Biomedical subjects

William Byne

Publications and source records attributed to William Byne.

16 recordsLinked to original sources

PubMed2006

Reduction of right medial pulvinar volume and neuron number in schizophrenia.

Several studies have described a reduction of pulvinar volume and/or neuronal number in schizophrenia (SZ). In order to better localize these changes, we assessed volume and neuronal number of the pulvinar and several of its subdivisions in postmortem material from subjects with chronic SZ and subjects with no psychiatric history. Total pulvinar volume and neuronal number were significantly lower in SZ and these differences were significant in only in its medial division. The medial pulvinar interconnects various heteromodal cortical regions suggesting that these deficits may contribute to the abnormalities of higher order integrative functions characteristic of schizophrenia.

Aged↗

PubMed2006

Metabolic thalamocortical correlations during a verbal learning task and their comparison with correlations among regional volumes.

Methods based on the analysis of metabolic and volumetric interregional correlations have been used in neuroimaging research, yet metabolic and volumetric interregional correlations for identical regions of interest have never been compared in the same group of subjects. Magnetic resonance and [18F]-fluorodeoxyglucose positron emission tomography brain images were acquired in 59 healthy subject. Correlation matrices for relative glucose metabolic rates during a verbal learning task and for relative gray matter volumes were compiled between the manually traced mediodorsal, centromedian, and pulvinar nuclei of the thalamus and 39 cortical Brodmann's areas. Metabolic correlations between the cortex and these thalamic nuclei followed the known patterns of anatomical connectivity in non-human primates. Intercorrelations of the mediodorsal nucleus were widespread with the prefrontal cortex (9 out of 10 Brodmann's areas in the left hemisphere) and temporal lobe (10 out of 11 Brodmann's areas in the left hemisphere) while the pulvinar correlated only with the parietal and occipital cortical areas. Different correlation patterns were observed for the regional gray matter volumes whereby only the pulvinar yielded extensive cortical intercorrelations, primarily with the occipital, parietal, anterior cingulate, and orbitofrontal areas in the right hemisphere. Metabolic thalamocortical correlations were much more extensive for the mediodorsal and centromedian nuclei whereas structural correlations were more extensive for the pulvinar. Therefore, metabolic and volumetric correlational methods are sensitive to different aspects of interregional relations in the brain and their comparison in the same group of subjects may render complementary and only partially overlapping connectivity information.

Adult↗

PubMed2006

Thalamocortical circuits: fMRI assessment of the pulvinar and medial dorsal nucleus in normal volunteers.

This fMRI study investigates the activation of the thalamic nuclei in a spatial focusing-of-attention task previously shown to activate the pulvinar with FDG-PET and assesses the connectivity of the thalamic nuclei with cortical areas. Normal right-handed subjects (eight men, eight women, average age=32 years) viewed four types of stimuli positioned to the right or left of the central fixation point (left hemifield-large letter, left hemifield-small letter display with flanking letters; right hemifield-large letter, right hemifield-small letter display with flankers). BOLD responses to small letters surrounded by flankers were compared with responses to large isolated letters. To examine maximum functional regional connectivity, we modeled "subject" as a random effect and attained fixed effect parameter estimates and t-statistics for functional connectivity between each of the thalamic nuclei (pulvinar, medial dorsal, and anterior) as the seed region and each non-seed voxel. Greater BOLD activation for letters surrounded by flankers than for large letters was observed in the pulvinar as anticipated and was also marked in the medial dorsal nucleus (MDN), anterior and superior cingulate (BA24 and BA24'), dorsolateral prefrontal cortex, and frontal operculum and insula. For the MDN, maximal functional connectivity was with the dorsolateral prefrontal cortex; correlations with left superior temporal, parietal, posterior frontal, and occipital regions were also observed. For the pulvinar, maximal functional connectivity was with parietal BA39; for anterior thalamus, with anterior cingulate.

Adult↗

PubMed2006

Schizophrenia-associated reduction of neuronal and oligodendrocyte numbers in the anterior principal thalamic nucleus.

The anterior principal thalamic nucleus provides a nodal link for intralimbic circuits involved in the execution of multiple complex functions that are impaired in schizophrenia (SZ). Using stereologic sampling procedures, we assessed the volume and the number of neurons and oligodendrocytes in this nucleus in well-characterized postmortem material from 23 neuroleptic treated subjects with chronic SZ (SZs) and 12 comparison subjects (Cs) with no psychiatric history. Volume was decreased on average by 17% in SZ, but this difference was not statistically significant. For neuronal number, there was a significant sex by diagnosis interaction with neuronal number being lower in male (p = .002) but not female (p = .374) SZs relative to their respective Cs. For the number of oligodendrocytes, there was a main effect of diagnosis and a diagnosis by sex interaction such that number was significantly reduced in male SZs (p < .001) with a similar trend in female SZs (p = .051) relative to their respective controls. The ratio of oligodendrocytes to neurons was significantly decreased in SZs (p = .045) with no sex by diagnosis interaction. These findings are consistent with a previous report of reduced neuronal number in the anterior principal nucleus of male SZs and add to a growing body of evidence implicating oligodendrocyte abnormalities in SZ.

Aged↗

PubMed2006

Developmental endocrine influences on gender identity: implications for management of disorders of sex development.

When a baby is born, the first medical pronouncement is usually, "It's a boy," or "It's a girl." In most cases, this pronouncement is based simply upon the appearance of the child's external genitalia. Due to variations in the process of sexual differentiation, sometimes the gender that should be assigned is not apparent from inspection of the external genitalia, either because they are "ambiguous" or because their appearance is not congruent with the internal anatomy. Decisions must be made not only about the most appropriate gender to assign the infant but also about the medical and rearing practices that will facilitate optimal psychological development and quality of life for the affected individual. This article will review the approach to managing gender disorders that has evolved since the 1950s. Three issues are identified as central to current shifts that are occurring in the management of these disorders: (a) increased understanding of the biological substrates of gender identity; (b) questions regarding the indications for irreversible cosmetic genital surgeries as a means of reinforcing gender assignments in infancy, and (c) ethical issues pertaining to informed consent and who is entitled to give it, particularly with regard to surgical gender reassignments in infancy. In keeping with the neuropsychiatry theme of this issue, the focus of this article is on prenatal sexual differentiation of the brain as it pertains to the question of psychosexual neutrality at birth.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Correlations between volumes of the pulvinar, centromedian, and mediodorsal nuclei and cortical Brodmann's areas in schizophrenia.

Correlations between the MRI-assessed volumes of the pulvinar, centromedian, and mediodorsal nuclei of the thalamus and 39 cortical Brodmann's areas were evaluated and compared in 41 unmedicated schizophrenia patients and 59 healthy comparison subjects. For the right pulvinar, positive intercorrelations with ipsilateral orbitofrontal and occipital cortices were significantly weaker while negative intercorrelations with dorsolateral prefrontal and temporopolar/entorhinal cortices were stronger in schizophrenia patients compared to healthy subjects. For the centromedian nucleus, positive correlation with the dorsolateral prefrontal area 46 in the right hemisphere was significantly weaker in patients than in healthy subjects. Higher cortical/pulvinar volume ratios for the right frontotemporal regions with stronger negative correlations in patients were associated with better performance on recall and semantic memory tasks. Right pulvinocortical disconnections in patients with schizophrenia may be related to visual attentional deficits whereas stronger-than-normal inverse pulvinar associations with the heteromodal cortical regions may reflect compensatory reliance on alternative information-processing strategies.

Adolescent↗

PubMed2005

Thalamic and prefrontal FDG uptake in never medicated patients with schizophrenia.

OBJECTIVE: Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit. METHOD: Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained. During FDG uptake, subjects performed a spatial attention task previously shown to activate the pulvinar region of the thalamus. RESULTS: Diminished regional glucose metabolism was found in the medial dorsal nucleus, posterior thalamus, and prefrontal cortex of patients with schizophrenia relative to normal volunteers, extending earlier results from studies of medicated and previously medicated patients. CONCLUSIONS: The finding of lower relative metabolic rates in the frontothalamic circuits of patients with schizophrenia is consistent with extended circuit deficits involving interactions of frontal executive areas with thalamic sensory and association processes.

Adult↗

PubMed2005

Metabolic disconnection between the mediodorsal nucleus of the thalamus and cortical Brodmann's areas of the left hemisphere in schizophrenia.

OBJECTIVE: The authors' goal was to examine interregional correlations of thalamocortical metabolic activity during a verbal learning task in schizophrenia. METHOD: They used [18F]fluorodeoxyglucose positron emission tomography in 41 unmedicated patients with schizophrenia and 59 normal comparison subjects. RESULTS: A metabolic disconnection was observed in patients with schizophrenia in the left hemisphere between the mediodorsal nucleus and widespread frontotemporal cortical regions, and stronger-than-normal intercorrelations were found between the pulvinar and superior temporal, selected parietal, posterior cingulate, and occipital areas. CONCLUSIONS: Deficits in the functional interrelationships between the left frontotemporal cortices and the left mediodorsal nucleus of the thalamus complement inferences from postmortem and magnetic resonance imaging volumetric studies identifying a thalamic diathesis in schizophrenia.

Adolescent↗

PubMed2004

Thalamus size and outcome in schizophrenia.

The size of the thalamus was assessed in 106 patients with schizophrenia and 42 normal controls using high-resolution magnetic resonance imaging. The thalamus was traced at five axial levels proportionately spaced from dorsal to ventral directions. Patients with schizophrenia had significantly smaller thalamic areas at more ventral levels. Thalamic size was positively associated with frontal lobe and temporal lobe size. The effects were most marked in the patients with poorer clinical outcome (i.e., "Kraepelinian" patients). These findings are consistent with post-mortem and MRI measurement suggesting reduction in volume of the pulvinar, which occupies a large proportion of the ventral thalamus and which has prominent connections to the temporal lobe.

Adult↗

PubMed2004

Abnormal glucose metabolism in the mediodorsal nucleus of the thalamus in schizophrenia.

OBJECTIVE: Three thalamic nuclei--the mediodorsal nucleus, pulvinar, and centromedian nucleus--each have unique reciprocal circuitry with cortical and subcortical areas known to be affected in schizophrenia. To determine if the disorder is also associated with dysfunction in the mediodorsal nucleus, pulvinar, and centromedian nucleus, relative glucose metabolism in these regions was measured in a large group of unmedicated patients with schizophrenia. METHOD: [18F]-deoxyglucose positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) scans were obtained for 41 unmedicated patients with schizophrenia and 60 age- and sex-matched healthy subjects. The PET and MRI images for each subject were coregistered, and the whole thalamus, mediodorsal nucleus, pulvinar, and centromedian nucleus were traced on the MRI image. Relative glucose metabolism in these regions was assessed. RESULTS: Patients with schizophrenia showed significantly lower relative glucose metabolism in the mediodorsal nucleus and the centromedian nucleus and significantly higher relative glucose metabolism in the pulvinar, compared with the healthy subjects. Lower relative glucose metabolism in the total thalamus, mediodorsal nucleus, and pulvinar was associated with greater overall clinical symptoms as measured by the Brief Psychiatric Rating Scale. Lower relative glucose metabolism in the pulvinar was associated with more hallucinations and more positive symptoms, while lower relative glucose metabolism in the mediodorsal nucleus was associated with more negative symptoms. CONCLUSIONS: The findings suggest that patients with schizophrenia exhibit dysfunction in thalamic subdivisions with distinct cortical connections and that these thalamic subdivisions have specific associations with clinical symptoms.

Adolescent↗

PubMed2003

Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia.

BACKGROUND: Brain imaging, molecular genetic, and ultrastructural evidence indicate the existence of pathologic alterations in the cortical and subcortical white matter of schizophrenic patients. METHODS: We performed a stereologic analysis of numbers, densities, and spatial distribution of oligodendrocytes in layer III and in the gyral white matter of Brodmann's area 9 in the superior frontal gyrus to assess whether these cells are affected in schizophrenia. Counts were obtained on Nissl-stained materials and on sections immunolabeled for the oligodendrocyte marker 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in seven schizophrenic and seven age-matched control cases. RESULTS: A 28% decrease in total numbers (or densities) of cortical layer III oligodendrocytes and a 27% decrease in the white matter were detected in schizophrenic compared with control cases based on CNPase immunostaining. Nissl and CNPase immunohistochemistry yielded comparable results. The spatial distribution of oligodendrocytes in area 9 white matter exhibited a less clustered arrangement in schizophrenic cases. CONCLUSIONS: These results suggest a severe pathology of oligodendrocytes in schizophrenia and provide a quantitative cellular correlate of the white matter changes observed by brain imaging in vivo, showing reduced fractional anisotropy in schizophrenia. The data support recent evidence that several genes encoding myelin-related proteins consistently exhibit reduced expression in schizophrenia.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2003

Magnetic resonance imaging of mediodorsal, pulvinar, and centromedian nuclei of the thalamus in patients with schizophrenia.

BACKGROUND: Postmortem and magnetic resonance imaging (MRI) data have suggested volume reductions in the mediodorsal (MDN) and pulvinar nuclei (PUL) of the thalamus. The centromedian nucleus (CMN), important in attention and arousal, has not been previously studied with MRI. METHODS: A sample of 41 patients with schizophrenia (32 men and 9 women) and 60 healthy volunteers (45 men and 15 women) underwent assessment with high-resolution 1.2-mm thick anatomical MRI. Images were differentiated to enhance the edges and outline of the whole thalamus, and the MDN, PUL, and CMN were outlined on all slices by a tracer masked to diagnostic status. RESULTS: Significantly smaller volumes of the MDN and PUL were found in patients with schizophrenia compared with controls. Volume relative to brain size was reduced in all 3 nuclei; differences in relative reduction did not differ among the nuclei. The remainder of the thalamic volume (whole thalamus minus the volume of the 3 delineated nuclei) was not different between schizophrenic patients and controls, indicating that the volume reduction was specific to these nuclei. Volume relative to brain size was reduced in all 3 nuclei and remained significant when only patients who had never been exposed to neuroleptic medication (n = 15) were considered. For the MDN, women had larger relative volumes than men among controls, but men had larger volumes than women among schizophrenic patients. CONCLUSIONS: Three association regions of the thalamus that have reciprocal connectivity to schizophrenia-associated regions of the cortex have significantly smaller volumes on MRI in patients with schizophrenia.

Adolescent↗

PubMed2002

Evidence for a decrease in basilar dendrites of pyramidal cells in schizophrenic medial prefrontal cortex.

A variety of lines of converging evidence implicates the prefrontal cortex (PFC) in schizophrenia. Previous neuroanatomical studies have shown schizophrenia-associated changes in neuron density, soma size and spine number. We recently demonstrated a schizophrenia-associated decrease in microtubule-associated protein 2 (MAP2) immunostaining in laminae III and V of medial prefrontal area 32 and interpreted that finding as suggestive of a loss of dendritic material. We now present data from medial prefrontal area 32 of 11 schizophrenics and 11 comparison subjects. In Golgi-stained material, we describe a significant decrease in the number of both primary (29%) and secondary (46%) basilar dendrites on pyramidal neurons in layer V. Similarly, in layer III there was also a decrease in both primary (17%) and secondary (15%) basilar dendrites. These findings suggest a decrease in synaptic surface area which could lead to aberrant information processing.

Adult↗

PubMed2002

Alterations in MAP2 immunocytochemistry in areas 9 and 32 of schizophrenic prefrontal cortex.

A variety of lines of converging evidence implicate the prefrontal cortex (PFC) in schizophrenia. Studies employing Nissl stains have suggested that PFC dendrites may be atrophic in schizophrenia; however, Nissl stains do not reveal dendrites. We employed MAP2 immunocytochemistry, which stains dendrites to examine cortical layers III and V in two areas of the PFC (areas 9 and 32). Occipital cortex (area 17) was examined as a control region. Tissues from seven schizophrenics and seven non-psychiatric controls were examined. Immunostaining was quantitated by area fraction analysis. MAP2 area fraction was decreased in both layers in both regions of PFC, but not in occipital cortex. Area 9 exhibited a 42% reduction in layer V and a 36% reduction in layer III. Area 32 exhibited a 31% reduction in layer V and a 36% reduction in layer III. Neither region exhibited a significant change in the density of pyramidal cells. These data are consistent with the hypothesis of a schizophrenia-associated decrease in dendritic material in the PFC.

Adult↗

PubMed2002

A lack of dimorphism of sex or sexual orientation in the human anterior commissure.

Four studies have examined the cross-sectional area of the anterior commissure (AC) for variation with sex, with conflicting results. One also reported the AC to be larger in homosexual as opposed to heterosexual men. We examined the cross-sectional area of the AC in postmortem material from 120 individuals, and found no variation in the size of the AC with age, HIV status, sex, or sexual orientation.

Adult↗

PubMed2002

Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia.

OBJECTIVE: The authors assessed schizophrenia-associated changes in volume and neuronal number in the mediodorsal nucleus and the pulvinar regions of the thalamus. METHOD: Right-hemisphere thalami obtained at autopsy from 14 schizophrenic and eight comparison subjects were examined. Computer-assisted morphometric techniques were used to determine volumes for the mediodorsal nucleus, pulvinar, and the anterior and centromedian nuclei as well as the parvocellular, magnocellular, and caudodorsal subdivisions of the mediodorsal nucleus. Neurons in the mediodorsal nucleus and pulvinar were counted and measured by using a stereology-based sampling strategy. RESULTS: Four schizophrenic and three comparison subjects had Alzheimer's type pathology, leaving 10 schizophrenic and five comparison subjects without other documented neuropathological changes. In analyses that included either the full cohort or only the subjects without Alzheimer's type pathology, volumes of the mediodorsal nucleus and pulvinar, but not the anterior or centromedian nuclei, were significantly smaller in the schizophrenic subjects. For the schizophrenic subjects, neuronal number in the mediodorsal nucleus, parvocellular subdivision, and pulvinar was significantly lower, and neuronal size in the mediodorsal nucleus, caudodorsal subdivision, and pulvinar was significantly smaller. CONCLUSIONS: Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered.

Aged↗