Biomedical subjects

Barbara J Knowlton

Publications and source records attributed to Barbara J Knowlton.

At least 19 recordsLinked to original sources

PubMed2006

Remember-Know judgments and retrieval of contextual details.

The Remember-Know (R-K) task is commonly used to differentiate between recollection and familiarity-based recognition memory. To further validate this test, we assessed the number of contextual details available to participants after giving R or K responses. We also examined the effect of retention interval on the episodic character of memories by administering the R-K task after both 10-minute and 1-week retention intervals. At 1 week, items receiving R responses were accompanied by a significant number of episodic details, while K responses were not. A large number of items that received R responses at the 10-minute delay received K responses at 1 week, and these items were not accompanied by episodic detail during the later test. Items that were judged familiar at 10-minutes but were labeled as recollected at 1 week were also not accompanied by significant memory of the study episode, suggesting that these items were recollected from the first test session. Overall, the data are consistent with the idea that R responses, unlike K responses, are accompanied by memory for episodic detail, and that the loss of memory for episodic detail over time parallels the conversion of R responses to K responses.

Cues↗

PubMed2005

Backward inhibition in Parkinson's disease.

Parkinson's disease has been associated with executive dysfunction, especially task-switching deficits. One factor contributing to task-switching costs is backward inhibition, as measured by less efficient performance when switching back to a task from which one has recently switched away. This alternating-switch cost is considered to be due to persisting inhibition of elements of the previous task set after a switch. In this study, patients with mild to moderate Parkinson's disease and controls performed three tasks (A-C) in an intermixed fashion. Patients with mild to moderate Parkinson's disease and controls showed equivalent response times. However, the patients made significantly more errors during an alternating switch (i.e., ABA) than did control participants. In contrast, there was no group difference in accuracy in the comparable condition of two consecutive switches between different tasks (i.e., CBA). In addition, accuracy for the two groups was similar for trials in which the task was repeated. These data suggest that Parkinson's disease is associated with either increased backward inhibition, or a reduced ability to overcome this inhibition when reactivating a recently abandoned task set.

Aged↗

PubMed2005

Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning.

Actions become compulsive when they are no longer controlled by their consequences. Compulsivity can be assessed using the omission procedure in which animals are required to withhold a previously reinforced action to earn reward. The current study tested the hypothesis that inactivation of the dorsolateral striatum (DLS), a structure implicated in habitual behavior, can enhance sensitivity to changes in the action-outcome contingency during omission training, thus leading to a reduction in compulsive responding. Over 10 days rats were trained to press a freely available lever for sucrose reward delivered on interval schedules of reinforcement. After learning to press the lever at a stable and high rate, rats in the omission group received a session in which the rewards were now delayed by pressing the lever; i.e. withholding lever pressing resulted in increased access to reward. A control group was yoked to the omission group and received the same number and pattern of reward delivery but without the omission contingency. Half the rats in each group received infusions of vehicle into the DLS prior to this training whereas the remainder received an infusion of the GABA-A receptor agonist muscimol. On the next day, the effect of these treatments was assessed on a probe test in which the tendency of the various groups to press the lever was assessed in extinction and without drug infusion. Rats that received vehicle infusions prior to the omission session showed complete insensitivity to the newly imposed omission contingency. In contrast, rats given the infusion of muscimol selectively reduced lever pressing compared to yoked controls. Thus, extended training with interval schedules resulted in compulsive lever pressing that prevented the learning of the omission contingency, whereas inactivation of the DLS appeared to enhance the rats' sensitivity to this change in the action-outcome contingency.

Analysis of Variance↗

PubMed2005

The neural correlates of motor skill automaticity.

Acquisition of a new skill is generally associated with a decrease in the need for effortful control over performance, leading to the development of automaticity. Automaticity by definition has been achieved when performance of a primary task is minimally affected by other ongoing tasks. The neural basis of automaticity was examined by testing subjects in a serial reaction time (SRT) task under both single-task and dual-task conditions. The diminishing cost of dual-task performance was used as an index for automaticity. Subjects performed the SRT task during two functional magnetic imaging sessions separated by 3 h of behavioral training over multiple days. Behavioral data showed that, by the end of testing, subjects had automated performance of the SRT task. Before behavioral training, performance of the SRT task concurrently with the secondary task elicited activation in a wide network of frontal and striatal regions, as well as parietal lobe. After extensive behavioral training, dual-task performance showed comparatively less activity in bilateral ventral premotor regions, right middle frontal gyrus, and right caudate body; activity in other prefrontal and striatal regions decreased equally for single-task and dual-task conditions. These data suggest that lateral and dorsolateral prefrontal regions, and their corresponding striatal targets, subserve the executive processes involved in novice dual-task performance. The results also showed that supplementary motor area and putamen/globus pallidus regions showed training-related decreases for sequence conditions but not for random conditions, confirming the role of these regions in the representation of learned motor sequences.

Adult↗

PubMed2005

A dissociation of encoding and retrieval processes in the human hippocampus.

The hippocampal formation performs two related but distinct memory functions: encoding of novel information and retrieval of episodes. Little evidence, however, resolves how these two processes are implemented within the same anatomical structure. Here we use high-resolution functional magnetic resonance imaging to show that distinct subregions of the hippocampus are differentially involved in encoding and retrieval. We found that regions early in the hippocampal circuit (dentate gyrus and CA fields 2 and 3) were selectively active during episodic memory formation, whereas a region later in the circuit (the subiculum) was active during the recollection of the learning episode. Different components of the hippocampal circuit likely contribute to different degrees to the two basic memory functions.

Adult↗

PubMed2005

The role of the dorsomedial striatum in instrumental conditioning.

Considerable evidence suggests that, in instrumental conditioning, rats learn the relationship between actions and their specific consequences or outcomes. The present study examined the role of the dorsomedial striatum (DMS) in this type of learning after excitotoxic lesions and reversible, muscimol-induced inactivation. In three experiments, rats were first trained to press two levers for distinct outcomes, and then tested after training using a variety of behavioural assays that have been established to detect action-outcome learning. In Experiment 1, pre-training lesions of the posterior DMS abolished the sensitivity of rats' instrumental performance to both outcome devaluation and contingency degradation when tested in extinction, whereas lesions of the anterior DMS had no effect. In Experiment 2, both pre-training and post-training lesions of the posterior DMS were equally effective in reducing the sensitivity of performance both to devaluation and degradation treatments. In Experiment 3, the infusion of muscimol into the posterior DMS selectively abolished sensitivity of performance to devaluation and contingency degradation without impairing the ability of rats to discriminate either the instrumental actions performed or the identity of the earned outcomes. Taken together, these results suggest that the posterior region of the DMS is a crucial neural substrate for the acquisition and expression of action-outcome associations in instrumental conditioning.

Animals↗

PubMed2005

Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning.

Although there is consensus that instrumental conditioning depends on the encoding of action-outcome associations, it is not known where this learning process is localized in the brain. Recent research suggests that the posterior dorsomedial striatum (pDMS) may be the critical locus of these associations. We tested this hypothesis by examining the contribution of N-methyl-D-aspartate receptors (NMDARs) in the pDMS to action-outcome learning. Rats with bilateral cannulae in the pDMS were first trained to perform two actions (left and right lever presses), for sucrose solution. After the pre-training phase, they were given an infusion of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (APV, 1 mg/mL) or artificial cerebral spinal fluid (ACSF) before a 30-min session in which pressing one lever delivered food pellets and pressing the other delivered fruit punch. Learning during this session was tested the next day by sating the animals on either the pellets or fruit punch before assessing their performance on the two levers in extinction. The ACSF group selectively reduced responding on the lever that, in training, had earned the now devalued outcome, whereas the APV group did not. Experiment 2 replicated the effect of APV during the critical training session but found no effect of APV given after acquisition and before test. Furthermore, Experiment 3 showed that the effect of APV on instrumental learning was restricted to the pDMS; infusion into the dorsolateral striatum did not prevent learning. These experiments provide the first direct evidence that, in instrumental conditioning, NMDARs in the dorsomedial striatum are involved in encoding action-outcome associations.

2-Amino-5-phosphonovalerate↗

PubMed2004

Watching social interactions produces dorsomedial prefrontal and medial parietal BOLD fMRI signal increases compared to a resting baseline.

Some human brain areas are tonically active in a resting state when subjects are not engaged in any overt task. The activity of these areas decreases when subjects are engaged in a wide variety of laboratory tasks designed to study cognitive operations. It has been suggested that these areas, among them the medial parietal (precyneus) and the dorsomedial prefrontal cortices, may support a "default state" of the human brain. Passive visual observation of laboratory stimuli typically yields no change in activity in these default areas compared to rest. Here we report functional magnetic resonance imaging (fMRI) data on normal subjects watching realistic movie clips depicting everyday social interactions. In contrast with previous findings on default state brain areas, the observation of the relational segment of the movie clip, during which two persons interact, yielded increased activity in the medial parietal (precuneus) and dorsomedial prefrontal cortices, compared to rest and to observation of the segment of the movie clip depicting a single individual engaged in everyday activities. To the best of our knowledge, this is the first report of joint increased activity in medial parietal and dorsomedial prefrontal cortices. We suggest that the default state areas may participate in the processing of social relations in concert with regions previously identified as critical for social cognition that were also activated by our stimuli, including the inferior frontal cortex, the superior temporal cortex, and the fusiform gyrus.

Adult↗

PubMed2004

Visual feature learning in artificial grammar classification.

The Artificial Grammar Learning task has been used extensively to assess individuals' implicit learning capabilities. Previous work suggests that participants implicitly acquire rule-based knowledge as well as exemplar-specific knowledge in this task. This study investigated whether exemplar-specific knowledge acquired in this task is based on the visual features of the exemplars. When a change in the font and case occurred between study and test, there was no effect on sensitivity to grammatical rules in classification judgments. However, such a change did virtually eliminate sensitivity to training frequencies of letter bigrams and trigrams (chunk strength) in classification judgments. Performance of a secondary task during study eliminated this font sensitivity and generally reduced the contribution of chunk strength knowledge. The results are consistent with the idea that perceptual fluency makes a contribution to artificial grammar judgments.

Artificial Intelligence↗

PubMed2004

An implicit learning task activates medial temporal lobe in patients with Parkinson's disease.

Recent studies provide evidence for an interaction between a declarative memory system, dependent on the medial temporal lobe (MTL), and a habit memory system, dependent on the basal ganglia. Using functional MRI, the authors studied this interaction when 1 system was compromised by neurological disease. Neural activity when performing a habit-learning task was compared in normal controls and subjects with Parkinson's disease (PD). Patients with PD showed less activation in the caudate nucleus and greater activation in a region of prefrontal cortex that has been associated with explicit memory retrieval. Patients with PD also showed activation of the MTL during the weather-prediction task. These findings are consistent with an interaction between memory systems of the MTL and the striatum.

Basal Ganglia↗

PubMed2004

Relational integration, inhibition, and analogical reasoning in older adults.

The difficulty of reasoning tasks depends on their relational complexity, which increases with the number of relations that must be considered simultaneously to make an inference, and on the number of irrelevant items that must be inhibited. The authors examined the ability of younger and older adults to integrate multiple relations and inhibit irrelevant stimuli. Young adults performed well at all but the highest level of relational complexity, whereas older adults performed poorly even at a medium level of relational complexity, especially when irrelevant information was presented. Simulations based on a neurocomputational model of analogical reasoning, Learning and Inference with Schemas and Analogies (LISA), suggest that the observed decline in reasoning performance may be explained by a decline in attention and inhibitory functions in older adults.

Adolescent↗

PubMed2004

Relational integration and executive function in Alzheimer's disease.

Executive functions depend on the ability to represent relations between objects and events, and the prefrontal cortex provides the neural substrate for this capacity. Patients with probable Alzheimer's disease (AD) and control participants were administered measures of working memory and reasoning that varied systematically in their relational complexity. AD patients showed impairment on reasoning measures that required the online integration of relations but performed as well as control participants on nonrelational items and items requiring the processing of only single relations. When AD patients were divided into subgroups based on their performance on relational reasoning measures, the subgroup that showed significant impairment on relational integration measures exhibited a neuropsychological profile consistent with prefrontal cortical dysfunction.

Aged↗

PubMed2004

Neurologically plausible distinctions in cognition relevant to drug use etiology and prevention.

This article outlines several distinctions in cognition and related topics in emotion that receive support from work in cognitive neuroscience and have important implications for prevention: implicit cognition, working memory, nonverbal memory, and neurobiological systems of habit. These distinctions have not been widely acknowledged or applied in drug use prevention research, despite their neural plausibility and the availability of methods to make this link. The authors briefly review the basis for the distinctions and indicate general implications and assessment possibilities for prevention researchers conducting large-scale field trials. Subse-quently, the article outlines a connectionist framework for specific applications in prevention interventions. These possibilities begin the attempt to derive useful fusions of normally distinct areas of prevention and cognitive neuroscience, in the spirit of a transdisciplinary approach.

Cognition↗

PubMed2004

Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning.

Habits are controlled by antecedent stimuli rather than by goal expectancy. Interval schedules of feedback have been shown to generate habits, as revealed by the insensitivity of behaviour acquired under this schedule to outcome devaluation treatments. Two experiments were conducted to assess the role of the dorsolateral striatum in habit learning. In Experiment 1, sham operated controls and rats with dorsolateral striatum lesions were trained to press a lever for sucrose under interval schedules. After training, the sucrose was devalued by inducing taste aversion to it using lithium chloride, whereas saline injections were given to the controls. Only rats given the devaluation treatment reduced their consumption of sucrose and this reduction was similar in both the sham and the lesioned groups. All rats were then returned to the instrumental chamber for an extinction test, in which the lever was extended but no sucrose was delivered. In contrast to sham operated controls, rats with dorsolateral striatum lesions refrained from pressing the lever if the outcome was devalued. To assess the specificity of the role of dorsolateral striatum in this effect a second experiment was conducted in which a group with lesions of dorsomedial striatum was added. In relation now to both the sham and the dorsomedial lesioned groups, only rats with lesions of dorsolateral striatum significantly reduced responding after outcome devaluation. In conclusion, this study provides direct evidence that the dorsolateral striatum is necessary for habit formation. Furthermore, it suggests that, when the habit system is disrupted, control over instrumental performance reverts to the system controlling the performance of goal-directed instrumental actions.

Animals↗

PubMed2004

An event-related fMRI study of artificial grammar learning in a balanced chunk strength design.

Artificial grammar learning (Reber, 1967) is a form of implicit learning in which cognitive, rather than motor, implicit learning has been found. After viewing a series of letter strings formed according to a finite state rule system, people are able to classify new letter strings as to whether or not they are formed according to these grammatical rules despite little conscious insight into the rule structure. Previous research has shown that these classification judgments are based on knowledge of abstract rules as well as superficial similarity ("chunk strength") to training strings. Here we used event-related fMRI to identify neural regions involved in using both sources of information as test stimuli were designed to unconfound chunk strength from rule use. Using functional connectivity analyses, the extent to which the sources of information are complementary or competitive was also assessed. Activation in the right caudate was associated with rule adherence, whereas medial temporal lobe activations were associated with chunk strength. Additionally, functional connectivity analyses revealed caudate and medial temporal lobe activations to be strongly negatively correlated (r= -.88) with one another during the performance of this task.

Adult↗

PubMed2004

A neurocomputational model of analogical reasoning and its breakdown in frontotemporal lobar degeneration.

Analogy is important for learning and discovery and is considered a core component of intelligence. We present a computational account of analogical reasoning that is compatible with data we have collected from patients with cortical degeneration of either their frontal or anterior temporal cortices due to frontotemporal lobar degeneration (FTLD). These two patient groups showed different deficits in picture and verbal analogies: frontal lobe FTLD patients tended to make errors due to impairments in working memory and inhibitory abilities, whereas temporal lobe FTLD patients tended to make errors due to semantic memory loss. Using the "Learning and Inference with Schemas and Analogies" model, we provide a specific account of how such deficits may arise within neural networks supporting analogical problem solving.

Aged↗

PubMed2003

Working memory and relational reasoning in Klinefelter syndrome.

Klinefelter syndrome (KS) is a sex chromosome abnormality associated with male infertility and mild cognitive deficits. Individuals with KS have been reported to have impaired verbal ability, as well as deficits in executive function. To further understand the nature of their deficits, we assessed specific elements of frontal lobe function such as working memory and relational reasoning. Men with KS exhibited a deficit in a transitive inference task in which participants ordered a set of names based on a list of propositions about the relative heights of the people named. This deficit was present even for items in which the propositions were given in order, so a chaining strategy could be used. Men with KS are also impaired on the n-back task, which uses letters as stimuli. In contrast, these men performed as well as controls in nonverbal reasoning (Raven's Progressive Matrices). These results suggest that men with KS have intact nonverbal reasoning abilities, but that a difficulty in encoding verbal information into working memory may underlie their executive and linguistic impairments.

Adult↗

PubMed2002

Learning and memory functions of the Basal Ganglia.

Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

Animals↗