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P G Nestor

Publications and source records attributed to P G Nestor.

At least 19 recordsLinked to original sources
PubMed2005

DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity.

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Adolescent↗
PubMed2003

An fMRI study of semantic processing in men with schizophrenia.

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.

Adult↗
PubMed2001

The P3 auditory event-related brain potential indexes major personality traits.

BACKGROUND: The amplitude of the auditory P3 event-related potential is reduced in patients with axes I and II disorders. Data regarding P3 amplitude and normal personality traits in healthy individuals have been inconsistent, however, although more extreme variants of dimensional traits such as neuroticism and extraversion are associated with psychiatric morbidity. METHODS: Male subjects (n = 18) recruited from the community completed the NEO Five-Factor Inventory, which consists of five scales: Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. P3 potentials were generated using an auditory discrimination paradigm to which a third, novel stimulus was added. Partial least squares analysis, a multivariate statistical procedure, was used to test the relationship, in both stimulus conditions, between P3 amplitude at six electrode sites and the five personality dimensions. RESULTS: P3 amplitude across conditions and sites was positively related to Extraversion, Openness, Agreeableness, and Conscientiousness and negatively related to Neuroticism. CONCLUSIONS: Previous studies have shown that both reduced P3 amplitude and a high Neuroticism/low Extraversion-Openness-Agreeableness-Conscientiousness trait pattern are associated with the presence of, and risk for, substantial psychiatric morbidity. Our results suggest that processes indexed by auditory P3 amplitude are related to these broad personality dimensions in healthy individuals.

Adult↗
PubMed2001

Perceptual asymmetries in schizophrenia: subtype differences in left hemisphere dominance for dichotic fused words.

OBJECTIVE: Dichotic listening techniques have been used to study hemispheric dominance for language in schizophrenia. The authors' goal was to compare subjects with paranoid and undifferentiated subtypes of schizophrenia. METHOD: The Fused Rhymed Words Test was used to compare perceptual asymmetries in 16 patients with paranoid schizophrenia, 28 patients with undifferentiated schizophrenia, and 29 healthy comparison subjects. RESULTS: Patients with paranoid schizophrenia had the largest left hemisphere advantage and patients with undifferentiated schizophrenia had the smallest. The asymmetry of healthy subjects was intermediate. Hemisphere advantage varied as a function of gender only in the patients with undifferentiated schizophrenia. CONCLUSIONS: The findings support the hypotheses that undifferentiated schizophrenia is associated with underactivation of left hemisphere resources for verbal processing and that paranoid schizophrenia is characterized by preserved left hemisphere processing.

Adult↗
PubMed2000

Personality traits in schizophrenia: comparison with a community sample.

The objective of this study was to compare personality trait profiles in patients with schizophrenia and healthy controls. Male outpatients with schizophrenia (N = 24) and a male nonpsychiatric community sample (N = 46) completed the NEO-FFI personality questionnaire. Multivariate analyses were used to compare mean scale scores and scale profiles for each group. The overall personality profile of clinically stable patients with schizophrenia differed significantly from that of a community sample. On individual scales, patients scored significantly higher on neuroticism and significantly lower on conscientiousness. These results confirm and extend those of previous studies that used normative data for comparison and a much longer version of the same personality questionnaire. Prospective studies of populations at risk are needed to determine whether group differences reflect a premorbid diathesis for schizophrenia or a secondary effect of serious mental illness.

Age of Onset↗
PubMed2000

Abnormal angular gyrus asymmetry in schizophrenia.

OBJECTIVE: Few studies have evaluated the parietal lobe in schizophrenia despite the fact that it has an important role in attention, memory, and language-all functions that have been reported to be abnormal in schizophrenia. The inferior parietal lobule, in particular, is of interest because it is not only part of the heteromodal association cortex but also is part of the semantic-lexical network, which also includes the planum temporale. Both the inferior parietal lobule, particularly the angular gyrus of the inferior parietal lobule, and the planum temporale are brain regions that play a critical role as biological substrates of language and thought. The authors compared volume and asymmetry measures of the individual gyri of the parietal lobe by means of magnetic resonance imaging (MRI) scans. METHOD: MRI scans with a 1. 5-Tesla magnet were obtained from 15 male chronic schizophrenic and 15 comparison subjects matched for age, gender, and parental socioeconomic status. RESULTS: Inferior parietal lobule volumes showed a leftward asymmetry (left 7.0% larger than right) in comparison subjects and a reversed asymmetry (left 6.3% smaller than right) in schizophrenic subjects. The angular gyrus accounted for this difference in asymmetry, with the left angular gyrus being significantly larger (18.7%) than the right in comparison subjects, a finding that was not observed in schizophrenic patients. A further test of angular gyrus asymmetry showed a reversal of the normal left-greater-than-right asymmetry in the schizophrenic patients. CONCLUSIONS: Patients with schizophrenia showed a reversed asymmetry in the inferior parietal lobule that was localized to the angular gyrus, a structure belonging to the heteromodal association cortex as well as being part of the semantic-lexical network. This finding contributes to a more comprehensive understanding of the neural substrates of language and thought disorder in schizophrenia.

Adult↗
PubMed2000

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.

Adult↗
PubMed1999

Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.

Acoustic Stimulation↗
PubMed1999

Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects.

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 the extent of "search" for a semantic match to a word. In a short stimulus-onset-asynchrony condition, both schizophrenic and schizotypal personality disorder subjects showed, compared with controls, a reduced N400 amplitude to the target words that were related to cues, e.g. cat-dog, a result compatible with behavioral data. Other N400 data strongly and directly suggest that schizophrenics do not efficiently utilize context.

Brain↗
PubMed1999

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.

Brain Mapping↗
PubMed1999

Competence to stand trial: a neuropsychological inquiry.

How might the deconstruction of the legal theory of competence be related to modern neuropsychological models of cognition? To address this question, we examined retrospectively the relationship between clinical judgments of competence of defendants committed to a maximum security psychiatric facility and their neuropsychological test scores on measures of intelligence, memory, attention, academics, and executive function. In addition, based on both neuropsychological and legal theory, we examined whether subtypes of memory, namely episodic and semantic, and intelligence, specifically social intelligence, would have special relevance to these clinical judgements of competence. Results indicated that in relation to the defendants recommended as incompetent to stand trial (IST), defendants recommended as competent to stand trial (CST) scored significantly higher on summary indexes of psychometric intelligence, attention, and memory, especially verbal memory, but not significantly higher on tests of academics or executive function. Moreover, CST defendants scored significantly higher than did IST defendants on selective tests of episodic memory and social intelligence, but not on measures of semantic memory. Partial correlation also revealed a significant relationship between the likelihood of an IST recommendation and lower scores on tests of episodic memory and social intelligence, but not on measures of semantic memory. These findings illustrate the theoretical import of neuropsychological methods and concepts to the burgeoning nomological net known as competence.

Adolescent↗
PubMed1999

Quantitative volumetric MRI study of the cerebellum and vermis in schizophrenia: clinical and cognitive correlates.

OBJECTIVE: Recent evidence suggests that the cerebellum may play a role in higher cognitive functions and, therefore, may play an important role in schizophrenia. METHOD: The authors used magnetic resonance imaging to measure cerebellum and vermis volume in 15 patients with schizophrenia and 15 normal comparison subjects. RESULTS: They found that 1) vermis volume was greater in patients with schizophrenia than in normal subjects, 2) greater vermis white matter volume in the patients with schizophrenia significantly correlated with severity of positive symptoms and thought disorder and with impairment in verbal logical memory, and 3) patients with schizophrenia showed a trend for more cerebellar hemispheric volume asymmetry (left greater than right). CONCLUSIONS: These data suggest that an abnormality in the vermis may contribute to the pathophysiology of schizophrenia.

Cerebellum↗
PubMed1998

A neuropsychological analysis of schizophrenic thought disorder.

We examined the relationship of schizophrenic thought disorder, as measured by the Thought Disorder Index (TDI), with (1) neuropsychological measures of verbal memory, abstraction, executive function, visual memory, and working memory; and (2) quantitative MRI measures of prefrontal and basal ganglia structures. TDI scores correlated strongly with tests of verbal memory, abstraction and executive functions, modestly with tests of working memory, but did not correlate with scores on tests of visual memory. Neither TDI scores nor their neuropsychological correlates were associated with frontal or basal ganglia magnetic resonance imaging (MRI) measures, with the exception of the measures of working memory that demonstrated a modest relationship with frontal and basal ganglia structures. These findings suggest that schizophrenic thought disorder may be strongly related to neuropsychological impairments in verbal memory, abstraction and executive functions, and modestly related to problems with working memory in this sample of patients.

Adult↗
PubMed1998

Word recall in schizophrenia: a connectionist model.

OBJECTIVE: The authors examined word recall of patients with schizophrenia by using an experimental paradigm generated from connectionist models of memory. METHOD: Schizophrenic patients and normal comparison subjects first studied and then recalled a list of 32 words of equal difficulty. Both the connectivity (associative strength) and the network size (number of associates) of the words varied in such a way that the list contained equal proportions of four types of words: 1) high connectivity-small network size, 2) low connectivity-small network size, 3) high connectivity-large network size, and 4) low connectivity-large network size. RESULTS: The schizophrenic patients recalled fewer words and showed a particularly pronounced effect of the connectivity of the to-be-remembered words. For the patients, regardless of network size, recall improved substantially for words of high connectivity and declined dramatically for words of low connectivity. By contrast, the comparison subjects showed the expected effects, with the best recall for words of high connectivity-small network size, followed by words of low connectivity-small network size, then by words of high connectivity-large network size, and finally by words of low connectivity-large network size. CONCLUSIONS: Schizophrenia may be characterized by faulty modulation of associative links within a putative lexicon that is thought to be widely distributed across frontal and temporal lobes.

Adult↗
PubMed1997

ERP assessment of visual and auditory language processing in schizophrenia.

Language disturbance in schizophrenia has been recently attributed to disturbed priming mechanisms. In the present study, event-related potentials (ERPs), were recorded to final words in sentences presented to 13 chronic patients with schizophrenia and 12 normal controls. Half of the final words fit a sentence context and another half did not. The N400 (the ERP sensitive to language) latency was prolonged, and its amplitude was more negative to both correct and incorrect sentence endings in the group with schizophrenia relative to the group of normal controls. The early ERP components, N100 and P200, were similar in both groups. These results suggest that language abnormalities in schizophrenia are related to a dysfunction in the language system and not to a general cognitive dysfunction, and may be related to poor use of context in patients with schizophrenia.

Adult↗
PubMed1997

Aberrant semantic activation in schizophrenia: a neurophysiological study.

OBJECTIVE: Schizophrenia has long been thought to be characterized by a fundamental disturbance in semantic associations, which has often been presumed to be of neurobiological origin. The authors examined the neurophysiological characteristics of semantic processing in schizophrenic patients. METHOD: During EEG recording, 15 schizophrenic patients and 15 age-matched comparison subjects read sentences that had either sensible or nonsensical endings. The authors recorded the N400 component, a specific negative event-related brain potential occurring approximately 400 msec after the final word in the sentence. N400 is highly, if not uniquely, sensitive to semantic expectancy and context, and larger, more negative N400 amplitude is associated with increased semantic unexpectancy. RESULTS: In relation to the normal comparison subjects, the schizophrenic patients demonstrated prolonged N400 latency after nonsensical sentence endings and also showed enhanced N400 negativity, regardless of the sense of the sentence ending. CONCLUSIONS: These findings suggest slower and more diffuse semantic activation in patients with schizophrenia, perhaps reflective of a disease-related failure to maintain and to use semantic context.

Adult↗
PubMed1997

Not guilty by reason of insanity of murder: clinical and neuropsychological characteristics.

We examined archivally clinical status, neuropsychological functioning, and perpetrator-victim relationships of 28 adult patients who had committed homicide and had been subsequently involuntarily committed to a forensic hospital. We divided patients into two groups: (1) not guilty by reason of insanity (NGRI) acquittees (n = 13) and (2) convicted murderers (n = 15). In comparison with convicted murderers, NGRI acquittees were more likely to be seen as psychotic at the time of the index offense and also were more likely to have killed blood relatives, especially a parent. By contrast, convicted murderers were more likely to have killed a significant other, mainly a spouse or lover. At the time of the index offense, substance abuse was more likely to have occurred in the convicted murderers than in the NGRI acquittees. NGRI acquittees and convicted murderers did not differ on neuropsychological tests, with both groups generally scoring within normal limits on all tests. Taken together, these results suggested that NGRI murderers may be driven by acute psychosis directed toward blood relatives and occurring against a backdrop of relatively preserved neuropsychological functioning.

Adult↗