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Biomedical subjects

M A Gluck

Publications and source records attributed to M A Gluck.

At least 19 recordsLinked to original sources
PubMed2006

Conditional discrimination and reversal in amnesia subsequent to hypoxic brain injury or anterior communicating artery aneurysm rupture.

Human anterograde amnesia can develop following bilateral damage to the hippocampus and medial temporal lobes, as in hypoxic brain injury, or following damage to the basal forebrain, as following anterior communicating artery (ACoA) aneurysm rupture. In both cases, the mnestic deficit may be similar when assessed by standard neuropsychological measures. However, animal and computational models suggest that there are qualitative differences in the pattern of impaired and spared memory abilities following damage to hippocampus versus basal forebrain. Here, we show such a dissociation in human amnesia using a single two-stage task, involving conditional discrimination and reversal. Consistent with a prior study, 10 individuals with anterograde amnesia subsequent to hypoxic brain injury were spared on acquisition but impaired at reversal. However, 10 individuals with amnesia subsequent to ACoA aneurysm showed the opposite pattern of impaired acquisition but spared reversal. The differences between groups cannot be easily ascribed to severity of mnestic or cognitive deficit, since the two amnesic groups performed similarly on neuropsychological tests of memory, intelligence and attention. The results illustrate qualitative differences in memory impairments in hypoxic and ACoA amnesics and highlight the importance of considering etiology in evaluating mnemonic deficits in amnesic populations.

Adult↗
PubMed2005

Integrating incremental learning and episodic memory models of the hippocampal region.

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic memory and incremental learning, by drawing on an earlier mathematical model of conditioning, SOP (A. Wagner, 1981). The model describes how a familiarity signal may arise from parahippocampal cortices, giving a novel explanation for the finding that the neural response to a stimulus in these regions decreases with increasing stimulus familiarity. Recollection is ascribed to the hippocampus proper. It is shown how the properties of episodic representations in the neocortex, parahippocampal gyrus, and hippocampus proper may explain phenomena in classical conditioning. The model reproduces the effects of hippocampal, septal, and broad hippocampal region lesions on contextual modulation of classical conditioning, blocking, learned irrelevance, and latent inhibition.

Hippocampus↗
PubMed2004

Cortico-striatal contributions to feedback-based learning: converging data from neuroimaging and neuropsychology.

The striatum has been widely implicated in cognition, but a precise understanding of its role remains elusive. Here we present converging evidence for the role of the striatum in feedback-based learning. In a prior functional imaging study, healthy controls showed striatal activity during a feedback-based learning task, which was decreased when the same task was learned without feedback. In the present study, we show that individuals with striatal dysfunction due to Parkinson's disease are impaired on the feedback-based task, but not on a non-feedback version of the same task. Parkinson's patients and controls also used different learning strategies depending on feedback structure. This study provides direct behavioural evidence from humans that cortico-striatal systems are necessary for feedback-based learning on a cognitive task. These findings also link between learning impairments in Parkinson's disease and the physiological and computational evidence for the role of midbrain dopaminergic systems in feedback processing.

Aged↗
PubMed2004

Human midbrain sensitivity to cognitive feedback and uncertainty during classification learning.

Mesencephalic dopaminergic system (MDS) neurons may participate in learning by providing a prediction error signal to their targets, which include ventral striatal, orbital, and medial frontal regions, as well as by showing sensitivity to the degree of uncertainty associated with individual stimuli. We investigated the mechanisms of probabilistic classification learning in humans using functional magnetic resonance imaging to examine the effects of feedback and uncertainty. The design was optimized for separating neural responses to stimulus, delay, and negative and positive feedback components. Compared with fixation, stimulus and feedback activated brain regions consistent with the MDS, whereas the delay period did not. Midbrain activity was significantly different for negative versus positive feedback (consistent with coding of the "prediction error") and was reliably correlated with the degree of uncertainty as well as with activity in MDS target regions. Purely cognitive feedback apparently engages the same regions as rewarding stimuli, consistent with a broader characterization of this network.

Adult↗
PubMed2004

Role of the basal ganglia in category learning: how do patients with Parkinson's disease learn?

The purpose of the present study was to gain a deeper understanding of the role of the basal ganglia in learning and memory by examining learning strategies among patients with basal ganglia dysfunction. Using a probabilistic category learning task (the "weather prediction" task) previously shown to be sensitive to basal ganglia function, the authors examined patterns of performance during learning and used mathematical models to capture different learning strategies. Results showed that patients with Parkinson's disease exhibit different patterns of strategy use. Specifically, most controls initially used a simple, but suboptimal, strategy that focused on single-cue-outcome associations; eventually, however, most controls adopted a more complex, optimal learning strategy, integrating single-cue associations to predict outcomes for multiple-cue stimuli. In contrast, the majority of individuals with Parkinson's disease continued to rely on simple single-cue learning strategies throughout the experiment.

Aged↗
PubMed2001

Interactive memory systems in the human brain.

Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates. A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies and neuroimaging, activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning.

Adult↗
PubMed2001

Basal forebrain stimulation changes cortical sensitivities to complex sound.

Experience affects how brains respond to sound. Here, we examined how the sensitivity and selectivity of auditory cortical neuronal responses were affected in adult rats by the repeated presentation of a complex sound that was paired with basal forebrain stimulation. The auditory cortical region that was responsive to complex sound was 2-5 five times greater in area in paired-stimulation rats than in naive rats. Magnitudes of neuronal responses evoked by complex sounds were also greatly increased by associative pairing, as were the percentages of neurons that responded selectively to the specific spectrotemporal features that were paired with stimulation. These findings demonstrate that feature selectivity within the auditory cortex can be flexibly altered in adult mammals through appropriate intensive training.

Acoustic Stimulation↗
PubMed2001

Cerebellar substrates for error correction in motor conditioning.

The authors evaluate a mapping of Rescorla and Wagner's (1972) behavioral model of classical conditioning onto the cerebellar substrates for motor reflex learning and illustrate how the limitations of the Rescorla-Wagner model are just as useful as its successes for guiding the development of new psychobiological theories of learning. They postulate that the inhibitory pathway that returns conditioned response information from the cerebellar interpositus nucleus back to the inferior olive is the neural basis for the error correction learning proposed by Rescorla and Wagner (Gluck, Myers, & Thompson, 1994; Thompson, 1986). The authors' cerebellar model expects that behavioral processes described by the Rescorla-Wagner model will be localized within the cerebellum and related brain stem structures, whereas behavioral processes beyond the scope of the Rescorla-Wagner model will depend on extracerebellar structures such as the hippocampus and related cortical regions. Simulations presented here support both implications. Several novel implications of the authors' cerebellar error-correcting model are described including a recent empirical study by Kim, Krupa, and Thompson (1998), who verified that suppressing the putative error correction pathway should interfere with the Kamin (1969) blocking effect, a behavioral manifestation of error correction learning. The authors also discuss the model's implications for understanding the limits of cerebellar contributions to associative learning and how this informs our understanding of hippocampal function in conditioning. This leads to a more integrative view of the neural substrates of conditioning in which the authors' real-time circuit-level model of the cerebellum can be viewed as a generalization of the long-term memory module of Gluck and Myers' (1993) trial-level theory of cerebellar-hippocampal interaction in motor conditioning.

Animals↗
PubMed2001

Spectrotemporal sensitivities in rat auditory cortical neurons.

Studies in several mammalian species have demonstrated that auditory cortical neurons respond strongly to single frequency-modulated (FM) sweeps, and that most responses are selective for sweep direction and/or rate. In the present study, we used extracellular recordings to examine how neurons in the auditory cortices of anesthetized rats respond to continuous, periodic trains of FM sweeps (described previously by deCharms et al., Science 280 (1998) pp. 1439-1444, as moving auditory gratings). Consistent with previous observations in owl monkeys, we found that the majority of cortical neurons responded selectively to trains of either up-sweeps or down-sweeps; selectivity for down-sweeps was most common. Periodic responses were typically evoked only by sweep trains with repetition rates less than 12 sweeps per second. Directional differences in responses were dependent on repetition rate. Our results support the proposal that a combination of both spectral and temporal acoustic features determines the responses of auditory cortical neurons to sound, and add to the growing body of evidence indicating that the traditional view of the auditory cortex as a frequency analyzer is not sufficient to explain how the mammalian brain represents complex sounds.

Acoustic Stimulation↗
PubMed2001

A computational model of mechanisms controlling experience-dependent reorganization of representational maps in auditory cortex.

Cortical representations of sound can be modified by repeatedly pairing presentation of a pure tone with electrical stimulation of neuromodulatory neurons located in the basal forebrain (Bakin & Weinberger, 1996; Kilgard & Merzenich, 1998a). We developed a computational model to investigate the possible effects of basal forebrain modulation on map reorganization in the auditory cortex. The model is a self-organizing map with acoustic response characteristics mimicking those observed in the mammalian auditory cortex. We simulated the effects of basal forebrain modulation, using parameters intrinsic to the self-organizing map, such as the learning rate (controlling the adaptability of map nodes) and the neighborhood function (controlling the excitability of map nodes). Previous research has suggested that both parameters can be useful for characterizing the effects of neuromodulation on plasticity (Kohonen, 1993; Myers et al., 1996; Myers, Ermita, Hasselmo, & Gluck, 1998). The model successfully accounts for experimentally observed effects of pairing basal forebrain stimulation with the presentation of a single tone, but not of two tones, suggesting that auditory cortical plasticity is constrained in ways not accounted for by current theories. Despite this limitation, the model provides a useful framework for describing experience-induced changes in auditory representations and for relating such changes to variations in the excitability and adaptability of cortical neurons produced by neuromodulation.

Animals↗
PubMed2001

Impaired delay eyeblink classical conditioning in individuals with anterograde amnesia resulting from anterior communicating artery aneurysm rupture.

Anterior communicating artery (ACoA) aneurysm rupture can lead to an anterograde amnesia syndrome similar to that observed after damage to the hippocampus and medial temporal lobes (MT). It is currently believed that ACoA amnesia results from basal forebrain damage that disrupts hippocampal processing without direct hippocampal damage. Converging evidence from animal studies and computational modeling suggests that qualitative differences may exist in the pattern of memory impairment after basal forebrain or MT damage. For example, animals with basal forebrain but not hippocampal damage are impaired at delay eyeblink classical conditioning (EBCC). In this study, individuals with ACoA amnesia were shown to be impaired at delay EBCC compared with matched controls; this contrasts with the spared delay EBCC previously observed in MT amnesia. This finding suggests the beginning of a possible dissociation between the memory impairments in MT versus ACoA amnesia.

Adult↗
PubMed2000

Latent learning in medial temporal amnesia: evidence for disrupted representational but preserved attentional processes.

Damage to the hippocampus and medial temporal (MT) structures can lead to anterograde amnesia and may also impair latent learning, in which prior exposure to cues affects their subsequent associability. Normally, latent learning may reflect both representational and attentional mechanisms. Prior work has suggested that individuals with MT amnesia have specific deficits in representational processing; thus, latent learning that invokes primarily representational mechanisms might be especially impaired in MT amnesia. The current results provide preliminary confirmation of this prediction. In Experiment 1, a latent learning paradigm expected to invoke representational mechanisms was impaired in individuals with MT amnesia, whereas in Experiment 2, a paradigm expected to invoke other attentional mechanisms was spared in individuals with MT amnesia. This suggests the representational and attentional components of latent learning are dissociable and differentially affected in anterograde amnesia.

Adult↗
PubMed2000

Stimulus exposure effects in human associative learning.

Learning that one cue (CS) predicts a second, salient cue (US) can often be slowed by prior exposure to one or both stimuli. In animals, CS-US learning is more strongly retarded following uncorrelated exposure to both CS and US than following exposure to the US alone. In this paper we present several studies showing a similar effect in humans, using a computer-based task. Experiments 1 and 2 used a between-groups design and demonstrated a strong CS/US exposure effect, whether or not the US was signalled by a neutral cue during exposure. Experiment 3 demonstrated similar effects using a within-subjects design. Overall, these results are consistent with several theoretical interpretations and suggest that uncorrelated CS/US exposure leads to a robust retardation of subsequent CS-US learning in humans.

Acoustic Stimulation↗
PubMed2000

Nonlinear autoassociation is not equivalent to PCA.

A common misperception within the neural network community is that even with nonlinearities in their hidden layer, autoassociators trained with backpropagation are equivalent to linear methods such as principal component analysis (PCA). Our purpose is to demonstrate that nonlinear autoassociators actually behave differently from linear methods and that they can outperform these methods when used for latent extraction, projection, and classification. While linear autoassociators emulate PCA, and thus exhibit a flat or unimodal reconstruction error surface, autoassociators with nonlinearities in their hidden layer learn domains by building error reconstruction surfaces that, depending on the task, contain multiple local valleys. This interpolation bias allows nonlinear autoassociators to represent appropriate classifications of nonlinear multimodal domains, in contrast to linear autoassociators, which are inappropriate for such tasks. In fact, autoassociators with hidden unit nonlinearities can be shown to perform nonlinear classification and nonlinear recognition.

Linear Models↗
PubMed2000

Dissociating entorhinal and hippocampal involvement in latent inhibition.

This study used anatomical cues to suggest a functional dissociation between the roles of the entorhinal cortex and the hippocampus in learning. The authors proposed that the highly convergent inputs to the entorhinal cortex indicate this region may be particularly important for selecting or compressing information. This hypothesis was tested in rabbits (Oryctolagus cunniculus) trained on an associative learning task that is a common index of stimulus selection. In this task, known as latent inhibition, preexposure to a stimulus (such as a tone) leads to slowed learning when the same tone is subsequently paired with an outcome (such as an airpuff to the eye). As hypothesized, rabbits with neurotoxic lesions of the entorhinal cortex failed to show slowed learning following preexposure (no latent inhibition) and learned the association faster than control rabbits. In contrast, hippocampal-lesioned animals showed normal (slowed) learning.

Animals↗
PubMed1997

Psychobiological models of hippocampal function in learning and memory.

We review current computational models of hippocampal function in learning and memory, concentrating on those that make strongest contact with psychological issues and behavioral data. Some models build upon Marr's early theories for modeling hippocampal field CA3's putative role in the fast, temporary storage of episodic memories. Other models focus on hippocampal involvement in incrementally learned associations, such as classical conditioning. More recent efforts have attempted to bring functional interpretations of the hippocampal region in closer contact with underlying anatomy and physiology. In reviewing these psychobiological models, three major themes emerge. First, computational models provide the conceptual glue to bind together data from multiple levels of analysis. Second, models serve as important tools to integrate data from both animal and human studies. Third, previous psychological models that capture important behavioral principles of memory provide an important top-down constraint for developing computational models of the neural bases of these behaviors.

Animals↗
PubMed1996

Integrating behavioral and physiological models of hippocampal function.

In recent modeling of hippocampal function, we have attempted to integrate formal behavioral analyses of classical conditioning with psychobiological data on brain lesions (Gluck and Myers [1993] Hippocampus 3:491-516; Myers and Gluck [1994] Behav Neurosci 108(5):835-847). Based on comparative behavioral analyses, we have argued that animals with hippocampal region damage are unable to alter stimulus similarity based on experience. While hippocampal-damaged animals can still learn whether to respond to an individual stimulus, they are notably impaired at many tasks involving learning relationships between stimuli-especially in the absence of explicit reinforcement. These analyses lead to a computational theory which identifies two representational recoding processes-predictive differentiation and redundancy compression-which alter stimulus similarity relationships in intact animals but are dependent on intact hippocampal region processing. More recent, and ongoing, modeling aims to broaden this model of hippocampal region function in classical conditioning, with an emphasis on physiological and anatomical constraints, including the role of the fornix and subcortical modulation, preprocessing in sensory cortices, and localization of the proposed representational functions within more precisely identified hippocampal region substrates (Myers et al. [1995] Psychology 23(2):116-138; Myers and Gluck [1996] Behav Neurosci; Myers et al. [1996] Neurobiol Learning Memory). Working to bridge between behavioral and physiological levels of analysis, we ultimately hope to develop a more complete understanding of hippocampal region function in memory across a wider range of behavioral paradigms, elucidating how this functionality emerges from underlying physiological and anatomical substrates.

Amnesia↗