Biomedical subjects

Pamela D Butler

Publications and source records attributed to Pamela D Butler.

16 recordsLinked to original sources

PubMed2006

Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments.

Visual processing deficits are an integral component of schizophrenia and are sensitive predictors of schizophrenic decompensation in healthy adults. The primate visual system consists of discrete subcortical magnocellular and parvocellular pathways, which project preferentially to dorsal and ventral cortical streams. Subcortical systems show differential stimulus sensitivity, while cortical systems, in turn, can be differentiated using surface potential analysis. The present study examined contributions of subcortical dysfunction to cortical processing deficits using high-density event-related potentials. Event-related potentials were recorded to stimuli biased towards the magnocellular system using low-contrast isolated checks in Experiment 1 and towards the magnocellular or parvocellular system using low versus high spatial frequency (HSF) sinusoidal gratings, respectively, in Experiment 2. The sample consisted of 23 patients with schizophrenia or schizoaffective disorder and 19 non-psychiatric volunteers of similar age. In Experiment 1, a large decrease in the P1 component of the visual event-related potential in response to magnocellular-biased isolated check stimuli was seen in patients compared with controls (F = 13.2, P = 0.001). Patients also showed decreased slope of the contrast response function over the magnocellular-selective contrast range compared with controls (t = 9.2, P = 0.04) indicating decreased signal amplification. In Experiment 2, C1 (F = 8.5, P = 0.007), P1 (F = 33.1, P < 0.001) and N1 (F = 60.8, P < 0.001) were reduced in amplitude to magnocellular-biased low spatial frequency (LSF) stimuli in patients with schizophrenia, but were intact to parvocellular-biased HSF stimuli, regardless of generator location. Source waveforms derived from inverse dipole modelling showed reduced P1 in Experiment 1 and reduced C1, P1 and N1 to LSF stimuli in Experiment 2, consistent with surface waveforms. These results indicate pervasive magnocellular dysfunction at the subcortical level that leads to secondary impairment in activation of cortical visual structures within dorsal and ventral stream visual pathways. Our finding of early visual dysfunction is consistent with and explanatory of classic literature showing subjective complaints of visual distortions and is consistent with early visual processing deficits reported in schizophrenia. Although deficits in visual processing have frequently been construed as resulting from failures of top-down processing, the present findings argue strongly for bottom-up rather than top-down dysfunction at least within the early visual pathway. Deficits in magnocellular processing in this task may reflect more general impairments in neuronal systems functioning, such as deficits in non-linear amplification and may thus represent an organizing principle for predicting neurocognitive dysfunction in schizophrenia.

Adult↗

PubMed2006

A new dimension of sensory dysfunction: stereopsis deficits in schizophrenia.

BACKGROUND: Schizophrenia is a neurocognitive disorder with a wide range of cognitive and sensory impairments. Early visual processing has been shown to be especially impaired. This article investigates the integrity of binocular depth perception (stereopsis) in schizophrenia. METHODS: Seventeen schizophrenia patients and 19 healthy control subjects were compared on the Graded Circles Stereo Test. Results of stereoacuity were compared between patients and control subjects using t test. RESULTS: Schizophrenia patients demonstrated significantly (p = .006) reduced stereoacuity (mean = 142 arcseconds) versus control subjects (mean = 55 arcseconds). At the normative level for adults, patients performed below chance. CONCLUSIONS: These findings demonstrate an impairment of binocular depth perception and further confirm deficits of early visual processing in schizophrenia. Findings are discussed in context of magnocellular/dorsal stream processing with implications for visual processing and cognitive deficits.

Adult↗

PubMed2006

Reading impairment and visual processing deficits in schizophrenia.

Individuals with schizophrenia show magnocellular visual pathway abnormalities similar to those described in dyslexia, predicting that reading disturbance should be a common concomitant of schizophrenia. To date, however, reading deficits have not been well established, and, in fact, reading is often thought to be normal in schizophrenia based upon results of tests such as the WRAT, which evaluate single word reading. This study evaluated "real world" reading ability in schizophrenia, relative to functioning of the magnocellular visual pathway. Standardized psychoeducational reading tests and contrast sensitivity measures were administered to 19 patients and 10 controls. Analyses of between group differences were further refined by classification of participants into reading vs. non-reading impaired groups using a priori and derived theoretical models. Patients with schizophrenia, as a group, showed highly significant impairments in reading (p<0.04-p<0.001), with particular deficits on tests of rate, comprehension and phonological awareness. Between 21% and 63% of patients met criteria for dyslexia depending upon diagnostic model vs. 0-20% of the controls. The degree of deficit correlated significantly with independent measures of magnocellular dysfunction. Reading impairment in schizophrenia reaches the level of dyslexia and is associated with compromised magnocellular processing as hypothesized. Findings related to symptoms, functioning and recommendations for reading ability assessment are discussed.

Adolescent↗

PubMed2006

Voxelwise correlational analyses of white matter integrity in multiple cognitive domains in schizophrenia.

Patients with schizophrenia show deficits in several neurocognitive domains. However, the relationship between white matter integrity and performance in these domains is poorly understood. The authors conducted neurocognitive testing and diffusion tensor imaging in 25 patients with schizophrenia. Performance was examined for tests of verbal declarative memory, attention, and executive function. Relationships between fractional anisotropy and cognitive performance were examined by using voxelwise correlational analyses. In each case, better performance on these tasks was associated with higher levels of fractional anisotropy in task-relevant regions.

Adult↗

PubMed2006

Visual white matter integrity in schizophrenia.

OBJECTIVE: Patients with schizophrenia have visual-processing deficits. This study examines visual white matter integrity as a potential mechanism for these deficits. METHOD: Diffusion tensor imaging was used to examine white matter integrity at four levels of the visual system in 17 patients with schizophrenia and 21 comparison subjects. The levels examined were the optic radiations, the striate cortex, the inferior parietal lobule, and the fusiform gyrus. RESULTS: Schizophrenia patients showed a significant decrease in fractional anisotropy in the optic radiations but not in any other region. CONCLUSIONS: This finding indicates that white matter integrity is more impaired at initial input, rather than at higher levels of the visual system, and supports the hypothesis that visual-processing deficits occur at the early stages of processing.

Adult↗

PubMed2005

Magnocellular contributions to impaired motion processing in schizophrenia.

Patients with schizophrenia show impairments in motion processing, along with deficits in lower level processing primarily involving the magnocellular visual pathway. The present study investigates potential magnocellular contributions to impaired motion processing in schizophrenia using a combined neurophysiological and behavioral approach. As compared to prior motion studies in schizophrenia, thresholds were determined for both incoherent and coherent visual motion. In this study, velocity discrimination thresholds were measured for schizophrenia patients (n=14) and age-matched normal control subjects (n=16) using a staircase procedure. Early visual processing was evaluated using steady-state visual evoked potentials (ssVEP), with stimuli biased toward activation of either the magnocellular or parvocellular visual pathways through luminance contrast manipulation. Patients with schizophrenia showed poor velocity discrimination for both incoherent and coherent motion, with no significant group x task interaction. Further, when coherent motion performance was measured at individually determined incoherent motion thresholds, accuracy levels for patients were similar to controls, also indicating similarity of deficit for incoherent vs. coherent motion discrimination. Impairments in velocity discrimination correlated significantly with reduced amplitude of ssVEP elicited by magnocellular -- but not parvocellular -- selective stimuli. This study demonstrates that deficits in motion processing in schizophrenia are significantly related to reduced activation of the magnocellular visual system. Further, this study supports and extends prior reports of impaired motion processing in schizophrenia, and indicates significant bottom-up contributions to higher-order cognitive impairments.

Adult↗

PubMed2005

Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia.

Loss of cortical gray matter is accompanied by a commensurate increase in the sulcal and intraventricular cerebrospinal fluid volume. On diffusion-weighted magnetic resonance imaging, this would be reflected as a higher apparent diffusion coefficient in affected brain regions. On the basis of the above premise, we suggest that the apparent diffusion coefficient may be used as a surrogate marker for the assessment of regional brain volume deficits. We demonstrate this approach by voxelwise analysis of registered apparent diffusion coefficient images from a group of 15 patients with schizophrenia and 15 age-matched healthy controls. We found widespread regional apparent diffusion coefficient increases in patients. Affected areas included the bilateral insular cortex, hippocampus, temporal lobe, and occipital areas. These results largely concur with previous findings of cortical volume deficits in schizophrenia.

Adult↗

PubMed2005

Sensory contributions to impaired prosodic processing in schizophrenia.

BACKGROUND: Deficits in affect recognition are prominent features of schizophrenia. Within the auditory domain, patients show difficulty in interpreting vocal emotional cues based on intonation (prosody). The relationship of these symptoms to deficits in basic sensory processing has not been previously evaluated. METHODS: Forty-three patients and 34 healthy comparison subjects were tested on two affective prosody measures: voice emotion identification and voice emotion discrimination. Basic auditory sensory processing was measured using a tone-matching paradigm and the Distorted Tunes Test (DTT). A subset of subjects was also tested on facial affect identification and discrimination tasks. RESULTS: Patients showed significantly impaired performance on all emotion processing tasks. Within the patient group, a principal components analysis demonstrated significant intercorrelations between basic pitch perception and affective prosodic performance. In contrast, facial affect recognition deficits represented a distinct second component. Prosodic affect measures correlated significantly with severity of negative symptoms and impaired global outcome. CONCLUSIONS: These results demonstrate significant relationships between basic auditory processing deficits and impaired receptive prosody in schizophrenia. The separate loading of auditory and visual affective recognition measures suggests that within-modality factors may be more significant than cross-modality factors in the etiology of affect recognition deficits in schizophrenia.

Adult↗

PubMed2005

Early-stage visual processing and cortical amplification deficits in schizophrenia.

BACKGROUND: Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. OBJECTIVES: To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. DESIGN, SETTING, AND PARTICIPANTS: Between-group study at an inpatient state psychiatric hospital and outpatient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. MAIN OUTCOME MEASURES: (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. RESULTS: Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P = .001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P = .001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P = .002), which was in turn related to deficits in complex visual processing (P< or =.04). Both evoked potential (P< or =.04) and contrast sensitivity (P = .01) measures significantly predicted community functioning. CONCLUSIONS: These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits.

Adult↗

PubMed2005

Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia.

OBJECTIVE: Patients with schizophrenia demonstrate significant impairments of early visual processing, potentially implicating dysfunction of the magnocellular visual pathway. The present study evaluates transient visual evoked potential (tVEP) responses to stimuli biased toward the magnocellular (M) or parvocellular (P) systems in patients with schizophrenia vs. normal volunteers first to evaluate relative contributions of M and P systems to specific tVEP components in schizophrenia and, second, to evaluate integrity of early M and P processing in schizophrenia. METHODS: Seventy-four patients with schizophrenia and schizoaffective disorder were compared with 59 control subjects using separate stimuli to assess the tVEP response to M, P and mixed M/P conditions. Stimuli were biased toward M vs. P processing by manipulation of chromatic and achromatic contrast. C1, P1, N1 and P2 components were compared between patients and controls. All subjects showed 20/32 vision or better. RESULTS: Waveforms were obtained to low contrast (M), chromatic contrast (P) and high contrast (mixed M/P) stimuli in both patients and controls. C1 was present to P and mixed M/P stimuli. Patients showed a significant reduction in amplitude and an increase in latency of the C1 component. P1 was elicited primarily by M and mixed M/P stimuli, whereas N1 was elicited primarily by P and mixed M/P stimuli. Patients showed reductions in both P1 and N1 amplitudes across conditions. However, only reductions in P1 amplitude survived covariation for between group differences in visual acuity. Further, P1 amplitude reductions in the M condition correlated with a proxy measure of global outcome. CONCLUSIONS: M- and P-selective stimuli elicit differential components of the tVEP. Patients with schizophrenia show significant reductions in response even to simple visual stimuli. Deficits, particularly within the M system, may correlate significantly with global outcome and level of community functioning. SIGNIFICANCE: Whereas deficits in high-order cognitive processing have been extensively documented in schizophrenia, integrity of early-stage sensory processing has been studied to a lesser degree. The present findings suggest that deficits in early-stage visual processing are significantly related to overall clinical outcome in schizophrenia. Further, between-group differences in visual acuity may influence VEP results, even for subjects with 'normal' vision (20/32 or better).

Activities of Daily Living↗

PubMed2005

Early-stage visual processing deficits in schizophrenia.

PURPOSE OF REVIEW: While cognitive dysfunction including memory and attentional deficits are well known in schizophrenia, recent work has also shown basic sensory processing deficits. Deficits are particularly prominent in the visual system and may be related to cognitive deficits and outcome. This article reviews studies of early-stage visual processing in schizophrenia published during the past year. These studies reflect the growing interest and importance of sensory processing deficits in schizophrenia. RECENT FINDINGS: The visual system is divided into magnocellular and parvocellular pathways which project to dorsal and ventral visual areas. Recent electrophysiological and behavioral investigations have found preferential magnocellular/dorsal stream dysfunction, with some deficits in parvocellular function as well. These early-stage deficits appear to be related to higher level cognitive, social, and community function. Structural studies of occipital cortex and particularly optic radiations provide anatomical support for early visual processing dysfunction. SUMMARY: These findings highlight the importance of sensory processing deficits, in addition to higher cognitive dysfunction, for understanding the pathophysiology of schizophrenia. Understanding the nature of sensory processing deficits may provide insight into mechanisms of pathology in schizophrenia, such as N-methyl-D-aspartate dysfunction or impaired signal amplification, and could lead to treatment strategies including sensory processing rehabilitation that may improve outcome.

Journal Article↗

PubMed2004

Dysfunction of early-stage visual processing in schizophrenia: harmonic analysis.

Schizophrenia is associated with severe neurocognitive deficits that constitute a core feature of the disorder. Deficits have been most extensively studied in relationship to higher-order processes. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. Steady-state visual-evoked potentials (ssVEPs) were recorded over the occipital cortex (Oz) in patients with schizophrenia and schizoaffective disorder (N=26) and in age-matched comparison volunteers (N=22). Two stimuli were used: windmill-dartboard and partial-windmill, which are contrast-reversing ( approximately 4 Hz), radial patterns with dominant low spatial-frequency content. Each stimulus was presented for 1 min. Fourier analysis was performed on the ssVEP data to extract the relevant temporal frequency (i.e., harmonic) components. Magnitude-squared coherence (MSC) was computed to estimate the relative signal level for each frequency component. The patients showed reduced amplitude and coherence of second harmonic responses in both conditions, but intact first harmonic responses in the windmill-dartboard condition. This finding of a differential deficit may indicate a significant loss in the magnocellular pathway, which contributes to the generation of the second harmonic component under these conditions. Early sensory deficits may lead to impairments in subsequent stages of processing.

Adult↗

PubMed2004

DTI and impulsivity in schizophrenia: a first voxelwise correlational analysis.

Compromised white matter (WM) integrity in inferior frontal WM has been related to impulsivity in men with schizophrenia. However, these relationships may be more widespread. Fractional anisotropy (FA) derived from diffusion tensor imaging of 25 men with schizophrenia was transformed into Talairach space. Correlations between FA and impulsiveness were examined on a voxelwise basis. We found negative correlations between FA and impulsivity in inferior frontal WM, anterior cingulate, caudate, insula, and inferior parietal lobule. Positive correlations were obtained in the left postcentral gyrus, right superior/middle temporal gyrus, and bilateral fusiform gyrus. These areas may comprise a fronto-temporo-limbic circuit that modulates impulsivity. The voxelwise correlation method can serve as a hypothesis-generation method for relating target behaviors to their underlying neural networks.

Adult↗

PubMed2004

Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding.

Epidemiological studies suggest that prenatal malnutrition increases the risk of developing schizophrenia. Animal models indicate that prenatal protein deprivation (PPD) affects many aspects of adult brain function. We tested the hypothesis that PPD in rats would alter prepulse inhibition (PPI), which is an operational measure of sensorimotor gating that is deficient in schizophrenia patients. Additionally, we examined dopaminergic and glutaminergic receptor binding in the striatum and hippocampus, which have been suggested to play a role in the etiology of schizophrenia. Rat dams were fed normal (25%) or low (6%) protein diets beginning 5 weeks prior to, and throughout pregnancy. The pups were tested at postnatal days (PND) 35 and 56 for PPI. Striatal and hippocampal NMDA receptor, and striatal dopamine receptor binding were quantified post-mortem in a subset of these rats. Female rats exposed to PPD had reduced levels of PPI at PND 56, but not PND 35, suggesting the emergence of a sensorimotor gating deficit in early adulthood. Striatal NMDA receptor binding was increased in PPD females. A decrease in initial startle response (SR) was also observed in all PPD rats relative to control rats. These results suggest that PPD causes age- and sex-dependent decreases in PPI and increases in NMDA receptor binding. This animal model may be useful for the investigation of neurodevelopmental changes that are associated with schizophrenia in humans.

Animals↗

PubMed2003

Magnocellular and parvocellular contributions to backward masking dysfunction in schizophrenia.

Patients with schizophrenia have repeatedly shown deficits in visual processing. These deficits have been well documented using visual backward masking (VBM). The VBM deficit in schizophrenia is thought to be due to aberrant interactions between magnocellular (M) and parvocellular (P) visual pathways. To date, no study has studied these claims with rigorous stimuli isolating M and P pathway responses. This study examined the function of each pathway and their interactions by creating M- and P-biased targets based on their known physiological properties. The M system responds to very low luminance contrast whereas the P system does not, and the P system responds to color contrast whereas the M system generally does not. Thus, to activate the P system, target letters and masks utilized color contrast, and to activate the M system, target letters and masks utilized very low luminance contrast. Four conditions were presented such that M- and P-biased targets were paired with both M- and P-biased masks. A significant Group x Mask Condition interaction was found when a P target was used in combination with an M or P mask, but not when an M target was used. In particular, schizophrenia patients needed significantly longer interstimulus intervals (ISIs) than controls to escape from masking in the P target/M mask condition, but not in any of the other three conditions. In addition, the critical stimulus durations (CSDs) for unmasked stimuli were significantly increased for both M and P targets in patients relative to controls. These findings demonstrate a significant impairment in M, but not P pathway, function in patients with schizophrenia. Furthermore, deficits of letter identification, including those of P targets, may also reflect impairment of the M pathway given the priming function of the dorsal stream.

Adult↗

PubMed2003

Visual backward-masking deficits in schizophrenia: relationship to visual pathway function and symptomatology.

Patients with schizophrenia have information processing deficits which can be measured using visual backward-masking (VBM) tasks. There are two types of visual pathways: transient and sustained. The former is more sensitive to low spatial frequency (LSF) and the latter to high spatial frequency (HSF) stimuli. It has been hypothesized that the VBM deficit in schizophrenia is due to an overactive transient channel response to the mask. To examine this hypothesis, patients with schizophrenia and comparison volunteers were tested on a traditional backward-masking task as well as on tasks that altered the mask to bias stimulation toward transient (LSF) or sustained (HSF) channels. Medication effects and relationship to symptomatology were also examined. Patients with schizophrenia showed a significant deficit on the traditional backward-masking task and were also significantly impaired on the LSF- and HSF-masking tasks, though a differential deficit was not found on the latter two tasks. A U-shaped function, indicative of masking by interruption, was found on the LSF- and HSF-masking tasks. Masking performance was not altered when the same patients were tested on and off medication, and performance was related to positive and negative symptoms. In conclusion, the finding of a deficit in patients with schizophrenia on tasks producing a U-shaped function suggests that an aberrant transient response to the mask is producing increased interruption of the sustained response to the target.

Adult↗