Biomedical subjects

Sandra N Moses

Publications and source records attributed to Sandra N Moses.

13 recordsLinked to original sources

PubMed2006

An investigation of learning strategy supporting transitive inference performance in humans compared to other species.

Generalizations about neural function are often drawn from non-human animal models to human cognition, however, the assumption of cross-species conservation may sometimes be invalid. Humans may use different strategies mediated by alternative structures, or similar structures may operate differently within the context of the human brain. The transitive inference problem, considered a hallmark of logical reasoning, can be solved by non-human species via associative learning rather than logic. We tested whether humans use similar strategies to other species for transitive inference. Results are crucial for evaluating the validity of widely accepted assumptions of similar neural substrates underlying performance in humans and other animals. Here we show that successful transitive inference in humans is unrelated to use of associative learning strategies and is associated with ability to report the hierarchical relationship among stimuli. Our work stipulates that cross-species generalizations must be interpreted cautiously, since performance on the same task may be mediated by different strategies and/or neural systems.

Adult↗

PubMed2006

MEG reveals different contributions of somatomotor cortex and cerebellum to simple reaction time after temporally structured cues.

Magnetoencephalography (MEG) was used to measure brain activity while participants performed a simple reaction to targets after either a random interval (uncued targets) or a series of isochronous warning stimuli with 200-ms intervals that acted as a countdown. Targets could arrive "on time" or "early" relative to the preceding warning stimuli. Cerebellar activity before any stimulus onset predicted uncued simple reaction time. Onset of activity in somatomotor cortex relative to the target predicted reaction time after two warning stimuli when the target arrived on time or early. After three warning stimuli, when the target arrived on time and was certain to occur, prestimulus cerebellar activity and somatomotor onset were significant predictors of reaction time. When the target arrived early after three warning stimuli, prestimulus cerebellar and cingulate activity were predictive. The cerebellar results may reflect a number of possible factors, including a role in timing, response readiness, prediction and attention.

Acoustic Stimulation↗

PubMed2006

A comparison and evaluation of the predictions of relational and conjunctive accounts of hippocampal function.

Relational and conjunctive memory theory each postulate that the hippocampus participates in the formation of long-term memory representations comprised of associations between multiple elements. The goals of the current work were to clarify and contrast these theories by outlining the nature of the representations that are spared vs. impaired following hippocampal damage according to each theoretical perspective. Relational theory predicts that hippocampal lesions will impair performance on tasks that require the formation of new long-term representations in which distinct elements must be regarded in relation to all other elements. Representations that remain intact despite hippocampal damage include separate representations of distinct individual elements or multiple stimuli fused into a static "blend" such as several elements viewed from one vantage point. Additionally, the relational account predicts that rapid incidental online processing of the relations can be achieved through structures other than the hippocampus, but this information will not be stored. In contrast, conjunctive theory predicts that hippocampal damage will impair the rapid formation of unitary representations that contain features of elements and their relative relationships bound in an inflexible manner. Deficits in the rapid formation of these conjunctive representations result in impaired performance on tasks that require rapid incidental stimulus binding. However, intact formation of conjunctive representations can occur over multiple trials in the service of problem solving. Using these theoretical frameworks, recent findings from the human and nonhuman animal literature are reexamined in order to determine whether one theory better accounts for current findings. We discuss empirical studies that serve as "critical experiments" in addressing the relational vs. conjunctive debate, and find that the predictions of relational theory are supported by existing findings over those from the conjunctive account.

Animals↗

PubMed2005

The C50m response: conditioned magnetocerebral activity recorded from the human brain.

Recent advances in neuroimaging technology now permit a precise determination of the dynamics of specific neural activity underlying human associative learning. We used magnetoencephalography (MEG) to characterize the dynamics of conditioned responses (CRs) within auditory cortex during habituation, delay and trace conditioning training, and delay conditioning extinction. Conditioned stimuli (CS) were visually presented geometric figures, and unconditioned stimuli (US) were aversive noise bursts. CS+ stimuli were paired with the US on 50% of presentations: CS- stimuli were never paired with the US. Auditory cortex was activated following the paired CS+ at an average of 49-62 ms following US onset. Our data support the presence of a differential conditioned response (C50m) in auditory cortex following the unpaired CS+ at an average of 30-61 ms after US omission. The current source strength of the auditory C50m was subsequently quantified for the unpaired CS+ and CS- during training, the unpaired CS+ during extinction, and habituation. During delay and trace training, the C50m was stronger for the unpaired CS+ than for the CS-, and was also stronger for the unpaired CS+ during training compared to both habituation and extinction. This is the first description of magnetocerebral conditioning in normal human auditory cortex. The C50m activity in auditory cortex elicited by visual stimuli constitutes a direct observation of associative neural plasticity within the human auditory cortex.

Adult↗

PubMed2005

Differential contributions of hippocampus, amygdala and perirhinal cortex to recognition of novel objects, contextual stimuli and stimulus relationships.

This study examined contributions of the hippocampus, amygdala and perirhinal cortex to memory. Rats performed a cover task, and changes to stimulus identity or relationships were used to test incidental memory. Rats with hippocampal damage showed deficient responses to relationship changes, but demonstrated knowledge of the position and identity of the target object. They over-focused on the most predictive stimuli, and failed to acquire associations including surrounding cues. Rats with amygdala damage responded to changes involving distal stimuli, and showed deficient responses to novel objects and object relationships. These rats may be highly reliant on relational representations, resulting in a reduced salience for individual novel stimuli. Rats with perirhinal damaged responded to novel stimulus relationships and distal cues, but showed deficient responses to novel objects, suggesting that changes in identity had reduced salience. Implications for declarative and conjunctive hippocampal theories are discussed.

Amygdala↗

PubMed2005

Relational memory for object identity and spatial location in rats with lesions of perirhinal cortex, amygdala and hippocampus.

Previous studies dissociate medial temporal lobe regions using non-relational object versus relational spatial tasks. We compared a relational object identity task to the commonly used, relational spatial Morris water task. Lesions of perirhinal cortex, amygdala and hippocampus led to impaired performance on only the relational object preference task. Rats with perirhinal cortex and amygdala lesions performed normally on the Morris water task, but showed reduced perseveration in the correct quadrant on the probe trial. Rats with hippocampal damage were impaired on all measures of the Morris water task. Our findings demonstrate that perirhinal and amygdala damage creates impairments for relational tasks that rely on information processed by these structures (object identity and stimulus valence, respectively). In addition, these structures contribute non-essentially to performance of relational spatial tasks. The hippocampus is critical for all tasks that require the use of relational representations, regardless of whether the disambiguating information is provided by object identity or spatial arrangements. The current pattern of results suggests that the previous object-spatial dissociations among medial temporal lobe regions may be due to the relational nature of the spatial tasks versus the non-relational nature of the object tasks. Further, they illustrate that discrete dissociations among different types of processing may be an oversimplification.

Amygdala↗

PubMed2005

M50 sensory gating predicts negative symptoms in schizophrenia.

Impaired auditory sensory gating is considered characteristic of schizophrenia and a marker of the information processing deficit inherent to that disorder. Predominance of negative symptoms also reflects the degree of deficit in schizophrenia and is associated with poorer pre-morbid functioning, lower IQ, and poorer outcomes. However, a consistent relationship between auditory sensory gating and negative symptoms in schizophrenia has yet to be demonstrated. The absence of such a finding is surprising, since both impaired auditory gating and negative symptoms have been linked with impaired fronto-temporal cortical function. The present study measured auditory gating using the P50 event related potential (ERP) in a paired-click paradigm and capitalized on the relative localization advantage of magnetoencephalography (MEG) to assess auditory sensory gating in terms of the event related field (ERF) M50 source dipoles on bilateral superior temporal gyrus (STG). The primary hypothesis was that there would be a positive correlation between lateralized M50 auditory sensory gating measures and negative symptoms in patients with schizophrenia. A standard paired-click paradigm was used during simultaneous EEG and MEG data collection to determine S2/S1 sensory gating ratios in a group of 20 patients for both neuroimaging techniques. Participants were administered the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptom Scale (PANSS), and the Calgary Depression Scale for Schizophrenia. Consistent with previous reports, there was no relationship between ERP P50 sensory gating and negative symptoms. However, right (not left) hemisphere ERF M50 sensory gating ratio was significantly and positively correlated with negative symptoms. This finding is compatible with information processing theories of negative symptoms and with more recent findings of fronto-temporal abnormality in patients with predominantly negative symptoms.

Adolescent↗

PubMed2005

A specific test of hippocampal deficit in schizophrenia.

Despite numerous studies in which hippocampal abnormalities were found, schizophrenia patients' hippocampal neural activity has not been systematically evaluated on a specific hippocampal-dependent task. The transverse-patterning task (TP) is sensitive to the relational mnemonic capabilities of the hippocampus. Ten schizophrenia patients and 10 controls performed TP and control tasks that are not hippocampal dependent. As predicted, patients displayed a behavioral impairment in TP and not in control tasks. Magnetoencephalography showed controls activating right hippocampus during TP performance. Patients showed more bilateral or left hippocampal activation during TP, and greater left lateralization was associated with better performance on TP. Patients' abnormal hippocampal lateralization may play a role in the hippocampal-dependent behavioral deficit.

Adult↗

PubMed2005

Cross-modal generality of the gating deficit.

Auditory P50/M50 paired-click studies have established an association between schizophrenia and impaired sensory gating in the auditory modality. However, the presumed cross-modal generality of the gating deficit has received little study. The present study examined gating in area 3b of primary somatosensory cortex to evaluate patients' somatosensory gating at this first stage of cortical processing. One hundred twenty-two channels of magnetoencephalography (MEG) data were collected from 27 subjects with chronic schizophrenia and 21 controls during a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus interval. M20 somatosensory responses were localized using magnetic source imaging, and a gating ratio was calculated. In a subset of these subjects, MEG was also done for the standard auditory paradigm to assess M50 gating. Patients showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results argue against a cross-modal gating deficit in primary somatosensory cortex.

Acoustic Stimulation↗

PubMed2005

Distinct M50 and M100 auditory gating deficits in schizophrenia.

The time course of the schizophrenia auditory gating deficit may provide clues to mechanisms of impaired cognition. Magnetoencephalography was recorded during a standard paired-click paradigm. Using source strength of the M50 and M100 components for each click, calculated from dipole locations identified as underlying each component for the first click, a ratio of the second divided by the first was used to measure gating. Patients showed a left-hemisphere gating deficit in M50 and a bilateral gating deficit in M100. Hypothesizing that an early deficit may affect later processing, hierarchical regression was used to examine variance shared between the components. A left-hemisphere M100 gating deficit was coupled with the left M50 gating deficit. In contrast, a right-hemisphere M100 gating deficit was unrelated to M50 gating in either hemisphere. Investigations of interhemisphere gating relations may clarify group differences in regional connectivity and their role in gating.

Adult↗

PubMed2003

A non-invasive method for observing hippocampal function.

A non-invasive method for observing the functioning of the hippocampus could be invaluable in understanding the role of hippocampal abnormalities in many brain disorders. Transverse patterning, a hippocampal-dependent memory task, was used in an attempt to study the functioning hippocampus. Subjects performed transverse patterning while whole-head MEG data were collected. The MEG data were analyzed using a spatial-temporal multiple-dipole approach. Controls showed right hippocampal activation. Patients with unilateral hippocampal damage showed activation in undamaged hippocampus. MEG during transverse patterning performance is a promising, non-invasive tool for assessing hippocampal function.

Adult↗

PubMed2003

Lateralization of auditory sensory gating and neuropsychological dysfunction in schizophrenia.

OBJECTIVE: Sensory gating assessed via EEG in a paired-click paradigm has often served as a neurophysiological metric of attentional function in schizophrenia. However, the standard EEG measure of sensory gating using the P50 component at electrode Cz does not foster differential assessment of left and right hemisphere contributions. Magnetoencephalography (MEG) is complementary to EEG, and its analogous M50 component may be better suited for localization and analysis of such lateralized cortical generators. The authors hypothesized that 1) auditory gating would be evident in M50 sources in superior temporal gyrus, demonstrating ratios similar to P50; 2) M50 would resemble P50 in distinguishing gating in comparison subjects and patients with schizophrenia, but M50 would show lateralization of the gating deficit; and 3) P50 and M50 sensory gating ratios would predict neuropsychological measures in patients and comparison subjects, with the MEG identification of left and right hemisphere sources allowing for the evaluation of lateralization in brain-behavior relationships. METHOD: Event-related EEG and MEG recordings were simultaneously obtained from 20 patients with schizophrenia and 15 comparison subjects. P50 amplitudes, M50 dipole source strengths, and P50 and M50 gating ratios were compared and assessed with respect to scores on neuropsychological performance measures. RESULTS: M50 dipoles localizing to superior temporal gyrus demonstrated gating similar to that of P50. As expected, patients demonstrated less P50 gating than did comparison subjects. Left (but not right) hemisphere M50 gating 1) correlated with EEG gating, 2) differentiated patients and comparison subjects, and 3) correlated with neuropsychological measures of sustained attention and working memory. CONCLUSIONS: Converging evidence from EEG, MEG, and neuropsychological measures points to left hemisphere dysfunction as strongly related to the well-established sensory gating deficit in schizophrenia.

Acoustic Stimulation↗

PubMed2002

Differential involvement of amygdala and hippocampus in responding to novel objects and contexts.

Different medial temporal lobe structures are involved in memory for different types of novel cues and novel relationships among familiar cues. We measured the behavior of rats with amygdala or hippocampal damage, when confronted with novelty in an incidental learning paradigm. We examined both direct and indirect measures of memory. Following habituation to an environment, proximal objects or distal cues were manipulated in several ways. We found that rats with hippocampal damage exhibited a deficit on direct measures of memory, but performed normally on all indirect measures. Rats with amygdala damage exhibited a deficit on a direct measure, and performed normally on an indirect measure, of memory for proximal object identity. Thus, the hippocampus may be necessary for success on direct measures of memory for distal cues and proximal objects and the relationships among them. Likewise, the amygdala may be necessary for success on some direct measures of memory, such as memory for aspects of proximal object identity. Neither the amygdala nor the hippocampus functions as a generalized novelty detection system. To the extent that we tap implicit and explicit knowledge using this paradigm, we suggest that in the rat, the amygdala and hippocampal systems are necessary for at least some types of explicit knowledge.

Amygdala↗