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Harry B M Uylings

Publications and source records attributed to Harry B M Uylings.

At least 19 recordsLinked to original sources
PubMed2006

Specific configuration of dendritic degeneration in pyramidal neurons of the medial prefrontal cortex induced by differing corticosteroid regimens.

We previously demonstrated that hypercorticalism induces pronounced volumetric reductions in the rat medial prefrontal cortex (mPFC) and that these structural changes correlate with deficits in executive function. By applying 3-dimensional analysis of Golgi-Cox-stained material, we now demonstrate that corticosteroids can exert differential effects on dendritic arborizations of pyramidal neurons in lamina II/III of the mPFC. Treatment with the glucocorticoid receptor-selective agonist dexamethasone and with the natural adrenosteroid, corticosterone (CORT), results in significant reductions in the total length of apical dendrites in the pyramidal neurons in lamina II/III of the anterior cingulate/prelimbic and infralimbic cortices. Interestingly, although these treatments do not affect the number of dendritic branches, they are associated with impoverished arborizations in their distal portions and, in CORT-treated animals, with increased branching in the middle portions of the apical dendritic tree. Deprivation of corticosteroids by adrenalectomy leads to decreases in total apical dendritic length and spine number, but in this case, dendritic impoverishment was restricted to the middle/proximal segments of the dendritic trees. None of the treatments influenced the architecture of the basal dendrites. These results add to our knowledge of the morphological substrates through which corticosteroids may disrupt mPFC-dependent behaviors.

Adrenal Cortex Hormones↗
PubMed2006

The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture.

In an attempt to delineate the prefrontal cortex (PFC) in the Göttingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers were visualized using standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an MRI paramagnetic tracer. The in vivo tract tracing turned out to be very sensitive with a high correspondence to the histological labelling. Tracers injected into the mediodorsal thalamus labelled the medial and rostral pole of the frontal lobe as well as the anterior cingulate, anterior insular and dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of these connections were tested from injections into the traced frontal cortices indicating that the PFC has cortical connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Göttingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed that the Göttingen minipig PFC constitutes about 24% of the total neocortex volume and 10% of the total brain volume.

Animals↗
PubMed2006

Differential regional atrophy of the cingulate gyrus in Alzheimer disease: a volumetric MRI study.

Magnetic resonance imaging-based volumetric measurements provide a useful technique for quantifying in vivo regional cerebral atrophy in Alzheimer disease (AD). Histopathological studies have shown the cingulate cortex, a cytoarchitectonically heterogeneous region, to be severely affected in AD. In this study, we developed and validated a manual segmentation protocol, based on macroscopic characteristics such as gyri and sulci patterns, in order to assess volumetric changes in 4 cingulate regions of interest. Cingulate cortical volumes of 10 familial AD patients were compared with 10 age- and sex-matched controls. Inter- and intrarater reliability coefficients were high for all cingulate regions (91.9-99.4%). All 4 cingulate regions were significantly smaller (P < 0.05) in AD cases compared with controls: rostral anterior cingulate gyrus (22.5% smaller), caudal anterior cingulate gyrus (20.7% smaller), posterior cingulate gyrus (44.1% smaller), and retrosplenial cortex (21.5% smaller). The atrophy in the posterior cingulate region was significantly greater than that in other cingulate regions (P < 0.001), suggesting a higher vulnerability for this region in familial AD. Considering the functional and connectional differences of these 4 cingulate regions, detection and monitoring of their atrophy may provide insights into the natural history of AD and may help in the search for diagnostic markers for early AD.

Alzheimer Disease↗
PubMed2006

Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder.

CONTEXT: The orbitofrontal cortex (OFC)-striatal circuit, which is important for motivational behavior, is assumed to be involved in the pathophysiology of obsessive-compulsive disorder (OCD) according to current neurobiological models of this disorder. However, the engagement of this neural loop in OCD has not been tested directly in a cognitive activation imaging paradigm so far. OBJECTIVE: To determine whether the OFC and the ventral striatum show abnormal neural activity in OCD during cognitive challenge. DESIGN: A reversal learning task was employed in 20 patients with OCD who were not receiving medication and 27 healthy controls during an event-related functional magnetic resonance imaging experiment using a scanning sequence sensitive to OFC signal. This design allowed investigation of the neural correlates of reward and punishment receipt as well as of "affective switching," ie, altering behavior on reversing reinforcement contingencies. RESULTS: Patients with OCD exhibited an impaired task end result reflected by a reduced number of correct responses relative to control subjects but showed adequate behavior on receipt of punishment and with regard to affective switching. On reward outcome, patients showed decreased responsiveness in right medial and lateral OFC as well as in the right caudate nucleus (border zone ventral striatum) when compared with controls. During affective switching, patients recruited the left posterior OFC, bilateral insular cortex, bilateral dorsolateral, and bilateral anterior prefrontal cortex to a lesser extent than control subjects. No areas were found for which patients exhibited increased activity relative to controls, and no differential activations were observed for punishment in a direct group comparison. CONCLUSIONS: These data show behavioral impairments accompanied by aberrant OFC-striatal and dorsal prefrontal activity in OCD on a reversal learning task that addresses this circuit's function. These findings not only confirm previous reports of dorsal prefrontal dysfunction in OCD but also provide evidence for the involvement of the OFC-striatal loop in the pathophysiology of OCD.

Adult↗
PubMed2006

Left-right asymmetry in volume and number of neurons in adult Broca's area.

Total neuron number in, and volume of, Brodmann areas (BA) 44 and 45 (Broca's area) were studied in Nissl-stained sections from the left and right hemispheres of five adult men and five adult women. The volume of BA 44 was greater in the left hemisphere than in the right in all ten cases, although asymmetry was only significant for the subgroup of male subjects. For six of the ten subjects (including all females), the volume of BA 45 was greater in the left hemisphere than the right. This asymmetry was significant only for the women. A significant left-over-right asymmetry has been found in total neuron number in male BA 44. Although the total number of neurons in left BA 45 was larger in all five female subjects, this asymmetry did not reach significant difference. In the male subjects no significant asymmetry difference in total neuron number was found in BA 45 either. There was no significant hemispheric asymmetry or gender interaction for neuronal number density, either in BA 44 or 45. This study is the first quantitative study of total number of neurons in BA 44 and 45 in adult subjects, and demonstrates that both the volume and the total neuron number of BA 44 and 45 on the left are generally greater than that of the right hemisphere, with the possible exception of the male BA 45. In addition, it shows that the inter-individual variability was also very large (more than twofold) in the numerical values of all variables.

Adult↗
PubMed2005

Neural correlates of a reversal learning task with an affectively neutral baseline: an event-related fMRI study.

Reversal learning may conceptually be dissected into acquiring stimulus-reinforcement associations and subsequently altering behavior by switching to new associations as stimulus-reinforcement contingencies reverse (i.e., affective switching). Previous imaging studies have found regions of the ventrolateral and orbitofrontal cortex (OFC) to be involved in both subprocesses. However, these studies did not contain an affectively neutral baseline, which precluded adequate assessment of main effects of reward, punishment, and affective switching. We aimed to determine the neural substrate of these main effects, and of common and dissociable regions for reward and punishment. Furthermore, we aimed to discriminate between stimulus-punishment association and affective switching, i.e., to assess affective switching proper. To this end, we implemented a reversal learning task with an affectively neutral baseline condition that matched the experimental task in visual complexity and motor demands. Interestingly, we found dorsolateral prefrontal cortex (DLPFC) and anterior PFC to be engaged in affective switching, a finding that has not been reported before to our knowledge. Enhanced responses in these areas may represent their involvement in cognitive set shifting per se unrelated to the affective context in a reversal learning design. In addition, OFC, insular and medial prefrontal cortex regions were involved in affective switching. Left medial and lateral OFC were shown to be common areas for feedback processing, whereas left ventral striatum and left lateral OFC were specifically activated by reward and punishment, respectively. These results extend our understanding of the neural substrate of reversal learning in humans.

Adult↗
PubMed2005

Distributions of transmitter receptors in the macaque cingulate cortex.

The primate cingulate cortex is structurally and functionally complex. Although no studies have investigated the regional densities of multiple neurotransmitter receptor systems, such information would be useful for assessing its functions and disease vulnerabilities. We quantified nine different receptors in five transmitter systems by in vitro autoradiographic mapping of the cingulate cortex of macaque monkeys with the aim to link cytoarchitectonic regions and functional specialization. Receptor mapping substantiated the subdivision of the cingulate cortex into anterior versus posterior regions. In anterior cingulate cortex (ACC) AMPA glutamatergic receptors and GABA(A) inhibitory receptors were present in significantly higher concentrations than the modulatory alpha-adrenergic and muscarinic receptors. These differences were absent in the posterior cingulate cortex (PCC). By contrast, NMDA receptor densities were significantly higher than AMPA receptor densities in PCC, but not in ACC. The midcingulate area 24' shared more features with ACC than PCC. This area was characterized by the highest ratios of NMDA receptors to alpha-adrenergic, muscarinic and 5-HT2 receptors among all cingulate regions. Compared to rostrocaudal divisions, the differences between dorsoventral subdivisions a-c were small in all regions of cingulate cortex, and only muscarinic and alpha-adrenergic receptor densities followed the degree of cytoarchitectonic differentiation. We conclude that multiple receptor mapping reveals a highly differentiated classification of cingulate cortex with a characteristic predominance of fast ionotropic excitatory and inhibitory receptors in ACC, but a strong and varied complement of NMDA and metabotropic receptors in PCC.

Animals↗
PubMed2005

Random or selective neuroanatomical connectivity. Study of the distribution of fibers over two populations of identified interneurons in cerebral cortex.

We present a neuroanatomical tracing method in a stereological approach to study the proportional distribution of fibers of a particular projection over two chemically different populations of neurons. The fiber projection from the presubiculum to the medial division of the entorhinal cortex of the rat serves as a model projection. Potential target interneurons express calcium binding proteins, either parvalbumin or calretinin. The three markers were simultaneously stained in one and the same histological section. The procedure is according to a three-phase procedure, i.e., in vivo tracer injection phase, histology phase, laserscanning phase. Steps involved are: (1) Surgical application to the presubiculum (injection) of the neuroanatomical tracer, biotinylated dextran amine (BDA), with the purpose of labeling fibers innervating the entorhinal cortex. After surgery, transport of the tracer takes place during the one-week survival period; (2) Fluorescence detection of the labeled fibers through staining with fluorochromated avidin (avidin-Alexa Fluor 488 [green fluorescence]); (3) Simultaneous Immunofluorescence detection of two interneuron markers (using the appropriate primary antibodies and secondary antibodies conjugated to the fluorochromes Alexa Fluor 594 [red fluorescence] and Alexa Fluor 633 [infrared fluorescence]); (4) Acquisition of low-magnification images in a confocal laserscanning microscope and the preparation on a computer of a montage image covering the entire entorhinal cortex; (5) Overlaying this montage with a sampling grid; (6) Acquisition at high magnification of Z-series of confocal images in a statistical valid way based on this grid. Each marker was visualized in its own laser excitation/emission channel: 488, 568 and 647 nm; (7) Image processing and 3D reconstruction followed by evaluation of the results. The present approach can be used to examine whether or not a particular class of chemically identified neurons receives preferential innervation by a particular fiber projection.

Animals↗
PubMed2004

Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder.

BACKGROUND: Functional brain imaging studies in posttraumatic stress disorder (PTSD) have focused mostly on war or sexual abuse victims, many of whom also had comorbid disorders. The aim of this study was to examine the neuronal circuitry underlying responses to script-driven imagery in traumatized police officers with and without PTSD and with low comorbidity rates. METHODS: In a case-matched control study, 30 traumatized police officers with and without PTSD underwent clinical assessment and (99m)technetium-hexa-methyl-propylene-amine-oxime single photon emission computed tomography scanning with neutral and trauma scripts. Statistical parametric mapping was applied to analyze changes in regional cerebral blood flow. RESULTS: The main findings were significantly less activation in the medial frontal gyrus and more activation in the right cuneus in the PTSD group relative to the trauma-exposed control group in reaction to trauma versus neutral scripts. Within the PTSD group, subjects showed less activation in the superior temporal gyrus, left lentiform nucleus, left middle frontal gyrus, and left inferior frontal gyrus in reaction to trauma scripts. CONCLUSIONS: We confirmed previous findings of dysfunction of the medial frontal gyrus in PTSD in a new population with low comorbidity rates. Other alterations were found in certain brain structures involved in emotional, memory, linguistic, visuospatial, and motor processing.

Adult↗
PubMed2004

Cellular changes in the postmortem hippocampus in major depression.

BACKGROUND: Imaging studies report that hippocampal volume is decreased in major depressive disorder (MDD). A cellular basis for reduced hippocampal volume in MDD has not been identified. METHODS: Sections of right hippocampus were collected in 19 subjects with MDD and 21 normal control subjects. The density of pyramidal neurons, dentate granule cell neurons, glia, and the size of the neuronal somal area were measured in systematic, randomly placed three-dimensional optical disector counting boxes. RESULTS: In MDD, cryostat-cut hippocampal sections shrink in depth a significant 18% greater amount than in control subjects. The density of granule cells and glia in the dentate gyrus and pyramidal neurons and glia in all cornv ammonis (CA)/hippocampal subfields is significantly increased by 30%-35% in MDD. The average soma size of pyramidal neurons is significantly decreased in MDD. CONCLUSION: In MDD, the packing density of glia, pyramidal neurons, and granule cell neurons is significantly increased in all hippocampal subfields and the dentate gyrus, and pyramidal neuron soma size is significantly decreased as well. It is suggested that a significant reduction in neuropil in MDD may account for decreased hippocampal volume detected by neuroimaging. In addition, differential shrinkage of frozen sections of the hippocampus suggests differential water content in hippocampus in MDD.

Adult↗
PubMed2004

A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson's disease.

Hyposmia is one of the most prevalent symptoms of Parkinson's disease. It may occur even before the motor symptoms start. To determine whether the olfactory dysfunctions, like the motor symptoms, are associated with a loss of dopamine, the number of dopaminergic cells in the olfactory bulb of Parkinson's disease patients was studied using tyrosine hydroxylase immunohistochemistry. The quantitative analysis reveals that the total number of tyrosine hydroxylase-immunoreactive neurons in the olfactory bulb is twice as high in Parkinson patients compared to age and gender-matched controls. Because dopamine is known to inhibit olfactory transmission in the olfactory glomeruli, we suggest that the increase of dopaminergic neurons in the olfactory bulb is responsible for the hyposmia in Parkinson patients. The increase of dopamine in the olfactory bulb explains why olfaction does not improve with levodopa therapy.

Aged↗
PubMed2004

Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia.

OBJECTIVE: Structural deficits in the anterior cingulate cortex such as changes in glial cell and neuron numbers may be part of the anatomical substrate for schizophrenia and need to be investigated. The total number of neurons and glial cells in brains of 12 schizophrenia subjects and 14 comparison subjects were determined in two subdivisions of the prefrontal cortex: Brodmann's area 24, a part of the anterior cingulate cortex, and Brodmann's area 32 in the paracingulate cortex. METHOD: The estimate of the total cell number was obtained by multiplying the volume of the region (estimated by using Cavalieri's point counting method) by the numerical density obtained from optical disectors in the cytoarchitectonically defined areas from the prefrontal cortex. RESULTS: The average total of bilateral glial cells in Brodmann's area 24 was 201 x 10(6 )in subjects with schizophrenia and 302 x 10(6 )in comparison subjects, a statistically significant difference of 33%, whereas there was a nonsignificant difference between the schizophrenia subjects and the comparison subjects in total number of glial cells in Brodmann's area 32. The bilateral average total number of neurons in areas 24 and 32 did not differ significantly between the schizophrenia and comparison subjects. CONCLUSIONS: A selective reduction in glial cells in Brodmann's area 24 (but not in area 32) is seen in brains of subjects with schizophrenia relative to those of comparison subjects. Further investigations of the glial cells, their mutual relationship, and their relationship with neurons are needed to understand the role of specific glial components in this mental disorder.

Adult↗
PubMed2003

Do rats have a prefrontal cortex?

The lack of a single anatomical or functional definition of 'prefrontal cortex' has led to different and, in some respects, controversial views on the existence of a prefrontal cortex in non-primate mammals, in particular in rats. Until the classic paper by Rose and Woolsey [Res. Publ. Assoc. Nerv. Ment. Dis. 27 (1948) 210], the general idea was that a prefrontal cortex is unique to primate species. Rose and Woolsey's 'prefrontal cortex' definition was based upon a single anatomical criterion, i.e. the cortical projection area of the mediodorsal thalamic nucleus. Single criteria, however, do not appear to be sufficient for defining the prefrontal cortex. Therefore, other anatomical and functional characteristics are currently used to identify the prefrontal cortex in different species. Yet, recently the debate about the nature of the prefrontal cortex in non-primate species has been resumed. In the present paper we will compare the structural and functional characteristics of the prefrontal cortex of nonhuman primates and rats. We will argue that rats have a functionally divided prefrontal cortex that includes not only features of the medial and orbital areas in primates, but also some features of the primate dorsolateral prefrontal cortex.

Animals↗
PubMed2003

Decreased thalamic expression of the homeobox gene DLX1 in psychosis.

CONTEXT: A shared vulnerability to develop psychosis can be related to abnormalities in thalamic circuits in schizophrenia and bipolar disorder and could be a genetic link between these disorders. Homeobox genes involved in development and differentiation of the brain could play an important role in these disorders. OBJECTIVE: To determine whether patients with schizophrenia and bipolar disorder have different thalamic expression patterns of 2 homeobox genes, DLX1 and SHOX2 (alias OG12X or SHOT) compared with psychiatric and nonpsychiatric control subjects. DESIGN: Postmortem sections containing the thalamic mediodorsal nucleus were subjected to in situ hybridization with mouse Dlx1 and human SHOX2 RNA probes. The number of both DLX1- and SHOX2-positive neurons relative to Nissl-stained neurons was estimated in systematic randomly sampled volume probes. Patients Fifteen patients with schizophrenia, 15 with bipolar disorder with or without history of psychosis, 15 with major depressive disorder, and 15 nonpsychiatric controls from the Stanley Foundation Brain Bank. MAIN OUTCOME MEASURE: Relative numbers of DLX1- and SHOX2-positive neurons in patients with schizophrenia and bipolar disorder with history of psychosis compared with psychiatric and nonpsychiatric controls. RESULTS: Patients with a history of psychosis showed significantly decreased relative numbers of DLX1-positive neurons compared with patients without history of psychosis and nonpsychiatric controls (P =.02), whereas no differences could be found in relative numbers of SHOX2-positive neurons (P>.15). Results were obtained blind to diagnosis, symptoms, or any other variable except hemisphere. CONCLUSION: Decreased thalamic expression of DLX1 in schizophrenia and bipolar disorder with psychosis suggests shared genetic deficits in expression of this homeobox gene.

Adult↗
PubMed2003

Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions.

The thalamus plays a crucial role in memory, executive functioning and attention. It remains, however, unclear whether thalamic structures have specific roles in each of these functions. We tested 22 cases of thalamic infarction, proven with MR imaging, using experimental and established neuropsychological tests. We performed a lesion-overlap study in standardised stereotactic space of patients sharing a certain deficit, corrected for the lesion distribution of patients without such deficits and determined the regions of interest using an atlas of the human thalamus. We checked for additional, non-thalamic, damage and for deficient comprehension and perception that would preclude interpretation of the results. Non-thalamic damage such as white matter lesions, hippocampal atrophy, sulcal widening and infarctions occur significantly more often in patients aged over 60. The patients with additional damage overlapped to a major degree with those who showed loss of orientation, or lack of comprehension of the test requirements. In the 10 patients judged 'clean', we observed a deficit of episodic long-term memory with relative sparing of intellectual capacities and short-term memory when the mammillo-thalamic tract was damaged. Lesions including the medial dorsal nucleus, midline nuclei and/or intralaminar nuclei accompany executive dysfunctioning. Reduced simple processing speed and attention are associated with age, but not with a particular structure in the thalamus. Complex attention deficits follow damage to the intralaminar nuclei.We conclude that the analysis of structure-function relationships must take into account extra-structure damage which may explain cognitive deficits. Separate thalamic structures are involved in memory, executive functioning and attention.

Adult↗
PubMed2002

Neuronal changes in normal human aging and Alzheimer's disease.

This article discusses age-related changes in brain weight, total number of cortical neurons, cortical dendrites, spine, and synapse density. The conclusion is that the present outlook is less grim than it was 30 years ago. Age-related reduction appears to be specific to brain region and cortical layer rather than a general feature. In addition, we describe a different pattern of changes that occur in Alzheimer's disease patients. This review concludes that the association cortices in particular are affected in aging and Alzheimer's disease and that the primary visual and somatosensory cortices are relatively spared.

Aged↗
PubMed2002

Branching rates and growth functions in the outgrowth of dendritic branching patterns.

The outgrowth of dendritic branching patterns proceeds by neurite elongation and branching. These actions are supported by growth cones, specialized dynamic structures at the tips of outgrowing neurites, in response to a multitude of intracellular and extracellular signals and mechanisms. Branching rates of growth cones and their temporal patterns thus reflect the extent and changes in these responses. The present study outlines a model framework to relate branching rates of individual growth cones with the growth rate of the entire dendritic tree. The branching rate of an individual growth cone is assumed to depend on the total number of growth cones at any given moment (representing competition between growth cones), on its position along the dendrite, and on a baseline component representing all other factors. Four different strategies are discussed for determining quantitatively these components from experimental data. The methods are applied in the analysis of dendritic trees of Wistar rat multipolar non-pyramidal neurons, quantitatively reconstructed at several developmental stages (Parnavelas J G and Uylings H B M 1980 Brain Res. 193 373-82, Uylings H B M, Parnavelas J G, Walg H and Veltman W A M 1980 Mikroskopie 37 220-4). It is shown that the baseline branching rate is a rapidly decreasing function of time, indicating the largest baseline drive for branching in the early days of outgrowth.

Animals↗