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T S Braver

Publications and source records attributed to T S Braver.

13 recordsLinked to original sources
PubMed2001

Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia.

BACKGROUND: Previously we proposed that dorsolateral prefrontal cortex (PFC) supports a specific working memory (WM) subcomponent: the ability to represent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented in such a form that it supports selection of the appropriate behavioral response. Furthermore, we hypothesized that WM deficits in schizophrenia reflect impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medication-naive, first-episode patients with schizophrenia during a WM, task-isolating context processing. METHODS: Fourteen first-episode, medication-naive patients with schizophrenia and 12 controls similar in age, sex, and parental education underwent functional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test. RESULTS: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed intact activation of posterior and inferior PFC. In addition, patients demonstrated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands. CONCLUSIONS: These results demonstrate selectivity in dorsolateral PFC dysfunction among medication-naive first-episode patients with schizophrenia, suggesting that a specific deficit in PFC function is present at illness onset, prior to the administration of medication or the most confounding effects of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impairment in context processing due to a disturbance in dorsolateral PFC function.

Adult↗
PubMed2001

Sensitivity of prefrontal cortex to changes in target probability: a functional MRI study.

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right-handed adults were scanned using a gradient-echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but "X". The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability.

Adolescent↗
PubMed2000

Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex.

Investigations of working memory (WM) systems in the frontal cortex have revealed two stimulus dimensions along which frontal cortical representations may be functionally organized. One hypothesized dimension dissociates verbal from nonverbal WM processes, dividing left from right frontal regions. The second hypothesized dimension dissociates spatial from nonspatial WM, dividing dorsal from ventral frontal regions. Here we used functional magnetic resonance imaging to probe WM processes associated with three different types of stimuli: letters (verbal and nonspatial), abstract shapes (nonverbal and nonspatial), and locations (nonverbal and spatial). In a series of three experiments using the "n-back" WM paradigm, direct statistical comparisons were made between activation patterns in each pairwise combination of the three stimulus types. Across the experiments, no regions that demonstrated responses to WM manipulations were discovered to be unique to any of the three stimulus types. Therefore, no evidence was found to support either a left/right verbal/nonverbal dissociation or a dorsal/ventral spatial/nonspatial dissociation. While this could reflect a limitation of the present behavioral and imaging techniques, other factors that could account for the data are considered, including subjects' strategy selection, encoding of information into WM, and the nature of representational schemes in prefrontal cortex.

Adolescent↗
PubMed2000

Anterior cingulate and the monitoriing of response conflict: evidence from an fMRI study of overt verb generation.

Studies of a range of higher cognitive functions consistently activate a region of anterior cingulate cortex (ACC), typically posterior to the genu and superior to the corpus collosum. In particular, this ACC region appears to be active in task situations where there is a need to override a prepotent response tendency, when responding is underdetermined, and when errors are made. We have hypothesized that the function of this ACC region is to monitor for the presence of "crosstalk" or competition between incompatible responses. In prior work, we provided initial support for this hypothesis, demonstrating ACC activity in the same region both during error trials and during correct trials in task conditions designed to elicit greater response competition. In the present study, we extend our testing of this hypothesis to task situations involving underdetermined responding. Specifically, 14 healthy control subjects performed a verb-generation task during event-related functional magnetic resonance imaging (fMRI), with the on-line acquisition of overt verbal responses. The results demonstrated that the ACC, and only the ACC, was more active in a series of task conditions that elicited competition among alternative responses. These conditions included a greater ACC response to: (1) Nouns categorized as low vs. high constraint (i.e., during a norming study, multiple verbs were produced with equal frequency vs. a single verb that produced much more frequently than any other); (2) the production of verbs that were weak associates, rather than, strong associates of particular nouns; and (3) the production of verbs that were weak associates for nouns categorized as high constraint. We discuss the implication of these results for understanding the role that the ACC plays in human cognition.

Adolescent↗
PubMed1999

Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function.

Behavioral deficits suffered by patients with schizophrenia in a wide array of cognitive domains can be conceptualized as failures of cognitive control, due to an impaired ability to internally represent, maintain, and update context information. A theory is described that postulates a single neurobiological mechanism for these disturbances, involving dysfunctional interactions between the dopamine neurotransmitter system and the prefrontal cortex. Specifically, it is hypothesized that in schizophrenia, there is increased noise in the activity of the dopamine system, leading to abnormal "gating" of information into prefrontal cortex. The theory is implemented as an explicit connectionist computational model that incorporates the roles of both dopamine and prefrontal cortex in cognitive control. A simulation is presented of behavioral performance in a version of the Continuous Performance Test specifically adapted to measure critical aspects of cognitive control function. Schizophrenia patients exhibit clear behavioral deficits on this task that reflect impairments in both the maintenance and updating of context information. The simulation results suggest that the model can successfully account for these impairments in terms of abnormal dopamine activity. This theory provides a potential point of contact between research on the neurobiological and psychological aspects of schizophrenia, by illustrating how a particular physiological disturbance might lead to precise and quantifiable consequences for behavior.

Cognition Disorders↗
PubMed1999

Overt verbal responding during fMRI scanning: empirical investigations of problems and potential solutions.

This paper presents a pair of studies designed to empirically explore the severity of potential artifacts associated with overt verbal responding during fMRI scanning and to examine several different solutions to these artifacts. In Study One, we compared susceptibility artifacts, signal-to-noise ratios, and activation patterns when overt versus covert verbal responses were elicited during fMRI scanning, using both individual and group analyses. The results indicated that different patterns of brain activation were elicited during covert as compared to overt verbal responses. This suggests that covert responses cannot be used as a simple substitute for overt verbal responses. Further, the results suggested that the use of overt verbal responses during fMRI scanning can produce interpretable results if: (1) the primary comparison is between two conditions that both use overt verbal responses, and (2) analyses are conducted on pooled group data rather than individual participant data. In Study Two, we evaluated the feasibility and validity of a method for acquiring participants' overt responses during fMRI scanning. The results indicated that our method was very accurate in acquiring the content of participant's responses. Further, inspection of the responses demonstrated that participants do not always comply with task instructions and highlighted the importance of obtaining behavioral performance measures during fMRI scanning.

Adult↗
PubMed1998

Anterior cingulate cortex, error detection, and the online monitoring of performance.

An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.

Brain Mapping↗
PubMed1997

Temporal dynamics of brain activation during a working memory task.

Working memory is responsible for the short-term storage and online manipulation of information necessary for higher cognitive functions, such as language, planning and problem-solving. Traditionally, working memory has been divided into two types of processes: executive control (governing the encoding manipulation and retrieval of information in working memory) and active maintenance (keeping information available 'online'). It has also been proposed that these two types of processes may be subserved by distinct cortical structures, with the prefrontal cortex housing the executive control processes, and more posterior regions housing the content-specific buffers (for example verbal versus visuospatial) responsible for active maintenance. However, studies in non-human primates suggest that dorsolateral regions of the prefrontal cortex may also be involved in active maintenance. We have used functional magnetic resonance imaging to examine brain activation in human subjects during performance of a working memory task. We used the temporal resolution of this technique to examine the dynamics of regional activation, and to show that prefrontal cortex along with parietal cortex appears to play a role in active maintenance.

Adult↗
PubMed1997

A parametric study of prefrontal cortex involvement in human working memory.

Although recent neuroimaging studies suggest that prefrontal cortex (PFC) is involved in working memory (WM), the relationship between PFC activity and memory load has not yet been well-described in humans. Here we use functional magnetic resonance imaging (fMRI) to probe PFC activity during a sequential letter task in which memory load was varied in an incremental fashion. In all nine subjects studied, dorsolateral and left inferior regions of PFC were identified that exhibited a linear relationship between activity and WM load. Furthermore, these same regions were independently identified through direct correlations of the fMRI signal with a behavioral measure that indexes WM function during task performance. A second experiment, using whole-brain imaging techniques, both replicated these findings and identified additional brain regions showing a linear relationship with load, suggesting a distributed circuit that participates with PFC in subserving WM. Taken together, these results provide a "dose-response curve" describing the involvement of both PFC and related brain regions in WM function, and highlight the benefits of using graded, parametric designs in neuroimaging research.

Adolescent↗
PubMed1997

Dissociating working memory from task difficulty in human prefrontal cortex.

A functional magnetic resonance imaging (fMRI) study was conducted to determine whether prefrontal cortex (PFC) increases activity in working memory (WM) tasks as a specific result of the demands placed on WM, or to other processes affected by the greater difficulty of such tasks. Increased activity in dorsolateral PFC (DLPFC) was observed during task conditions that placed demands on active maintenance (long retention interval) relative to control conditions matched for difficulty. Furthermore, the activity was sustained over the entire retention interval and did not increase when task difficulty was manipulated independently of WM requirements. This contrasted with the transient increases in activity observed in the anterior cingulate, and other regions of frontal cortex, in response to increased task difficulty but not WM demands. Thus, this study established a double-dissociation between regions responsive to WM versus task difficulty, indicating a specific involvement of DLPFC and related structures in WM function.

Adult↗
PubMed1997

Issues concerning relative speed of processing hypotheses, schizophrenic performance deficits, and prefrontal function: comment on Schooler et al. (1997)

The authors have found the data presented in the C. Schooler, E. Neumann, L. J. Caplan, and B. R. Roberts (1997) article to be interesting and of potential value in constraining the further development of detailed theoretical models of Stroop performance. However, the authors have found that the relative speed of processing account of stimulus onset asynchrony (SOA) effects given by Schooler et al. in Experiment 1 fails to address several important and vexing issues faced by such accounts, which have been highlighted by existing formal models. The authors also have expressed concerns about Schooler et al.'s, interpretation of the reduction in Stroop interference observed among individuals with schizophrenia in Experiment 2. Whereas the authors have acknowledged that it is plausible to relate this to a dysfunction of prefrontal cortex, they have pointed to equally plausible alternative explanations, which are not addressed by the experiment or in the discussion in the Schooler et al. article.

Attention↗
PubMed1996

A computational approach to prefrontal cortex, cognitive control and schizophrenia: recent developments and current challenges.

In this chapter we consider the mechanisms involved in cognitive control-from both a computational and a neurobiological perspective- and how these might be impaired in schizophrenia. By 'control', we mean the ability of the cognitive system to flexibly adapt its behaviour to the demands of particular tasks, favouring the processing of task-relevant information over other sources of competing information, and mediating task-relevant behaviour over habitual, or otherwise prepotent responses. There is a large body of evidence to suggest that the prefrontal cortex (PFC) plays a critical role in cognitive control. In previous work, we have used a computational framework to understand and develop explicit models of this function of PFC, and its impairment in schizophrenia. This work has lead to the hypothesis that PFC houses a mechanism for representing and maintaining context information. We have demonstrated that this mechanism can account for the behavioural inhibition and active memory functions commonly ascribed to PFC, and for human performance in simple attention, language and memory tasks that draw upon these functions for cognitive control. Furthermore, we have used our models to simulate detailed patterns of cognitive deficit observed in schizophrenia, an illness associated with marked disturbances in cognitive control, and well established deficits of PFC. Here, we review results of recent empirical studies that test predictions made by our models regarding schizophrenic performance in tasks designed specifically to probe the processing of context. These results showed selective schizophrenic deficits in tasks conditions that placed the greatest demands on memory and inhibition, both of which we have argued rely on the processing of context. Furthermore, we observed predicted patterns of deterioration in first episode vs multi-episode patients. We also discuss recent developments in our computational work, that have led to refinements of the models that allow us to simulate more detailed aspects of task performance, such as reaction time data and manipulations of task parameters such as interstimulus delay. These refined models make several provocative new predictions, including conditions in which schizophrenics and control subjects are expected to show similar reaction time performance, and we provide preliminary data in support of these predictions. These successes notwithstanding, our theory of PFC function and its impairment in schizophrenia is still in an early stage of development. We conclude by presenting some of the challenges to the theory in its current form, and new directions that we have begun to take to meet these challenges. In particular, we focus on refinements concerning the mechanisms underlying active maintenance of representations within PFC, and the characteristics of these representations that allow them to support the flexibility of cognitive control exhibited by normal human behaviour. Taken in toto, we believe that this work illustrates the value of a computational approach for understanding the mechanisms responsible for cognitive control, at both the neural and psychological levels, and the specific manner in which they break down in schizophrenia.

Cognition↗