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Nikos Makris

Publications and source records attributed to Nikos Makris.

50 records · Page 3Linked to original sources

Selectively reduced regional cortical volumes in post-traumatic stress disorder.

Different subterritories of anterior cingulate cortex (ACC) and adjacent ventromedial frontal cortex have been shown to serve distinct functions. This scheme has influenced contemporary pathophysiologic models of psychiatric disorders. Prevailing neurocircuitry models of post-traumatic stress disorder (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as well as amygdala and hippocampus. In the current study, cortical parcellation of magnetic resonance imaging data was performed to test for volumetric differences in pregenual ACC and SC, between women with PTSD and trauma-exposed women without PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC volumes. These results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD.

Cerebral Cortex↗

Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging.

We describe a system of surface-assisted parcellation (SAP) of the human cerebellar cortex derived from neural systems functional and behavioral anatomy. This system is based on MRI and preserves the unique morphologic and topographic features of the individual cerebellum. All major fissures of the cerebellum were identified and traced in the flattened representation of the cerebellar cortex using the program "FreeSurfer." Parcellation of the cerebellar cortex followed using the fissure information in conjunction with landmarks using the program "Cardviews" to create 64 gyral-based cerebellar parcellation units. Computer-assisted algorithms enable the execution of the cerebellar parcellation procedure as well as volumetric measurements and topographic localization. The SAP technique makes it possible to represent multimodal structural and functional imaging data on the flattened surface of the cerebellar cortex as illustrated in one functional MRI experiment.

Adult↗

Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies.

Several studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit structural brain abnormalities that may be manifestations of genes that predispose to schizophrenia. In this work, we examine the utility of such measures for linkage analyses. Subjects were 45 nonpsychotic first-degree adult relatives of schizophrenic patients and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5-T magnet. We used factor analysis to derive MRI-based phenotypes for analysis. The factor analyses produced three factors that significantly discriminated relatives from controls. We used a linear combination of the three factor scores to derive an MRI phenotype. A receiver operating characteristic (ROC) analysis of this phenotype estimated an area under the curve (AUC) statistic of 0.85. The phenotype also discriminated nonpsychotic relatives having two schizophrenic relatives from those having only one. The nonpsychotic relatives of schizophrenic patients show deviant values on MRI measures of brain structure and the distribution of these deviations among relatives and controls suggests that if these results can be replicated, an MRI-derived phenotype could be useful for genetic linkage and association analyses.

Adult↗

A preliminary morphometric magnetic resonance imaging study of regional brain volumes in body dysmorphic disorder.

Morphometric magnetic resonance imaging (MRI) was used to compare regional brain volumes in eight women with body dysmorphic disorder (BDD) and eight healthy comparison subjects. The BDD group exhibited a relative leftward shift in caudate asymmetry and greater total white matter vs. the comparison group. Findings with respect to the caudate nucleus are consistent with both the conceptualization of BDD as an obsessive-compulsive spectrum disorder, and the 'striatal topography model' of obsessive-compulsive disorders.

Brain↗

MRI volumetric analysis in rasmussen encephalitis: a longitudinal study.

PURPOSE: Rasmussen encephalitis is a progressive inflammatory process with difficult-to-control focal or lateralized seizure activity, leading to hemispheric dysfunction and atrophy in advanced stages. Anatomic changes of atrophy may be subtle in earlier phases of the disease, and progressive changes on serial scans may be difficult to detect. We report a case of early-stage Rasmussen encephalitis with a relatively stable clinical course in whom we performed magnetic resonance imaging (MRI)-based volumetric analysis over an interval of 1 year, to assess for volumetric changes. METHODS: Volumetric analysis was performed on two successive MRI scans obtained at age 5 and 6 years, by using the CARDVIEWS program (J Cogn Neurosci, 1996). The images were segmented into gray- and white-matter structures according to signal intensity of their borders semiautomatically, with manual corrections. The cerebral cortex was further subdivided into smaller parcellation units according to anatomic landmarks identifiable on MRI. RESULTS: Stable left cerebral hemispheric atrophy and progressive atrophy in the left precentral gyrus, left inferior frontal gyrus, and left cerebellar atrophy were detected over the 1-year interval. CONCLUSIONS: Volumetric analysis enables early detection and quantification of anatomic changes, identification of focal involvement, and assists in determining the severity of disease and timing for surgical interventions such as hemispherectomy.

Atrophy↗

A review and new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric family study of the parahippocampal gyrus.

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

Adult↗

Somatotopic activation in the human trigeminal pain pathway.

Functional magnetic resonance imaging was used to image pain-associated activity in three levels of the neuraxis: the medullary dorsal horn, thalamus, and primary somatosensory cortex. In nine subjects, noxious thermal stimuli (46 degrees C) were applied to the facial skin at sites within the three divisions of the trigeminal nerve (V1, V2, and V3) and also to the ipsilateral thumb. Anatomical and functional data were acquired to capture activation across the spinothalamocortical pathway in each individual. Significant activation was observed in the ipsilateral spinal trigeminal nucleus within the medulla and lower pons in response to at least one of the three facial stimuli in all applicable data sets. Activation from the three facial stimulation sites exhibited a somatotopic organization along the longitudinal (rostrocaudal) axis of the brain stem that was consistent with the classically described "onion skin" pattern of sensory deficits observed in patients after trigeminal tractotomy. In the thalamus, activation was observed in the contralateral side involving the ventroposteromedial and dorsomedial nuclei after stimulation of the face and in the ventroposterolateral and dorsomedial nuclei after stimulation of the thumb. Activation in the primary somatosensory cortex displayed a laminar sequence that resembled the trigeminal nucleus, with V2 more rostral, V1 caudal, and V3 medial, abutting the region of cortical activation observed for the thumb. These results represent the first simultaneous imaging of pain-associated activation at three levels of the neuraxis in individual subjects. This approach will be useful for exploring central correlates of plasticity in models of experimental and clinical pain.

Adult↗

Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain.

We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease.

Aged↗

Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging.

BACKGROUND: Previous studies suggest that the impact of early insults predisposing to schizophrenia may have differential consequences by sex. We hypothesized that brain regions found to be structurally different in normal men and women (sexual dimorphisms) and abnormal in schizophrenia would show significant sex differences in brain abnormalities, particularly in the cortex, in schizophrenia. METHODS: Forty outpatients diagnosed as having schizophrenia by DSM-III-R were systematically sampled to be comparable within sex with 48 normal comparison subjects on the basis of age, ethnicity, parental socioeconomic status, and handedness. A comprehensive assessment of the entire brain was based on T1-weighted 3-dimensional images acquired from a 1.5-T magnet. Multivariate general linear models for correlated data were used to test for sex-specific effects regarding 22 hypothesized cortical, subcortical, and cerebrospinal fluid brain volumes, adjusted for age and total cerebrum size. Sex x group interactions were also tested on asymmetries of the planum temporale, Heschl's gyrus, and superior temporal gyrus, additionally controlled for handedness. RESULTS: Normal patterns of sexual dimorphisms were disrupted in schizophrenia. Sex-specific effects were primarily evident in the cortex, particularly in the frontomedial cortex, basal forebrain, cingulate and paracingulate gyri, posterior supramarginal gyrus, and planum temporale. Normal asymmetry of the planum was also disrupted differentially in men and women with schizophrenia. There were no significant differential sex effects in subcortical gray matter regions or cerebrospinal fluid. CONCLUSION: Factors that produce normal sexual dimorphisms may be associated with modulating insults producing schizophrenia, particularly in the cortex.

Adult↗

Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives.

BACKGROUND: Clues to the causes of schizophrenia can be derived from studying first-degree relatives because they are genetically related to an ill family member. Abnormalities observed in nonpsychotic relatives are indicators of possible genetic vulnerability to illness, independent of psychosis. We tested 4 hypotheses: (1) that hippocampal volume is smaller in nonpsychotic relatives than in controls, particularly in the left hemisphere; (2) that hippocampi will be smaller in multiplex relatives as compared with simplex relatives, and both will be smaller than in controls; (3) that hippocampal volumes and verbal declarative memory function will be positively correlated; and (4) that hippocampi will be smaller in patients with schizophrenia than in their nonpsychotic relatives or in controls. METHODS: Subjects were 45 nonpsychotic adult first-degree relatives from families with either 2 people ("multiplex," n = 17) or 1 person ("simplex," n = 28) diagnosed with schizophrenia, 18 schizophrenic relatives, and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3-dimensional magnetic resonance images of the brain were acquired on a 1.5-T magnet. Volumes of the total cerebrum and the hippocampus were measured. RESULTS: Compared with controls, relatives, particularly from multiplex families, had significantly smaller left hippocampi. Verbal memory and left hippocampal volumes were significantly and positively correlated. Within families, hippocampal volumes did not differ between schizophrenic patients and their nonpsychotic relatives. CONCLUSIONS: Results support the hypothesis that the vulnerability to schizophrenia includes smaller left hippocampi and verbal memory deficits. Findings suggest that smaller left hippocampi and verbal memory deficits are an expression of early neurodevelopmental compromise, reflecting the degree of genetic liability to schizophrenia.

Adult↗

Abnormal asymmetry in language association cortex in autism.

Autism is a neurodevelopmental disorder affecting cognitive, language, and social functioning. Although language and social communication abnormalities are characteristic, prior structural imaging studies have not examined language-related cortex in autistic and control subjects. Subjects included 16 boys with autism (aged 7-11 years), with nonverbal IQ greater than 80, and 15 age- and handedness-matched controls. Magnetic resonance brain images were segmented into gray and white matter; cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Asymmetry was assessed a priori in language-related inferior lateral frontal and posterior superior temporal regions and assessed post hoc in all regions to determine specificity of asymmetry abnormalities. Boys with autism had significant asymmetry reversal in frontal language-related cortex: 27% larger on the right in autism and 17% larger on the left in controls. Only one additional region had significant asymmetry differences on post hoc analysis: posterior temporal fusiform gyrus (more left-sided in autism), whereas adjacent fusiform gyrus and temporooccipital inferior temporal gyrus both approached significance (more right-sided in autism). These inferior temporal regions are involved in visual face processing. In boys with autism, language and social/face processing-related regions displayed abnormal asymmetry. These structural abnormalities may relate to language and social disturbances observed in autism.

Autistic Disorder↗

High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity.

Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy. Ma

Anisotropy↗

Adjustment for whole brain and cranial size in volumetric brain studies: a review of common adjustment factors and statistical methods.

In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volume differences may, instead, be wholly or partly attributable to individual differences in overall dimension (e.g., for head, brain, or body size). What quantitative approaches can be used to take these factors into account? Here, we provide a review of volumetric and nonvolumetric adjustment factors. We consider three examples of common statistical methods by which one can adjust for the effects of body, head, or brain size on regional volumetric measures: the analysis of covariance, the proportion, and the residual approaches. While the nature of the adjustment will help dictate which method is most appropriate, the choice is context sensitive, guided by numerous considerations-chiefly the experimental hypotheses, but other factors as well (including characteristic features of the disorder and sample size). These issues come into play in logically framing the assessment of putative abnormalities in regional brain volumes.

Analysis of Variance↗