Biomedical subjects

Michael E Brandt

Publications and source records attributed to Michael E Brandt.

9 recordsLinked to original sources

PubMed2006

Motor learning in children with spina bifida: intact learning and performance on a ballistic task.

Learning and performance on a ballistic task were investigated in children with spina bifida meningomyelocele (SBM), with either upper level spinal lesions (n = 21) or lower level spinal lesions (n = 81), and in typically developing controls (n = 35). Participants completed three phases (20 trials each) of an elbow goniometer task that required a ballistic arm movement to move a cursor to one of two target positions on a screen, including (1) an initial learning phase, (2) an adaptation phase with a gain change such that recalibration of the ballistic arm movement was required, and (3) a learning reactivation phase under the original gain condition. Initial error rate, asymptotic error rate, and learning rate did not differ significantly between the SBM and control groups. Relative to controls, the SBM group had reduced volumes in the cerebellar hemispheres and pericallosal gray matter (the region including the basal ganglia), although only the pericallosal gray matter was significantly correlated with motor adaptation. Congenital cerebellar dysmorphology is associated with preserved motor skill learning on voluntary, nonreflexive tasks in children with SBM, in whom the relative roles of the cerebellum and basal ganglia may differ from those in the adult brain.

Adaptation, Physiological↗

PubMed2005

Space-based inhibition of return in children with spina bifida.

Inhibition of return (IOR) refers to an increase in time to react to a target in a previously attended location. Children with spina bifida meningomyelocele (SBM) and hydrocephalus have congenital dysmorphology of the midbrain, a brain region associated with the control of covert orienting in general and with IOR in particular. The authors studied exogenously cued covert orienting in 8- to 19-year-old children and adolescents (84 with SBM and 37 age-matched, typically developing controls). The exogenous cue was a luminance change in a peripheral box that was 50% valid for the upcoming target location. Compared with controls, children with SBM showed attenuated IOR in the vertical plane, a deficit that was associated with midbrain dysmorphology in the form of tectal beaking but not with posterior brain volume loss. The data add to the emerging evidence for SBM deficits in attentional orienting to salient information.

Adolescent↗

PubMed2005

Spinal lesion level in spina bifida: a source of neural and cognitive heterogeneity.

OBJECT: The aim of this study was to evaluate whether the level of a spinal lesion is associated with variations in anomalous brain development and neurobehavioral outcomes in children suffering from the meningomyelocele form of spina bifida and hydrocephalus (SBM-H). METHODS: Two hundred sixty-eight children with SBM-H were divided into upper (T-12 and above; 82 patients) and lower (L-1 and below; 186 patients) lesion-level groups. Magnetic resonance images were qualitatively coded by radiologists and quantitatively segmented for cerebrum and cerebellum volumes. Psychometric assessments of handedness, intelligence, academic skills, and adaptive behavior were compared between lesion-level groups and also used to determine the number of children who met research-based criteria for mental retardation, attention deficit hyperactivity disorder, and learning disabilities. The magnetic resonance images obtained in children with upper-level spinal lesions demonstrated more qualitative abnormalities in the midbrain and tectum, pons, and splenium, although not in the cerebellum, compared with images obtained in children with lower-level spinal lesions. Upper-level lesions were also associated with reductions in cerebrum and cerebellum volumes, lower scores on measures of intelligence, academic skills, and adaptive behavior, and with a higher frequency of individuals meeting the criteria for mental retardation. Hispanic children (who were also more economically disadvantaged) were more likely to have upper-level lesions and poorer neurobehavioral outcomes, but lesion-level effects were generally independent of ethnicity. CONCLUSIONS: A higher level of spinal lesion in SBM-H is a marker for more severe anomalous brain development, which is in turn associated with poorer neurobehavioral outcomes in a wide variety of domains that determine levels of independent functioning for these children at home and school.

Adolescent↗

PubMed2004

Covert orienting to exogenous and endogenous cues in children with spina bifida.

Children with spina bifida meningomyelocele and hydrocephalus (SBM) have congenital dysmorphology of the midbrain and thinning of the posterior cortex, brain regions associated with the control of covert orienting. We studied cued covert orienting in 92 children with SBM, and 40 age-matched typically developing controls. Cues were of three types: exogenous (luminance change in a peripheral box either valid or invalid for upcoming target location), endogenous arrow (a central arrow either valid or invalid for upcoming target location), or endogenous word (a central word either valid or invalid for upcoming target location). Compared to controls, children with SBM showed slowed covert orienting to both exogenous and endogenous cues and a higher cost of attentional disengagement (e.g., a greater cue-validity effect) for exogenous although not for endogenous cues. Covert orienting deficits were associated with midbrain dysmorphology in the form of beaking of the tectum, and with right posterior brain volume loss.

Adolescent↗

PubMed2004

Motor learning in children with spina bifida: dissociation between performance level and acquisition rate.

The cerebellum is part of a neural circuit involved in procedural motor learning. We examined how congenital cerebellar malformations affect mirror drawing performance, a procedural learning task that involves learning to trace the outline of a star while looking at the reflection of the star in a mirror. Participants were 88 children with spina bifida myelomeningocele, a neural tube defect that results in lesions of the spinal cord, dysmorphology of the cerebellum, and requires shunt treatment for hydrocephalus, and 35 typically developing controls. Participants completed 10 trials in the morning and 10 trials following a 3-hr delay. Although children with spina bifida myelomeningocele were initially slower at tracing and made more errors than controls, all participants improved their performance of the task, as demonstrated by increased speed and accuracy across trials. Moreover, degree of cerebellar dysmorphology was not correlated with level of performance, rate of acquisition, or retention of mirror drawing. The results suggest that congenital cerebellar dysmorphology in spina bifida does not impair motor skill learning as measured by acquisition and retention of the mirror drawing task.

Adolescent↗

PubMedDate not supplied

Dynamics of HTLV-1 leukemogenesis: data acquisition for computer modeling.

A literature search for HTLV-1-induced adult T-cell leukemia (ATL) at the National Library of Medicine resulted in 1003 publications which were evaluated with regard to HTLV-1 virus load, apoptosis and peripheral blood leukocyte changes during the latent period and leukemia development following virus infection. The data are presented in a comparable way to previous publications of infections with HHV-6 and HIV (which target the same CD4+ cell for infection) to be used for computer validation studies. After initial infection, HTLV-1 remains clinically latent for many years at low provirus copy numbers in CD4 cells. Once immune surveillance deteriorates and viral replication progresses, provirus copy numbers increase rapidly. Unlike other virus infections, apoptotic death of virus-infected "atypical" lymphocytes decreases with increasing viral load, thus favoring continued proliferation of these cells and further virus replication at the same time. Changes in the peripheral blood are characterized by coincident rises in oligoclonal lymphocyte populations including HTLV-1-positive CD4+ T-lymphocytes and their precursors with a progressive shift to immature cells as disease progresses. The pathogenesis of HTLV-1-induced adult T-cell leukemia is an example of dysregulative leukemogenesis ideal for validation of respective computer simulation models.

Adult↗

PubMedDate not supplied

A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma.

OBJECTIVE: The objective of this study was to simulate changes in the human T cell system representing Canale-Smith syndrome using a dynamic computer model of T cell development and comparing with available human data. STUDY DESIGN: Physiological stepwise maturation and function of T lymphocytes in the computer model is altered by introducing functional disturbances following lymphotropic virus infection. In the present model, acute and chronic persistent infection with the human herpesvirus-6 (HHV-6) was simulated, and ensuing changes in T cell populations were compared with those measured in human patients. RESULTS: Using our computer model we previously found that simulated acute HHV-6 infection produced T cell computer data, which resembled an infectious mononucleosis-like disease in patients. Simulated chronic persistent infection, instead, resulted in variable cell changes comparing well to patients with chronic fatigue syndrome. In one setting, however, persistent immature lymphocytosis was observed similar to what initial has been described in this journal as Canale-Smith syndrome. CONCLUSION: Using a computer model developed by us we were able to produce simulations that resemble the immune system features of Canale-Smith syndrome. Further understanding of these simulation results may possibly guide future investigations into this disorder.

Adult↗

PubMedDate not supplied

TCM-1: a nonlinear dynamical computational model to simulate cellular changes in the T cell system; conceptional design and validation.

Based upon a previously developed theory of dysregulative lymphoma pathogenesis, a computer model is designed in order to simulate cell changes occurring in disturbances of the T cell immune system and in lymphoproliferative diseases. The model is based upon the concept that factors identified as proliferation factors, differentiation factors and inhibition factors exert a network regulation upon development and function of the T cell system, and that selective disturbances of these factors may lead to hyperplastic, aplastic or neoplastic diseases. The resulting computer model (TCM-1) was validated by comparing it with data from human diseases such as acute HHV-6 (viral) infection, chronic persistent HHV-6 infection, progressive HIV1 infection and HTLV-1 infection, and comparing the simulation results with the actual cell data in the human patients. All these infections target the same T cell population (i.e. CD4 + T helper cells), yet cause different prototypical reactions (hyperplastic, aplastic, neoplastic). The described computer model, which was successfully used to simulate changes in the benign lymphoproliferative disease, Canale-Smith syndrome, will serve as the basis model for further supplementation to accommodate identified factorial influences such as by cytokines, chemokines and others.

Adult↗

PubMedDate not supplied

Feed-forward and feedback mechanisms in a dynamic model of human T cell development and regulation.

We describe a computational model of human T cell regulatory dynamics. We used this model to simulate changes in T cell pool numbers and for studying feedback and feed-forward responses in and among these pools. The pools identified were the bone marrow stem cell compartment, early and late thymocyte compartments and the peripheral compartment of mature T lymphocytes. Simulated data showed variable intercompartmental strengths indicative of a range of sensitivities to feedback regulation and respective variable feed-forward responses. The results compare well to known clinical and experimental data, rendering the computational model a good basis for further research in T cell development and regulation.

Cell Division↗