M. Shenton - Academia.edu (original) (raw)

Papers by M. Shenton

Social Psychiatry and Psychiatric Epidemiology, Nov 28, 2018

Purpose: The current study evaluates the demographic, clinical, and neurocognitive characteristic... more Purpose: The current study evaluates the demographic, clinical, and neurocognitive characteristics of a recruited FEP research sample, a research control group, and a FEP clinic sample that were assessed and treated within the same center and time period. Methods: This study utilized data collected through an observational study and a retrospective chart review. Samples were ascertained in the Longitudinal Assessment and Monitoring of Clinical

ABSTRACT Background / Purpose: The cingulum bundle is the major white matter tract connecting the... more ABSTRACT Background / Purpose: The cingulum bundle is the major white matter tract connecting the cortex and limbic system, and is involved in memory, reasoning and emotion. It has been observed to be abnormal in patients with chronic schizophrenia (Kubicki et al 2007), but it has been less studied in first episode (FE).18 patients with FE schizophrenia, 20 patients with chronic schizophrenia (CSZ) and 20 controls were matched to each patient group (FENC and CSZNC), and received diffusion imaging on a 3T GE MRI. Two regions of interest, anterior and posterior portions of the cingulum bundle, were manually placed for each subject to initiate streamlined tractography. After successful fiber tracking, mean trace (TR), fractional anisotropy (FA), axial and radial diffusivity (AD and RD) were calculated for each subject. Main conclusion: FE exhibited higher TR in comparison to FENC in both hemispheres and on the left in comparison to CSZ. AD was increased in the FE bilaterally in comparison to FENC and CSZ. RD was higher in FE compared to FENC bilaterally and was correlated with delusions of reference.These results suggest that both axial and radial diffusivity contribute to the change in overall white matter health and organization between first episode and chronic schizophrenia, reflecting abnormalities in both axon integrity and myelination. In particular anomalies in myelin integrity may be related to the severity of delusions of reference. This is consistent with abnormal myelin development that results in partial degeneration of the underlying axons.

American Journal of Psychiatry

Objective: Studies of schizophrenia have not clearly defined handedness as a differentiating vari... more Objective: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and lefthanded comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. Method: Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. Results: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. Conclusions: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.

Seeking to unite psychological and biological approaches, this paper links cognitive and cellular... more Seeking to unite psychological and biological approaches, this paper links cognitive and cellular hypotheses and data about thought and language abnormalities in schizophrenia. The common thread, it is proposed, is a dysregulated suppression of associations (at the behavioral and functional neural systems level), paralleled by abnormalities of inhibition at the cellular and molecular level, and by an abnormal anatomical substrate (reduced MRI gray matter volume) in areas subserving language. At the level of behavioral experiments and connectionist modeling, data suggest an abnormal semantic network connectivity (strength of associations) in schizophrenia, but not an abnormality of network size (number of associates). This connectivity abnormality is likely to be a preferential processing of the dominant (strongest) association, with the neglect of preceding contextual information. At the level of functional neural systems, the N400 event-related potential amplitude is used to index ...

Schizophrenia Research, 2003

measured using coronal IR sequence MRI scans (4mm slice thickness, 1 mm interslice gap). Scans we... more measured using coronal IR sequence MRI scans (4mm slice thickness, 1 mm interslice gap). Scans were acquired and measured from subjects with first-episode psychosis (FEP, n=35), chronic schizophrenia (n=21), and healthy comparison subjects (n=24). An ANCO-VA revealed a significant group effect for total AIC volume (F(2, 74)=10.46, p=.0001) and thatamic volume (F(2, 74)=8.93, p=.0003) but not for PIC volume after covarying for age, gender, and total intracranial volume. Post-hoc analysis showed that both FEP and chronic subjects had smaller total AIC volumes compared with healthy subjects (smaller by 15.0%, p=.0002 and 17.7%, p=.0001, respectively). FEP subjects had smaller thalamic volumes than healthy subjects (smaller by 4.7%, p=.0206) and subjects with chronic schizophrenia (smaller by 8.5%, p=.0001). In contrast, chronic subjects had larger thalamic volumes than healthy controls (larger by 4.0%, p=.0688). An additional ANCOVA revealed a significant difference in asymmetry index in the AIC and thalamus but not in the PIC after covarying for age and gender. Healthy subjects had a greater degree of fight-left (R>L) asymmetry than schizophrenia subjects in both the AIC and the thalamus (p=.0001 and p=.0239, respectively). White matter abnormalities in a region containing important cortico-thalamic pathways may contribute to functional disruption of neural circuits in schizophrenia.

Schizophrenia Research, 1998

AJNR. American journal of neuroradiology, 2006

Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractog... more Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractography has found only limited applications in clinical research in which specific anatomic connections between distant regions need to be evaluated. We introduce a robust method for fiber clustering that guides the separation of anatomically distinct fiber tracts and enables further estimation of anatomic connectivity between distant brain regions. Line scanning diffusion tensor images (LSDTI) were acquired on a 1.5T magnet. Regions of interest for several anatomically distinct fiber tracts were manually drawn; then, white matter tractography was performed by using the Runge-Kutta method to interpolate paths (fiber traces) following the major directions of diffusion, in which traces were seeded only within the defined regions of interest. Next, a fully automatic procedure was applied to fiber traces, grouping them according to a pairwise similarity function that takes into account the sha...

Schizophrenia Research, 1994

Premorbid adjustment in schizophrenia is thought important (1) as a predictor of current patholog... more Premorbid adjustment in schizophrenia is thought important (1) as a predictor of current pathology and course, and (2) as a psychosocial expression of brain pathology preceding psychosis. Its valid and reliable measurement, however, pose a major challenge. To address this issue we interviewed 12 chronic male schizophrenic veterans and their first degree relatives, plus 12 age and social class of origin matched normal controls and their relatives, using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS), for which we developed our own semi-structured interview. Objective data from school records were also obtained. Schizophrenic's PAS scores were significantly poorer, irrespective of whether PAS scores were based on information from subjects, first degree relatives or from 'combined sources'. PAS scores were worse at all developmental epochs, with a marked divergence beginning in late adolescence. Worse premorbid adjustment in schizophrenia was also highly correlated with current clinical state, more current negative symptoms, less independent living and longer duration of hospitalization. Additionally, worse premorbid adjustment in schizophrenia was associated with larger Magnetic Resonance (MR) Ventricular Brain Ratio (VBR) in an exploratory analysis using a subset of these patients. Premorbid adjustment, rigorously measured, is poorer in schizophrenics than in normal controls and correlates with psychosocial and ventricular pathology in schizophrenia.

Schizophrenia Research, 2004

Structural MRI findings of abnormalities in the prefrontal cortex in schizophrenia and affective ... more Structural MRI findings of abnormalities in the prefrontal cortex in schizophrenia and affective disorder have been inconsistent likely due to small, heterogeneous samples, the evaluation of prefrontal gray and white matter combined, and the fact that prefrontal cortex is typically not delineated into separate gyri (e.g., Shenton et al., 2001; Strakowski et al., 2002). We previously reported smaller prefrontal gray matter in first-episode schizophrenia relative to first-episode affective psychosis and controls (Hirayasu et al., 2001). One unresolved question in the literature is whether or not further volume reduction will be observed over time, the focus of this report. Prefrontal gray and white matter volumes were measured (see Fig. 1) in patients at the time of first hospitalization for schizophrenia (n=12, 3 females) or affective psychosis (n=10, 1 female, 9 bipolar, 1 unipolar), and psychiatrically well subjects (n=15, 1 female). Subjects were rescanned approximately 1.5 years later. Seven schizophrenia, six affective, and four comparison subjects were previously described solely at first scan (Hirayasu et al., 2001). Samples did not differ in age (28.1±8.4; 22.9±2.8; 25.4±4.5; F(2,34)=2.2, p=0.12) or WAIS Information scores (11.8±3.4; 12.2±3.1, 11.8±2.0; F(2.32)=0.6, p=0.9), nor in parental socioeconomic status (F(2.34)=2.32, p=0.11) or handedness (F(2.33)=1.6, p=0.22). BPRS scores were higher in schizophrenics (41.2±13.2) than affectives (33.8±8.0) (F(1,20)=5.71, p=0.027). Similar neuroleptics were prescribed for the patient groups (schizophrenics: 7 typical, 4 atypical, 1 none; affectives: 6 typical, 3 atypical, 1 none). Relative volumes [i.e., absolute volumes divided by intracranial contents (ICC)] were used in the analyses. Repeated-measures ANOVA was performed with diagnosis as the between

Schizophrenia Research, 1991

As an initial approach to computer-automated segmentation of cerebral spinal fluid (CSF) vs. brai... more As an initial approach to computer-automated segmentation of cerebral spinal fluid (CSF) vs. brain parenchyma in MR scans, and the transformation of these data sets into volumetric information and 3D display, we examined the ventricular system in a sample of ten chronic schizophrenics with primarily positive symptoms and 12 normal subjects. While no significant differences were noted between groups on volumetric measures of ventricular brain ratio or lateral ventricle size, normals showed a pattern of left > right lateral ventricular volume asymmetry not present in the schizophrenics. Within the schizophrenic group, departure from the normal left > right pattern was highly correlated with thought disorder.

Psychophysiology, 2000

Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memo... more Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memory maintenance. Event-related potentials (ERPs) were recorded while sentences reading "THE NOUN WAS ADJECTIVE/VERB" were presented to 34 schizophrenic and 34 control subjects. Some nouns were homographs with dominant and subordinate meanings. Their sentence ending presented information crucial for interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to subordinate homograph-meaning sentence endings in schizophrenia would reflect a semantic bias to strong associates. N400 to all endings would reflect faulty verbal working memory maintenance. Schizophrenic subjects showed N400 activity to all endings, suggesting problems in contextual maintenance independent of content, but slightly greater N400 activity to subordinate endings that correlated with the severity of psychosis. Future research should help determine whether a semantic activation bias in schizophrenia toward strong associates is reflected in ERP activity or whether this effect is overshadowed by faulty verbal working memory maintenance of context.

NeuroImage, 2003

As a means toward understanding the neural bases of schizophrenic thought disturbance, we examine... more As a means toward understanding the neural bases of schizophrenic thought disturbance, we examined brain activation patterns in response to semantically and superficially encoded words in patients with schizophrenia. Nine male schizophrenic and 9 male control subjects were tested in a visual levels of processing (LOP) task first outside the magnet and then during the fMRI scanning procedures (using a different set of words). During the experiments visual words were presented under two conditions. Under the deep, semantic encoding condition, subjects made semantic judgments as to whether the words were abstract or concrete. Under the shallow, nonsemantic encoding condition, subjects made perceptual judgments of the font size (uppercase/lowercase) of the presented words. After performance of the behavioral task, a recognition test was used to assess the depth of processing effect, defined as better performance for semantically encoded words than for perceptually encoded words. For the scanned version only, the words for both conditions were repeated in order to assess repetition-priming effects. Reaction times were assessed in both testing scenarios. Both groups showed the expected depth of processing effect for recognition, and control subjects showed the expected increased activation of the left inferior prefrontal cortex (LIPC) under semantic encoding relative to perceptual encoding conditions as well as repetition priming for semantic conditions only. In contrast, schizophrenics showed similar patterns of fMRI activation regardless of condition. Most striking in relation to controls, patients showed decreased LIFC activation concurrent with increased left superior temporal gyrus activation for semantic encoding versus shallow encoding. Furthermore, schizophrenia subjects did not show the repetition priming effect, either behaviorally or as a decrease in LIPC activity. In patients with schizophrenia, LIFC underactivation and left superior temporal gyrus overactivation for semantically encoded words may reflect a disease-related disruption of a distributed frontal temporal network that is engaged in the representation and processing of meaning of words, text, and discourse and which may underlie schizophrenic thought disturbance.

Journal of Clinical Neurophysiology, 1998

The perception of a visual stimulus can be inhibited by occipital transcranial magnetic stimulati... more The perception of a visual stimulus can be inhibited by occipital transcranial magnetic stimulation. This visual suppression effect has been attributed to disruption in the cortical gray matter of primary visual cortex or in the fiber tracts leading to V1 from the thalamus. However, others have suggested that the visual suppression effect is caused by disruption in secondary visual cortex. Here the authors used a figure-eight coil, which produces a focal magnetic field, and a Quadropulse stimulator to produce visual suppression contralateral to the stimulated hemisphere in five normal volunteer subjects. The authors coregistered the stimulation sites with magnetic resonance images in these same subjects using optical digitization. The stimulation sites were mapped onto the surface of the occipital lobes in three-dimensional reconstructions of the cortical surface to show the distribution of the visual suppression effect. The results were consistent with disruption of secondary visual cortical areas.

Harvard Review of Psychiatry, 1993

Postmortem, magnetic resonance, and event-related potential studies suggest the presence of tempo... more Postmortem, magnetic resonance, and event-related potential studies suggest the presence of temporal lobe abnormalities in schizophrenia. Analyses using convergent measurements of brain structure and function, however, have rarely been done in the same patients. We recently developed a protocol using high-spatial-resolution magnetic resonance scans, auditory P300 event-related potentials, and thought disorder scales to examine temporal lobe structure and function in the same patients. We report a case of schizophrenia that showed left-lateralized volume reduction in the superior temporal gyrus, hippocampus, and parahippocampal gyrus (also on right), with associated P300 amplitude reduction and thought disorder marked by word-finding difficulties and perseverations.

European Psychiatry, 2008

Biological Psychiatry, 1996

Biological Psychiatry, 1996

Biological Psychiatry, 1994

ratings of sulcal prominence most robustly distinguish patients from controis, and that other mor... more ratings of sulcal prominence most robustly distinguish patients from controis, and that other morphologic markers (ventricular volume, mesiotemporal volume, and hemisphere asymmetries) account for additional variance between the groups. These findings support the hypothesis that different morphologic abnormalities may mark independent pathologic processes in schizophrenia.

Biological Psychiatry, 1996

Biological Psychiatry, 1998

Social Psychiatry and Psychiatric Epidemiology, Nov 28, 2018

Purpose: The current study evaluates the demographic, clinical, and neurocognitive characteristic... more Purpose: The current study evaluates the demographic, clinical, and neurocognitive characteristics of a recruited FEP research sample, a research control group, and a FEP clinic sample that were assessed and treated within the same center and time period. Methods: This study utilized data collected through an observational study and a retrospective chart review. Samples were ascertained in the Longitudinal Assessment and Monitoring of Clinical

ABSTRACT Background / Purpose: The cingulum bundle is the major white matter tract connecting the... more ABSTRACT Background / Purpose: The cingulum bundle is the major white matter tract connecting the cortex and limbic system, and is involved in memory, reasoning and emotion. It has been observed to be abnormal in patients with chronic schizophrenia (Kubicki et al 2007), but it has been less studied in first episode (FE).18 patients with FE schizophrenia, 20 patients with chronic schizophrenia (CSZ) and 20 controls were matched to each patient group (FENC and CSZNC), and received diffusion imaging on a 3T GE MRI. Two regions of interest, anterior and posterior portions of the cingulum bundle, were manually placed for each subject to initiate streamlined tractography. After successful fiber tracking, mean trace (TR), fractional anisotropy (FA), axial and radial diffusivity (AD and RD) were calculated for each subject. Main conclusion: FE exhibited higher TR in comparison to FENC in both hemispheres and on the left in comparison to CSZ. AD was increased in the FE bilaterally in comparison to FENC and CSZ. RD was higher in FE compared to FENC bilaterally and was correlated with delusions of reference.These results suggest that both axial and radial diffusivity contribute to the change in overall white matter health and organization between first episode and chronic schizophrenia, reflecting abnormalities in both axon integrity and myelination. In particular anomalies in myelin integrity may be related to the severity of delusions of reference. This is consistent with abnormal myelin development that results in partial degeneration of the underlying axons.

American Journal of Psychiatry

Objective: Studies of schizophrenia have not clearly defined handedness as a differentiating vari... more Objective: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and lefthanded comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. Method: Left-handed male patients (N=8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N=10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. Results: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. Conclusions: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.

Seeking to unite psychological and biological approaches, this paper links cognitive and cellular... more Seeking to unite psychological and biological approaches, this paper links cognitive and cellular hypotheses and data about thought and language abnormalities in schizophrenia. The common thread, it is proposed, is a dysregulated suppression of associations (at the behavioral and functional neural systems level), paralleled by abnormalities of inhibition at the cellular and molecular level, and by an abnormal anatomical substrate (reduced MRI gray matter volume) in areas subserving language. At the level of behavioral experiments and connectionist modeling, data suggest an abnormal semantic network connectivity (strength of associations) in schizophrenia, but not an abnormality of network size (number of associates). This connectivity abnormality is likely to be a preferential processing of the dominant (strongest) association, with the neglect of preceding contextual information. At the level of functional neural systems, the N400 event-related potential amplitude is used to index ...

Schizophrenia Research, 2003

measured using coronal IR sequence MRI scans (4mm slice thickness, 1 mm interslice gap). Scans we... more measured using coronal IR sequence MRI scans (4mm slice thickness, 1 mm interslice gap). Scans were acquired and measured from subjects with first-episode psychosis (FEP, n=35), chronic schizophrenia (n=21), and healthy comparison subjects (n=24). An ANCO-VA revealed a significant group effect for total AIC volume (F(2, 74)=10.46, p=.0001) and thatamic volume (F(2, 74)=8.93, p=.0003) but not for PIC volume after covarying for age, gender, and total intracranial volume. Post-hoc analysis showed that both FEP and chronic subjects had smaller total AIC volumes compared with healthy subjects (smaller by 15.0%, p=.0002 and 17.7%, p=.0001, respectively). FEP subjects had smaller thalamic volumes than healthy subjects (smaller by 4.7%, p=.0206) and subjects with chronic schizophrenia (smaller by 8.5%, p=.0001). In contrast, chronic subjects had larger thalamic volumes than healthy controls (larger by 4.0%, p=.0688). An additional ANCOVA revealed a significant difference in asymmetry index in the AIC and thalamus but not in the PIC after covarying for age and gender. Healthy subjects had a greater degree of fight-left (R>L) asymmetry than schizophrenia subjects in both the AIC and the thalamus (p=.0001 and p=.0239, respectively). White matter abnormalities in a region containing important cortico-thalamic pathways may contribute to functional disruption of neural circuits in schizophrenia.

Schizophrenia Research, 1998

AJNR. American journal of neuroradiology, 2006

Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractog... more Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractography has found only limited applications in clinical research in which specific anatomic connections between distant regions need to be evaluated. We introduce a robust method for fiber clustering that guides the separation of anatomically distinct fiber tracts and enables further estimation of anatomic connectivity between distant brain regions. Line scanning diffusion tensor images (LSDTI) were acquired on a 1.5T magnet. Regions of interest for several anatomically distinct fiber tracts were manually drawn; then, white matter tractography was performed by using the Runge-Kutta method to interpolate paths (fiber traces) following the major directions of diffusion, in which traces were seeded only within the defined regions of interest. Next, a fully automatic procedure was applied to fiber traces, grouping them according to a pairwise similarity function that takes into account the sha...

Schizophrenia Research, 1994

Premorbid adjustment in schizophrenia is thought important (1) as a predictor of current patholog... more Premorbid adjustment in schizophrenia is thought important (1) as a predictor of current pathology and course, and (2) as a psychosocial expression of brain pathology preceding psychosis. Its valid and reliable measurement, however, pose a major challenge. To address this issue we interviewed 12 chronic male schizophrenic veterans and their first degree relatives, plus 12 age and social class of origin matched normal controls and their relatives, using the Cannon-Spoor et al. Premorbid Adjustment Scale (PAS), for which we developed our own semi-structured interview. Objective data from school records were also obtained. Schizophrenic's PAS scores were significantly poorer, irrespective of whether PAS scores were based on information from subjects, first degree relatives or from 'combined sources'. PAS scores were worse at all developmental epochs, with a marked divergence beginning in late adolescence. Worse premorbid adjustment in schizophrenia was also highly correlated with current clinical state, more current negative symptoms, less independent living and longer duration of hospitalization. Additionally, worse premorbid adjustment in schizophrenia was associated with larger Magnetic Resonance (MR) Ventricular Brain Ratio (VBR) in an exploratory analysis using a subset of these patients. Premorbid adjustment, rigorously measured, is poorer in schizophrenics than in normal controls and correlates with psychosocial and ventricular pathology in schizophrenia.

Schizophrenia Research, 2004

Structural MRI findings of abnormalities in the prefrontal cortex in schizophrenia and affective ... more Structural MRI findings of abnormalities in the prefrontal cortex in schizophrenia and affective disorder have been inconsistent likely due to small, heterogeneous samples, the evaluation of prefrontal gray and white matter combined, and the fact that prefrontal cortex is typically not delineated into separate gyri (e.g., Shenton et al., 2001; Strakowski et al., 2002). We previously reported smaller prefrontal gray matter in first-episode schizophrenia relative to first-episode affective psychosis and controls (Hirayasu et al., 2001). One unresolved question in the literature is whether or not further volume reduction will be observed over time, the focus of this report. Prefrontal gray and white matter volumes were measured (see Fig. 1) in patients at the time of first hospitalization for schizophrenia (n=12, 3 females) or affective psychosis (n=10, 1 female, 9 bipolar, 1 unipolar), and psychiatrically well subjects (n=15, 1 female). Subjects were rescanned approximately 1.5 years later. Seven schizophrenia, six affective, and four comparison subjects were previously described solely at first scan (Hirayasu et al., 2001). Samples did not differ in age (28.1±8.4; 22.9±2.8; 25.4±4.5; F(2,34)=2.2, p=0.12) or WAIS Information scores (11.8±3.4; 12.2±3.1, 11.8±2.0; F(2.32)=0.6, p=0.9), nor in parental socioeconomic status (F(2.34)=2.32, p=0.11) or handedness (F(2.33)=1.6, p=0.22). BPRS scores were higher in schizophrenics (41.2±13.2) than affectives (33.8±8.0) (F(1,20)=5.71, p=0.027). Similar neuroleptics were prescribed for the patient groups (schizophrenics: 7 typical, 4 atypical, 1 none; affectives: 6 typical, 3 atypical, 1 none). Relative volumes [i.e., absolute volumes divided by intracranial contents (ICC)] were used in the analyses. Repeated-measures ANOVA was performed with diagnosis as the between

Schizophrenia Research, 1991

As an initial approach to computer-automated segmentation of cerebral spinal fluid (CSF) vs. brai... more As an initial approach to computer-automated segmentation of cerebral spinal fluid (CSF) vs. brain parenchyma in MR scans, and the transformation of these data sets into volumetric information and 3D display, we examined the ventricular system in a sample of ten chronic schizophrenics with primarily positive symptoms and 12 normal subjects. While no significant differences were noted between groups on volumetric measures of ventricular brain ratio or lateral ventricle size, normals showed a pattern of left > right lateral ventricular volume asymmetry not present in the schizophrenics. Within the schizophrenic group, departure from the normal left > right pattern was highly correlated with thought disorder.

Psychophysiology, 2000

Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memo... more Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memory maintenance. Event-related potentials (ERPs) were recorded while sentences reading "THE NOUN WAS ADJECTIVE/VERB" were presented to 34 schizophrenic and 34 control subjects. Some nouns were homographs with dominant and subordinate meanings. Their sentence ending presented information crucial for interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to subordinate homograph-meaning sentence endings in schizophrenia would reflect a semantic bias to strong associates. N400 to all endings would reflect faulty verbal working memory maintenance. Schizophrenic subjects showed N400 activity to all endings, suggesting problems in contextual maintenance independent of content, but slightly greater N400 activity to subordinate endings that correlated with the severity of psychosis. Future research should help determine whether a semantic activation bias in schizophrenia toward strong associates is reflected in ERP activity or whether this effect is overshadowed by faulty verbal working memory maintenance of context.

NeuroImage, 2003

As a means toward understanding the neural bases of schizophrenic thought disturbance, we examine... more As a means toward understanding the neural bases of schizophrenic thought disturbance, we examined brain activation patterns in response to semantically and superficially encoded words in patients with schizophrenia. Nine male schizophrenic and 9 male control subjects were tested in a visual levels of processing (LOP) task first outside the magnet and then during the fMRI scanning procedures (using a different set of words). During the experiments visual words were presented under two conditions. Under the deep, semantic encoding condition, subjects made semantic judgments as to whether the words were abstract or concrete. Under the shallow, nonsemantic encoding condition, subjects made perceptual judgments of the font size (uppercase/lowercase) of the presented words. After performance of the behavioral task, a recognition test was used to assess the depth of processing effect, defined as better performance for semantically encoded words than for perceptually encoded words. For the scanned version only, the words for both conditions were repeated in order to assess repetition-priming effects. Reaction times were assessed in both testing scenarios. Both groups showed the expected depth of processing effect for recognition, and control subjects showed the expected increased activation of the left inferior prefrontal cortex (LIPC) under semantic encoding relative to perceptual encoding conditions as well as repetition priming for semantic conditions only. In contrast, schizophrenics showed similar patterns of fMRI activation regardless of condition. Most striking in relation to controls, patients showed decreased LIFC activation concurrent with increased left superior temporal gyrus activation for semantic encoding versus shallow encoding. Furthermore, schizophrenia subjects did not show the repetition priming effect, either behaviorally or as a decrease in LIPC activity. In patients with schizophrenia, LIFC underactivation and left superior temporal gyrus overactivation for semantically encoded words may reflect a disease-related disruption of a distributed frontal temporal network that is engaged in the representation and processing of meaning of words, text, and discourse and which may underlie schizophrenic thought disturbance.

Journal of Clinical Neurophysiology, 1998

The perception of a visual stimulus can be inhibited by occipital transcranial magnetic stimulati... more The perception of a visual stimulus can be inhibited by occipital transcranial magnetic stimulation. This visual suppression effect has been attributed to disruption in the cortical gray matter of primary visual cortex or in the fiber tracts leading to V1 from the thalamus. However, others have suggested that the visual suppression effect is caused by disruption in secondary visual cortex. Here the authors used a figure-eight coil, which produces a focal magnetic field, and a Quadropulse stimulator to produce visual suppression contralateral to the stimulated hemisphere in five normal volunteer subjects. The authors coregistered the stimulation sites with magnetic resonance images in these same subjects using optical digitization. The stimulation sites were mapped onto the surface of the occipital lobes in three-dimensional reconstructions of the cortical surface to show the distribution of the visual suppression effect. The results were consistent with disruption of secondary visual cortical areas.

Harvard Review of Psychiatry, 1993

Postmortem, magnetic resonance, and event-related potential studies suggest the presence of tempo... more Postmortem, magnetic resonance, and event-related potential studies suggest the presence of temporal lobe abnormalities in schizophrenia. Analyses using convergent measurements of brain structure and function, however, have rarely been done in the same patients. We recently developed a protocol using high-spatial-resolution magnetic resonance scans, auditory P300 event-related potentials, and thought disorder scales to examine temporal lobe structure and function in the same patients. We report a case of schizophrenia that showed left-lateralized volume reduction in the superior temporal gyrus, hippocampus, and parahippocampal gyrus (also on right), with associated P300 amplitude reduction and thought disorder marked by word-finding difficulties and perseverations.

European Psychiatry, 2008

Biological Psychiatry, 1996

Biological Psychiatry, 1996

Biological Psychiatry, 1994

ratings of sulcal prominence most robustly distinguish patients from controis, and that other mor... more ratings of sulcal prominence most robustly distinguish patients from controis, and that other morphologic markers (ventricular volume, mesiotemporal volume, and hemisphere asymmetries) account for additional variance between the groups. These findings support the hypothesis that different morphologic abnormalities may mark independent pathologic processes in schizophrenia.

Biological Psychiatry, 1996

Biological Psychiatry, 1998