficients of prefrontal and posterior regions of interest were compared between groups. RESULTS: Bipolar adolescents showed significantly decreased fractional anisotropy only in superior-frontal white matter tracts. Trace apparent diffusion coefficients did not significantly differ in any regions examined. CONCLUSIONS: These findings suggest that prefrontal white matter abnormalities are present early in bipolar disorder and may consist largely of axonal disorganization. The presence of changes in young first-episode patients also suggests that white matter pathology may represent an early marker of bipolar disorder.

Adolescent↗

PubMed2006

Making memories: a cross-sectional investigation of episodic memory encoding in childhood using FMRI.

In adults, the neural substrate associated with encoding memories connected to a specific time and place include the prefrontal cortex and medial temporal lobe (MTL). Using functional magnetic resonance imaging, this research studied the developmental trajectory of this frontal-MTL system by comparing 7- and 8-year-old children to those who were 10 or older in conditions that promoted episodic encoding. In 1 condition, participants generated verbs from nouns heard; in another, they listened to short stories for comprehension. Regions in which brain activation predicted subsequent recognition memory performance were identified. These included the left prefrontal cortex, but not MTL, in the verb generation condition for both age groups. In the story comprehension condition, activation in left posterior MTL predicted subsequent memory performance in both age groups, and activation in left anterior MTL (including the hippocampus proper) and left prefrontal cortex predicted subsequent memory only for the older children. These results illustrate both similarities and differences in how brain systems interact in development to mediate the formation of episodic memories.

Adolescent↗

PubMed2006

Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy.

Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8). However, caspase-3 was not activated, and very few cells completed the apoptosis process. Instead, many damaged neurons showed features of autophagic/lysosomal cell death. At the tissue level, ischemia-hypoxia caused persistent cerebral perfusion deficits even after release of the carotid artery occlusion. These changes were associated with both platelet deposition and fibrin accumulation within the cerebral circulation and would be expected to contribute to infarction. Complementary studies in fibrinogen-deficient mice revealed that the absence of fibrin and/or secondary fibrin-mediated inflammatory processes significantly attenuated brain damage. Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain.

Animals↗

PubMed2005

Sex differences in the activation of language cortex during childhood.

Sex differences have been well documented in the behavioral literature but have occurred inconsistently in the neuroimaging literature. This investigation examined the impact of subject age, language task, and cortical region on the occurrence of sex differences in functional magnetic resonance imaging. Two hundred and five (104 m, 101 f) right handed, monolingual English speaking children between the ages of 5 and 18 years were enrolled in this study. The study used fMRI at 3T to evaluate BOLD signal variation associated with sex, age, and their interaction. Children completed up to four language tasks, which involved listening to stories, prosody processing, single word vocabulary identification, and verb generation. A sex difference for behavioral performance was found for the prosodic processing task only. Brain activation in the classical left hemisphere language areas of the brain and their right homologues were assessed for sex differences. Although left lateralization was present for both frontal and temporal regions for all but the prosody task, no significant sex differences were found for the degree of lateralization. Sex x age interaction effects were found for all but the task involving single word vocabulary. However effect sizes associated with the sex differences were small, which suggests that relatively large sample sizes would be needed to detect these effects reliably.

Adolescent↗

PubMed2005

Cognitive modules utilized for narrative comprehension in children: a functional magnetic resonance imaging study.

The ability to comprehend narratives constitutes an important component of human development and experience. The neural correlates of auditory narrative comprehension in children were investigated in a large-scale functional magnetic resonance imaging (fMRI) study involving 313 subjects ages 5-18. Using group independent component analysis (ICA), bilateral task-related components were found comprising the primary auditory cortex, the mid-superior temporal gyrus, the hippocampus, the angular gyrus, and medial aspect of the parietal lobule (precuneus/posterior cingulate). In addition, a right-lateralized component was found involving the most posterior aspect of the superior temporal gyrus, and a left-lateralized component was found comprising the inferior frontal gyrus (including Broca's area), the inferior parietal lobule, and the medial temporal gyrus. Using a novel data-driven analysis technique, increased task-related activity related to age was found in the components comprising the mid-superior temporal gyrus (Wernicke's area) and the posterior aspect of the superior temporal gyrus, while decreased activity related to age was found in the component comprising the angular gyrus. The results are discussed in light of recent hypotheses involving the functional segregation of Wernicke's area and the specific role of the mid-superior temporal gyrus in speech comprehension.

Adolescent↗

PubMed2005

Sound blending in the brain: a functional magnetic resonance imaging investigation.

The presence of high levels of background noise is a serious concern for functional magnetic resonance imaging studies of phonological processing using conventional methods. As a result, many such studies have focused on phonological units larger than phonemes (e.g. syllables) or used stimuli presented in the visual (e.g. printed letters) rather than the auditory domain. We used a recently developed functional magnetic resonance imaging method to present spoken stimuli without the scanner's background noise. Young adult participants mentally blended phonemes in a series (e.g. /b/, /ae/, /t/), counted the number of discrete tones, or rested. Relative to tone counting, sound blending elicited activation in bilateral temporal and prefrontal cortices with left asymmetry. Activation within the dorsoposterior inferior frontal gyrus, a subregion of Broca's area, was negatively correlated with sound-blending accuracy. Our findings are consistent with prior studies ascribing a role of general sequencing, motor and articulatory programming, and vocal or subvocal articulatory rehearsal to this brain region.

Acoustic Stimulation↗

PubMed2005

Cortical reorganization in children with unilateral sensorineural hearing loss.

Previous studies have shown evidence of cortical reorganization following unilateral sensorineural hearing loss (USNHL). In addition, study participants with right USNHL have shown greater deficits in academic and language performance compared with those with left USNHL. A preliminary functional magnetic resonance imaging investigation was performed on a small cohort of participants, four with left USNHL and four with right USNHL, using the paradigm of listening to random tones. While the participants with left USNHL displayed greater activation in the right superior temporal gyrus, those with right USNHL displayed greater activation in the left inferior frontal area immediately anterior to the superior temporal gyrus. The results provide preliminary evidence of disparate neural circuitry supporting auditory processing in participants with left and right USNHL.

Acoustic Stimulation↗

PubMed2005

Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study.

A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5-18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full-scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito-parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts.

Adolescent↗

PubMed2005

Abnormal FMRI brain activation in euthymic bipolar disorder patients during a counting Stroop interference task.

BACKGROUND: Bipolar disorder is characterized by disturbed mood homeostasis accompanied by cognitive impairments that appear to persist during euthymia. Cognitive probes, coupled with neuroimaging, provide an approach toward clarifying the neurophysiology of bipolar disorder. METHOD: Sixteen patients with euthymic bipolar disorder and 16 healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a counting Stroop interference task and a control condition. Task performance was correlated with regional brain activation differences between groups, and the effect on brain activation of receiving versus not receiving medications was evaluated. RESULTS: Bipolar patients exhibited impaired task performance relative to the healthy subjects. In addition, the two groups demonstrated significantly different patterns of brain activation during the interference task. Healthy subjects exhibited relatively increased activation in temporal cortical regions, middle frontal gyrus, putamen, and midline cerebellum. Bipolar subjects exhibited relatively greater activation in the medial occipital cortex. The groups demonstrated different associations between task performance and fMRI activation in these brain regions. No differences in activation in these regions were observed between patients who were versus those who were not receiving medications; however, patients receiving medications exhibited greater activation in the anterior cingulate and dorsolateral prefrontal cortex. CONCLUSIONS: These differences suggest that patients with euthymic bipolar disorder fail to activate brain regions associated with performance of an interference task, which may contribute to impaired task performance. Medications do not explain these differences but may influence activation of brain regions primarily associated with performing an interference task.

Adult↗

PubMed2004

BOLD fMRI signal increases with age in selected brain regions in children.

To determine whether the BOLD signal used in fMRI is age dependent in childhood, 332 healthy children (age 4.9-18.9 years) performed tasks in a periodic block design during 3 T fMRI: (1) a verb generation task interleaved with a finger tapping task; (2) a word-picture matching task interleaved with an image discrimination task. Significant correlations between percent signal change in BOLD effect and age occurred in left Broca's, middle frontal, Wernicke's, and inferior parietal regions, and anterior cingulate during the verb generation task; in precentral, postcentral, middle frontal, supplementary motor, and precuneus regions during the finger tapping task; and in bilateral lingula gyri during the word-picture matching task. Thus, BOLD effect increases with age in children during sensorimotor and language tasks.

Adolescent↗

PubMed2004

Voxel-based morphometry in adolescents with bipolar disorder: first results.

Bipolar disorder is an increasingly recognized cause of significant morbidity in the pediatric age group. However, there is still a large degree of uncertainty regarding the underlying neurobiological deficits. In this preliminary study, we performed automated volumetric studies and whole-brain voxel-based morphometry (VBM) on gray matter. Imaging data from 10 adolescents with bipolar disorder were compared with data from 52 age- and gender-matched healthy controls. Previously defined brain parcellations and optimized VBM protocols were used, based on custom-made pediatric reference data. An additional, exploratory whole-brain comparison was also implemented. The volumetric region-of-interest study revealed significantly greater gray matter volume in central gray matter structures bilaterally (including the basal ganglia and the thalamus) and the left temporal lobe in the bipolar group. VBM confirmed bilaterally larger basal ganglia. Localized gray matter deficits in bipolar subjects were found in the medial temporal lobe, orbito-frontal cortex, and the anterior cingulate, confirming and extending earlier studies.

Adolescent↗

PubMed2004

The effect of musical training on the neural correlates of math processing: a functional magnetic resonance imaging study in humans.

The neural correlates of the previously hypothesized link between formal musical training and mathematics performance are investigated using functional magnetic resonance imaging (fMRI). FMRI was performed on fifteen normal adults, seven with musical training since early childhood, and eight without, while they mentally added and subtracted fractions. Musical training was associated with increased activation in the left fusiform gyrus and prefrontal cortex, and decreased activation in visual association areas and the left inferior parietal lobule during the mathematical task. We hypothesize that the correlation between musical training and math proficiency may be associated with improved working memory performance and an increased abstract representation of numerical quantities.

Adult↗

PubMed2004

Comparison of three methods for generating group statistical inferences from independent component analysis of functional magnetic resonance imaging data.

PURPOSE: To evaluate the relative effectiveness of three previously proposed methods of performing group independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data. MATERIALS AND METHODS: Data were generated via computer simulation. Components were added to a varying number of subjects between 1 and 20, and intersubject variability was simulated for both the added sources and their associated time courses. Three methods of group ICA analyses were performed: across-subject averaging, subject-wise concatenation, and row-wise concatenation (e.g., across time courses). RESULTS: Concatenating across subjects provided the best overall performance in terms of accurate estimation of the sources and associated time courses. Averaging across subjects provided accurate estimation (R > 0.9) of the time courses when the sources were present in a sufficient fraction (about 15%) of 100 subjects. Concatenating across time courses was shown not to be a feasible method when unique sources were added to the data from each subject, simulating the effects of motion and susceptibility artifacts. CONCLUSION: Subject-wise concatenation should be used when computationally feasible. For studies involving a large number of subjects, across-subject averaging provides an acceptable alternative and reduces the computational load.

Computer Simulation↗