Publications by authors named "Jeffrey J Hutsler"

11 Publications

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Supernumerary neurons within the cerebral cortical subplate in autism spectrum disorders.

Brain Res 2021 Jun 16;1760:147350. Epub 2021 Feb 16.

Program in Neuroscience, University of Nevada, Reno, United States. Electronic address:

Autism spectrum disorders (ASDs) involve alterations to cortical connectivity that manifest as reduced coordinated activity between cortical regions. The neurons of the cortical subplate are a major contributor to establishing thalamocortical, corticothalamic and corticocortical long-range connections and only a subset of this cell population survives into adulthood. Previous reports of an indistinct gray-white matter boundary in subjects with ASD suggest that the adjacent subplate may also show organizational abnormalities. Frozen human postmortem tissue samples from the parietal lobe (BA7) were used to evaluate white-matter neuron densities adjacent to layer VI with an antibody to NeuN. In addition, fixed postmortem tissue samples from frontal (BA9), parietal (BA7) and temporal lobe (BA21) locations, were stained with a Golgi-Kopsch procedure, and used to examine the morphology of these neuronal profiles. Relative to control cases, ASD subjects showed a large average density increase of NeuN-positive profiles of 44.7 percent. The morphologies of these neurons were consistent with subplate cells of the fusiform, polymorphic and pyramidal cell types. Lower ratios of fusiform to other cell types are found early in development and although adult ASD subjects showed consistently lower ratios, these differences were not significant. The increased number of retained subplate profiles, along with cell type ratios redolent of earlier developmental stages, suggests either an abnormal initial population or a partial failure of the apoptosis seen in neurotypical development. These results indicate abnormalities within a neuron population that plays multiple roles in the developing and mature cerebral cortex, including the establishment of long-range cortical connections.
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http://dx.doi.org/10.1016/j.brainres.2021.147350DOI Listing
June 2021

Atypical Asymmetry for Processing Human and Robot Faces in Autism Revealed by fNIRS.

PLoS One 2016 7;11(7):e0158804. Epub 2016 Jul 7.

Department of Psychology, Program in Neuroscience, University of Nevada, Reno, Reno, Nevada, United States of America.

Deficits in the visual processing of faces in autism spectrum disorder (ASD) individuals may be due to atypical brain organization and function. Studies assessing asymmetric brain function in ASD individuals have suggested that facial processing, which is known to be lateralized in neurotypical (NT) individuals, may be less lateralized in ASD. Here we used functional near-infrared spectroscopy (fNIRS) to first test this theory by comparing patterns of lateralized brain activity in homologous temporal-occipital facial processing regions during observation of faces in an ASD group and an NT group. As expected, the ASD participants showed reduced right hemisphere asymmetry for human faces, compared to the NT participants. Based on recent behavioral reports suggesting that robots can facilitate increased verbal interaction over human counterparts in ASD, we also measured responses to faces of robots to determine if these patterns of activation were lateralized in each group. In this exploratory test, both groups showed similar asymmetry patterns for the robot faces. Our findings confirm existing literature suggesting reduced asymmetry for human faces in ASD and provide a preliminary foundation for future testing of how the use of categorically different social stimuli in the clinical setting may be beneficial in this population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158804PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936708PMC
July 2017

Review: Cortical construction in autism spectrum disorder: columns, connectivity and the subplate.

Neuropathol Appl Neurobiol 2016 Feb 2;42(2):115-34. Epub 2015 May 2.

Department of Psychiatry and Behavioral Science, University of Louisville School of Medicine, Louisville, USA.

The cerebral cortex undergoes protracted maturation during human development and exemplifies how biology and environment are inextricably intertwined in the construction of complex neural circuits. Autism spectrum disorders are characterized by a number of pathological changes arising from this developmental process. These include: (i) alterations to columnar structure that have significant implications for the organization of cortical circuits and connectivity; (ii) alterations to synaptic spines on individual cortical units that may underlie specific types of connectional changes; and (iii) alterations within the cortical subplate, a region that plays a role in proper cortical development and in regulating interregional communication in the mature brain. Although the cerebral cortex is not the only structure affected in the disorder, it is a fundamental contributor to the behaviours that characterize autism. These alterations to cortical circuitry likely underlie the behavioural phenotype in autism and contribute to the unique pattern of deficits and strengths that characterize cognitive functioning. Recent findings within the cortical subplate may indicate that alterations to cortical construction begin prenatally, before activity-dependent connections are established, and are in need of further study. A better understanding of cortical development in autism spectrum disorders will draw bridges between the microanatomical computational circuitry and the atypical behaviours that arise when that circuitry is modified. In addition, it will allow us to better exploit the constructional plasticity within the brain to design more targeted interventions that better manage atypical cortical construction and that can be applied very early in postnatal life.
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http://dx.doi.org/10.1111/nan.12227DOI Listing
February 2016

Sigmoid fits to locate and characterize cortical boundaries in human cerebral cortex.

J Neurosci Methods 2013 Jan 5;212(2):242-6. Epub 2012 Nov 5.

Psychology Department, Program in Neuroscience, University of Nevada, Reno, NV 89557, USA.

Quantitative evaluation of neuropathology within the cortex often requires a significant investigator time commitment. Here we elaborate on a method of quantifying the distinctiveness of the gray-white matter boundary using function fitting methods (Avino and Hutsler, 2010) and demonstrate that it can also be adapted to reliably identify the location of the gray matter/white matter (GM-WM) boundary in microscopic images, even when that boundary is indistinct. Multiple images of the gray-white matter boundary were acquired from sixteen subjects. Density profiles across the cortical layers were acquired and sigmoid functions were iteratively fit to the density profiles until a best fit was found. The slope of the resulting sigmoid was used to describe both the position and distinctiveness of the GM-WM boundary. Subsequently, two raters laid cortical boundaries on the same set of images and agreement between the raters, as well as agreement between each rater and the transverse-based boundaries, was assessed. Computer-generated boundaries showed reliably higher agreement with each individual rater, relative to the agreement between individual raters. Error between the raters and the transverse-based boundaries was associated with those images where the boundary was less distinct as assessed by the sigmoid slopes. These findings suggest that transverse-based boundaries are superior to user-generated boundaries. Furthermore, these findings suggest that rater-based boundary definitions in both neurotypical and pathological cases may become unreliable as the number of cell profiles found in the subplate region increases, as is the case in both autism and schizophrenia.
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http://dx.doi.org/10.1016/j.jneumeth.2012.10.007DOI Listing
January 2013

Abnormal cell patterning at the cortical gray-white matter boundary in autism spectrum disorders.

Brain Res 2010 Nov 25;1360:138-46. Epub 2010 Sep 25.

Psychology Department, University of Nevada, Reno, NV 89557, USA.

Previous research on neuronal spacing and columnar organization indicates the presence of cell patterning alterations within the cerebral cortex of individuals with autism spectrum disorders (ASD). These patterning abnormalities include irregularities at the gray-white matter boundary and may implicate early neurodevelopmental events such as migration in altering cortical organization in ASD. The present study utilized a novel method to quantify the gray-white matter boundary in eight ASD and eight typically developing control subjects. Digital photomicrographs of the gray-white matter boundary were acquired from multiple positions within the superior temporal gyrus (BA21), dorsolateral frontal lobe (BA9), and dorsal parietal lobe (BA7) of each case. A sigmoid curve was fitted to the transition zone between layer VI and underlying white matter (subplate), and the slope of the resulting curve was used as a measure of the spatial extent of the transition zone. For all three cortical regions examined, ASD subjects showed "shallower" sigmoid curves compared to neurotypicals, indicating the presence of an indistinct boundary between cortical layer VI and the underlying white matter. These results may reflect the presence of supernumerary neurons beneath the cortical plate that could be the result of migration deficits or failed apoptosis in the subplate region. Furthermore, these findings raise questions regarding the validity of cortical measures that rely on gray-white matter parcellation, since an indistinct transition zone could lead to a misplaced cortical boundary and errors in both thickness and volume measures.
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http://dx.doi.org/10.1016/j.brainres.2010.08.091DOI Listing
November 2010

Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders.

Brain Res 2010 Jan 6;1309:83-94. Epub 2009 Nov 6.

Psychology Department, Program in Neuroscience, University of Nevada, Reno, NV 89557-0296, USA.

Multiple types of indirect evidence have been used to support theories of altered cortical connectivity in autism spectrum disorders (ASD). In other developmental disorders reduced spine expression is commonly found, while conditions such as fragile X syndrome show increased spine densities. Despite its relevance to theories of altered cortical connectivity, synaptic spine expression has not been systematically explored in ASD. Here we examine dendritic spines on Golgi-impregnated cortical pyramidal cells in the cortex of ASD subjects and age-matched control cases. Pyramidal cells were studied within both the superficial and deep cortical layers of frontal, temporal, and parietal lobe regions. Relative to controls, spine densities were greater in ASD subjects. In analyses restricted to the apical dendrites of pyramidal cells, greater spine densities were found predominantly within layer II of each cortical location and within layer V of the temporal lobe. High spine densities were associated with decreased brain weights and were most commonly found in ASD subjects with lower levels of cognitive functioning. Greater spine densities in ASD subjects provide structural support for recent suggestions of connectional changes within the cerebral cortex that may result in altered cortical computations.
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http://dx.doi.org/10.1016/j.brainres.2009.09.120DOI Listing
January 2010

Histological and magnetic resonance imaging assessment of cortical layering and thickness in autism spectrum disorders.

Biol Psychiatry 2007 Feb 3;61(4):449-57. Epub 2006 Apr 3.

Department of Psychology, University of Michigan, Ann Arbor, Michigan, USA.

Background: Qualitative reports of the cerebral cortex in a small number of autism spectrum disorder (ASD) cases have suggested an increase in thickness and disruptions in migration and lamination patterns.

Methods: We examined postmortem ASD individuals and age-matched controls using magnetic resonance imaging (MRI) to evaluate total cortical thickness, and histological samples to evaluate the pattern of cortical layering.

Results: Overall, thickness measures from ASD subjects were equivalent to control cases. Individual regions showed marginal but nonsignificant thickness differences in the temporal lobes. Cortical thickness values in ASD subjects decreased significantly with age. Quantitative examination of proportional layer thickness in histological sections indicated that the pattern of cortical layering was largely undisturbed, while qualitative examination of these same samples revealed evidence of cell clustering and supernumerary cells in layer I and the subplate. These features were not severe and were never found in a majority of cases.

Conclusions: These findings support limited disturbances in cortical cell patterning, but do not indicate a major deficit in the orderly migration of cortical neuroblasts during development, or their subsequent aggregation into the laminar pattern found in typically developing individuals.
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http://dx.doi.org/10.1016/j.biopsych.2006.01.015DOI Listing
February 2007

Comparative analysis of cortical layering and supragranular layer enlargement in rodent carnivore and primate species.

Brain Res 2005 Aug;1052(1):71-81

Department of Psychology, 525 E. University Ave., University of Michigan, Ann Arbor, MI 48109-1109, USA.

The mammalian cerebral cortex is composed of individual layers characterized by the cell types they contain and their afferent and efferent connections. The current study examined the raw, and size-normalized, laminar thicknesses in three cortical regions (somatosensory, motor, and premotor) of fourteen species from three orders of mammals: primates, carnivores, and rodents. The proportional size of the pyramidal cell layers (supra- and infragranular) varied between orders but was similar within orders despite wide variance in absolute cortical thickness. Further, supragranular layer thickness was largest in primates (46 +/- 3 percent), followed by carnivores (36 +/- 3 percent), and then rodents (19 +/- 4 percent), suggesting a distinct difference in the proportion of cortex devoted to corticocortical connectivity across these orders. Although measures of supragranular layer thickness are highly correlated with measures of overall brain size, such associations are not present when independent contrasts are used to control for phylogenetic inertia. Interestingly, neurogenesis time span remains strongly associated with supragranular layer thickness despite size normalization and controlling for phylogenetic inertia. Such layering differences between orders, and similarities amongst species within an order, suggest that supragranular layer expansion may have occurred early in mammalian evolution and may be related to ontogenetic variables such as neurogenesis time span rather than measures of overall size.
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http://dx.doi.org/10.1016/j.brainres.2005.06.015DOI Listing
August 2005

Visual and tactile interhemispheric transfer compared with the method of Poffenberger.

Exp Brain Res 2004 Sep 31;158(1):67-74. Epub 2004 Mar 31.

Department of Neurology II, Otto-von-Guericke University, Magdeburg, Germany.

In a simple manual reaction time task, reaction times are longer if the responding hand and visual field of the stimulus are contralateral than when the hand and field are ipsilateral. This small crossed vs. uncrossed difference (CUD) has often been attributed to the interhemispheric transmission time incurred when the hemisphere receiving the sensory input is not the one initiating the motor response. We assessed the generality of the visual CUD by comparing it to the CUD for tactile stimuli. Visual and tactile CUDs did not differ significantly in magnitude, and in both modalities the CUD showed a strong asymmetry, with a positive CUD occurring only for the left hand. This outcome indicates that the properties of the visual CUD are not determined by neural pathways, or hemispheric asymmetries, that are specific to the visual system.
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http://dx.doi.org/10.1007/s00221-004-1873-6DOI Listing
September 2004

The specialized structure of human language cortex: pyramidal cell size asymmetries within auditory and language-associated regions of the temporal lobes.

Brain Lang 2003 Aug;86(2):226-42

Program in Neuroscience, University of Michigan, 525 E University Ave, Ann Arbor, MI 48109-1109, USA.

Functional lateralization of language within the cerebral cortex has long driven the search for structural asymmetries that might underlie language asymmetries. Most examinations of structural asymmetry have focused upon the gross size and shape of cortical regions in and around language areas. In the last 20 years several labs have begun to document microanatomical asymmetries in the structure of language-associated cortical regions. Such microanatomic results provide useful constraints and clues to our understanding of the biological bases of language specialization in the cortex. In a previous study we documented asymmetries in the size of a specific class of pyramidal cells in the superficial cortical layers. The present work uses a nonspecific stain for cell bodies to demonstrate the presence of an asymmetry in layer III pyramidal cell sizes within auditory, secondary auditory and language-associated regions of the temporal lobes. Specifically, the left hemisphere contains a greater number of the largest pyramidal cells, those that are thought to be the origin of long-range cortico-cortical connections. These results are discussed in the context of cortical columns and how such an asymmetry might alter cortical processing. These findings, in conjunction with other asymmetries in cortical organization that have been documented within several labs, clearly demonstrate that the columnar and connective structure of auditory and language cortex in the left hemisphere is distinct from homotopic regions in the contralateral hemisphere.
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http://dx.doi.org/10.1016/s0093-934x(02)00531-xDOI Listing
August 2003

Does microwaving enhance the Golgi methods? A quantitative analysis of disparate staining patterns in the cerebral cortex.

J Neurosci Methods 2003 Apr;124(2):145-55

Department of Psychology and Program in Neuroscience, University of Michigan, 525 East University Avenue, Ann Arbor, MI 48109-1109, USA.

As a family of techniques, the Golgi methods have long been used for studying the morphology and structure of the central nervous system. Due to their capricious nature, many modifications have been employed to improve the reliability and quality of the technique, including the recent addition of microwave energy. In the present study, we evaluated the effectiveness of adding microwave energy to two Golgi methods: the Golgi-Cox method and the rapid Golgi method. These methods were selected for their widespread use in animal research and human postmortem studies. Control tissue was compared to tissue exposed to microwave energy for varying lengths of time during the chromating step of both methods. As assessed by stereological cell counts and qualitative observation, the addition of microwave energy improved the quality of the impregnations and the number of labeled profiles in both methods up to a specific limit of exposure. Surprisingly, increases in the number of profiles were often the result of increased non-neuronal staining at the expense of neuronal staining. This result appears to be due to the fact that different classes of labeled profiles displayed distinct staining time courses.
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http://dx.doi.org/10.1016/s0165-0270(03)00002-5DOI Listing
April 2003