ABSTRACT
BACKGROUND: Clinicians working with patients at risk of suicide often experience high stress, which can result in negative emotional responses (NERs). Such negative emotional responses may lead to less empathic communication (EC) and unintentional rejection of the patient, potentially damaging the therapeutic alliance and adversely impacting suicidal outcomes. Therefore, clinicians need training to effectively manage negative emotions toward suicidal patients to improve suicidal outcomes. METHODS: This study investigated the impact of virtual human interaction (VHI) training on clinicians' self-awareness of their negative emotional responses, assessed by the Therapist Response Questionnaire Suicide Form, clinicians' verbal empathic communication assessed by the Empathic Communication and Coding System, and clinical efficacy (CE). Clinical efficacy was assessed by the likelihood of subsequent appointments, perceived helpfulness, and overall interaction satisfaction as rated by individuals with lived experience of suicide attempts. Two conditions of virtual human interactions were used: one with instructions on verbal empathic communication and reminders to report negative emotional responses during the interaction (scaffolded); and the other with no such instructions or reminders (non-scaffolded). Both conditions provided pre-interaction instructions and post-interaction feedback aimed at improving clinicians' empathic communication and management of negative emotions. Sixty-two clinicians participated in three virtual human interaction sessions under one of the two conditions. Linear mixed models were utilized to evaluate the impact on clinicians' negative emotional responses, verbal empathic communication, and clinical efficacy; and to determine changes in these outcomes over time, as moderated by the training conditions. RESULTS: Clinician participants' negative emotional responses decreased after two training sessions with virtual human interactions in both conditions. Participants in the scaffolded condition exhibited enhanced empathic communication after one training session, while two sessions were required for participants in the non-scaffolded condition. Surprisingly, after two training sessions, clinical efficacy was improved in the non-scaffolded group, while no similar improvements were observed in the scaffolded group. CONCLUSION: Lower clinical efficacy after virtual human interaction training in clinicians with higher verbal empathic communication suggests that nonverbal expressions of empathy are critical when interacting with suicidal patients. Future work should explore virtual human interaction training in both nonverbal and verbal empathic communication.
Subject(s)
Empathy , Suicidal Ideation , Humans , Emotions , Communication , Treatment OutcomeABSTRACT
BACKGROUND: Diminished uptake of fluorodeoxyglucose (FDG) has been observed in patients with alcohol use disorder (AUD) but little statistical contrast of the regional brain deficits has been undertaken. This study examined prefrontal cortex inter-regional Brodmann area differences to delineate patterns associated with behavioral, neurotransmitter, and general toxicity hypotheses of cerebral involvement in AUD. METHODS: We obtained data from FDG positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI) for 87 patients with AUD and 41 age- and sex-matched healthy volunteers. Patients were alcohol dependent and had negative breathalyzer tests at the time of imaging. They were assessed with the Beck Depression Inventory, Alcohol Urge Questionnaire, Obsessive Compulsive Drinking Scale, Spielberger State/Trait Anxiety Scale, Buss-Durkee Hostility Inventory, and the Drinker Inventory of Consequences (DrInC). PET images were co-registered to MRI and both voxel × voxel statistical mapping and stereotaxic regions of interest were obtained. RESULTS: Compared with healthy volunteers, patients with AUD had lower relative metabolic rates in the frontal, temporal, and parietal lobes, localizable most prominently to the dorsolateral and nearly all orbital prefrontal cortex, superior temporal gyrus, and inferior parietal lobule. In contrast, metabolic rates in the medial orbitofrontal and anterior cingulate cortex, and the subcortical structures (thalamus, cerebellum, ventral striatum, and the dorsal raphe nucleus) in patients were significantly greater. The severity of alcohol-related consequences as assessed by the DrInC scale was most highly associated with lower metabolism in the caudate, dorsolateral prefrontal, frontopolar, and anteroposterior cingulate cortex. CONCLUSIONS: Despite widespread metabolic abnormalities, decreases in AUD were most marked in frontal executive areas, consistent with diminished impulse control, and increases were most prominent in the striatum and cingulate areas, consistent with a suppressed reward system.
Subject(s)
Alcoholism , Alcoholism/metabolism , Brain/metabolism , Brain Mapping , Fluorodeoxyglucose F18/metabolism , Humans , Magnetic Resonance Imaging , Positron-Emission TomographyABSTRACT
We recruited 14 unmedicated patients with Kraepelinian schizophrenia (12 men and 2 women; mean age = 47 years old), 27 non-Kraepelinian patients (21 men and 6 women; mean age = 36.4 years old) and a group of 56 age- and sex-matched healthy volunteers. FDG positron emission tomography and MRI scans were coregistered for both voxel-by-voxel statistical mapping and stereotaxic regions of interest analysis. While both Kraepelinian and non-Kraepelinian patients showed equally lower uptake than healthy volunteers in the frontal lobe, the temporal lobes (Brodmann areas 20 and 21) showed significantly greater decreases in Kraepelinian than in non-Kraepelinian patients. Kraepelinian patients had lower FDG uptake in parietal regions 39 and 40, especially in the right hemisphere, while non-Kraepelinian patients had similar reductions in the left. Only non-Kraepelinian patients had lower caudate FDG uptake than healthy volunteers. While both patient groups had lower uptake than healthy volunteers in the medial dorsal nucleus of the thalamus, Kraepelinian patients alone had higher uptake in the ventral nuclei of the thalamus. Kraepelinian patients also showed higher metabolic rates in white matter. Our results are consistent with other studies indicating that Kraepelinian schizophrenia is a subgroup of schizophrenia, characterized by temporal and right parietal deficits and normal rather than reduced caudate uptake. It suggests that Kraepelinian schizophrenia may be more primarily characterized by FDG uptake decreased in both the frontal and temporal lobes, while non-Kraepelinian schizophrenia may have deficits more limited to the frontal lobe. This is consistent with some neuropsychological and prognosis reports of disordered sensory information processing in Kraepelinian schizophrenia in addition to deficits in frontal lobe executive functions shared with the non-Kraepelinian subtype.
Subject(s)
Catatonia/complications , Catatonia/diagnostic imaging , Dementia/complications , Dementia/diagnostic imaging , Positron-Emission Tomography , Schizophrenia/complications , Schizophrenia/diagnostic imaging , Adult , Aged , Analysis of Variance , Brain/diagnostic imaging , Brain/pathology , Case-Control Studies , Female , Fluorodeoxyglucose F18 , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Serial Learning/physiologyABSTRACT
Diminished prefrontal function, dopaminergic abnormalities in the striatum and thalamus, reductions in white matter integrity and frontotemporal gray matter deficits are the most replicated findings in schizophrenia. We used four imaging modalities (18F-fluorodeoxyglucose and 18F-fallypride PET, diffusion tensor imaging, structural MRI) in 19 healthy and 25 schizophrenia subjects to assess the relationship between functional (dopamine D2/D3 receptor binding potential, glucose metabolic rate) and structural (fractional anisotropy, MRI) correlates of schizophrenia and their additive diagnostic prediction potential. Multivariate ANOVA was used to compare structural and functional image sets for identification of schizophrenia. Integration of data from all four modalities yielded better predictive power than less inclusive combinations, specifically in the thalamus, left dorsolateral prefrontal and temporal regions. Among the modalities, fractional anisotropy showed highest discrimination in white matter whereas 18F-fallypride binding showed highest discrimination in gray matter. Structural and functional modalities displayed comparable discriminative power but different topography, with higher sensitivity of structural modalities in the left prefrontal region. Combination of functional and structural imaging modalities with inclusion of both gray and white matter appears most effective in diagnostic discrimination. The highest sensitivity of 18F-fallypride PET to gray matter changes in schizophrenia supports the primacy of dopaminergic abnormalities in its pathophysiology.
Subject(s)
Fluorodeoxyglucose F18 , Schizophrenia , Benzamides , Diffusion Tensor Imaging , Humans , Magnetic Resonance Imaging , Positron-Emission Tomography , Schizophrenia/diagnosisABSTRACT
Reading impairments are prominent trait-like features of cognitive deficits in schizophrenia, predictive of overall cognitive functioning and presumably linked to dopaminergic abnormalities. To evaluate this, we used 18F-fallypride PET in 19 healthy and 21 antipsychotic-naïve schizophrenia subjects and correlated dopamine receptor binding potentials in relevant AFNI-derived regions and voxelwise with group performance on WRAT4 single-word reading subtest. Healthy subjects' scores were positively and linearly associated with D2/D3 receptor availability in the rectus, orbital and superior frontal gyri, fusiform and middle temporal gyri, as well as middle occipital gyrus and precuneus, all predominantly in the left hemisphere and previously implicated in reading, hence suggesting that higher dopamine receptor density is cognitively advantageous. This relationship was weakened in schizophrenia subjects and in contrast to healthy participants followed an inverted U-shaped curve both in the cortex and dorsal striatum, indicating restricted optimal range of dopamine D2/D3 receptor availability for cognitive performance in schizophrenia.
Subject(s)
Schizophrenia , Cognition , Dopamine , Humans , Positron-Emission Tomography , Reading , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/metabolism , Schizophrenia/diagnostic imaging , Schizophrenia/metabolismABSTRACT
OBJECTIVE: To compare progressive changes in lateral ventricular size in chronic schizophrenia patients with good and poor outcomes. BACKGROUND: Several longitudinal studies associated excessive ventricular enlargement with poor outcome early in the course of schizophrenia. Changes in its chronic phase have not been as well ascertained. METHODS: We used MRI to evaluate progression of the lateral ventricular size in 49 chronic schizophrenia patients (26 with poor outcome, 23 with good outcome) and 16 healthy comparison participants, scanned twice 4 years apart. RESULTS: In comparison with healthy participants, schizophrenia patients displayed significantly enlarged body, and anterior and posterior horns of the lateral ventricles at baseline and follow-up, but no between-group differences in their longitudinal expansion were observed. Progressive enlargement of the posterior horn in the poor-outcome (Kraepelinian) group, however, was more pronounced than in schizophrenia patients with good outcome. CONCLUSIONS: Excessive ventricular enlargement in the chronic phase of schizophrenia may be specifically associated with poor functional outcome of the illness.
Subject(s)
Lateral Ventricles/pathology , Schizophrenia/diagnosis , Schizophrenia/pathology , Adult , Chronic Disease , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Middle Aged , PrognosisABSTRACT
Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and 18F-fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D2/D3 receptor density and white matter fractional anisotropy in each diagnostic group. AFNI regions of interest were acquired for 42 cortical Brodmann areas and subcortical gray matter structures as well as stereotaxically placed in representative white matter areas implicated in schizophrenia neuroimaging literature. Welch's t-test with permutation-based p value adjustment was used to compare means of z-transformed correlations between fractional anisotropy and 18F-fallypride binding potentials in hypothesis-driven regions of interest in the diagnostic groups. Healthy subjects displayed an extensive pattern of predominantly negative correlations between 18F-fallypride binding across a range of cortical and subcortical gray matter regions and fractional anisotropy in rostral white matter regions (internal capsule, frontal lobe, anterior corpus callosum). These patterns were disrupted in subjects with schizophrenia, who displayed significantly weaker overall correlations as well as comparatively scant numbers of significant correlations with the internal capsule and frontal (but not temporal) white matter, especially for dopamine receptor density in thalamic nuclei. Dopamine D2/D3 receptor density and white matter integrity appear to be interrelated, and their decreases in schizophrenia may stem from hyperdopaminergia with dysregulation of dopaminergic impact on axonal myelination.
Subject(s)
Schizophrenia , Animals , Anisotropy , Benzamides , Brain/diagnostic imaging , Diffusion Tensor Imaging , Dopamine , Humans , Magnetic Resonance Imaging , Positron-Emission Tomography , Schizophrenia/diagnostic imagingABSTRACT
Objectives: Overlapping decreases in extrastriatal dopamine D2/D3-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental.Methods: To ascertain this, we used two consecutive 18F-fluorodeoxyglucose and 18F-fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between 18F-fluorodeoxyglucose uptake and 18F-fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups.Results:18F-fluorodeoxyglucose uptake and 18F-fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D2/D3-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis.Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.
Subject(s)
Fluorodeoxyglucose F18 , Schizophrenia , Benzamides , Dopamine , Fluorine Radioisotopes , Gray Matter/diagnostic imaging , Gray Matter/metabolism , Humans , Positron-Emission Tomography , Receptors, Dopamine D2/metabolism , Receptors, Dopamine D3/metabolism , Schizophrenia/diagnostic imagingABSTRACT
Decreased fractional anisotropy and increased glucose utilization in the white matter have been reported in schizophrenia. These findings may be indicative of an inverse relationship between these measures of white matter integrity and metabolism. We used 18F-fluorodeoxyglucose positron emission tomography and diffusion-tensor imaging in 19 healthy and 25 schizophrenia subjects to assess and compare coterritorial correlation patterns between glucose utilization and fractional anisotropy on a voxel-by-voxel basis and across a range of automatically placed representative white matter regions of interest. We found a pattern of predominantly negative correlations between white matter metabolism and fractional anisotropy in both healthy and schizophrenia subjects. The overall strength of the relationship was attenuated in subjects with schizophrenia, who displayed significantly fewer and weaker correlations in all regions assessed with the exception of the corpus callosum. This attenuation was most prominent in the left prefrontal white matter and this region also best predicted the diagnosis of schizophrenia. There exists an inverse relationship between the measures of white matter integrity and metabolism, which may therefore be physiologically linked. In subjects with schizophrenia, hypermetabolism in the white matter may be a function of lower white matter integrity, with lower efficiency and increased energetic cost of task-related computations.
Subject(s)
Diffusion Tensor Imaging , Glucose/metabolism , Schizophrenia/physiopathology , White Matter/physiopathology , Anisotropy , Corpus Callosum/physiopathology , Female , Humans , Male , Positron-Emission Tomography , Young AdultABSTRACT
Transdiagnostic approach has a long history in neuroimaging, predating its recent ascendance as a paradigm for new psychiatric nosology. Various psychiatric disorders have been compared for commonalities and differences in neuroanatomical features and activation patterns, with different aims and rationales. This review covers both structural and functional neuroimaging publications with direct comparison of different psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, conduct disorder, anorexia nervosa, and bulimia nervosa. Major findings are systematically presented along with specific rationales for each comparison.
Subject(s)
Mental Disorders/diagnostic imaging , Neuroimaging/methods , Psychiatry/methods , Adult , Female , Humans , MaleABSTRACT
Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered 18fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.
Subject(s)
Autism Spectrum Disorder/metabolism , Brain/metabolism , Glucose/metabolism , Positron-Emission Tomography , Schizophrenia/metabolism , Adult , Autism Spectrum Disorder/diagnostic imaging , Autism Spectrum Disorder/psychology , Brain/diagnostic imaging , Brain Mapping , Female , Fluorodeoxyglucose F18 , Humans , Learning , Magnetic Resonance Imaging , Male , Radiopharmaceuticals , Schizophrenia/diagnostic imaging , Schizophrenic Psychology , Social BehaviorABSTRACT
Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.
Subject(s)
Autism Spectrum Disorder/metabolism , Brain/metabolism , Schizophrenia/metabolism , White Matter/metabolism , Adult , Autism Spectrum Disorder/diagnostic imaging , Brain/diagnostic imaging , Female , Fluorodeoxyglucose F18 , Functional Laterality , Gray Matter/diagnostic imaging , Gray Matter/metabolism , Humans , Male , Positron-Emission Tomography , Radiopharmaceuticals , Schizophrenia/diagnostic imaging , White Matter/diagnostic imagingABSTRACT
Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.
Subject(s)
Amygdala/physiopathology , Borderline Personality Disorder/physiopathology , Neural Pathways/physiopathology , Prefrontal Cortex/physiopathology , Adult , Aggression/physiology , Amygdala/metabolism , Amygdala/pathology , Atrophy/diagnostic imaging , Atrophy/pathology , Atrophy/physiopathology , Borderline Personality Disorder/diagnostic imaging , Borderline Personality Disorder/metabolism , Emotions/physiology , Energy Metabolism/physiology , Female , Fluorodeoxyglucose F18 , Glucose/metabolism , Humans , Impulsive Behavior/diagnostic imaging , Impulsive Behavior/metabolism , Impulsive Behavior/physiopathology , Male , Middle Aged , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Piperazines , Positron-Emission Tomography , Predictive Value of Tests , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/metabolism , Serotonin Receptor AgonistsABSTRACT
BACKGROUND: Prior voxelwise studies of white matter anisotropy found widespread reductions involving all major fiber tracts of the schizophrenic brain. We set out to confirm these exploratory findings and evaluate their relation to illness severity using a hypothesis-driven region-of-interest approach. METHODS: 104 schizophrenia patients (51 with good outcomes, 53 with poor outcomes) and 41 matched comparison subjects participated in the study. Regions of interest were selected on the basis of published voxelwise findings and placed within major fiber tracts using Talairach's stereotaxic coordinates. RESULTS: Fractional anisotropy reductions in schizophrenia patients were confirmed in the left cingulum, anterior thalamic radiation, fronto-occipital and inferior longitudinal fasciculi, as well as bilaterally in the corpus callosum, anterior and posterior limbs of internal capsule, superior longitudinal fasciculus, optic radiation, and frontotemporal extrafascicular white matter. Anisotropy reductions were more extensive in patients with poor outcomes ("Kraepelinian"), particularly in the posterior corpus callosum, fronto-occipital fasciculus, left optic radiation and frontotemporal white matter. Lower anisotropy in the right hemisphere tracts was associated with more prominent positive symptomatology, whereas negative symptoms were inversely associated with anisotropy values in both hemispheres. CONCLUSIONS: These results support a global neural disconnectivity in schizophrenia patients, which is more severe in those with poor clinical outcomes.
Subject(s)
Association , Corpus Callosum/anatomy & histology , Diffusion Magnetic Resonance Imaging , Internal Capsule/anatomy & histology , Nerve Fibers/pathology , Nerve Net/physiopathology , Schizophrenia , Adult , Female , Humans , Male , Schizophrenia/diagnosis , Schizophrenia/physiopathology , Schizophrenia/therapy , Treatment FailureABSTRACT
Autism spectrum disorders and schizophrenia have been variously characterized as separate nosological entities with overlapping deficits in social cognition or diametrical extremes of a phenotypic continuum. This study aimed to determine how these models apply to comparative morphometric data. MRI scans of the brain were obtained in 49 subjects with schizophrenia, 20 subjects with autism and 39 healthy controls. Images were parcellated into 40 Brodmann areas and entered into repeated-measures ANOVA for between-group comparison of global and localized gray and white matter volumes. A pattern of lower gray mater volumes and greater white matter volumes was found in subjects with schizophrenia in comparison to subjects with autism. For both gray and white matter, this pattern was most pronounced in regions associated with motor-premotor and anterior frontal cortex, anterior cingulate, fusiform, superior and middle temporal gyri. Patient groups tended to diverge from healthy controls in opposite directions, with greater-than-normal gray matter volumes and lower-than-normal white matter volumes in subjects with autism and reversed patterns in subjects with schizophrenia. White matter reductions in subjects with autism were seen in posterior frontal lobe and along the cingulate arch. Normal hemispheric asymmetry in the temporal lobe was effaced in subjects with autism and schizophrenia, especially in the latter. Nearly identical distribution of changes and diametrically divergent volumetry suggest that autism and schizophrenia may occupy opposite extremes of the same cognitive continuum.
Subject(s)
Autism Spectrum Disorder/diagnostic imaging , Brain/diagnostic imaging , Gray Matter/diagnostic imaging , Schizophrenia/diagnostic imaging , White Matter/diagnostic imaging , Adult , Autism Spectrum Disorder/pathology , Brain/pathology , Female , Gray Matter/pathology , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Organ Size , Schizophrenia/pathology , White Matter/pathologyABSTRACT
OBJECTIVE: Disparate white matter fractional anisotropy (FA) findings have been reported in patients with schizophrenia in recent years. This may in part reflect heterogeneity of subjects in the studies, including differences in outcome and severity of the illness. We examined whether there is a relationship between white matter FA and outcome in patients with schizophrenia. METHOD: Diffusion-tensor images were obtained in 41 normal subjects and 104 patients with schizophrenia, divided into good-outcome (n=51) and poor-outcome (Kraepelinian; n=53) subtypes based on their ability for self-care. White matter FA and its relationship to regional tissue volumes were evaluated across 40 individual Brodmann's areas using a semi-automated parcellation technique. RESULTS: Overall white matter FA was lower in schizophrenia patients than normal subjects, with regional reductions in widespread temporoparietal and selected prefrontal white matter regions. In schizophrenia patients, lower regional white matter FA was associated with lower regional gray matter volumes. In comparison to normal subjects, overall white matter FA was reduced in patients with poor outcomes in both hemispheres, but to a lesser extent and only in the right hemisphere in good-outcome patients. Lower regional FA was associated with larger regional white matter volumes in good-outcome group. CONCLUSIONS: Global FA reductions implicate white matter as tissue type in the pathophysiology of schizophrenia. In contrast to poor outcome, good outcome in schizophrenia patients may be associated with less extensive FA reductions, higher FA in regional frontal and cingulate white matter, and correlated increases in regional white matter volumes, particularly in the left hemisphere.
Subject(s)
Brain/anatomy & histology , Brain/physiopathology , Schizophrenia/physiopathology , Adult , Anisotropy , Brain/pathology , Diffusion Magnetic Resonance Imaging , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/pathology , Functional Laterality/physiology , Humans , Male , Schizophrenia/epidemiology , Schizophrenia/pathology , Severity of Illness IndexABSTRACT
Methods based on the analysis of metabolic and volumetric interregional correlations have been used in neuroimaging research, yet metabolic and volumetric interregional correlations for identical regions of interest have never been compared in the same group of subjects. Magnetic resonance and [18F]-fluorodeoxyglucose positron emission tomography brain images were acquired in 59 healthy subject. Correlation matrices for relative glucose metabolic rates during a verbal learning task and for relative gray matter volumes were compiled between the manually traced mediodorsal, centromedian, and pulvinar nuclei of the thalamus and 39 cortical Brodmann's areas. Metabolic correlations between the cortex and these thalamic nuclei followed the known patterns of anatomical connectivity in non-human primates. Intercorrelations of the mediodorsal nucleus were widespread with the prefrontal cortex (9 out of 10 Brodmann's areas in the left hemisphere) and temporal lobe (10 out of 11 Brodmann's areas in the left hemisphere) while the pulvinar correlated only with the parietal and occipital cortical areas. Different correlation patterns were observed for the regional gray matter volumes whereby only the pulvinar yielded extensive cortical intercorrelations, primarily with the occipital, parietal, anterior cingulate, and orbitofrontal areas in the right hemisphere. Metabolic thalamocortical correlations were much more extensive for the mediodorsal and centromedian nuclei whereas structural correlations were more extensive for the pulvinar. Therefore, metabolic and volumetric correlational methods are sensitive to different aspects of interregional relations in the brain and their comparison in the same group of subjects may render complementary and only partially overlapping connectivity information.
Subject(s)
Brain Mapping , Cerebral Cortex/physiology , Neural Pathways/physiology , Thalamus/physiology , Verbal Learning/physiology , Adult , Aged , Aged, 80 and over , Cerebral Cortex/diagnostic imaging , Female , Fluorodeoxyglucose F18/metabolism , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neural Pathways/diagnostic imaging , Positron-Emission Tomography/methods , Statistics as Topic , Thalamus/diagnostic imagingABSTRACT
Correlations between the MRI-assessed volumes of the pulvinar, centromedian, and mediodorsal nuclei of the thalamus and 39 cortical Brodmann's areas were evaluated and compared in 41 unmedicated schizophrenia patients and 59 healthy comparison subjects. For the right pulvinar, positive intercorrelations with ipsilateral orbitofrontal and occipital cortices were significantly weaker while negative intercorrelations with dorsolateral prefrontal and temporopolar/entorhinal cortices were stronger in schizophrenia patients compared to healthy subjects. For the centromedian nucleus, positive correlation with the dorsolateral prefrontal area 46 in the right hemisphere was significantly weaker in patients than in healthy subjects. Higher cortical/pulvinar volume ratios for the right frontotemporal regions with stronger negative correlations in patients were associated with better performance on recall and semantic memory tasks. Right pulvinocortical disconnections in patients with schizophrenia may be related to visual attentional deficits whereas stronger-than-normal inverse pulvinar associations with the heteromodal cortical regions may reflect compensatory reliance on alternative information-processing strategies.
Subject(s)
Cerebral Cortex/pathology , Intralaminar Thalamic Nuclei/pathology , Mediodorsal Thalamic Nucleus/pathology , Pulvinar/pathology , Schizophrenia/pathology , Adolescent , Adult , Aged , Brain Mapping , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Statistics as Topic/methodsABSTRACT
OBJECTIVE: The authors' goal was to examine interregional correlations of thalamocortical metabolic activity during a verbal learning task in schizophrenia. METHOD: They used [18F]fluorodeoxyglucose positron emission tomography in 41 unmedicated patients with schizophrenia and 59 normal comparison subjects. RESULTS: A metabolic disconnection was observed in patients with schizophrenia in the left hemisphere between the mediodorsal nucleus and widespread frontotemporal cortical regions, and stronger-than-normal intercorrelations were found between the pulvinar and superior temporal, selected parietal, posterior cingulate, and occipital areas. CONCLUSIONS: Deficits in the functional interrelationships between the left frontotemporal cortices and the left mediodorsal nucleus of the thalamus complement inferences from postmortem and magnetic resonance imaging volumetric studies identifying a thalamic diathesis in schizophrenia.