Age-related deficits in component processes of working memory., 2007 Sep.
Neuropsychology. 21:532-9. Abstract
Working memory deficits in normal aging have been well documented, and studies suggest that high memory load plus the presence of distraction negatively impacts successful memory performance to a greater degree in older individuals. However, characterization of the component processes that are impaired by these task manipulations is not clear. In this behavioral study, younger and older subjects were tested with a delayed-recognition and recall task in which the encoding and delay period were both manipulated. During the encoding period, the subjects were presented with either a single letter or multiple letters at their predetermined forward letter span, and the delay period was either uninterrupted or interrupted with a visual distraction. There was an age-related impairment of working memory recognition accuracy only in the combination of high memory load and distraction. These results suggest that when working memory maintenance systems are taxed, faulty recognition processes may underlie cognitive aging deficits in healthy older individuals.
Distinct mechanisms in visual category learning., 2007 Sep.
Cognitive, affective & behavioral neuroscience. 7:251-9. Abstract
The ways in which visual categories are learned, and in which well-established categories are represented and retrieved, are fundamental issues of cognitive neuroscience. Researchers have typically studied these issues separately, and the transition from the initial phase of category learning to expertise is poorly characterized. The acquisition of novel categories has been shown to depend on the striatum, hippocampus, and prefrontal cortex, whereas visual category expertise has been shown to involve changes in inferior temporal cortex. The goal of the present experiment is to understand the respective roles of these brain regions in the transition from initial learning to expertise when category judgments are being made. Subjects were explicitly trained, over 2 days, to classify realistic faces. Subjects then performed the categorization task during fMRI scanning, as well as a perceptual matching task, in order to characterize how brain regions respond to these faces when not explicitly categorizing them. We found that, during face categorization, face-selective inferotemporal cortex, lateral prefrontal cortex, and dorsal striatum are more responsive to faces near the category boundary, which are most difficult to categorize. In contrast, the hippocampus and left superior frontal sulcus responded most to faces farthest from the category boundary. These dissociable effects suggest that there are several distinct neural mechanisms involved in categorization, and provide a framework for understanding the contribution of each of these brain regions in categorization.
Functional interactions between prefrontal and visual association cortex contribute to top-down modulation of visual processing., 2007 Sep.
Cerebral cortex (New York, N.Y. : 1991). 17 Suppl 1:i125-35. Abstract
Attention-dependent modulation of neural activity in visual association cortex (VAC) is thought to depend on top-down modulatory control signals emanating from the prefrontal cortex (PFC). In a previous functional magnetic resonance imaging study utilizing a working memory task, we demonstrated that activity levels in scene-selective VAC (ssVAC) regions can be enhanced above or suppressed below a passive viewing baseline level depending on whether scene stimuli were attended or ignored (Gazzaley, Cooney, McEvoy, et al. 2005). Here, we use functional connectivity analysis to identify possible sources of these modulatory influences by examining how network interactions with VAC are influenced by attentional goals at the time of encoding. Our findings reveal a network of regions that exhibit strong positive correlations with a ssVAC seed during all task conditions, including foci in the left middle frontal gyrus (MFG). This PFC region is more correlated with the VAC seed when scenes were remembered and less correlated when scenes were ignored, relative to passive viewing. Moreover, the strength of MFG-VAC coupling correlates with the magnitude of attentional enhancement and suppression of VAC activity. Although our correlation analyses do not permit assessment of directionality, these findings suggest that PFC biases activity levels in VAC by adjusting the strength of functional coupling in accordance with stimulus relevance.
Reducing vascular variability of fMRI data across aging populations using a breathholding task., 2007 Sep.
Human brain mapping. 28:846-59. Abstract
The magnitude and shape of blood oxygen level-dependent (BOLD) responses in functional MRI (fMRI) studies vary across brain regions, subjects, and populations. This variability may be secondary to neural activity or vasculature differences, thus complicating interpretations of BOLD signal changes in fMRI experiments. We compare the BOLD responses to neural activity and a vascular challenge and test a method to dissociate these influences in 26 younger subjects (ages 18-36) and 24 older subjects (ages 51-78). Each subject performed a visuomotor saccade task (a vascular response to neural activity) and a breathholding task (vascular dilation induced by hypercapnia) during separate runs in the same scanning session. For the saccade task, signal magnitude showed a significant decrease with aging in FEF, SEF, and V1, and a delayed time-to-peak with aging in V1. The signal magnitudes from the saccade and hypercapnia tasks showed significant linear regressions within subjects and across individuals and populations. These two tasks had weaker, but sometimes significant linear regressions for time-to-peak and coherence phase measures. The significant magnitude decrease with aging in V1 remained after dividing the saccade task magnitude by the hypercapnia task magnitude, implying that the signal decrease is neural in origin. These findings may lead to a method to identify vascular reactivity-induced differences in the BOLD response across populations and the development of methods to account for the influence of these vasculature differences in a simple, noninvasive manner.
Efficiency of the prefrontal cortex during working memory in attention-deficit/hyperactivity disorder., 2007 Oct.
Journal of the American Academy of Child and Adolescent Psychiatry. 46:1357-66. Abstract
OBJECTIVE: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical (PFC) activation compared to age-matched control participants. This pattern may reflect cortical inefficiency. We examined this hypothesis using a working memory task in a group of adolescent girls with and without ADHD. METHOD: Functional magnetic resonance imaging was used to investigate blood oxygenated level-dependent signal during a working memory task for 10 adolescents from each group, ages 11 to 17 years. We analyzed brain-behavior relationships with anatomically defined regions of interest in the PFC and primary motor cortex. RESULTS: The relationship between brain activity in the dorsolateral PFC and ventrolateral PFC and memory retrieval speed differed by group membership, whereby comparison girls had a more efficient brain-behavior relationship than girls with ADHD. There were no such group differences in brain-behavior relationships for primary motor cortex. CONCLUSIONS: These findings lend support to the idea that cognitive and behavioral deficits experienced by children and adolescents with ADHD may in part be related to relatively low efficiency of PFC function.
Regional specificity and practice: dynamic changes in object and spatial working memory., 2007 Nov 14.
Brain research. 1180:78-89. Abstract
Working memory (WM) tasks engage a network of brain regions that includes primary, unimodal, and multimodal associative cortices. Little is known, however, about whether task practice influences these types of regions differently. In this experiment, we used event-related fMRI to examine practice-related activation changes in different region types over the course of a scanning session while participants performed a delayed-recognition task. The task contained separate WM processing stages (encoding, maintenance, retrieval) and different materials (object, spatial), which allowed us to investigate the influence of practice on different component processes. We observed significant monotonic decreases, and not increases, in fMRI signal primarily in unimodal and multimodal regions. These decreases occurred during WM encoding and retrieval, but not during maintenance. Finally, regions specific to the type of memoranda (e.g., spatial or object) showed a lesser degree of sensitivity to practice as compared to regions activated by both types of memoranda, suggesting that these regions may be specialized more for carrying out processing within a particular modality than for experience-related flexibility. Overall, these findings indicate that task practice does not have a uniform effect on stages of WM processing, the type of WM memoranda being processed or on different types of brain regions. Instead, regions engaged during WM encoding and retrieval may have greater capacity for functional plasticity than WM maintenance. Additionally, the degree of specialization within brain regions may determine processing efficiency. Unimodal and multimodal regions that participate in both object and spatial processing may be specialized for flexible experience-related change, while those supporting primary sensorimotor processing may operate at optimal efficiency and are less susceptible to practice.
Functional plasticity in ventral temporal cortex following cognitive rehabilitation of a congenital prosopagnosic., 2007 Nov.
Journal of cognitive neuroscience. 19:1790-802. Abstract
We used functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to measure neural changes associated with training configural processing in congenital prosopagnosia, a condition in which face identification abilities are not properly developed in the absence of brain injury or visual problems. We designed a task that required discriminating faces by their spatial configuration and, after extensive training, prosopagnosic MZ significantly improved at face identification. Event-related potential results revealed that although the N170 was not selective for faces before training, its selectivity after training was normal. fMRI demonstrated increased functional connectivity between ventral occipital temporal face-selective regions (right occipital face area and right fusiform face area) that accompanied improvement in face recognition. Several other regions showed fMRI activity changes with training; the majority of these regions increased connectivity with face-selective regions. Together, the neural mechanisms associated with face recognition improvements involved strengthening early face-selective mechanisms and increased coordination between face-selective and nonselective regions, particularly in the right hemisphere.
Neurocognitive inefficacy of the strategy process., 2007 Nov.
Annals of the New York Academy of Sciences. 1118:163-85. Abstract
The most widely used (and taught) protocols for strategic analysis-Strengths, Weaknesses, Opportunities, and Threats (SWOT) and Porter’s (1980) Five Force Framework for industry analysis-have been found to be insufficient as stimuli for strategy creation or even as a basis for further strategy development. We approach this problem from a neurocognitive perspective. We see profound incompatibilities between the cognitive process-deductive reasoning-channeled into the collective mind of strategists within the formal planning process through its tools of strategic analysis (i.e., rational technologies) and the essentially inductive reasoning process actually needed to address ill-defined, complex strategic situations. Thus, strategic analysis protocols that may appear to be and, indeed, are entirely rational and logical are not interpretable as such at the neuronal substrate level where thinking takes place. The analytical structure (or propositional representation) of these tools results in a mental dead end, the phenomenon known in cognitive psychology as functional fixedness. The difficulty lies with the inability of the brain to make out meaningful (i.e., strategy-provoking) stimuli from the mental images (or depictive representations) generated by strategic analysis tools. We propose decreasing dependence on these tools and conducting further research employing brain imaging technology to explore complex data handling protocols with richer mental representation and greater potential for strategy creation.
From cognitive to neural models of working memory., 2007 May 29.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 362:761-72. Abstract
Working memory refers to the temporary retention of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be stored for longer periods of time through active maintenance or rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behaviour. Empirical studies of working memory using neuroscientific techniques, such as neuronal recordings in monkeys or functional neuroimaging in humans, have advanced our knowledge of the underlying neural mechanisms of working memory. This rich dataset can be reconciled with behavioural findings derived from investigating the cognitive mechanisms underlying working memory. In this paper, I review the progress that has been made towards this effort by illustrating how investigations of the neural mechanisms underlying working memory can be influenced by cognitive models and, in turn, how cognitive models can be shaped and modified by neuroscientific data. One conclusion that arises from this research is that working memory can be viewed as neither a unitary nor a dedicated system. A network of brain regions, including the prefrontal cortex (PFC), is critical for the active maintenance of internal representations that are necessary for goal-directed behaviour. Thus, working memory is not localized to a single brain region but probably is an emergent property of the functional interactions between the PFC and the rest of the brain.
Impulsive personality predicts dopamine-dependent changes in frontostriatal activity during component processes of working memory., 2007 May 16.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 27:5506-14. Abstract
Dopaminergic drugs affect a variety of cognitive processes, but the direction and extent of effects vary across individuals and tasks. Paradoxical effects are observed, by which the same drug causes cognitive enhancing as well as adverse effects. Here, we demonstrate that individual differences in impulsive personality account for the contrasting effects of dopaminergic drugs on working memory and associated frontostriatal activity. We observed that the dopamine D2 receptor agonist bromocriptine improved the flexible updating (switching) of relevant information in working memory in high-impulsive subjects, but not in low-impulsive subjects. These behavioral effects in high-impulsive subjects accompanied dissociable effects on frontostriatal activity. Bromocriptine modulated the striatum during switching but not during distraction from relevant information in working memory. Conversely, the lateral frontal cortex was modulated by bromocriptine during distraction but not during switching. The present results provide a key link between dopamine D2 receptor function, impulsivity, and frontostriatal activity during component processes of working memory.
Functional connectivity of cortical networks involved in bimanual motor sequence learning., 2007 May.
Cerebral cortex (New York, N.Y. : 1991). 17:1227-34. Abstract
Motor skill learning requires the involvement and integration of several cortical and subcortical regions. In this study, we focus on how the functional connectivity of cortical networks changes with the acquisition of a novel motor skill. Using functional magnetic resonance imaging, we measured the localized blood oxygenation level-dependent (BOLD) signal in cortical regions while subjects performed a bimanual serial reaction time task under 2 conditions: 1) explicitly learning a novel sequence (NOVEL) and 2) playing a previously learned sequence (LEARNED). To investigate stages of learning, each condition was further divided into nonoverlapping early and late conditions. Functional connectivity was measured using a task-specific low-frequency coherence analysis of the data. We show that within the cortical motor network, the sensorimotor cortex, premotor cortex, and supplementary motor area have significantly greater inter- and intrahemispheric coupling during the early NOVEL condition compared with the late NOVEL condition. Additionally, we observed greater connectivity between frontal regions and cortical motor regions in the early versus late NOVEL contrast. No changes in functional connectivity were observed in the LEARNED condition. These results demonstrate that the functional connectivity of the cortical motor network is modulated with practice and suggest that early skill learning is mediated by enhanced interregional coupling.
Selection and maintenance of stimulus-response rules during preparation and performance of a spatial choice-reaction task., 2007 Mar 9.
Brain research. 1136:77-87. Abstract
The ability to select an appropriate response among competing alternatives is a fundamental requirement for successful performance of a variety of everyday tasks. Recent research suggests that a frontal-parietal network of brain regions (including dorsal prefrontal, dorsal premotor and superior parietal cortices) mediate response selection for spatial material. Most of this research has used blocked experimental designs. Thus, the frontal-parietal activity reported may be due either to tonic activity across a block or to processing occurring at the trial level. Our current event-related fMRI study investigated response selection at the level of the trial in order to identify possible response selection sub-processes. In the study, participants responded to a visually presented stimulus with either a spatially compatible or incompatible manual response. On some trials, several seconds prior to stimulus onset, a cue indicated which task was to be performed. In this way we could identify separate brain regions for task preparation and task performance, if they exist. Our results showed that the frontal-parietal network for spatial response selection activated both during task preparation as well as during task performance. We found no evidence for preparation specific brain mechanisms in this task. These data suggest that spatial response selection and response preparation processes rely on the same neurocognitive mechanisms.
Too many trees to see the forest: performance, event-related potential, and functional magnetic resonance imaging manifestations of integrative congenital prosopagnosia., 2007 Jan.
Journal of cognitive neuroscience. 19:132-46. Abstract
Neuropsychological, event-related potential (ERP), and functional magnetic resonance imaging (fMRI) methods were combined to provide a comprehensive description of performance and neurobiological profiles for K.W., a case of congenital prosopagnosia. We demonstrate that K.W.’s visual perception is characterized by almost unprecedented inability to identify faces, a large bias toward local features, and an extreme deficit in global/configural processing that is not confined to faces. This pattern could be appropriately labeled congenital integrative prosopagnosia, and accounts for some, albeit not all, cases of face recognition impairments without identifiable brain lesions. Absence of face selectivity is evident in both biological markers of face processing, fMRI (the fusiform face area [FFA]), and ERPs (N170). Nevertheless, these two neural signatures probably manifest different perceptual mechanisms. Whereas the N170 is triggered by the occurrence of physiognomic stimuli in the visual field, the deficient face-selective fMRI activation in the caudal brain correlates with the severity of global processing deficits. This correlation suggests that the FFA might be associated with global/configural computation, a crucial part of face identification.
Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls., 2007 Feb.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 32:439-49. Abstract
The opioid receptor antagonist naltrexone (NTX) is one of few approved treatments for alcoholism, yet the mechanism by which it reduces drinking remains unclear. In rats, NTX reduces morphine-induced impulsive choice bias; however, nothing is known about the drug’s effect on discrete aspects of impulsive behavior in humans, such as decision-making and inhibitory control. Here, we used a modified delay discounting procedure to investigate whether NTX improves decision-making or inhibitory control in humans. We measured the effect of acute NTX (50 mg) on choice between smaller sooner (SS) and larger later monetary rewards and on response errors (motor mismatch) in a high conflict condition in a group of abstinent alcoholics (AA) and healthy control subjects (CS). We previously reported that AA selected the SS option significantly more often than did CS in this paradigm. If the choice bias of AA is due to enhanced endogenous opioid signaling in response to potential reward, NTX should reduce such bias in the AA group. We found that NTX did not reliably reduce impulsive choice in the AA group; however, NTX’s effect on choice bias across individuals was robustly predictable. NTX’s effect on choice bias was significantly correlated with scores on Rotter’s Locus of Control (LOC) scale; increasingly internal LOC scores predicted increasing likelihood of impulsive choices on NTX. In addition, we found that NTX significantly enhanced control of motor responses, particularly within the CS group. These results suggest that endogenous opioids may impair response selection during decision-making under conflict, and that NTX’s effects on explicit decision-making are personality-dependent. Determining the biological basis of this dependence could have important implications for effective alcoholism treatment.
Top-down modulation and normal aging., 2007 Feb.
Annals of the New York Academy of Sciences. 1097:67-83. Abstract
Normal aging is characterized by cognitive deficits that cross multiple domains and impair the ability of some older individuals to lead productive, high-quality lives. One of the primary goals of research in our laboratories is to study age-related alterations in neural mechanisms that underlie a wide range of cognitive processes so that we may generate a unifying principle of cognitive aging. Top-down modulation is the mechanism by which we enhance neural activity associated with relevant information and suppress activity for irrelevant information, thus establishing a foundation for both attention and memory processes. We use three converging technologies of human neurophysiology to study top-down modulation in aging: functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and transcranial magnetic stimulation (TMS). Using these tools we have discovered that healthy older adults exhibit a selective inability to effectively suppress neural activity associated with distracting information and that this top-down suppression deficit is correlated with their memory impairment. We are now further characterizing the basis of these age-related alterations in top-down modulation and investigating interventions to remedy them.
Immediate reward bias in humans: fronto-parietal networks and a role for the catechol-O-methyltransferase 158(Val/Val) genotype., 2007 Dec 26.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 27:14383-91. Abstract
The tendency to choose lesser immediate benefits over greater long-term benefits characterizes alcoholism and other addictive disorders. However, despite its medical and socioeconomic importance, little is known about its neurobiological mechanisms. Brain regions that are activated when deciding between immediate or delayed rewards have been identified (McClure et al., 2004, 2007), as have areas in which responses to reward stimuli predict a paper-and-pencil measure of temporal discounting (Hariri et al., 2006). These studies assume "hot" and "cool" response selection systems, with the hot system proposed to generate impulsive choices in the presence of a proximate reward. However, to date, brain regions in which the magnitude of activity during decision making reliably predicts intertemporal choice behavior have not been identified. Here we address this question in sober alcoholics and non-substance-abusing control subjects and show that immediate reward bias directly scales with the magnitude of functional magnetic resonance imaging bold oxygen level-dependent (BOLD) signal during decision making at sites within the posterior parietal cortex (PPC), dorsal prefrontal cortex (dPFC), and rostral parahippocampal gyrus regions. Conversely, the tendency of an individual to wait for a larger, delayed reward correlates directly with BOLD signal in the lateral orbitofrontal cortex. In addition, genotype at the Val158Met polymorphism of the catechol-O-methyltransferase gene predicts both impulsive choice behavior and activity levels in the dPFC and PPC during decision making. These genotype effects remained significant after controlling for alcohol abuse history. These results shed new light on the neurobiological underpinnings of temporal discounting behavior and identify novel behavioral and neural consequences of genetic variation in dopamine metabolism.
Segregation of function in the lateral prefrontal cortex during visual object working memory., 2007 Dec 12.
Brain research. 1184:217-25. Abstract
Working memory is a set of cognitive operations facilitating higher order cognition and complex behavior. A particularly important aspect of working memory is the linkage of past sensory events to planned actions. While the lateral prefrontal cortex has been proposed to serve this temporal integrative function, the precise mapping of specific components of this process within the lateral prefrontal cortex has yet to be clarified. In this human fMRI experiment, we employed a paradigm that segregates retrospective sensory maintenance from prospective action planning processes. Our results suggest that the ventrolateral PFC supports retrospective sensory representations while the dorsolateral PFC supports prospective action representations.
Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex., 2007 Dec.
Journal of cognitive neuroscience. 19:2082-99. Abstract
The prefrontal cortex (PFC) is central to flexible and organized action. Recent theoretical and empirical results suggest that the rostro-caudal axis of the frontal lobes may reflect a hierarchical organization of control. Here, we test whether the rostro-caudal axis of the PFC is organized hierarchically, based on the level of abstraction at which multiple representations compete to guide selection of action. Four functional magnetic resonance imaging (fMRI) experiments parametrically manipulated the set of task-relevant (a) responses, (b) features, (c) dimensions, and (d) overlapping cue-to-dimension mappings. A systematic posterior to anterior gradient was evident within the PFC depending on the manipulated level of representation. Furthermore, across four fMRI experiments, activation in PFC subregions was consistent with the sub- and superordinate relationships that define an abstract representational hierarchy. In addition to providing further support for a representational hierarchy account of the rostro-caudal gradient in the PFC, these data provide important empirical constraints on current theorizing about control hierarchies and the PFC.
Reward modulation of prefrontal and visual association cortex during an incentive working memory task., 2007 Apr 13.
Brain research. 1141:168-77. Abstract
Cognitive performance differs with motivation, but little direct evidence exists regarding the neural mechanisms of the influence of reward motivation on working memory (WM). We tested the effects of motivation on the top-down control in visual WM. Encoding relevant stimuli for maintenance, while suppressing inappropriate inputs is considered a core process in cognition. Prior functional magnetic resonance imaging (fMRI) results demonstrated that stimulus-specific visual association cortex serves as a marker of activation differences for task-relevant and task-irrelevant inputs, such that enhanced activity occurs when attention is directed to relevant stimuli and suppressed activity occurs when attention is directed away from irrelevant stimuli [Gazzaley, A., Cooney, J., McEvoy, K., Knight, R.T., and D’Esposito, M. J. Cogn. Neurosci. 17, 507-517]. We used fMRI to test whether differential WM performance, indexed by lowered response times on a delayed-recognition task, was associated with amplification of enhancement and suppression effects during stimulus encoding within visual association cortex. Our results indicate that enhancement and suppression are amplified for trials with the highest reward level relative to non-rewarded trials for a scene-selective cortical region. In a face-selective region, similar modulation of enhancement for the highest reward level relative to non-rewarded trials was found. Prefrontal cortex also showed enhanced activity during high reward trials. Overall these results reveal that reward motivation can play a pivotal role in driving performance through top-down signaling in frontal regions involved in WM, as well as visual association regions selective to processing the perceptual inputs of the items to be remembered.