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Biomedical subjects

B S Peterson

Publications and source records attributed to B S Peterson.

At least 19 recordsLinked to original sources

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.

BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Adolescent↗

The question of PANDAS in adults.

BACKGROUND: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a well-defined cause of obsessive-compulsive disorder in children. However, they have not been described or fully investigated in adults newly diagnosed with obsessive-compulsive disorder. METHODS: We describe an adult with onset of obsessive-compulsive disorder at 25 years of age after a severe antibiotic-responsive pharyngitis. He was evaluated with multiple psychiatric rating scales for obsessive-compulsive disorder and Tourette's syndrome, as well as with serologic assays and radiologic studies. RESULTS: In all respects except age our patient fulfilled established criteria for PANDAS. Assays for antibodies to group A beta-hematolytic streptococci, serum D8,17 lymphocytes, antistriatal (neuronal) antibodies, and anticytoskeletal antibodies all supported the hypothesis that a poststreptococcal process was active. Magnetic resonance imaging was abnormal and is described. CONCLUSIONS: The findings suggest that this patient's illness is similar to PANDAS in presentation and that poststreptococcal disease may result in adult-onset obsessive-compulsive disorder.

Adult↗

Regional brain and ventricular volumes in Tourette syndrome.

BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve disturbances in cortico-striato-thalamo-cortical circuitry. The morphological characteristics of the cortical and associated white matter portions of these circuits have not been previously examined in TS subjects. METHODS: High-resolution anatomical magnetic resonance images were acquired in 155 TS and 131 healthy children and adults. The cerebrums and ventricles were isolated and then parcellated into subregions using standard anatomical landmarks. RESULTS: For analyses that included both children and adults, TS subjects were found to have larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital regions, and smaller inferior occipital volumes. Significant inverse associations of cerebral volumes with age were seen in TS subjects that were not seen in healthy controls. Sex differences in the parieto-occipital regions of healthy subjects were diminished in the TS group. The age-related findings were most prominent in TS children, whereas the diminished sex differences were most prominent in TS adults. Group differences in regional ventricular volumes were less prominent than in the cerebrum. Regional cerebral volumes were significantly associated with the severity of tic symptoms in orbitofrontal, midtemporal, and parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are involved in the pathophysiology of TS. Developmental processes, sexual dimorphisms, and compensatory responses in these cortical regions may help to modulate the course and severity of tic symptoms.

Adolescent↗

Neonatal auditory activation detected by functional magnetic resonance imaging.

The objective of this study was to detect auditory cortical activation in non-sedated neonates employing functional magnetic resonance imaging (fMRI). Using echo-planar functional brain imaging, subjects were presented with a frequency-modulated pure tone; the BOLD signal response was mapped in 5 mm-thick slices running parallel to the superior temporal gyrus. Twenty healthy neonates (13 term, 7 preterm) at term and 4 adult control subjects. Blood oxygen level-dependent (BOLD) signal in response to auditory stimulus was detected in all 4 adults and in 14 of the 20 neonates. FMRI studies of adult subjects demonstrated increased signal in the superior temporal regions during auditory stimulation. In contrast, signal decreases were detected during auditory stimulation in 9 of 14 newborns with BOLD response. fMRI can be used to detect brain activation with auditory stimulation in human infants.

Acoustic Stimulation↗

Mutual information analysis of the EEG in patients with Alzheimer's disease.

OBJECTIVE: Mutual information provides a measure of both the linear and nonlinear statistical dependencies between two time series. Cross-mutual information (CMI) is used to quantify the information transmitted from one time series to another, while auto mutual information (AMI) in a time series estimates how much on average the value of the time series can be predicted from values of the time series at preceding points. The aim of this study is to assess information transmission between different cortical areas in Alzheimer's disease (AD) patients by estimating the average CMI between EEG electrodes. METHODS: We recorded the EEG from 16 scale electrodes in 15 AD patients and 15 age-matched normal controls, and estimated the local, distant, and interhemispheric CMIs of the EEG in both groups. The rate of decrease (with increasing delay) of the AMI of the EEG was also measured to evaluate the complexity of the EEG in AD patients. RESULTS: The local CMI in AD subjects was lower than that in normal controls, especially over frontal and antero-temporal regions. A prominent decrease in information transmission between distant electrodes in the right hemisphere and between corresponding interhemispheric electrodes was detected in the AD patients. In addition, the AMIs throughout the cerebrums of the AD patients decreased significantly more slowly with delay than did the AMIs of normal controls. CONCLUSIONS: These results are consistent with previous findings that suggest the association of EEG abnormalities in AD patients with functional impairment of information transmission in long cortico-cortical connections.

Aged↗

Prospective, longitudinal study of tic, obsessive-compulsive, and attention-deficit/hyperactivity disorders in an epidemiological sample.

OBJECTIVE: Understanding the interrelatedness of tics, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD) has been complicated by studying only cross-sectional samples of clinically referred subjects. The authors report the cross-sectional and longitudinal associations of these disorders in an epidemiological sample of children followed prospectively into early adulthood. METHOD: Structured diagnostic interview information was acquired on 976 children, aged 1 to 10 years, who were randomly selected from families living in upstate New York in 1975. Reassessments were acquired in 776 of these subjects 8, 10, and 15 years later. Diagnostic prevalences were estimated at each time point. The associations among tics, OCD, and ADHD were assessed within and across time points, as were their associations with comorbid illnesses and demographic risk factors. RESULTS: In temporal cross-section, tics and ADHD symptoms were associated with OCD symptoms in late adolescence and early adulthood after demographic features and comorbid psychiatric symptoms were controlled. In prospective analyses, tics in childhood and early adolescence predicted an increase in OCD symptoms in late adolescence and early adulthood. ADHD symptoms in adolescence predicted more OCD symptoms in early adulthood, and OCD in adolescence predicted more ADHD symptoms in adulthood. The associations of tics with ADHD were unimpressive in temporal cross-section and were not significant in prospective analyses. Tics, OCD, and ADHD shared numerous complex associations with demographic and psychopathological risk factors. ADHD was associated with lower IQ and lower social status, whereas OCD was associated with higher IQ. CONCLUSIONS: Tics and OCD were significantly associated in this sample, as were OCD and ADHD. These findings are in general consistent with those from family studies, and they help to define the natural history, comorbid illnesses, and interrelatedness of these conditions.

Age Distribution↗

Automated measurement of latent morphological features in the human corpus callosum.

Our objective was to develop a novel factor-based analysis of the morphology of the corpus callosum and assess its applicability to the study of normal development, intelligence, and other subject characteristics. The contour of the corpus callosum was defined in the midsagittal planes of the MRI scans of 325 subjects, 6 to 88 years of age. The contours were coregistered, rescaled, and resampled to 50 points that were then entered into a principal components analysis with varimax rotation. The analysis yielded 8 factors for the contours of 138 healthy subjects. A second analysis of contours from 187 subjects in a patient group extracted 8 similar factors. Correlations of factor scores with conventional measures of callosum shape supported the construct validity of the assignment of morphological features to each of the factors. Correlations of factor scores with age, sex, handedness, ventricular volume, and IQ demonstrated the predictive validity of the factor structure and helped to define the neural correlates of these subject characteristics. We conclude that factor-based measures capture latent morphological features of the corpus callosum that are reliable and valid. Future studies will determine whether these novel measures are more closely related to neurobiologically important features of the corpus than are conventional measures of callosum size and shape.

Adolescent↗

Regional brain volume abnormalities and long-term cognitive outcome in preterm infants.

CONTEXT: Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits. OBJECTIVE: To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes. DESIGN AND SETTING: Case-control study conducted in 1998 and 1999 at 2 US university medical schools. PARTICIPANTS: A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status. MAIN OUTCOME MEASURES: Volumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children. RESULTS: Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P =.01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P =.01]; right, 7.4% [P =.005]), and subgenual (left, 8.9% [P =.03]; right, 11.7% [P =.01]) cortices. Preterm children's brain volumes were significantly larger (by 105. 7%-271.6%) in the occipital and temporal horns of the ventricles (P<. 001 for all) and smaller in the cerebellum (6.7%; P =.02), basal ganglia (11.4%-13.8%; P</=.005), amygdala (left, 20.2% [P =.001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P =.001]; right, 12.0% [P =.007]), and corpus callosum (13.1%-35.2%; P</=.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all). CONCLUSIONS: Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome. JAMA. 2000;284:1939-1947.

Brain↗

Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders.

BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders. METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.

Adult↗

An event-related functional MRI study of the stroop color word interference task.

In this study we have attempted to define the neural circuits differentially activated by cognitive interference. We used event-related functional magnetic resonance imaging (fMRI) to identify areas of the brain that are activated by the Stroop word-color task in two experiments. In the first experiment, we used infrequent, incongruent colored word stimuli to elicit strong Stroop interference (the 'conventional Stroop' paradigm). In the second experiment, we used infrequent, congruent colored words (the 'inverse Stroop' paradigm) to confirm that the regions identified in the first experiment were in fact specifically related to the Stroop effect and not to nonspecific oddball effects associated with the use of infrequent stimuli. Performance of the conventional Stroop specifically activated the anterior cingulate, insula, premotor and inferior frontal regions. These activated regions in the current experiment are consistent with those activated in fMRI experiments that use a more traditional block design. Finally, analysis of the time course of fMRI signal changes demonstrated differential onset and offset of signal changes in these activated regions. The time course results suggest that the action of various brain areas can be temporally dissociated.

Adult↗

An fMRI study of Stroop word-color interference: evidence for cingulate subregions subserving multiple distributed attentional systems.

BACKGROUND: The goal of this study was to model the functional connectivity of the neural systems that subserve attention and impulse control. Proper performance of the Stroop Word-Color Interference Task requires both attention and impulse control. METHODS: Word-color interference was studied in 34 normal adult subjects using functional magnetic resonance imaging. RESULTS: Interregional correlation analyses suggested that the anterior cingulate is coupled functionally with multiple regions throughout the cerebrum. A factor analysis of the significant regional activations further emphasized this functional coupling. The cingulate or related mesial frontal cortices loaded on each of the seven factors identified in the factor analysis. Other regions that loaded significantly on these factors have been described previously as belonging to anatomically connected circuits believed to subserve sensory tuning, receptive language, vigilance, working memory, response selection, motor planning, and motor response functions. These seven factors appeared to be oriented topographically within the anterior cingulate, with sensory, working memory, and vigilance functions positioned more rostrally, and response selection, motor planning, and motor response positioned progressively more caudally. CONCLUSIONS: These findings support a parallel distributed processing model for word-color interference in which portions of the anterior cingulate cortex modify the strengths of multiple neural pathways used to read and name colors. Allocation of attentional resources is thought to modify pathway strengths by reducing cross-talk between information processing modules that subserve the competing demands of reading and color naming. The functional topography of these neural systems observed within the cingulate argues for the presence of multiple attentional subsystems, each contributing to improved task performance. The topography also suggests a role for the cingulate in coordinating and integrating the activity of these multiple attentional subsystems.

Adolescent↗

The temporal dynamics of tics in Gilles de la Tourette syndrome.

BACKGROUND: Statistical characterization of tic behavior in Gilles de la Tourette syndrome (GTS) may provide insight into the dynamic functioning of the human central nervous system, as well as improve the quantitative assessment of tic symptom severity. METHODS: Twenty-two medication-free GTS subjects underwent videotaping of their tics. The intervals between temporally adjacent tics were measured, and the statistical properties of these intervals were assessed through graphical representation of frequency distributions, autoregressive integrated moving average (ARIMA) modeling, spectral analysis, and construction of first return maps. RESULTS: The frequency distribution of tic interval durations followed an inverse power law of temporal scaling. Spectral analyses similarly demonstrated that the spectral power density of tic interval duration scales inversely with frequency. ARIMA modeling suggested that the time series for tics are nonstationary as well as moving average processes. The first return maps demonstrated "burstlike" behavior and short-term periodicity in tics, and proved that successive tic intervals are not statistically independent. Graphic display of the time series confirmed shortterm periodicity, and in addition suggested the presence of period doubling. CONCLUSIONS: These findings are suggestive though not conclusive evidence for the presence of a fractal, deterministic, and possibly chaotic process in the tic time series. These analytic methods provide insight into the temporal features of tics that commonly are described clinically (such as short-term bouts or bursting, and longer term waxing and waning), and they reveal certain important temporal features of tics that have not been clinically described. The methods may also prove useful in the improved characterization of tic symptom severity.

Adolescent↗

A functional magnetic resonance imaging study of tic suppression in Tourette syndrome.

BACKGROUND: The inability to inhibit unwanted behaviors and impulses produces functional debility in a broad range of neuropsychiatric disorders. A potentially important model of impulse control is volitional tic suppression in Tourette syndrome. METHODS: Tic suppression was studied in 22 adult subjects with Tourette syndrome by using functional magnetic resonance imaging. Images acquired during periods of voluntary tic suppression were compared with images acquired when subjects allowed the spontaneous expression of their tics. The magnitudes of signal change in the images were then correlated with measures of the severity of tic symptoms. CONCLUSIONS: Significant changes in signal intensity were seen in the basal ganglia and thalamus and in anatomically connected cortical regions believed to subserve attention-demanding tasks. The magnitudes of regional signal change in the basal ganglia and thalamus correlated inversely with the severity of tic symptoms. These findings suggest that the pathogenesis of tics involves an impaired modulation of neuronal activity in subcortical neural circuits.

Adolescent↗

A double-blind, placebo-controlled, crossover trial of an antiandrogen in the treatment of Tourette's syndrome.

The objective of this study was to document the effects of androgen receptor blockade on tic and obsessive-compulsive symptoms in Tourette's syndrome (TS) patients. Thirteen adult TS subjects, 10 men and 3 women, completed 3 weeks of each phase of a double-blind, placebo-controlled, crossover trial of flutamide, a selective androgen receptor antagonist. Symptom severity ratings and hormone levels were obtained at each of the trial's six clinic visits. Flutamide was well-tolerated and produced a significant reduction in motor but not phonic tic symptom severity. It modestly improved symptoms of obsessive-compulsive disorder in the men who had this disorder. Changes in hormone levels during flutamide administration provided evidence for the existence of physiologic mechanisms that compensate for the blocking of the androgen receptor. The therapeutic effects of flutamide are modest in magnitude and they seem to be short-lived, possibly because of physiologic compensation for androgen receptor blockade. Given the potentially serious side effects of flutamide, the use of this agent in the treatment of tics should be reserved for patients who have relatively debilitating symptoms. The therapeutic and endocrine findings may have implications for understanding the sex differences in TS prevalence and the sex-specific variability in the phenotypic expression of the putative TS vulnerability genes.

Adult↗

Course of tic severity in Tourette syndrome: the first two decades.

OBJECTIVE: Prevalence studies indicate a 10-fold higher rate of Tourette syndrome (TS) among children compared with adults. The purpose of this investigation was to examine the course of tic severity during the first 2 decades of life. METHOD: A birth-year cohort of 42 TS patients followed at the Yale Child Study Center was recontacted an average of 7.3 years after their initial clinical evaluation. Data concerning the onset and course of tic severity until 18 years of age were available on 36 TS patients. A variety of statistical techniques were used to model aspects of the temporal patterning of tic severity. RESULTS: Mean (SD) tic onset at 5.6 (2. 3) years of age was followed by a progressive pattern of tic worsening. On average, the most severe period of tic severity occurred at 10.0 (2.4) years of age. In eight cases (22%), the frequency and forcefulness of the tics reached a severe level during the worst-ever period such that functioning in school was impossible or in serious jeopardy. In almost every case this period was followed by a steady decline in tic severity. By 18 years of age nearly half of the cohort was virtually tic-free. The onset of puberty was not associated with either the timing or severity of tics. CONCLUSIONS: A majority of TS patients displayed a consistent time course of tic severity. This consistency can be accurately modeled mathematically and may reflect normal neurobiological processes. Determination of the model parameters that describe each patient's course of tic severity may be of prognostic value and assist in the identification of factors that differentially influence the course of tic severity.

Adolescent↗