Biomedical subjects

Paul G Nestor

Publications and source records attributed to Paul G Nestor.

At least 19 recordsLinked to original sources

PubMed2007

Dissociable contributions of MRI volume reductions of superior temporal and fusiform gyri to symptoms and neuropsychology in schizophrenia.

We sought to identify the functional correlates of reduced magnetic resonance imaging (MRI) volumes of the superior temporal gyrus (STG) and the fusiform gyrus (FG) in patients with chronic schizophrenia. MRI volumes, positive/negative symptoms, and neuropsychological tests of facial memory and executive functioning were examined within the same subjects. The results indicated two distinct, dissociable brain structure-function relationships: (1) reduced left STG volume-positive symptoms-executive deficits; (2) reduced left FG-negative symptoms-facial memory deficits. STG and FG volume reductions may each make distinct contributions to symptoms and cognitive deficits of schizophrenia.

Adolescent↗

PubMed2007

Functional neuroimaging of word priming in males with chronic schizophrenia.

Word-priming studies have suggested that the associative disturbance of schizophrenia may reflect aberrant spread of activation through the lexicon of the brain. To explore this, we examined lexical activation using a semantic word-priming paradigm coupled with functional magnetic resonance imaging (fMRI). We also wanted to determine whether brain activation to this paradigm correlated with relevant clinical symptom measures. In addition to completing clinical symptom measures, twelve chronic patients and twelve demographically matched control subjects completed a lexical-decision semantic-priming paradigm developed as an event-related BOLD fMRI task. This paradigm consisted of words that differed in connectivity. Words with many connections between shared semantic associates are considered high in connectivity and produce the largest behavioral semantic priming effects in control subjects, while words with few connections between shared semantic associates are considered low in connectivity and produce a relatively smaller amount of semantic priming. In fMRI, a respective step-wise increase in activation from high connectivity to low connectivity to unrelated word pairs was expected for normal subjects. Controls showed the expected pattern of activation to word connectivity; however, patients showed a less robust pattern of activation to word connectivity. Furthermore, this aberrant response correlated with measures of Auditory Hallucinations, Distractive Speech, Illogicality, and Incoherence. The patients did not display left frontal and temporal activation as a function of the degree of word connectivity as seen in healthy controls. This may reflect a disease-related disturbance in functional connectivity of lexical activation, which in turn may be associated with clinical symptomatology.

Adult↗

PubMed2006

The role of retrieval inhibition in the associative memory impairment of schizophrenia.

To examine retrieval-induced forgetting (RIF) in schizophrenia, subjects studied category-exemplar words taken from either strong or weak categories, and then practiced retrieval by completing category word-stems on half of the word pairs. Patients had reduced recall and recognition, but showed the expected RIF effect of better recall of unpracticed items from unpracticed categories than for unpracticed items from practiced categories. By contrast, patients and controls showed differing RIF for recognition as a function of categorical dominance: whereas controls showed RIF only for dominant category exemplar word pairs, patients showed RIF for both dominant and weak categories. Different patterns of baseline practiced retrieval for weak associate pairs in schizophrenia may explain this finding. The results failed to support faulty RIF in the associative memory impairment of schizophrenia.

Adult↗

PubMed2006

Attentional networks and cingulum bundle in chronic schizophrenia.

Thirty patients with chronic schizophrenia and 30 age-matched controls performed the Attention Network Test (ANT). A subset of the patient group (n=18) also had available magnetic resonance diffusion tensor imaging (DTI) measures of the cingulum bundle (CB) fractional anisotropy and volume. The patients showed a significantly different pattern of ANT performance, characterized primarily by decreased alerting efficiency. In addition, left CB fractional anisotropy correlated significantly with orienting of attention. Smaller right CB volume also correlated with reduced alertness, but not when covarying for medication and illness duration.

Adolescent↗

PubMed2006

Fornix integrity and hippocampal volume in male schizophrenic patients.

BACKGROUND: The hippocampus has been shown to be abnormal in schizophrenia. The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia. METHODS: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. We used high spatial resolution magnetic resonance imaging (MRI) to measure hippocampal volume. RESULTS: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. D(m) was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean D(m) and reduced cross-sectional area of the fornix for patients. Patients also showed a significant correlation between reduced scores on neuropsychologic measures of declarative-episodic memory and reduced hippocampal volumes. CONCLUSIONS: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia.

Adult↗

PubMed2006

fMRI of lexical-semantic priming in a chronic schizophrenia patient.

A neuropsychological hallmark of schizophrenia is a breakdown in semantic association networks that often impacts language and formal thought. Although computational models simulating this breakdown exist, studies have yet to investigate this phenomena using functional MRI (fMRI) coupled with an auditory lexical-decision semantic priming paradigm. Thus, this serves to functionally map brain activation to word pairs that differed with respect to a concept called "connectivity" in a patient with schizophrenia and a demographically matched control adult. Analyses revealed a striking difference with respect to the expected stepwise modulation of activation, with the control participant showing significantly greater areas of modulation than the participant with schizophrenia in regions classically implicated in language. Although the results are tentative because of the nature of this investigation (single-case study), they further support the characterization of schizophrenia as a breakdown in lexical-semantic association networks and represent one of the first fMRI studies of semantic priming in schizophrenia informed by a computer model.

Brain↗

PubMed2005

Word priming in schizophrenia: associational and semantic influences.

We examined semantic vs. associational influences on word priming in schizophrenia. Tested on three occasions, subjects made speeded lexical decisions to three kinds of prime-word relationships: semantic-only (e.g., Deer-Pony), associated-only (e.g., Bee-Honey), or semantic-and-associated (e.g., Doctor-Nurse). Controls showed greater priming of words related via two relationships (semantic-and-associated) than for words related only semantically.. However, patients showed greater priming for associated-only words than for words related only semantically. Schizophrenic patients may show an associational bias, restricting semantic integration and contributing to their disturbed thinking.

Adolescent↗

PubMed2005

Retrieval-induced forgetting in schizophrenia.

Retrieving category associates (e.g., FRUIT-ORANGE) may induce forgetting other category members (e.g., FRUIT-BANANA), a phenomenon known as retrieval-induced forgetting (RIF). We designed 2 experiments to examine the role of RIF in the associative memory impairment of schizophrenia (SZ). Subjects studied 36 category-exemplar pairs, generated from 6 categories composed of 6 members each. For half of the studied category-exemplar pairs, subjects practiced retrieval by completing word stems, followed by a delayed category-cued recall on all of the practiced and unpracticed items. Experiment 1 used unrelated category exemplars-pairs (e.g., FRUIT-ORANGE, METALS-IRON), whereas experiment 2 included related category exemplar pairs (e.g., COTTON-SHIRT, LEATHER-SKIRT). SZ showed reduced associative memory but normal RIF for unrelated categories used in experiment 1. For experiment 2, SZ showed a significant decline in associative memory for related but not unrelated category-exemplars in comparison to controls. Results suggested faulty specificity/distinctiveness for encoding and retrieval, but not abnormal RIF in the associative memory disturbance of SZ.

Adult↗

PubMed2005

Auditory P3 indexes personality traits and cognitive function in healthy men and women.

The relationship of the auditory P3 event-related potential to major personality dimensions and neuropsychological performance was examined in psychiatrically healthy men and women (28 male, 15 female) recruited from the community. An auditory oddball paradigm was used to collect P3 amplitude and latency data. Personality traits were measured with the NEO Five-Factor Inventory. Several Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Digit Symbol Test, and the Trail Making Test comprised the neuropsychological tests. A multivariate statistical procedure (Partial Least Squares) was used to quantify the relationships between P3 variables and personality and neuropsychological performance variables. P3 amplitude was negatively related to Neuroticism and positively related to Extraversion, Openness, Agreeableness and Conscientiousness. Better neuropsychological performance was associated with greater P3 amplitude and earlier latency. Thus, greater P3 amplitude was associated with less deviant personality scores and better neuropsychological performance in healthy subjects. Earlier P3 latency was also associated with better neuropsychological performance. The physiological significance of these relationships is not yet clear, but these results suggest that neural assemblies indexed by P3 may subserve both elemental cognition and healthy personality function.

Adolescent↗

PubMed2005

Personality differences in schizophrenia are related to performance on neuropsychological tasks.

Altered cognition and personality appear to emerge in tandem and adversely affect outcome in schizophrenia, yet little research has been done to determine whether these are related or independent domains. In this study, the relationship between the Big Five personality traits--neuroticism, extraversion, openness, agreeableness, conscientiousness--and cognitive and motor performance in outpatients with chronic, clinically stable schizophrenia (N = 30) and age-matched healthy comparison subjects (N = 45) was examined. Subjects completed tests of attention, executive and motor functions, and the NEO-Five Factor Personality Inventory. Patients scored significantly higher on neuroticism and lower on extraversion and agreeableness, but after variance due to neuropsychological performance was statistically removed from NEO scale scores, personality dimensions and profiles no longer differed between groups. Neuropsychological performance and demographic variables, but not diagnosis, uniquely accounted for statistically significant amounts of personality variance, and neuropsychological task performance was correlated with personality dimensions in both patients and comparison subjects. These cross-sectional data provide preliminary evidence that personality dysfunction in schizophrenia may be mediated by disease-related changes in cognitive operations, or the neural processes underlying them. Longitudinal studies utilizing more comprehensive measures of neurocognitive performance are needed to define further the relationship between neuropsychological function and personality in schizophrenia.

Adult↗

PubMed2005

Association between reduced extraversion and right posterior fusiform gyrus gray matter reduction in chronic schizophrenia.

OBJECTIVE: The authors examined the association between volume of the fusiform gyrus, a region involved in face processing, and the personality trait of extraversion in patients with schizophrenia. METHOD: Male patients (N=24) and age-matched male comparison subjects (N=26) completed NEO Five-Factor Inventory personality measures of extraversion and underwent high-spatial-resolution magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter. RESULTS: Low extraversion scores were significantly correlated with gray matter volume reductions in the right posterior fusiform gyrus for patients but not comparison subjects. CONCLUSIONS: Reduced right posterior fusiform gyrus volume may contribute to disease-related social disturbances, characterized by both low extraversion and reduced sensitivity to human faces.

Adult↗

PubMed2004

Neural synchrony indexes disordered perception and cognition in schizophrenia.

Current views of schizophrenia suggest that it results from abnormalities in neural circuitry, but empirical evidence in the millisecond range of neural activity has been difficult to obtain. In pursuit of relevant evidence, we previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phaselocking of the electroencephalogram in the gamma band (30-100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use gamma-band oscillations as a mechanism for synchronization. Here, we report the unique finding that, in both healthy controls and schizophrenia patients, visual Gestalt stimuli elicit a gamma-band oscillation that is phase-locked to reaction time and hence may reflect processes leading to conscious perception of the stimuli. However, the frequency of this oscillation is lower in schizophrenics than in healthy individuals. This finding suggests that, although synchronization must occur for perception of the Gestalt, it occurs at a lower frequency because of a reduced capability of neural networks to support high-frequency synchronization in the brain of schizophrenics. Furthermore, the degree of phase locking of this oscillation is correlated with visual hallucinations, thought disorder, and disorganization in the schizophrenia patients. These data provide support for linking dysfunctional neural circuitry and the core symptoms of schizophrenia.

Adolescent↗

PubMed2004

Shape of caudate nucleus and its cognitive correlates in neuroleptic-naive schizotypal personality disorder.

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

Adult↗

PubMed2004

Neuropsychological correlates of diffusion tensor imaging in schizophrenia.

Patients with schizophrenia (n = 41) and healthy comparison participants (n = 46) completed neuropsychological measures of intelligence, memory, and executive function. A subset of each group also completed magnetic resonance diffusion tensor imaging (DTI) studies (fractional anisotropy and cross-sectional area) of the uncinate fasciculus (UF) and cingulate bundle (CB). Patients with schizophrenia showed reduced levels of functioning across all neuropsychological measures. In addition, selective neuropsychological-DTI relationships emerged. Among patients but not controls, lower levels of declarative-episodic verbal memory correlated with reduced left UF, whereas executive function errors related to performance monitoring correlated with reduced left CB. The data suggested abnormal DTI patterns linking declarative-episodic verbal memory deficits to the left UF and executive function deficits to the left CB among patients with schizophrenia.

Adolescent↗

PubMed2004

Processing sentence context in women with schizotypal personality disorder: an ERP study.

Accumulating evidence suggests that schizophrenic patients do not use context efficiently. Also, studies suggest similarities in clinical and cognitive profiles between schizophrenic and schizotypal personality disorder (SPD) individuals, and epidemiological studies point to a genetic link between the two disorders. This study examined electrophysiological correlates of processing sentence context in a group of SPD women in a classical N400 sentence paradigm. The study assessed if the dysfunction in context use found previously in schizophrenia and male SPD also exists in female SPD. We tested 17 SPD and 16 matched normal control women. The results suggest the presence of abnormality in context use in female SPD similar to that previously reported for male schizophrenic and SPD individuals, but of lesser degree of severity. In SPD women, relative to their comparison group, a more negative N400 was found only to auditory congruent sentences.

Adult↗

PubMed2003

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study.

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.

Adult↗

PubMed2003

The startle reflex in schizophrenia: habituation and personality correlates.

Schizophrenia has long been associated with abnormal patterns of arousal that are thought to reflect disturbances in the reticular-activating system of the brain. Psychophysiological investigations of sensory responsivity have repeatedly demonstrated reduced reactivity and habituation to moderately intense stimuli in patients with schizophrenia. While not traditionally used as a measure of physiological arousal, the startle reflex represents an alternative method for studying reactivity and habituation in schizophrenia. This study examined eye blink responsivity to a repeatedly presented intense acoustic startle probe in men with chronic schizophrenia and healthy normal controls. Subjects' personality profiles were also measured, as increased reactivity and arousal have been traditionally implicated as a physiological component to the personality trait of neuroticism. Results indicated that schizophrenic subjects did demonstrate significantly reduced rates of habituation to the acoustic startle probe and higher scores on measures of neuroticism in comparison to normal controls. However, no correlation between habituation rate and neuroticism emerged. These studies replicate previous findings of habituation in schizophrenia and provide further evidence for sensory reactivity disturbances in schizophrenia. The relationship of these findings to cognitive disturbances in schizophrenia is considered and directions for future research are discussed.

Acoustic Stimulation↗

PubMed2003

Abnormal neural synchrony in schizophrenia.

Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. We used measures of phase locking and phase coherence in the scalp-recorded electroencephalogram to examine the synchronization of neural circuits in schizophrenia. Compared with matched control subjects, schizophrenia patients demonstrated: (1) absence of the posterior component of the early visual gamma band response to Gestalt stimuli; (2) abnormalities in the topography, latency, and frequency of the anterior component of this response; (3) delayed onset of phase coherence changes; and (4) the pattern of anterior-posterior coherence increases in response to Gestalt stimuli found in controls was replaced by a pattern of interhemispheric coherence decreases in patients. These findings support the hypothesis that schizophrenia is associated with impaired neural circuitry demonstrated as a failure of gamma band synchronization, especially in the 40 Hz range.

Adolescent↗