Search

We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way. We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions. We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P  = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P  = .04) with a left (P  = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P  = .045) driven by differences in left hemisphere limbic (P  = .007) and associative (P  = .01), but not sensorimotor, striatum. These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2020.)

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5 years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal-retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

Objective: The striatum receives segregated and integrative white matter tracts from the cortex facilitating information processing in the cortico-basal ganglia network. The authors examined both types of input tracts in the striatal associative loop in chronic schizophrenia patients and healthy control subjects., Method: Structural and diffusion MRI scans were acquired on a 3-T system from 26 chronic schizophrenia patients and 26 matched healthy control subjects. Using FreeSurfer, the associative cortex was parcellated into ventrolateral prefrontal cortex and dorsolateral prefrontal cortex subregions. The striatum was manually parcellated into its associative and sensorimotor functional subregions. Fractional anisotropy and normalized streamlines, an estimate of fiber counts, were assessed in four frontostriatal tracts (dorsolateral prefrontal cortex-associative striatum, dorsolateral prefrontal cortex-sensorimotor striatum, ventrolateral prefrontal cortex-associative striatum, and ventrolateral prefrontal cortex-sensorimotor striatum). Furthermore, these measures were correlated with a measure of cognitive control, the Trail-Making Test, Part B., Results: Results showed reduced fractional anisotropy and fewer streamlines in chronic schizophrenia patients for all four tracts, both segregated and integrative. Post hoc t tests showed reduced fractional anisotropy in the left ventrolateral prefrontal cortex-associative striatum and left ventrolateral prefrontal cortex-sensorimotor striatum and fewer normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum and in the left and right ventrolateral prefrontal cortex-sensorimotor striatum in chronic schizophrenia patients. Furthermore, normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum negatively correlated with Trail-Making Test, Part B, time spent in healthy control subjects but not in chronic schizophrenia patients., Conclusions: These findings demonstrated that structural connectivity is reduced in both segregated and integrative tracts in the striatal associative loop in chronic schizophrenia and that reduced normalized streamlines in the right-hemisphere dorsolateral prefrontal cortex-sensorimotor striatum predicted worse cognitive control in healthy control subjects but not in chronic schizophrenia patients, suggesting a loss of a "normal" brain-behavior correlation in chronic schizophrenia.

We combined diffusion tension imaging (DTI) of prefrontal white matter integrity and neuropsychological measures to examine the functional neuroanatomy of human intelligence. Healthy participants completed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) along with neuropsychological tests of attention and executive control, as measured by Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). Stochastic tractography, considered the most effective DTI method, quantified white matter integrity of the medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) circuitry. Based on prior studies, we hypothesized that posterior mOFC-rACC connections may play a key structural role linking attentional control processes and intelligence. Behavioral results provided strong support for this hypothesis, specifically linking attentional control processes, measured by Trails B and WCST perseverative errors, to intelligent quotient (IQ). Hierarchical regression results indicated left posterior mOFC-rACC fractional anisotropy (FA) and Trails B performance time, but not WCST perseverative errors, each contributed significantly to IQ, accounting for approximately 33.95-51.60% of the variance in IQ scores. These findings suggested that left posterior mOFC-rACC white matter connections may play a key role in supporting the relationship of executive functions of attentional control and general intelligence in healthy cognition., (Copyright © 2016. Published by Elsevier Ltd.)

We examined intelligence and memory in 25 healthy participants who had both prior magnetic resonance imaging (MRI) of gray matter volumes of medial orbital frontal cortex (mOFC) and rostral anterior cingulate cortex (rACC), along with diffusion tensor imaging (DTI) of posterior and anterior mOFC-rACC white matter microstructure, as assessed by fractional anisotropy (FA). Results showed distinct relationships between these basic structural brain parameters and higher cognition, highlighted by a highly significant correlation of left rACC gray matter volume with memory, and to a lesser extent, though still statistically significant, correlation of left posterior mOFC-rACC FA with intelligence. Regression analyses showed that left posterior mOFC-rACC connections and left rACC gray matter volume each contributed to intelligence, with left posterior mOFC-rACC FA uniquely accounting for between 20.43 and 24.99% of the variance in intelligence, in comparison to 13.54 to 17.98% uniquely explained by left rACC gray matter volume. For memory, only left rACC gray matter volume explained neuropsychological performance, uniquely accounting for a remarkably high portion of individual variation, ranging from 73.61 to 79.21%. These results pointed to differential contributions of white mater microstructure connections and gray matter volumes to individual differences in intelligence and memory, respectively.

The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%-34% of the variance in IQ, in comparison to 11%-16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence.

In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p=0.004), bilateral MFG (left: p=0.007; right: p=0.007), and bilateral IFG (left: p<0.001; right: p=0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R=-0.465, p=0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R=0.440, p=0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching., (© 2013.)

We examined social cognition in a sample of healthy participants who had prior magnetic resonance imaging (MRI) gray matter volume studies of the orbital frontal cortex (OFC) that was parcellated into three regions: gyrus rectus, middle orbital gyrus and lateral orbital gyrus. These subjects also completed a self-report measure of Machiavelli personality traits, along with psychometric tests of social comprehension and declarative episodic memory, all of which we used as proxy measures to examine various features of social cognition. The data pointed to distinct functional-anatomical relationships highlighted by strong correlations of left lateral orbital gyrus and Machiavellian scores and right middle orbital gyrus with social comprehension and declarative episodic memory. In addition, hierarchical regression analyses revealed statistical evidence of a double dissociation between Machiavellian scores and left lateral orbital gyrus on one hand, and social comprehension with right middle orbital gyrus, on the other hand. To our knowledge, these findings are the first to show evidence linking normal variation in OFC subregions and different aspects of social cognition.

The authors examined the relationship between neuropsychological performance and MRI of the orbital frontal cortex (OFC) and diffusion tensor imaging (DTI) of the cingulum bundle (CB) within groups of patients with schizophrenia and healthy subjects. The authors analyzed data from subjects, who had participated in prior MRI, DTI, and neuropsychological studies (Nakamura et al., 2008; Nestor et al., 2008). In comparison to healthy subjects, patients showed the expected reductions across CB fractional anisotropy (white matter) and OFC gray matter volume as well as lower neuropsychological scores. In addition, in comparison to healthy subjects, patients showed a very different pattern of functional-anatomical correlates. For patients, CB white matter but not OFC gray matter correlated with various aspects of intelligence, including general abilities and working memory. For controls, OFC gray matter but not CB white matter correlated with scores on tests of intelligence and decision making. These results point to the potentially important role of CB white matter in the neuropsychological disturbance in schizophrenia., (Copyright 2009 APA, all rights reserved.)

In 1908, Bleuler proposed a unitary theory of schizophrenia, hypothesizing a "loosening of associations" as the central mechanism underlying disturbances in thinking, motivation, and affective expression. Here, we test Bleuler's model in an archival sample of 79 healthy controls and 76 patients with chronic schizophrenia who had completed neuropsychological tests, including a measure of learning of novel word pairs, which was specifically selected to probe the structure and formation of new verbal associations. The patients also had positive and negative symptoms ratings, including measures of flat affect, anhedonia, and thought disorder. A subset of patients and controls (n = 39) had available prior archival 3-T magnetic resonance imaging (MRI) measures of prefrontal cortex (PFC) gray matter volumes. In relation to controls, patients showed evidence of a selective impairment in associative learning, independent of their overall reduced neuropsychological functioning. This neuropsychological impairment, in turn, correlated significantly with overall levels of negative but not positive symptoms, with the data showing an especially strong contribution of flattened emotional expression to verbal associate learning deficits in this patient sample. Moreover, the archival MRI data were consistent with prior research pointing to an important role of the PFC in supporting verbal associate learning and memory in patients and controls. Taken together, the current results provided evidence of a selective impairment in schizophrenia on a PFC-supported verbal associate learning and memory task, which was accompanied by negative symptoms in general, and flattened emotional expression, in particular. [ABSTRACT FROM AUTHOR]

The somatic marker hypothesis (SMH) represents a rich neuropsychological framework to study emotion-based decision-making. It originates from early brain lesion studies using the Iowa Gambling Task (IGT), which showed that adaptive decision-making relies on intact ventromedial prefrontal cortex for the integration of so-called "hot" affective signals and rational "cold" perceptual cognitive computations. Subsequent studies over the past 20 years have provided converging evidence for the reliability and validity of the IGT in assessing decision-making in both healthy and clinical samples, although some discrepancies remain. In healthy individuals, it has been shown that differences in emotional states prior to taking the IGT result in different outcomes, thus potentially accounting for some of the variation within this group. However, the precise role of such transient modulations of emotional states remains unclear. In this study we sought to examine the role of specific induced moods under carefully controlled conditions. Accordingly, we randomly assigned 44 healthy college undergraduates to a positive, negative, or neutral affect condition in which they simultaneously viewed images and listened to music that previous studies had shown to induce specific moods. Results indicated that mood induction was successful, and the positive affect group showed a clearly different pattern of IGT performance compared to the other two groups, in that they showed a rapidly established and stable bias favoring the positive expected value (EV) card decks. The negative affect group showed significantly lower bias towards the positive EV decks, although this group was not different from the neutral affect group. Bayesian analyses confirmed these findings. While consistent with SMH, these current findings may be best understood in support of a more general effect of normal mood on cognition as outlined in the broaden-and-build theory of positive emotions. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Cognitive and emotional functioning is mediated by frontal–subcortical feedback loops. The striatum, a component of this circuitry, thus is a possible neural substrate of schizophrenia. Striatum volume, however, is believed to be differentially influenced by neuroleptic treatment due to an anterior–posterior D2 receptor density gradient. We thus rigorously parcellated it into subregions in order to assess whether neuroleptic effect on group differences is regionally specific. Methods: 29 chronic, male, schizophrenia patients and 28 male, normal controls (NCs), group-matched for handedness, age, and parental SES, underwent structural brain imaging on a 1.5Tesla GE system. We manually measured the volume, normalized for intracranial contents, of the striatum parcellated into anatomic subregions and their corresponding limbic, associative and sensorimotor functional subregions and performed clinical correlations. Results: First, we found a localized bilateral enlargement of the posterior putamen in medicated chronic schizophrenia. Second, we showed associative striatal subregion volumes correlated with executive function in schizophrenia subjects and, to a lesser extent, in NCs. Third, we showed associative striatal subregions inversely correlated with negative symptoms but conversely, the ventral/limbic striatum did not correlate with positive or negative clinical symptoms. Discussion: Our novel parcellation strategy, based on rigorous delineation of the ventral striatum, allowed for the demonstration of localized volumetric differences between schizophrenia and NCs. Furthermore, by parcellating the striatum into functional subregions we demonstrated significant positive correlations between the volume of the associative striatum and executive functioning in schizophrenia, adding further support to the importance of its role in the pathophysiology of schizophrenia. [Copyright &y& Elsevier]

Abstract: Introduction: Higher cognitive functioning is mediated by frontal-subcortical cognitive and limbic feedback sub-loops. The thalamo-cortical projection through the anterior limb of the internal capsule (ALIC) serves as the final step in these feedback sub-loops. We evaluated abnormalities in the ALIC fiber tract in schizophrenia using both structural MRI and diffusion tensor imaging (DTI). Methods: 20 chronic schizophrenia patients and 22 male, normal controls group matched for handedness, age, and parental SES, underwent structural and DTI brain imaging on a 1.5Tesla GE system. We manually measured ALIC volume normalized for intracranial contents (ICC) using structural brain images and then registered these high resolution structural brain scan derived ALIC label maps to DTI space allowing for the measurement in the ALIC of diffusion indices including, fractional anisotropy (FA) mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Results: We found in the ALIC of chronic schizophrenia subjects, compared with normal controls, bilaterally lower FA and bilaterally higher RD, but no differences in AD, MD, or relative volume. Cognitive correlations in schizophrenia patients showed, in particular, that higher left ALIC FA correlated positively with better verbal and nonverbal declarative/episodic memory performance. Discussion: Using a novel approach to assess both diffusion and volume measures in the ALIC in schizophrenia, we found abnormalities in measures of diffusion, but not volume, supporting their importance as sensitive indices of abnormalities in white matter fiber bundles in schizophrenia. Our findings also support the role of ALIC white matter tract FA abnormalities in declarative/episodic memory in schizophrenia. [Copyright &y& Elsevier]

Abstract: Frontal-subcortical cognitive and limbic feedback loops modulate higher cognitive functioning. The final step in these feedback loops is the thalamo-cortical projection through the anterior limb of the internal capsule (AL-IC). Using diffusion tensor imaging (DTI), we evaluated abnormalities in the AL-IC fiber tract in schizophrenia. Participants comprised 16 chronic schizophrenia patients and 19 male, normal controls, who were group matched for handedness, age, and parental socioeconomic status, and underwent DTI on a 1.5 Tesla GE system. We measured the diffusion indices, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), and manually segmented, based on FA maps, AL-IC volume, normalized for intracranial contents (ICC). The results showed a significant reduction in the ICC-corrected volume of the AL-IC in schizophrenia, but did not show diffusion measure group differences in the AL-IC in FA, MD, RD or AD. In addition, in the schizophrenia patients, AL-IC FA correlated positively with performance on measures of spatial and verbal declarative/episodic memory, and right AL-IC ICC-corrected volume correlated positively with more perseverative responses on the Wisconsin Card Sort Test (WCST). We found a reduction in AL-IC ICC-corrected volume in schizophrenia, without FA, MD, RD or AD group differences, implicating the presence of a structural abnormality in schizophrenia in this subcortical white matter region which contains important cognitive, and limbic feedback pathways that modulate prefrontal cortical function. Despite not demonstrating a group difference in FA, we found that AL-IC FA was a good predictor of spatial and verbal declarative/episodic memory performance in schizophrenia. [ABSTRACT FROM AUTHOR]

: BackgroundWe measured the shape of the head of the caudate nucleus with a new approach based on magnetic resonance imaging (MRI) in schizotypal personality disorder (SPD) subjects in whom we previously reported decreased caudate nucleus volume. We believe MRI shape analysis complements traditional MRI volume measurements.: MethodsMagnetic resonance imaging scans were used to measure the shape of the caudate nucleus in 15 right-handed male subjects with SPD, who had no prior neuroleptic exposure, and in 14 matched normal comparison subjects. With MRI processing tools, we measured the head of the caudate nucleus using a shape index, which measured how much a given shape deviates from a sphere.: ResultsIn relation to comparison subjects, neuroleptic never-medicated SPD subjects had significantly higher (more “edgy”) head of the caudate shape index scores, lateralized to the right side. Additionally, for SPD subjects, higher right and left head of the caudate SI scores correlated significantly with poorer neuropsychological performance on tasks of visuospatial memory and auditory/verbal working memory, respectively.: ConclusionsThese data confirm the value of measuring shape, as well as volume, of brain regions of interest and support the association of intrinsic pathology in the caudate nucleus, unrelated to neuroleptic medication, with cognitive abnormalities in the schizophrenia spectrum. [Copyright &y& Elsevier]

Abstract: Background: Structural abnormalities in the callosal fibers connecting the heteromodal association areas of the prefrontal and temporoparietal cortices bilaterally have been suggested to play a role in the etiology of schizophrenia. Aims: To investigate for geometric abnormalities in these callosal fibers in schizophrenia patients by using a novel Diffusion-Tensor Imaging (DTI) metric of fiber geometry named Shape-Normalized Dispersion (SHD). Methods: DTIs (3T, 51 gradient directions, 1.7mm isotropic voxels) were acquired from 26 schizophrenia patients and 23 matched healthy controls. The prefrontal and temporoparietal fibers of the corpus callosum were extracted by means of whole-brain tractography, and their mean SHD calculated. Results: The schizophrenia patients exhibited subnormal levels of SHD in the prefrontal callosal fibers when controlling for between-group differences in Fractional Anisotropy. Reduced SHD could reflect either irregularly turbulent or inhomogeneously distributed fiber trajectories in the corpus callosum. Conclusions: The results suggest that the transcallosal misconnectivity thought to be associated with schizophrenia could reflect abnormalities in fiber geometry. These abnormalities in fiber geometry could potentially be underpinned by neurodevelopmental irregularities. [Copyright &y& Elsevier]