197 research outputs found
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The Brain in Schizotypal Personality Disorder: A Review of Structural MRI and CT Findings
Studies of schizotypal personality disorder (SPD) are important because the condition is genetically related to schizophrenia and because data accumulating to confirm its biological underpinnings are challenging some traditional views about the nature of personality disorders. This review of 17 structural imaging studies in SPD indicates that individuals with this disorder show brain abnormalities in the superior temporal gyrus, parahippocampus, temporal horn region of the lateral ventricles, corpus callosum, thalamus, and septum pellucidum, as well as in total cerebrospinal fluid volume, similar to those seen in persons with schizophrenia. Differences between SPD and schizophrenia include lack of abnormalities in the medial temporal lobes and lateral ventricles in SPD. Whether the normal volume, and possibly normal functioning, of the medial temporal lobes in individuals with SPD may help to suppress psychosis in this disorder remains an intriguing but still unresolved question. Such speculation must be tempered due to a paucity of studies, and additional work is needed to confirm these preliminary findings. The imaging findings do suggest, however, that SPD probably represents a milder form of disease along the schizophrenia continuum. With further clarification of the neuroanatomy of SPD, researchers may be able to identify which neuroanatomical abnormalities are associated with the frank psychosis seen in schizophrenia
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Combining ERP and Structural MRI Information in First Episode Schizophrenia and Bipolar Disorder
The electrical activity in the electroencephalogram (EEG) and the event-related potentials extracted from the EEG provide the greatest temporal resolution for examining brain function. When coupled with the high spatial resolution of structural magnetic resonance imaging (sMRI), the combined techniques provide a powerful tool for neuroscience in the examination of brain abnormalities in major psychiatric illnesses. Over the last 20 years, our work has examined brain structure and function in schizophrenia. Both EEG and MRI measures have indicated profound abnormalities in schizophrenia within the temporal lobe, particularly marked over the left hemisphere. Our studies of patients first hospitalized due to psychosis revealed the early course of the disease to be characterized by progressive impairment and cortical gray matter reduction, most intense near the time of first hospitalization. Knowledge of those locations and brain signals affected early should help understand the basic physiological defect underlying this progression, with potential implications for new therapeutic interventions
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Semantic bias, homograph comprehension, and event-related potentials in schizophrenia
Objectives: It is controversial whether a semantic processing bias for strong associates is present in schizophrenia, and unknown whether the language abnormalities observed in schizophrenia can be attributed to dysfunctions early or late in cognitive processing. Combined behavioral and event-related potential (ERP) data can indicate the nature and timing of such abnormalities. Methods: Sensibility judgements of dominant and subordinate homograph sentences were measured in 12 schizophrenia patients and 13 normal controls. ERPs were recorded to the disambiguating sentence-ending word. Results: All subjects showed greatest misinterpretation of subordinate homograph sentences, but schizophrenia patients particularly misinterpreted these sentence types. For control subjects, subordinate homograph sentences that were classified as nonsensical showed greater N400 than those classified as sensible. By contrast, the N400 of patients was large, regardless of the sensibility judgement – patients’ brains initially responded to all subordinate sentences as if nonsensical. These data are consonant with a semantic bias. However, the patients’ N400 to dominant homograph sentence endings was also larger than that of controls, a finding not consonant with a semantic bias. Conclusions: The behavioral results indicate a selective comprehension abnormality in schizophrenia dependent on the content of verbal memory. The ERP results suggest a pervasive contextual memory failure. A semantic activation decay model is proposed to explain these results
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Sensory-Evoked Gamma Oscillations in Chronic Schizophrenia
Background: The early visual-evoked gamma oscillation (VGO) elicited by Gestalt stimuli is reduced in schizophrenia patients compared to healthy individuals, but it is unknown whether this effect is specific to these particular stimuli and task. In contrast, the early auditory-evoked gamma oscillation (AGO) was reported to be unaffected in a sample of unmedicated, mostly first-episode schizophrenics (Gallinat et al, 2004, Clin Neurophysiol), but it is unknown whether this oscillation is abnormal in chronic, medicated patients. We investigated these issues by examining the VGO and AGO in chronic schizophrenics (SZ) and matched healthy controls (HC). Methods: Subjects (21 HC, 23 SZ) performed visual and auditory oddball tasks. Visual stimuli were letters, and auditory stimuli were simple tones. Event-related spectral measures (phase locking factor and evoked power) were computed on Morlet wavelet-transformed single epochs from the standard trials. Results: VGO phase locking at occipital electrodes was reduced in SZ compared to HC. In contrast, AGO phase locking and evoked power did not differ between groups. Conclusions: The VGO deficit may be a general phenomenon in schizophrenia, while the AGO evoked by simple tone stimuli does not appear to be abnormal in chronic, medicated schizophrenics
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The Application of DTI to Investigate White Matter Abnormalities in Schizophrenia
Schizophrenia is a serious and disabling mental disorder that affects approximately 1% of the general population, with often devastating effects on the psychological and financial resources of the patient, family, and larger community. The etiology of schizophrenia is not known, although it likely involves several interacting biological and environmental factors that predispose an individual to schizophrenia. However, although the underlying pathology remains unknown, it has been believed that brain abnormalities would ultimately be linked to the etiology of schizophrenia. This theory was rekindled in the 1970s, when the first computer-assisted tomography (CT) study showed enlarged lateral ventricles in schizophrenia. Since that time, there have been many improvements in MR acquisition and image processing, including the introduction of positron emission tomography (PET), followed by functional MR (fMRI), and diffusion tensor imaging (DTI). These advances have led to an appreciation of the critical role that brain abnormalities play in schizophrenia. While structural MRI has proven to be useful in investigating and detecting gray matter abnormalities in schizophrenia, the investigation of white matter has proven to be more challenging as white matter appears homogeneous on conventional MRI and the fibers connecting different brain regions cannot be appreciated. With the development of DTI, we are now able to investigate white matter abnormalities in schizophrenia
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Progressive and Interrelated Functional and Structural Evidence of Post-Onset Brain Reduction in Schizophrenia
Context: Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes. Objective: To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally. Design: Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up). Setting: A private psychiatric hospital. Participants: Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status. Interventions: Electrophysiologic testing and high-resolution structural magnetic resonance imaging. Main Outcome Measures: Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes. Results: Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=−0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04).
Conclusions: At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention
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Event-related potentials elicited during a context-free homograph task in normal versus schizophrenic subjects
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
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Associative memory in chronic schizophrenia: a computational model
We developed a computer model to simulate associative memory recall of patients with chronic schizophrenia. Model inputs consisted of words derived from normative data that differed in terms of connectivity and network size, with the former quantitatively represented by parametric weights and the latter by the specific number of word associates that formed a particular network. Previous behavioral studies of normal subjects indicated better recall for words of high connectivity-small network (HCSN), followed by low connectivity-small network (LCSN), high connectivity-large network (HCLN), and low connectivity-large network (LCLN). This pattern of recall differed from that observed in behavioral studies of schizophrenic patients, which showed better recall for high connectivity words, regardless of network size. Holding constant network size while manipulating connection weights effectively simulated this schizophrenic pattern of recall. That is, manipulation of parametric weights coupled with a slight increase in noise significantly and reliably elicited the response pattern of abnormal connectivity demonstrated in the prior behavioral study of patients with chronic schizophrenia. An increase in noise was a necessary, but insufficient step in modeling the response pattern of abnormal connectivity. These findings provide support for the use of computational models to investigate dynamics of associative word recall in patients with chronic schizophrenia
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ERP abnormalities during semantic processing in schizophrenia
To examine the neurophysiological and cognitive characteristics of thought disturbance in schizophrenic patients, we examined the amplitude, latency, and topography of a specific event-related brain potential (ERP), the N400, which is elicited by semantically incongruent words and phrases. Twelve chronic schizophrenic patients and twelve age-matched control subjects read sentences presented visually that had either semantically correct (e.g., ‘People pray in their local church’) or incorrect endings (e.g., ‘Every Sunday morning people pray in their local nest’). Relative to normal controls, schizophrenic patients had significantly reduced N400 amplitude and increased latency to semantically anomalous endings. Additionally, a late positive component which follows the N400 was significantly reduced in amplitude in schizophrenic patients. However, patients and controls did not differ significantly in terms of the topographical distribution of either the N400 or its late positive potential, examined at 28 electrode sites. Thus, N400 topography in schizophrenic patients was not accompanied by the asymmetry which frequently characterizes the well known auditory P300 disturbance in schizophrenic patients. We concluded that these findings may reflect a profound disturbance in attentional processes in chronic schizophrenia
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A comparative profile analysis of neuropsychological function in men and women with schizotypal personality disorder
The purpose of this study was to compare the cognitive profiles of men and women with clinically defined schizotypal personality disorder (SPD). We examined the neuropsychological profile of SPD in 26 right-handed females and 31 right-handed males who met DSM-IV criteria for SPD, and matched comparison subjects. Cognitive performance was assessed on measures of abstraction, verbal and spatial intelligence, learning and memory, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of comparison groups matched for sex, age, handedness, ethnicity and parental SES. Overall, SPD subjects showed mild, general decrements in performance in most cognitive domains. However, unlike male SPD subjects, female SPDs did not show relative deficits in verbal learning and abstraction. The results suggest a less severe pattern of cognitive deficits in women with SPD compared to men, consistent with hypotheses of gender differences in cognitive function in schizophrenia
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