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Biomedical subjects

A M Shelley

Publications and source records attributed to A M Shelley.

14 recordsLinked to original sources
PubMed2001

Adjunctive high-dose glycine in the treatment of schizophrenia.

Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.

Adult↗
PubMed2000

Deficits in auditory and visual context-dependent processing in schizophrenia: defining the pattern.

BACKGROUND: Brain mechanisms underlying deficits in precision of transient memory storage in schizophrenia were investigated using a combined behavioral and event-related potential approach. Performance was measured simultaneously in 2 tasks: an AX-type visual continuous performance test (AX-CPT), which required subjects to press a button whenever they saw a letter A followed by a letter X, and a mismatch negativity paradigm. The AX-CPT is designed to assess prefrontal function, whereas mismatch negativity assesses functioning of the auditory sensory memory system. METHODS: Subjects were 17 patients with chronic schizophrenia, 13 with recent-onset schizophrenia, and 20 normal comparison subjects. Potentials were recorded from 36 scalp locations in response to cue stimuli in the CPT and to duration- and pitch-deviant stimuli in the mismatch negativity paradigm. Behavioral measures including responses to incorrect cue-target sequences that should have been ignored ("false alarms") were analyzed as a function of cue-target interval. RESULTS: Chronic and recent-onset schizophrenic patients showed significantly decreased mismatch negativity amplitude but normal latency and topography. In the CPT, patients showed significantly higher rates of false alarms following incorrect cues ("BX" errors) and decreased rates of correct detections. Impaired performance correlated with decreased frontocentral event-related potential activation to incorrect cues that was manifest within several hundred milliseconds of cue presentation. All groups performed worse with increasing cue-target intervals. Patients were no more affected by increased cue-target interval than were controls. CONCLUSIONS: Schizophrenic patients are significantly impaired in their ability to form and utilize transient memory traces to guide behavior. These deficits are associated with failures of cortical activation occurring within several hundred milliseconds of stimulus presentation. A similar pattern of deficit is observed across sensory and cognitive systems. Arch Gen Psychiatry. 2000;57:1131-1137.

Adult↗
PubMed1999

Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implications for theories of cortical dysfunction.

Event-related potentials (ERPs) were recorded from 15 schizophrenic patients and 17 normal controls in an auditory oddball paradigm in order to investigate the effects of stimulus probability and interstimulus interval (ISI) on deficits in mismatch negativity (MMN) generation in schizophrenia. MMN amplitude was reduced for schizophrenics overall, with the degree of deficit increasing as deviant probability decreased. In contrast, schizophrenic subjects were no more affected by alterations in ISI than controls. The experimental design also permitted evaluation of N1 generation as a function of ISI in schizophrenia. Schizophrenic subjects showed decreased N1 amplitude across conditions, with the degree of deficit increasing with increasing ISI. For both MMN and N1, therefore, the degree of deficit increased with increasing component amplitude in normals, implying that the deficit in ERP generation in schizophrenia may reflect a decrease in maximal current flow through underlying neuronal ensembles. The observed pattern of dysfunction is consistent both with observations of impaired precision of processing in schizophrenia, and with predictions of the PCP/NMDA model.

Acoustic Stimulation↗
PubMed1999

Canalis sinuosus mimicking a periapical inflammatory lesion.

A case is presented in which an anatomical feature, canalis sinuosus, manifested as a periapical radiolucency on an upper canine. This may have been interpreted as an inflammatory lesion and led to the patient receiving inappropriate treatment had a further radiograph not been taken. The incisive foramen and mental foramen are well known anatomical features which may mimic periapical inflammatory lesions but it is less common for a neurovascular canal to manifest as a periapical radiolucency on an upper canine.

Adult↗
PubMed1999

Impaired categorical perception of synthetic speech sounds in schizophrenia.

BACKGROUND: Simple speech sounds such as /ba/ and /da/ differ in the frequency composition of their underlying formants. Normal volunteers asked to identify intermediate phonemes along the /ba/ to /da/ continuum abruptly switch from perceiving "ba" to perceiving "da". The present study investigates precision of phonemic processing in schizophrenia. METHODS: Categorical perception of speech sounds was evaluated in 15 schizophrenic and 14 control subjects, using a forced-choice phonemic discrimination paradigm. RESULTS: Patients and controls were equally able to recognize endpoint forms of both phonemes, but differed significantly in their perception of intermediate forms near the center of the continuum. Patients also showed a significantly shallower response curve, suggesting an impairment in boundary definition. Despite their impairment in categorical perception, schizophrenic subjects showed normal adaptation of response when test stimuli were preceded by a series of /ba/ or /da/ stimuli from the endpoints of the continuum. CONCLUSIONS: The present results suggest that precision of phonemic processing is impaired in schizophrenia. This categorical perception deficit may represent upward generalization of impaired memory-dependent acoustic processing. Deficits in the precision of cortical processing may contribute significantly to cognitive dysfunction in schizophrenia.

Adaptation, Psychological↗
PubMed1999

Panmodal processing imprecision as a basis for dysfunction of transient memory storage systems in schizophrenia.

Schizophrenia is a severe mental disorder associated with cognitive disturbances that may reflect underlying deficits in the functioning of brain transient memory storage systems. This study investigates performance in three distinct tasks that require transient memory storage: (1) tone discrimination, (2) object weight discrimination, and (3) "AX"-type visual continuous performance task. The tests used were chosen to investigate the degree to which a similar pattern of performance deficit could be observed across multiple sensory and cognitive domains in schizophrenia. In each of the paradigms, a similar pattern emerged: subjects with schizophrenia showed severe performance deficits whenever performance depended on functioning of transient memory systems. The deficits were apparent at both short and long interstimulus intervals (ISI), however, and schizophrenia subjects were no more affected by increasing ISI than were controls. Moreover, when short ISI performance was matched across groups by manipulating task difficulty, subsequent decay in performance was equivalent across groups. Thus, although schizophrenia subjects show severe performance deficits in memory-dependent tasks, the deficits do not appear to reflect impaired transient memory per se. Rather, they appear to reflect impaired precision of operation of such systems, irrespective of the duration over which representations must be maintained. The severe deficits in processing precision, despite the relatively preserved maintenance of representation, may be relevant to pathophysiological models of schizophrenia.

Adult↗
PubMed1998

Impaired mismatch negativity (MMN) generation in schizophrenia as a function of stimulus deviance, probability, and interstimulus/interdeviant interval.

Schizophrenia is a severe mental disorder associated with disturbances in perception and cognition. Event-related potentials (ERP) provide a mechanism for evaluating potential mechanisms underlying neurophysiological dysfunction in schizophrenia. Mismatch negativity (MMN) is a short-duration auditory cognitive ERP component that indexes operation of the auditory sensory ('echoic') memory system. Prior studies have demonstrated impaired MMN generation in schizophrenia along with deficits in auditory sensory memory performance. MMN is elicited in an auditory oddball paradigm in which a sequence of repetitive standard tones is interrupted infrequently by a physically deviant ('oddball') stimulus. The present study evaluates MMN generation as a function of deviant stimulus probability, interstimulus interval, interdeviant interval and the degree of pitch separation between the standard and deviant stimuli. The major findings of the present study are first, that MMN amplitude is decreased in schizophrenia across a broad range of stimulus conditions, and second, that the degree of deficit in schizophrenia is largest under conditions when MMN is normally largest. The pattern of deficit observed in schizophrenia differs from the pattern observed in other conditions associated with MMN dysfunction, including Alzheimer's disease, stroke, and alcohol intoxication.

Acoustic Stimulation↗
PubMed1997

The effect of decreased catecholamine transmission on ERP indices of selective attention.

This study examines the effect of decreased catecholamine transmission on event-related potential (ERP) indices of selective attention. Intravenous clonidine (1.5 micrograms/kg Catapres), droperidol (15 micrograms/kg Droleptan), or placebo were administered to healthy adult males prior to performance of a multidimensional auditory selective attention task (SAT) in which dichotically presented sequences of tone pips varied on dimensions of location (left or right ear), pitch (high or low), and duration (short or long). Subjects were required to make a button press response to infrequent "target" stimuli that matched a prespecified stimulus on the three dimensions. ERPs were recorded during the task. Clonidine led to a significant increase of processing negativity (PN) over 200-400 ms at the irrelevant location. Droperidol led to a significant increase in reaction time (RT), a significant decrease in hit rate, and an attenuation of PN over the 200- to 400-ms and 400- to 700-ms epochs. Neither substance led to a significant change in P3 amplitude. The role of catecholamines in the selective attention subprocesses of "tuning" and "switching" is discussed.

Adrenergic alpha-Agonists↗
PubMed1996

Premature disinhibition of P3 generation in schizophrenia.

P300 (P3) is a long-latency cognitive event-related potential (ERP) elicited by relevant target stimuli. P3 was recorded from 11 schizophrenics and 13 normal controls during a cued visual continuous performance task (CPT-AX). Cue-target sequences were presented at short and long interstimulus intervals (ISIs), in order to investigate working memory in schizophrenia. There was no significant between-group difference in P3 amplitude to validly or invalidly cued targets at short ISI. In contrast, P3 amplitude to invalidly cued targets at long ISI was significantly greater in schizophrenics than in controls, suggesting decreased ability to encode or maintain inhibitory representations of stimulus context. P3 amplitude is typically reduced in schizophrenic subjects in the auditory modality, and normal or reduced in the visual modality. This study, which demonstrates a paradoxical P3 increase to targets at long ISI, suggests that P3 impairment in schizophrenia cannot be attributed solely to structural deficits within P3-generator regions.

Adult↗
PubMed1995

Brain potential evidence for an auditory sensory memory deficit in schizophrenia.

OBJECTIVE: The multiple disorders of selective attention found in schizophrenia could be secondary to disturbances in sensory processing. The authors investigated this possibility by using an event-related potential index of auditory sensory memory, called "mismatch negativity." METHOD: Medicated (N = 11) and neuroleptic-free (N = 11) patients with schizophrenia and patients with bipolar affective disorder (N = 11) were compared with age- and sex-matched healthy comparison subjects. Auditory stimuli were presented while the subjects were distracted with an attention-demanding visual task. Event-related potentials were elicited by infrequently occurring auditory stimuli (deviants) and by regularly presented auditory stimuli (standards), which differed slightly in duration. The difference in amplitude between the event-related potentials elicited by the deviant and standard stimuli was the mismatch negativity. RESULTS: The amplitude of the mismatch negativity was significantly lower in both groups of schizophrenic patients than in the healthy comparison subjects. Mismatch negativity amplitude was significantly correlated with ratings of negative schizophrenic symptoms but not with positive symptoms. Compared with the matched comparison subjects, the bipolar affective disorder patients did not show lower amplitude of mismatch negativity. There was a significant negative correlation between age and mismatch negativity amplitude. CONCLUSIONS: The abnormal auditory sensory memory processing indicated by low mismatch negativity amplitude in the schizophrenic patients cannot be accounted for by neuroleptic medication status. Because this abnormality was significantly related to measures of negative symptoms only, it may be a chronicity marker or reflect a predisposition to the development to schizophrenia. These findings implicate the auditory cortex in the pathophysiology of schizophrenia.

Acoustic Stimulation↗
PubMed1993

Event-related potential indices of semantic processing in schizophrenia.

Event-related potentials (ERPs) were recorded while schizophrenic patients and healthy controls read congruous and incongruous sentences in anticipation of a memory test. The schizophrenic group performed more poorly in both recognition memory and cued recall tests. The two groups did not differ in the amplitude of the N400 component of the ERP but the difference between the ERPs to congruous and incongruous sentences persisted longer in the schizophrenic sample. The schizophrenic sample also showed reduced parietal positivity and a reduced effect of congruity on the late positive component that follows N400. Within the schizophrenic sample, measures of attentional impairment and positive thought disorder were correlated with mean amplitude of both the N400 and the subsequent positivity. The results imply that the structure and spread of activation within semantic memory is not impaired in schizophrenia. Rather, impairments appear to lie in processes required to integrate activated information with the current context.

Adolescent↗
PubMed1993

P300 indexes thought disorder in schizophrenics, but allusive thinking in normal subjects.

Loosening of thinking as assessed by the Object Sorting Test (OST) has been found in a percentage of normal subjects but in a higher percentage of schizophrenics, and is familially transmitted in both groups. Loosening of thinking in normal subjects is not associated with evidence of impaired function or increased psychopathology, and in recognition of this, it was termed allusive thinking rather than thought disorder. Both OST-assessed loosening and concreteness of thinking were found to be present independently in a high percentage of schizophrenics, so that both were considered to contribute to schizophrenic thought disorder. The presence of OST-assessed loosening in schizophrenics would, therefore, be predicted to correlate partially rather than totally with measures of schizophrenic thought disorder. It has been suggested that OST-assessed loosening in normal subjects is due to a genetically determined reduction in strength of an inhibitory process that limits the spread of activation of semantic associations and results in a predisposition to schizophrenia. The brain event-related potential P300, which is, in part, under genetic control, may index this inhibitory process. Therefore, it was predicted that in normal subjects, P300 would correlate with OST-assessed loosening of associations. If schizophrenic thought disorder is due to a further weakening of this inhibitory process, it can be predicted that P300 in schizophrenics correlates only weakly with OST-assessed loosening of thinking, but more strongly with schizophrenic thought disorder. In a study in which P300 was elicited using a difficult selective attention task with 15 unmedicated schizophrenics and 22 healthy subjects, all three predictions were supported.

Adult↗
PubMed1991

The effect of repeated testing on ERP components during auditory selective attention.

The present study examined long-term repetition effects on human auditory event-related potentials (ERPs). ERPs were recorded from subjects performing the same multidimensional auditory selective attention task on six separate occasions spaced one week apart. The task required subjects to attend to tones that varied along the dimensions of location (L), pitch (P), and duration (D) and to detect prespecified target (L + P + D +) combinations of these attributes. Processing negativity (PN) between 100-400 ms did not change in amplitude or onset latency as a function of repeated experience with the task. In contrast, two measures of "very late" PN were reduced with practice. Specifically, the location effect measured over the 400-700-ms epoch was significant only for Weeks 1 and 2, and the separation of the L + P + D- ERP from other D- ERPs, measured over the 700-1000-ms epoch, was significantly reduced from Week 1 to Week 2. A late negative component (700-1000 ms) elicited by correctly identified targets increased between Weeks 1 and 2, consistent with subjects adopting the strategy of rehearsal of the target itself rather than the L + P + D- standard. P2 amplitude increased significantly for all standards, possibly due to decreased latency jitter in later weeks. N1 latency became significantly shorter over weeks, reflecting either increasing confidence in stimulus discrimination with repeated testing or the overlapping of an unchanging N1 with an increasing P2.

Acoustic Stimulation↗