Showing papers on "Working memory published in 1997"

Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD.

Abstract: Attention deficit hyperactivity disorder (ADHD) comprises a deficit in behavioral inhibition. A theoretical model is constructed that links inhibition to 4 executive neuropsychological functions that appear to depend on it for their effective execution: (a) working memory, (b) self-regulation of affect-motivation-arousal, (c) internalization of speech, and (d) reconstitution (behavioral analysis and synthesis). Extended to ADHD, the model predicts that ADHD should be associated with secondary impairments in these 4 executive abilities and the motor control they afford. The author reviews evidence for each of these domains of functioning and finds it to be strongest for deficits in behavioral inhibition, working memory, regulation of motivation, and motor control in those with ADHD. Although the model is promising as a potential theory of self-control and ADHD, far more research is required to evaluate its merits and the many predictions it makes about ADHD.

The capacity of visual working memory for features and conjunctions

Abstract: Short-term memory storage can be divided into separate subsystems for verbal information and visual information, and recent studies have begun to delineate the neural substrates of these working-memory systems. Although the verbal storage system has been well characterized, the storage capacity of visual working memory has not yet been established for simple, suprathreshold features or for conjunctions of features. Here we demonstrate that it is possible to retain information about only four colours or orientations in visual working memory at one time. However, it is also possible to retain both the colour and the orientation of four objects, indicating that visual working memory stores integrated objects rather than individual features. Indeed, objects defined by a conjunction of four features can be retained in working memory just as well as single-feature objects, allowing sixteen individual features to be retained when distributed across four objects. Thus, the capacity of visual working memory must be understood in terms of integrated objects rather than individual features, which places significant constraints on cognitive and neurobiological models of the temporary storage of visual information.

The prefrontal cortex

Abstract: The Prefrontal Cortex, Fifth Edition, provides users with a thoroughly updated version of this comprehensive work that has historically served as the classic reference on this part of the brain. The book offers a unifying, interdisciplinary perspective that is lacking in other volumes written about the frontal lobes, and is, once again, written by the award-winning author who discovered "memory cells," the physiological substrate of working memory. The fifth edition constitutes a comprehensive update, including all the major advances made on the physiology and cognitive neuroscience of the region since publication in 2008. All chapters have been fully revised, and the overview of prefrontal functions now interprets experimental data within the theoretical framework of the new paradigm of cortical structure and dynamics (the Cognit Paradigm), addressing the accompanying social, economic, and cultural implications. * Provides a distinctly interdisciplinary view of the prefrontal cortex, covering all major methodologies, from comparative anatomy to modern imaging* Unique analysis and synthesis of a large body of basic and clinical data on the subject (more than 2000 references)* Written by an award-winning author who discovered "memory cells," the physiological substrate of working memory* Synthesizes evidence that the prefrontal cortex constitutes a complex pre-adaptive system* Incorporates emerging study of the role of the frontal lobes in social, economic, and cultural adaptation

Temporal dynamics of brain activation during a working memory task

Abstract: 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.

ADHD and the Nature of Self-Control

Abstract: ADHD and The Nature of Self-Control Russell A. Barkley. New York: The Guilford Press (www.guilford.com). 1997, 410 pp., $42.00 (hardcover). Russell Barkley has been among the most productive and prolific scientists in the field of Attention Deficit/Hyperactivity Disorder (ADHD). This work represents the culmination of a five-year project during which he attempted to develop a unifying explanatory model for ADHD. This model argues that the disorder fundamentally reflects a disruption in self-control mechanisms rather than attention per se. In this book, Barkley takes on the ambitious task of reviewing and synthesizing the voluminous theoretical and descriptive literature regarding ADHD and integrating it with related writings in philosophy, child development, and neuropsychology. Most of the ideas presented were previously published in a review article (Barkley, 1997), but are greatly expanded here. Essentially, Barkley argues that ADHD reflects a core deficit in inhibitory control, which then prevents the optimal use of "executive functions," all of the above thought to be mediated by the prefrontal cortex. Thus, ADHD is seen as a disruption in the developmental process of inhibition, mediated by the prefrontal cortex, whereby behavior is internalized, regulated, and directed toward the future. Deficits in attention are seen as secondary and not universal characteristics. Notably, this is a conceptual shift which is being increasingly embraced in the field. Barkley is not the first to focus on delays in the development of inhibition and self-regulation, nor is he the first to propose that prefrontal cortex and executive function deficits are central to ADHD. However, he goes beyond others in his scholarly presentation and discussion of relevant neuropsychological and developmental literature, and in his exacting effort to: (1) specify the nature of self-regulation, (2) show how the executive functions are involved in it, (3) articulate the basic number and nature of these functions, (4) demonstrate their critical dependence on behavioral inhibition, (5) argue that the purpose of executive functioning and selfregulation is to increase the control of behavior by time, and (6) specify that the ultimate utility function of all this activity is the net maximization of long-term consequences . . . (p. viii) Barkley builds what he terms a "hybrid" model for ADHD upon Bronowski's theory of human language, and upon Fuster's theory regarding the neuropsychological functions subserved by the prefrontal cortex. He ultimately posits five distinct components of impaired executive functions: nonverbal working memory; internalization of speech; self-regulation of affect; motivation and arousal; and reconstitution. For each, he eloquently describes how they might be affected by impaired inhibitory control, and how these resultant deficiencies may impact behavioral and cognitive functioning. This is an extremely important text, full of information and ideas. The first two chapters provide valuable in-depth reviews of existing literature regarding the clinical presentations of ADHD and various models of the biological etiology. He convincingly argues that it is a neurological disorder, on a developmental continuum, with a substantial genetic component. Derivatively, he argues against those who claim that ADHD is a result of poor parenting and social ills, and argues for the essential role of stimulant medication in treatment. …

High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice.

Abstract: Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higherfrequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. Increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases in alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during working memory.

A developmental functional mri study of prefrontal activation during performance of a go-no-go task

Abstract: This study examines important developmental differences in patterns of activation in the prefrontal cortex during performance of a Go-No-Go paradigm using functional magnetic resonance imaging (fMRI). Eighteen subjects (9 children and 9 adults) were scanned using gradient echo, echo planar imaging during performance of a response inhibition task. The results suggest four general findings. First, the location of activation in the prefrontal cortex was not different between children and adults, which is similar to our earlier pediatric fMRI results of prefrontal activation during a working memory task (Casey et al., 1995). Second, the volume of activation was significantly greater for children relative to adults. These differences in volume of activation were observed predominantly in the dorsal and lateral prefrontal cortices. Third, although inhibitory processes have typically been associated with more ventral or orbital frontal regions, the current study revealed activation that was distributed across both dorsolateral and orbitofrontal cortices. Finally, consistent with animal and human lesion studies, activity in orbital frontal and anterior cingulate cortices correlated with behavioral performance (i.e., number of false alarms). These results further demonstrate the utility of this methodology in studying pediatric populations.

Meta-analyses of age–cognition relations in adulthood: Estimates of linear and nonlinear age effects and structural models.

Abstract: A meta-analysis was conducted on 91 studies to derive a correlation matrix for adult age, speed of processing, primary-working memory, episodic memory, reasoning, and spatial ability. Structural equation modeling with a single latent common cognitive factor showed that all cognitive measures shared substantial portions of age-related variance. A mediational model revealed that speed of processing and primary-working memory appear to be important mediators of age-related differences in the other measures. However, not all of the age-related influences were mediated. An examination of quadratic age effects and correlational patterns for subsamples under and over 50 years of age revealed that (a) negative age-cognition relations were significant for the 18- to 50-year-old sample and (b) the age-related decline accelerated significantly over the adult life span for variables assessing speed, reasoning, and episodic memory.

Premotor and parietal cortex: corticocortical connectivity and combinatorial computations.

Abstract: The dorsal premotor cortex is a functionally distinct cortical field or group of fields in the primate frontal cortex Anatomical studies have confirmed that most parietal input to the dorsal premotor cortex originates from the superior parietal lobule However, these projections arise not only from the dorsal aspect of area 5, as has long been known, but also from newly defined areas of posterior parietal cortex, which are directly connected with the extrastriate visual cortex Thus, the dorsal premotor cortex receives much more direct visual input than previously accepted It appears that this fronto-parietal network functions as a visuomotor controller-one that makes computations based on proprioceptive, visual, gaze, attentional, and other information to produce an output that reflects the selection, preparation, and execution of movements

Transient and sustained activity in a distributed neural system for human working memory

Abstract: Working memory involves the short-term maintenance of an active representation of information so that it is available for further processing. Visual working memory tasks, in which subjects retain the memory of a stimulus over brief delays, require both the perceptual encoding of the stimulus and the subsequent maintenance of its representation after the stimulus is removed from view. Such tasks activate multiple areas in visual and prefrontal cortices. To delineate the roles these areas play in perception and working memory maintenance, we used functional magnetic resonance imaging (fMRI) to obtain dynamic measures of neural activity related to different components of a face working memory task-non-selective transient responses to visual stimuli, selective transient responses to faces, and sustained responses over memory delays. Three occipitotemporal areas in the ventral object vision pathway had mostly transient responses to stimuli, indicating their predominant role in perceptual processing, whereas three prefrontal areas demonstrated sustained activity over memory delays, indicating their predominant role in working memory. This distinction, however, was not absolute. Additionally, the visual areas demonstrated different degrees of selectivity, and the prefrontal areas demonstrated different strengths of sustained activity, revealing a continuum of functional specialization, from occipital through multiple prefrontal areas, regarding each area's relative contribution to perceptual and mnemonic processing.

Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia.

Abstract: Background: Impaired Wisconsin Card Sorting Test (WCST) performance has been one critical piece of evidence suggesting frontal lobe dysfunction in schizophrenia However, the specific cognitive processes underlying impaired performance have not been identified Impaired WCST performance in schizophrenia might in part reflect a fundamental working memory deficit Method: We examined the performance of 30 normal subjects and 36 patients with schizophrenia on a neuropsychological battery including a novel measure of working memory—letter-number (LN) span Results: Patients with schizophrenia were impaired on LN span performance, which was also highly correlated with WCST performance (r=074) Between-group WCST differences were eliminated when we covaried LN span Regression analyses suggested that LN span performance predicted the WCST category achieved score, whereas measures of set shifting, verbal fluency, and attention were predictive of perseveration Conclusion: Working memory may be a critical determinant of one aspect of WCST performance in schizophrenia

Integration of what and where in the primate prefrontal cortex.

Abstract: The visual system separates processing of an object’s form and color (“what”) from its spatial location (“where”). In order to direct action to objects, the identity and location of those objects must somehow be integrated. To examine whether this process occurs within the prefrontal (PF) cortex, the activity of 195 PF neurons was recorded during a task that engaged both what and where working memory. Some neurons showed either object-tuned (what) or location-tuned (where) delay activity. However, over half (52 percent, or 64/123) of the PF neurons with delay activity showed both what and where tuning. These neurons may contribute to the linking of object information with the spatial information needed to guide behavior.

Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET

Abstract: Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics, raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in the control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test. We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

Prefrontal cortex cognitive deficits in children treated early and continuously for PKU.

Abstract: To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed.

Verbal working memory load affects regional brain activation as measured by pet

Abstract: We report an experiment that assesses the effect of variations in memory load on brain activations that mediate verbal working memory. The paradigm that forms the basis of this experiment is the “n-back” task in which subjects must decide for each letter in a series whether it matches the one presented n items back in the series. This task is of interest because it recruits processes involved in both the storage and manipulation of information in working memory. Variations in task difficulty were accomplished by varying the value of n. As n increased, subjects showed poorer behavioral performance as well as monotonically increasing magnitudes of brain activation in a large number of sites that together have been identified with verbal working-memory processes. By contrast, there was no reliable increase in activation in sites that are unrelated to working memory. These results validate the use of parametric manipulation of task variables in neuroimaging research, and they converge with the subtraction paradigm used most often in neuroimaging. In addition, the data support a model of working memory that includes both storage and executive processes that recruit a network of brain areas, all of which are involved in task performance.

Functional and Anatomical Aspects of Prefrontal Pathology in Schizophrenia

Abstract: Clinical and experimental research have provided anatomical, pharmacological, and behavioral evidence for a prominent prefrontal dysfunction in schizophrenia. Negative symptoms and behavioral disorganization in the disorder can be understood as a failure in the working memory functions of the prefrontal cortex by which information is updated on a moment-to-moment basis or retrieved from long-term stores, held in mind, and used to guide behavior by ideas, concepts, and stored knowledge. This article recounts efforts to dissect the cellular and circuit basis of working memory with the goal of extending the insights gained from the study of normal brain organization in animal models to an understanding of the clinical disorder; it includes recent neuropathological findings that indicate that neural dystrophy rather than cell loss predominates in schizophrenia. Evidence from a variety of studies is accumulating to indicate that dopamine has a major role in regulating the excitability of the cortical neurons upon which the working memory function of the prefrontal cortex depends. Interactions between monoamines and a compromised cortical circuitry may hold the key to the salience of frontal lobe symptoms in schizophrenia, in spite of widespread pathological changes. We outline several direct and indirect intercellular mechanisms for modulating working memory function in the prefrontal cortex based on the localization of dopamine receptors on the distal dendrites and spines of glutamatergic pyramidal cells and on gamma-aminobutyric acid (GABA) ergic interneurons in the prefrontal cortex. Understanding the interactions between the major cellular constituents of cortical circuits-pyramidal and nonpyramidal cells-is a necessary step in unraveling the receptor mechanisms, which could lead to an effective pharmacological treatment of negative and cognitive symptoms, as well as improved insight into the pathophysiological basis of the disorder.

The role of working memory capacity in retrieval

Abstract: The verbal fluency task requires generation of category exemplars and appears to be an example of what M. Moscovitch (1995) calls a strategic test of memory retrieval. Four experiments explored the role of individual differences in working memory (WM) capacity on verbal fluency under various secondary load conditions. High WM participants consistently recalled more exemplars. However, load conditions caused a decline in recall only for high WM participants. Low WM participants showed no effect of secondary workload on exemplar generation. WM group differences and load effects were observed even in the 1st min of retrieval, which suggests that differences were not due to differences in knowledge. A model of retrieval is supported that relies on cue-based-automatic activation, monitoring of output for errors, controlled suppression of previously recalled items, and controlled strategic search.

Dissociable Forms of Inhibitory Control within Prefrontal Cortex with an Analog of the Wisconsin Card Sort Test: Restriction to Novel Situations and Independence from “On-Line” Processing

Abstract: Attentional set-shifting and discrimination reversal are sensitive to prefrontal damage in the marmoset in a manner qualitatively similar to that seen in man and Old World monkeys, respectively (Dias et al., 1996b). Preliminary findings have demonstrated that although lateral but not orbital prefrontal cortex is the critical locus in shifting an attentional set between perceptual dimensions, orbital but not lateral prefrontal cortex is the critical locus in reversing a stimulus-reward association within a particular perceptual dimension (Dias et al., 1996a). The present study presents this analysis in full and extends the results in three main ways by demonstrating that (1) mechanisms of inhibitory control and "on-line" processing are independent within the prefrontal cortex, (2) impairments in inhibitory control induced by prefrontal damage are restricted to novel situations, and (3) those prefrontal areas involved in the suppression of previously established response sets are not involved in the acquisition of such response sets. These findings suggest that inhibitory control is a general process that operates across functionally distinct regions within the prefrontal cortex. Although damage to lateral prefrontal cortex causes a loss of inhibitory control in attentional selection, damage to orbitofrontal cortex causes a loss of inhibitory control in affective processing. These findings provide an explanation for the apparent discrepancy between human and nonhuman primate studies in which disinhibition as measured on the Wisconsin Card Sort Test is associated with dorsolateral prefrontal damage, whereas disinhibition as measured on discrimination reversal is associated with orbitofrontal damage.

Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI.

Abstract: The lobular distributions of functional activation of the cerebellum during verbal working-memory and finger movement tasks were investigated using functional magnetic resonance imaging (fMRI). Relative to a rest control, finger tapping of the right hand produced ipsilateral-increased activation in HIV/HV [Roman numeral designations based on Larsell’s (Larsell and Jansen, 1972) nomenclature] and HVI and weaker activation in HVIII that was stronger on the ipsilateral side. For a working-memory task, subjects were asked to remember six (high load) or one (low load) visually presented letters across a brief delay. To assess the motoric aspects of rehearsal in the absence of working memory, we asked the subjects to repeatedly read subvocally six or one letters at a rate that approximated the internally generated rehearsal of working memory (motoric rehearsal task). For both tasks, bilateral regions of the superior cerebellar hemispheres (left superior HVIIA and right HVI) and portions of posterior vermis (VI and superior VIIA) exhibited increased activation during high relative to low load conditions. In contrast, the right inferior cerebellar hemisphere (HVIIB) exhibited this load effect only during the working-memory task. We hypothesize that HVI and superior HVIIA activation represents input from the articulatory control system of working memory from the frontal lobes and that HVIIB activation is derived from the phonological store in temporal and parietal regions. From these inputs, the cerebellum could compute the discrepancy between actual and intended phonological rehearsal and use this information to update a feedforward command to the frontal lobes, thereby facilitating the phonological loop.

Phonology, semantics, and the role of the left inferior prefrontal cortex

Abstract: Herbster et al. (1997) contribute to the growing literature on the functional neuroanatomy of word reading by evaluating stimulus-specific activation differences. The stimuli—regular words, irregular words, and nonwords—were specifically chosen to help tease apart contributions of orthography, phonology, and semantics to word pronunciation. The results, along with those from related studies [Fiez et al., 1993; Rumsey et al., 1997] have direct relevance for competing models of the transformation between orthography (how words look) and phonology (how words sound). Herbster et al. [1997] conclude that their results are consistent with connectionist models of word reading, and more specifically hypothesize that the left inferior frontal gyrus may be part of a phonological pathwaywhich supportsword reading, whereas the fusiform gyrus may be part of a semantic pathway. Zatorre et al. [1996] and Demonet et al. [1996] recently reviewed a series of neuroimaging studies that suggest the left inferior frontal gyrus is involved in phonological processing. For instance, greater activation in the left inferior frontal gyrus was found when subjects performed a phonological versus a pitch decision about pairs of auditory presented syllables [Zatorre et al., 1992], and when subjects performed a phonological versus an orthographic discrimination task on visually and auditorily presented words [Fiez et al., 1995]. Verbal working memory studies have also implicated this area in articulatory/phonological processes [e.g., see Awh et al., 1996; Paulesu et al., 1993]. However, evidence reviewed below also indicates that the left inferior frontal gyrus contributes to semantic processing. With respect to the conclusions reached by Herbster et al. [1997], this fact raises two questions: 1) How do the contributions of frontal and posterior regions (e.g., the fusiform gyrus) to semantic processing differ, and 2) are phonological versus semantic interpretations of left inferior prefrontal activation competing or complementary interpretations of the neuroimaging data?

Catecholamine regulation of the prefrontal cortex

Abstract: The catecholamines dopamine (DA) and norepinephrine provide an essential modulatory influence on the working memory and attentional functions of the prefrontal cortex (PFC). The following critique reviews evidence that (1) either insufficient or excessive DA D1 receptor stimulation is detrimental to PFC function, while DA stimulation of the D2 family of receptors may contribute to detrimental actions in PFC and (2) that norepinephrine has an important beneficial influence on PFC function through its actions at post-synaptic, alpha 2A adrenergic receptors, but impairs PFC function through actions at alpha 1 adrenergic receptors. Critical levels of catecholamine stimulation may be needed to optimize PFC cognitive function; high levels of catecholamine release during stress may serve to take the PFC 'off-line' to allow faster, more habitual responses mediated by the posterior and/or subcortical structures to regulate behavior. These studies have relevance to our understanding and treatment of disorders with prominent symptoms of PFC dysfunction.

The functional organization of working memory processes within human lateral frontal cortex: The contribution of functional neuroimaging.

Abstract: Recent functional neuroimaging studies have provided a wealth of new information about the likely organization of working memory processes within the human lateral frontal cprtex. This article seeks to evaluate the results of these studies in the context of two contrasting theoretical models of lateral frontal-lobe function, developed through lesion and electrophysiological recording work in non-human primates (Goldman-Rakic, 1994, 1995; Petrides, 1994, 1995). Both models focus on a broadly similar distinction between anatomically and cytoarchitectonically distinct dorsolateral and ventrolateral frontal cortical areas, but differ in the precise functions ascribed to those regions. Following a review of the relevant anatomical data, the origins of these two theoretical positions are considered in some detail and the main predictions arising from each are identified. Recent functional neuroimaging studies of working memory processes are then critically reviewed in order to assess the extent to which they support either, or both, sets of predictions. The results of this meta-analysis suggest that lateral regions of the frontal lobe are not functionally organized according to stimulus modality, as has been widely assumed, but that specific regions within the dorsolateral or ventrolateral frontal cortex make identical functional contributions to both spatial and non-spatial working memory.

Infrequent Events Transiently Activate Human Prefrontal and Parietal Cortex as Measured by Functional MRI

Abstract: McCarthy, Gregory, Marie Luby, John Gore, and Patricia Goldman-Rakic. Infrequent events transiently activate human prefrontal and parietal cortex as measured by functional MRI. J. Neurophysiol. 77:...

Attention and stimulus characteristics determine the locus of motor–sequence encoding a PET study.

Abstract: PET revealed the effects of stimulus characteristics on the neural substrate of motor learning. Right-handed subjects performed a serial reaction time task with colour-coded stimuli to eliminate the potential for learned eye-movements. The task was performed with the right hand under two different conditions. In one condition, subjects simultaneously performed a distractor task. Although they did show behavioural evidence of learning, they were not explicitly aware of the stimulus-response sequence. In the second condition, there was no distractor task, and seven out of the 11 subjects then became explicitly aware of the stimulus sequence. Metabolic correlates of learning were distinct in the two conditions. When learning was implicit under dual-task conditions, learning-related changes were observed in left motor and supplementary motor cortex as well as in the putamen. These regions are similar to those observed in a previous study in which the stimuli were cued by spatial position. Under single-task conditions, metabolic changes were found in the right prefrontal cortex and premotor cortex, as well as in the temporal lobe. A similar shift to the right hemisphere was observed in the spatial study during single-task learning. However, explicit learning of the task with colour stimuli activated more ventral regions. The areas supporting motor-sequence learning are contingent on both stimulus properties and attentional constraints.

Frontal-striatal cognitive deficits in patients with chronic schizophrenia.

Abstract: Spatial working memory and planning abilities were assessed in 36 hospitalized patients with chronic schizophrenia, using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB), and compared with those of normal subjects and patients with neurological disorders (frontal lobe lesions; temporal lobe and amygdalohippocampal lesions; Parkinson's disease), matched for age, sex and National Adult Reading Test IQ. The patients in the group with temporal lobe lesions were unimpaired in their performance on these tasks. Patients with schizophrenia were impaired on visuo-spatial memory span compared with all the other groups, while severity of Parkinson's disease was correlated with the degree of impairment on this task. The patients with schizophrenia and those with frontal lobe lesions were impaired on a 'spatial working memory' task, with increased 'between-search errors'. Patients with Parkinson's disease performed this task poorly compared with the younger control subjects. Patients with schizophrenia were unable to develop a systematic strategy to complete this task, relying instead on a limited visuo-spatial memory span. Higher level planning ability was investigated using the CANTAB 'Tower of London'. All groups were equally able to complete the task. However, the groups of patients with schizophrenia and frontal lobe lesions made fewer perfect solutions and required more moves for completion. Movement times were significantly slower in the schizophrenia group, suggesting impairment in the sensorimotor requirements of the task. The patients with schizophrenia were not impaired in their 'initial thinking' (planning) latencies, but had significantly prolonged 'subsequent thinking' (execution) latencies. This pattern resembled that of the group with frontal lobe lesions and contrasted with the prolonged 'initial thinking' time seen in Parkinson's disease. The results of this study are indicative of an overall deficit of executive functioning in schizophrenia, even greater than that seen in patients with frontal lobe lesions. However, the pattern of results in schizophrenia resembled that seen in patients with lesions of the frontal lobe or with basal ganglia dysfunction, providing support for the notion of a disturbance of frontostriatal circuits in schizophrenia. Our findings also indicate that there is a loss of the normal relationships between different domains of executive function in schizophrenia, with implications for impaired functional connectivity between different regions of the neocortex.