Biomedical subjects

James Gee

Publications and source records attributed to James Gee.

At least 19 recordsLinked to original sources

PubMed2007

Validation of plaster endocast morphology through 3D CT image analysis.

A crucial component of research on brain evolution has been the comparison of fossil endocranial surfaces with modern human and primate endocrania. The latter have generally been obtained by creating endocasts out of rubber latex shells filled with plaster. The extent to which the method of production introduces errors in endocast replicas is unknown. We demonstrate a powerful method of comparing complex shapes in 3-dimensions (3D) that is broadly applicable to a wide range of paleoanthropological questions. Pairs of virtual endocasts (VEs) created from high-resolution CT scans of corresponding latex/plaster endocasts and their associated crania were rigidly registered (aligned) in 3D space for two Homo sapiens and two Pan troglodytes specimens. Distances between each cranial VE and its corresponding latex/plaster VE were then mapped on a voxel-by-voxel basis. The results show that between 79.7% and 91.0% of the voxels in the four latex/plaster VEs are within 2 mm of their corresponding cranial VEs surfaces. The average error is relatively small, and variation in the pattern of error across the surfaces appears to be generally random overall. However, inferior areas around the cranial base and the temporal poles were somewhat overestimated in both human and chimpanzee specimens, and the area overlaying Broca's area in humans was somewhat underestimated. This study gives an idea of the size of possible error inherent in latex/plaster endocasts, indicating the level of confidence we can have with studies relying on comparisons between them and, e.g., hominid fossil endocasts.

Animals↗

PubMed2005

Large-scale neural network for sentence processing.

Our model of sentence comprehension includes at least grammatical processes important for structure-building, and executive resources such as working memory that support these grammatical processes. We hypothesized that a core network of brain regions supports grammatical processes, and that additional brain regions are activated depending on the working memory demands associated with processing a particular grammatical feature. We used functional magnetic resonance imaging (fMRI) to test this hypothesis by comparing cortical activation patterns during coherence judgments of sentences with three different syntactic features. We found activation of the ventral portion of left inferior frontal cortex during judgments of violations of each grammatical feature. Increased recruitment of the dorsal portion of left inferior frontal cortex was seen during judgments of violations of specific grammatical features that appear to involve a more prominent working memory component. Left posterolateral temporal cortex and anterior cingulate were also implicated in judging some of the grammatical features. Our observations are consistent with a large-scale neural network for sentence processing that includes a core set of regions for detecting and repairing several different kinds of grammatical features, and additional regions that appear to participate depending on the working memory demands associated with processing a particular grammatical feature.

Adolescent↗

PubMed2005

Volumetric, connective, and morphologic changes in the brains of children with chromosome 22q11.2 deletion syndrome: an integrative study.

Chromosome 22q11.2 deletion syndrome is a highly prevalent genetic disorder whose manifestations include developmental disability and sometimes mental retardation. The few studies that have examined brain morphology in different samples from this population have found similar general patterns, mostly using region of interest measures. We employed voxel-based techniques to concurrently examine specific morphologic changes in multiple brain tissue measures. Results were similar to previous findings of volumetric reductions in the posterior brain. They also extended them in two ways. First, our methods provided greater specificity in the localization of changes detected. Second, the combination of our measures of gray and white matter along with cerebrospinal fluid volume and fractional anisotropy, which indicates the structure of white matter, showed a posterior displacement of and morphologic changes to the corpus callosum in affected children.

Adolescent↗

PubMed2005

Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease.

We assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of neurodegenerative disease. CSF tau levels vary widely in reports of frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid beta1-42 (A1-42), and the isoprostane 8,12-iso-iPF2a-VI (iP) prospectively in 64 patients with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimer's disease (AD), and in 13 healthy seniors. To validate our observations in vivo, we correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel-based morphometry analyses of high-resolution magnetic resonance imaging. CSF levels of tau, Abeta1-42, and iP differed significantly in FTD compared with AD. Individual patient analyses showed that 34% of FD patients had significantly low levels of CSF tau, although this was never seen in AD. A discriminant analysis based on CSF levels of tau, Abeta1-42, and iP was able to classify 88.5% of these patients in a manner that corresponds to their clinical or autopsy diagnosis. Magnetic resonance imaging studies showed that CSF tau levels correlate significantly with right frontal and left temporal cortical atrophy, brain regions known to be atrophic in patients with autopsy-proved FTD. We conclude that CSF tau levels are significantly reduced in many patients with FTD.

Age of Onset↗

PubMed2005

Characterization of brain plasticity in schizophrenia using template deformation.

RATIONALE AND OBJECTIVE: Abnormal neurodevelopment may play a role in the pathophysiology of schizophrenia. We used deformation-based morphometry to examine voxel-wise age-related changes in patients with schizophrenia compared with healthy brains. MATERIALS AND METHODS: We used a set of skull-stripped brains from an image database of cranial magnetic resonance images. We then deformed a template brain to the rest of the brains creating a set of deformation fields. Using the Jacobian values of these deformation fields, we calculated the voxel-wise t-score for comparison of controls with patients. We also calculated the voxel-wise Pearson correlation of Jacobian with age for both controls and patients. RESULTS: By examining the volume renderings of these statistical fields, we found that healthy people undergo age-related expansion of the ventricles, the surrounding periventricular white matter, and a corresponding decline in the frontal lobes and cingulate gyrus. In contrast, patients show much less of this age-related expansion of the ventricles and less atrophy in the cerebral cortex. In addition, patients have larger ventricles and reduced volume in the frontal/parietal lobes. CONCLUSION: These constellations of findings suggest that otherwise normal age-related ventricular enlargement and cortical loss occurs in schizophrenia patients, albeit at an earlier age.

Adolescent↗

PubMed2005

Regional structural characterization of the brain of schizophrenia patients.

RATIONALE AND OBJECTIVES: We study morphologic characteristics and age-related changes in patients with schizophrenia to investigate whether abnormal neurodevelopment and brain structure have a role in the pathophysiological course of this disease. MATERIALS AND METHODS: Our data consist of a set of cranial magnetic resonance images of 46 patients with schizophrenia and age- and sex-matched healthy controls. We deformed a template brain image to our set of subject images. Jacobian fields of these deformations were reduced to sets of 52 normalized region volumes for each subject by using a neuroanatomic atlas. Normalized regional volumes of the control and patient groups were compared by using Student t-test, and age correlation of each region volume was calculated for the two groups. All results were corrected for multiple comparisons by using permutation testing. We used a classifier based on support vector machines and a feature selection method to determine our ability to discriminate brains of controls from those of patients. RESULTS: Analysis of normalized region volumes shows enlargement of the third ventricle in patients. The age-correlation study showed a significant positive correlation in the third ventricle and right thalamus of controls, but not patients. Using an average of 6.5 features, our classifier was able to correctly identify 72% of patients and 70% of controls. CONCLUSION: In addition to enlargement of the third ventricle, brains of patients with schizophrenia show a different pattern of age-related changes.

Adult↗

PubMed2005

Spinal cord diffusion tensor imaging and fiber tracking can identify white matter tract disruption and glial scar orientation following lateral funiculotomy.

Diffusion tensor magnetic resonance imaging (DTI) provides data concerning water diffusion in the spinal cord, from which white matter tracts may be inferred, and connectivity between spinal cord segments may be determined. We evaluated this potential application by imaging spinal cords from normal adult rats and rats that received cervical lateral funiculotomies, disrupting the rubrospinal tract (RST). Vitrogen and fibroblasts were transplanted into the surgical lesion at time of injury in order to fill the cavity. At 10 weeks, animals were sacrificed; the spinal cords were dissected out and then imaged in a 9.4-Tesla magnet. DTI tractography demonstrated the disruption of the rubrospinal tract axons while indicating which axon tracts were preserved. Additionally, DTI imaging could identify the orientation of glial processes in the gray matter adjacent to the site of injury. In the injured animals, reactive astrocytes in adjacent gray matter appeared to orient themselves perpendicular to white matter tracts. In summary, DTI identified not only white matter disruption following injury, but could distinguish the orientation of the accompanying glial scar.

Animals↗

PubMed2004

What's in a name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease, frontotemporal dementia and corticobasal degeneration.

Confrontation naming is impaired in neurodegenerative conditions like Alzheimer's disease (AD), frontotemporal dementia (FTD) and corticobasal degeneration (CBD). Some behavioural observations suggest a common source of impaired naming across these patient groups, while others find partially unique patterns of naming difficulty. We hypothesized that a large-scale neural network underlies naming, and that patterns of impaired naming in AD, FTD and CBD reflect cortical atrophy that interrupts this network in a manner that is partially shared and partially unique across these patient groups. We tested this hypothesis by correlating naming impairments with voxel-based morphometric (VBM) analyses of cortical atrophy in structural MRIs of 50 patients. We found significant naming deficits in all patient groups. Naming also correlated with lexical retrieval in all patient groups, including subgroups of patients with FTD. VBM analyses showed significant cortical atrophy, which was shared across AD, FTD and CBD patients in the left lateral temporal cortex; this area correlated with naming accuracy in all groups. Left lateral temporal atrophy thus appears to interfere with a lexical retrieval component of naming in AD, FTD and CBD. Impaired naming also correlated with semantic memory and visual perceptual-spatial functioning in specific groups of patients and, correspondingly, naming correlated with cortical atrophy in partially distinct neuroanatomical distributions in AD, FTD, CBD and subgroups of patients with FTD. These partially unique correlation profiles appear to reflect selective interruption of other components of the naming process, including semantic and visual perceptual-spatial functioning. These findings are consistent with the hypothesis that a large-scale neural network supports naming, and that this network is interrupted in several distinct ways in patients with neurodegenerative diseases.

Aged↗

PubMed2004

Confrontation naming and morphometric analyses of structural MRI in frontotemporal dementia.

We studied the neural basis for confrontation naming difficulty in 29 patients with frontotemporal dementia (FTD) by correlating naming with voxel-based morphometric analyses of gray matter volume in structural MRI. We found that naming is significantly impaired in FTD, including patients with semantic dementia (SD), progressive nonfluent aphasia (PNFA), and nonaphasic patients (NON-APH) with a disorder of social and executive functioning. Significant cortical atrophy was found in the left anterior temporal cortex in all three FTD subgroups relative to healthy seniors. We also found significant cortical atrophy in unique anatomic distributions in each FTD subgroup. This included: lateral, ventral, and parahippocampal regions of the left temporal lobe in SD; inferior, orbital, dorsolateral, and premotor regions of the left frontal lobe in PNFA, and bilateral frontal regions in NON-APH. Direct correlations between confrontation naming and gray matter volume revealed distinct patterns in each FTD subgroup. SD patients showed a significant correlation in the left lateral temporal cortex, PNFA patients in several left frontal regions, and NON-APH patients in the right dorsolateral prefrontal cortex. These findings suggest that confrontation naming is supported by a large-scale neural network, and that naming is compromised in FTD due to interruption of the network in several different ways.

Aged↗

PubMed2003

The shape operator for differential analysis of images.

This work provides a new technique for surface oriented volumetric image analysis. The method makes no assumptions about topology, instead constructing a local neighborhood from image information, such as a segmentation or edge map, to define a surface patch. Neighborhood constructions using extrinsic and intrinsic distances are given. This representation allows one to estimate differential properties directly from the image's Gauss map. We develop a novel technique for this purpose which estimates the shape operator and yields both principal directions and curvatures. Only first derivatives need be estimated, making the method numerically stable. We show the use of these measures for multi-scale classification of image structure by the mean and Gaussian curvatures. Finally, we propose to register image volumes by surface curvature. This is particularly useful when geometry is the only variable. To illustrate this, we register binary segmented data by surface curvature, both rigidly and non-rigidly. A novel variant of Demons registration, extensible for use with differentiable similarity metrics, is also applied for deformable curvature-driven registration of medical images.

Algorithms↗

PubMed2003

Neural basis for sentence comprehension deficits in frontotemporal dementia.

Many patients with frontotemporal dementia (FTD) have impaired sentence comprehension. However, the pattern of comprehension difficulty appears to vary depending on the clinical subgroup. The purpose of this study was to elucidate the neural basis for these deficits in FTD. We studied patients with two different presentations: Three patients with Progressive Non-Fluent Ahasia (PNFA), and five non-aphasic patients with a dysexecutive and social impairment (EXEC). The FTD patient subgroups were compared to a cohort of 11 healthy seniors with intact sentence comprehension. We monitored regional cerebral activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) while subjects read sentences featuring both a grammatically complex object-relative center-embedded clause and a long linkage between the head noun phrase (NP) and the gap where the NP is interpreted in the center-embedded clause. Subjects decided whether the agent of the action is a male or a female. Healthy seniors activated both ventral portions of inferior frontal cortex (vIFC) and dorsal portions of IFC (dIFC) in the left hemisphere, often associated with grammatical and working memory components of these sentences, respectively. PNFA patients differed from healthy controls since they have reduced activation of left vIFC, while EXEC patients have less recruitment of left dIFC. We conclude that FTD subgroups have distinct patterns of sentence comprehension difficulty in part because of selective interruptions of a large-scale neural network for sentence processing.

Aged↗

PubMed2003

Characterization of sexual dimorphism in the human corpus callosum.

Despite decades of research, there is still no agreement over the presence of gender-based morphologic differences in the human corpus callosum. We approached the problem using a highly precise computational technique for shape comparison. Starting with a prospectively acquired sample of cranial MRIs of healthy volunteers (age ranges 18-84), the variations of individual callosa are quantified with respect to a reference callosum shape in the form of Jacobian determinant maps derived from the geometric transformations that map the reference callosum into anatomic alignment with the subject callosa. Voxelwise t tests performed over the determinant values demonstrated that females had a larger splenium than males (P < 0.001 uncorrected for multiple comparisons) while males possessed a larger genu (P < 0.001). In addition, pointwise Pearson plots using age as a correlate showed a different pattern of age-related changes in male and female callosa, with female splenia tending to expand more with age, while the male genu tended to contract. Our results demonstrate significant morphologic differences in the corpus callosum between genders and a possible sex difference in the neuro-developmental cycle.

Adolescent↗

PubMed2003

Characterization of regional pulmonary mechanics from serial magnetic resonance imaging data.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate a method for quantifying lung motion from the registration of successive images in serial magnetic resonance imaging acquisitions during normal respiration. MATERIALS AND METHODS: Estimates of pulmonary motion were obtained by summing the normalized cross-correlation over serially acquired lung images to identify corresponding locations between the images. The estimated motions were modeled as deformations of an elastic body and thus reflect to a first order approximation the true physical behavior of lung parenchyma. The Lagrangian strain, derived from the calculated motion fields, were used to quantify the tissue deformation induced in the lung over the serial acquisition. RESULTS: The method was validated on a magnetic resonance imaging study, for which breath-hold images were acquired of a healthy volunteer at different phases of the respiratory cycle. Regional parenchymal strain was observed to be oriented toward the pulmonary hilum, with strain magnitude maximal at the midcycle of the expiratory phase. CONCLUSION: In vivo magnetic resonance imaging quantification of lung motion holds the potential of providing a new diagnostic dimension in the assessment of pulmonary function, augmenting the information provided by studies of ventilation and perfusion.

Adult↗

PubMed2003

Alzheimer's disease and frontotemporal dementia exhibit distinct atrophy-behavior correlates: a computer-assisted imaging study.

RATIONALE AND OBJECTIVES: The purpose of this study was to test the hypothesis that distinct patterns of gray matter atrophy are responsible for unique interruptions of the naming process in Alzheimer's disease (AD) and frontotemporal dementia (FTD). MATERIALS AND METHODS: Voxel-based morphometry (VBM) was performed to characterize at the voxel level the neuroanatomic changes that occur in AD and FTD based on high-resolution T1-weighted three-dimensional (3D) spoiled-gradient echo images of patients (AD, n = 12; FTD, n = 29) and healthy control subjects (n = 12). The cortical atrophy measurements were correlated with performance on behavioral measures of naming and related processes to identify brain regions that may contribute to this language function. RESULTS: Both AD and FTD have significant naming difficulty, and this difficulty in naming correlates with a measure of lexical retrieval in both patient groups as well. However, only FTD patients showed a correlation with semantic memory. Areas of cortical atrophy common to AD and FTD were found in the anterior temporal, posterolateral temporal, and dorsolateral prefrontal regions of the left hemisphere. Correlation with naming in both AD and FTD was seen in the left anterior temporal cortex, suggesting that this area may play a role in the lexical retrieval component of naming. We also observed several unique areas of cortical atrophy in temporal and frontal cortices of these patients. Right anterior temporal and left posterolateral temporal regions of atrophy correlated with naming difficulty in FTD, suggesting that these areas may contribute to the semantic memory component of naming. Cortical areas correlating with naming that are not atrophic may represent regions that play an optional role in naming. CONCLUSION: VBM provides an important first step in analyzing brain-behavior relations in vivo in patients with neurodegenerative diseases. More refined analyses of brain morphology via high-dimensional normalization methods that are capable of modeling local as well as global variability in neuroanatomical structure promise to be even more informative.

Aged↗

PubMed2002

Neural basis for sentence comprehension: grammatical and short-term memory components.

We monitored regional cerebral activity with BOLD fMRI while subjects were presented written sentences differing in their grammatical structure (subject-relative or object-relative center-embedded clauses) and their short-term memory demands (short or long antecedent-gap linkages). A core region of left posterior superior temporal cortex was recruited during all sentence conditions in comparison to a pseudofont baseline, suggesting that this area plays a central role in sustaining comprehension that is common to all sentences. Right posterior superior temporal cortex was recruited during sentences with long compared to short antecedent-gap linkages regardless of grammatical structure, suggesting that this brain region supports passive short-term memory during sentence comprehension. Recruitment of left inferior frontal cortex was most clearly associated with sentences that featured both an object-relative clause and a long antecedent-gap linkage, suggesting that this region supports the cognitive resources required to maintain long-distance syntactic dependencies during the comprehension of grammatically complex sentences.

Adult↗

PubMed2002

Neural representation of verb meaning: an fMRI study.

The neural basis for verb comprehension has proven elusive, in part because of the limited range of verb categories that have been assessed. In the present study, 16 healthy young adults were probed for the meaning associated with verbs of MOTION and verbs of COGNITION. We observed distinct patterns of activation for each verb subcategory: MOTION verbs are associated with recruitment of left ventral temporal-occipital cortex, bilateral prefrontal cortex and caudate, whereas COGNITION verbs are associated with left posterolateral temporal activation. These findings are consistent with the claim that the neural representations of verb subcategories are distinct. Although the "sensory-motor" hypothesis may play a role in explaining activation associated with MOTION verbs, the left posterolateral temporal distribution of cortical activation associated with COGNITION verbs cannot be easily explained by the "sensory-motor" hypothesis. We suggest that left posterolateral temporal activation supports aspects of lexical semantic processing concerned with the neural representation of propositional knowledge contributing to COGNITION verbs.

Adult↗

PubMed2002

Sentence processing strategies in healthy seniors with poor comprehension: an fMRI study.

We used fMRI to examine patterns of brain recruitment in 22 healthy seniors, half of whom had selective comprehension difficulty for grammatically complex sentences. We found significantly reduced recruitment of left posterolateral temporal [Brodmann area (BA) 22/21] and left inferior frontal (BA 44/6) cortex in poor comprehenders compared to the healthy seniors with good sentence comprehension, cortical regions previously associated with language comprehension and verbal working memory, respectively. The poor comprehenders demonstrated increased activation of left prefrontal (BA 9/46), right dorsal inferior frontal (BA 44/6), and left posterior cingulate (BA 31/23) cortices for the grammatically simpler sentences that they understood. We hypothesize that these brain regions support an alternate, nongrammatical strategy for processing complex configurations of symbolic information. Moreover, these observations emphasize the crucial role of the left perisylvian network for grammatically guided sentence processing in subjects with good comprehension.

Aged↗

PubMed2002

Age-related changes in working memory during sentence comprehension: an fMRI study.

Sentence comprehension declines with age, but the neural basis for this change is unclear. We monitored regional brain activity in 13 younger subjects and 11 healthy seniors matched for sentence comprehension accuracy while they answered a simple probe about written sentences. The sentences varied in their grammatical features (subject-relative vs object-relative subordinate clause) and their verbal working memory (WM) demands (short vs long antecedent noun-gap linkage). We found that young and senior subjects both recruit a core written sentence processing network, including left posterolateral temporal and bilateral occipital cortex for all sentences, and ventral portions of left inferior frontal cortex for object-relative sentences with a long noun-gap linkage. Differences in activation patterns for seniors compared to younger subjects were due largely to changes in brain regions associated with a verbal WM network. While seniors had less left parietal recruitment than younger subjects, left premotor cortex, and dorsal portions of left inferior frontal cortex showed greater activation in seniors compared to younger subjects. Younger subjects recruited right posterolateral temporal cortex for sentences with a long noun-gap linkage. Seniors additionally recruited right parietal cortex for this sentence-specific form of WM. Our findings are consistent with the hypothesis that the neural basis for sentence comprehension includes dissociable but interactive large-scale neural networks supporting core written sentence processes and related cognitive resources involved in WM. Seniors with good comprehension appear to up-regulate portions of the neural substrate for WM during sentence processing to achieve comprehension accuracy that equals young subjects.

Adult↗