Publications

2007

Makris N, Papadimitriou GM, van der Kouwe A, Kennedy DN, Hodge SM, Dale AM, Benner T, Wald LL, Wu O, Tuch DS, et al. Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI study.. Neurobiol Aging. 2007;28(10):1556–67. doi:10.1016/j.neurobiolaging.2006.07.005
Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging, white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus II and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus II and the cingulum bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional FA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey.
Caplan D, Waters G, Kennedy D, Alpert N, Makris N, Dede G, Michaud J, Reddy A. A study of syntactic processing in aphasia II: neurological aspects.. Brain Lang. 2007;101(2):151–77. doi:10.1016/j.bandl.2006.06.226
This paper presents the results of a study of the effects of left hemisphere strokes on syntactically-based comprehension in aphasic patients. We studied 42 patients with aphasia secondary to left hemisphere strokes and 25 control subjects for the ability to assign and interpret three syntactic structures (passives, object extracted relative clauses, and reflexive pronouns) in enactment, sentence-picture matching and grammaticality judgment tasks. We measured accuracy, RT and self-paced listening times in SPM and GJ. We obtained magnetic resonance (MR) and 5-deoxyglucose positron emission tomography (FDG PET) data on 31 patients and 12 controls. The percent of selected regions of interest (ROIs) that was lesioned on MR and the mean normalized PET counts per voxel in ROIs were calculated. In regression analyses, lesion measures in both perisylvian and non-perisylvian ROIs predicted performance. Patients who performed at similar levels behaviorally had lesions of very different sizes, and patients with equivalent lesion sizes varied greatly in their level of performance. The data are consistent with a model in which the neural tissue that is responsible for the operations underlying sentence comprehension and syntactic processing is localized in different neural regions in different individuals.
Makris N, Biederman J, Valera EM, Bush G, Kaiser J, Kennedy DN, Caviness VS, Faraone S V, Seidman LJ. Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder.. Cereb Cortex. 2007;17(6):1364–75. doi:10.1093/cercor/bhl047
Attention-deficit/hyperactivity disorder (ADHD) has been associated with structural alterations in brain networks influencing cognitive and motor behaviors. Volumetric studies in children identify abnormalities in cortical, striatal, callosal, and cerebellar regions. In a prior volumetric study, we found that ADHD adults had significantly smaller overall cortical gray matter, prefrontal, and anterior cingulate volumes than matched controls. Thickness and surface area are additional indicators of integrity of cytoarchitecture in the cortex. To expand upon our earlier results and further refine the regions of structural abnormality, we carried out a structural magnetic resonance imaging study of cortical thickness in the same sample of adults with ADHD (n = 24) and controls (n = 18), hypothesizing that the cortical networks underlying attention and executive function (EF) would be most affected. Compared with healthy adults, adults with ADHD showed selective thinning of cerebral cortex in the networks that subserve attention and EF. In the present study, we found significant cortical thinning in ADHD in a distinct cortical network supporting attention especially in the right hemisphere involving the inferior parietal lobule, the dorsolateral prefrontal, and the anterior cingulate cortices. This is the first documentation that ADHD in adults is associated with thinner cortex in the cortical networks that modulate attention and EF.
Keuthen NJ, Makris N, Schlerf JE, Martis B, Savage CR, McMullin K, Seidman LJ, Schmahmann JD, Kennedy DN, Hodge SM, et al. Evidence for reduced cerebellar volumes in trichotillomania.. Biol Psychiatry. 2007;61(3):374–81. doi:10.1016/j.biopsych.2006.06.013
BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM.

2006

Koo M-S, Dickey CC, Park H-J, Kubicki M, Ji NY, Bouix S, Pohl KM, Levitt JJ, Nakamura M, Shenton ME, et al. Smaller neocortical gray matter and larger sulcal cerebrospinal fluid volumes in neuroleptic-naive women with schizotypal personality disorder.. Arch Gen Psychiatry. 2006;63(10):1090–100. doi:10.1001/archpsyc.63.10.1090
CONTEXT: Structural brain abnormalities, including larger cerebrospinal fluid (CSF) volumes, have been observed in men diagnosed as having schizotypal personality disorder (SPD). OBJECTIVES: To determine whether women with SPD have abnormalities similar to those of men with SPD and to elucidate specific SPD regional volume deficits and symptom correlations. DESIGN: Naturalistic study. SETTING AND PARTICIPANTS: Thirty neuroleptic-naive women with SPD and 29 female control subjects, both recruited from the community. Participants were group matched for age, parental socioeconomic status, handedness, and IQ. INTERVENTIONS: A new segmentation method was applied to magnetic resonance images to automatically parcel the images into CSF, gray matter, and white matter. The neocortex was manually separated from subcortical and other nonneocortical structures. Voxel-based morphometry was applied to determine global and regional volume deficits. MAIN OUTCOME MEASURES: Left and right neocortical gray matter, white matter, and CSF relative volumes as well as clinical symptoms from the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire-Brief Version. RESULTS: Smaller left (3.84%) and right (3.83%) neocortical gray matter relative volumes associated with larger left (9.66%) and right (9.61%) sulcal CSF relative volumes were found in women with SPD compared with controls. Voxel-based morphometry showed that the neocortical deficits in SPD were especially prominent in the left superior and middle temporal gyri, left inferior parietal region with postcentral gyrus, and right superior frontal and inferior parietal gyri. In the SPD group, larger lateral ventricle volumes correlated with more severe symptoms on the Structured Interview for Schizotypy and the Schizotypal Personality Questionnaire-Brief Version. CONCLUSIONS: The smaller neocortical gray matter volume and larger sulcal CSF volume provide evidence of the brain basis of this personality disorder and emphasize the communality of brain abnormalities in the schizophrenia spectrum.
Niethammer M, Estepar RSJ, Bouix S, Shenton M, Westin C-F. On diffusion tensor estimation.. Conf Proc IEEE Eng Med Biol Soc. 2006;Suppl:6707–10. doi:10.1109/IEMBS.2006.260927
In this paper we propose a formal formulation for the estimation of Diffusion Tensors in the space of symmetric positive semidefinite (PSD) tensors. Traditionally, diffusion tensor model estimation has been carried out imposing tensor symmetry without constraints for negative eigenvalues. When diffusion weighted data does not follow the diffusion model,due to noise or signal drop, negative eigenvalues may arise. An estimation method that accounts for the positive definiteness is desirable to respect the underlying principle of diffusion. This paper proposes such an estimation method and provides a theoretical interpretation of the result. A closed-form solution is derived that is the optimal data-fit in the matrix 2-norm sense,removing the need for optimization-based tensor estimation.
Niethammer M, Estepar RSJ, Bouix S, Shenton M, Westin C-F. On diffusion tensor estimation.. Conf Proc IEEE Eng Med Biol Soc. 2006;1:2622–5. doi:10.1109/IEMBS.2006.259826
In this paper we propose a formal formulation for the estimation of Diffusion Tensors in the space of symmetric positive semidefinite (PSD) tensors. Traditionally, diffusion tensor model estimation has been carried out imposing tensor symmetry without constraints for negative eigenvalues. When diffusion weighted data does not follow the diffusion model, due to noise or signal drop, negative eigenvalues may arise. An estimation method that accounts for the positive definiteness is desirable to respect the underlying principle of diffusion. This paper proposes such an estimation method and provides a theoretical interpretation of the result. A closed-form solution is derived that is the optimal data-fit in the matrix 2-norm sense, removing the need for optimization-based tensor estimation.
Madore B, Hoge S, Kwong R. Extension of the UNFOLD method to include free breathing.. Magn Reson Med. 2006;55(2):352–62. doi:10.1002/mrm.20763
Unaliasing by Fourier-encoding the overlaps using the temporal dimension (UNFOLD) is a method to reduce the data acquisition burden in dynamic MRI. The method works by forcing aliased signals to behave in specific ways through time, so that these unwanted signals can be detected and removed. Unexpected events in time, such as displacements caused by breathing, have the potential to disturb the temporal strategy and may affect UNFOLD’s ability to suppress aliasing artifacts. This work presents an extension of the UNFOLD method to accommodate temporal encoding disruptions. While the main type of disruption considered here comes from respiratory motion, other types of disruption can be envisioned, such as departures from the usual UNFOLD k-space sampling scheme. This extended version of UNFOLD was incorporated into UNFOLD-sensitivity encoding (UNFOLD-SENSE), and should also be applicable to closely related methods such as temporal SENSE (TSENSE), k-t Broaduse Linear Acquisition Speed up Technique (k-t BLAST), and k-t SENSE. Five patients were imaged with a modified version of a myocardial-perfusion sequence, and UNFOLD was used either alone or in conjunction with SENSE to obtain an acceleration of 2.0 (in three patients) or 3.0 (in two patients). In both cases this extended version of UNFOLD was able to suppress artifacts caused by the presence of breathing motion.
Kyriakos WE, Hoge S, Mitsouras D. Generalized encoding through the use of selective excitation in accelerated parallel MRI.. NMR Biomed. 2006;19(3):379–92. doi:10.1002/nbm.1047
Selective RF excitation is employed in magnetic resonance imaging (MRI) to achieve a variety of effects, such as slice selection. More elaborate transverse magnetization patterns can be realized via tailored RF excitation pulses, useful for example to image any specific region geometry within the field of view, or, to acquire non-Fourier encoded samples of the underlying magnetization distribution. In this manuscript, we review prior work on the combination of selective RF excitation with parallel MRI acquisition techniques. This combination can be used both to advantageously manipulate the numerical conditioning of the reconstruction problem, as well as to compact the information content of the acquired data so as to improve the achievable acceleration rate. With the latter application it is possible to also consider the acceleration provided by parallel imaging alone as a compaction of information content, which in certain cases can be used to reduce the length of the selective excitations. The main contribution of this review is to show how the combination of selective excitation with parallel imaging provides the latter an added flexibility that can be used to either enhance image quality, increase imaging speed, or both.
Haidar H, Bouix S, Levitt JJ, McCarley RW, Shenton ME, Soul JS. Characterizing the shape of anatomical structures with Poisson’s equation.. IEEE Trans Med Imaging. 2006;25(10):1249–57.
Poisson’s equation, a fundamental partial differential equation in classical physics, has a number of properties that are interesting for shape analysis. In particular, the equipotential sets of the solution graph become smoother as the potential increases. We use the displacement map, the length of the streamlines formed by the gradient field of the solution, to measure the "complexity" (or smoothness) of the equipotential sets, and study its behavior as the potential increases. We believe that this function complexity = f(potential), which we call the shape characteristic, is a very natural way to express shape. Robust algorithms are presented to compute the solution to Poisson’s equation, the displacement map, and the shape characteristic. We first illustrate our technique on two-dimensional synthetic examples and natural silhouettes. We then perform two shape analysis studies on three-dimensional neuroanatomical data extracted from magnetic resonance (MR) images of the brain. In the first study, we investigate changes in the caudate nucleus in Schizotypal Personality Disorder (SPD) and confirm previously published results on this structure. In the second study, we present a data set of caudate nuclei of premature infants with asymmetric white matter injury. Our method shows structural shape differences that volumetric measurements were unable to detect.