Francisco Barceló

Construct validity of the Trail Making Test: Role of task-switching, working memory, inhibition/interference control, and visuomotor abilities

The aim of this study was to clarify which cognitive mechanisms underlie Trail Making Test (TMT) direct and derived scores. A comprehensive review of the literature on the topic was carried out to clarify which cognitive factors had been related to TMT performance. Following the review, we explored the relative contribution from working memory, inhibition/interference control, task-switching ability, and visuomotor speed to TMT performance. Forty-one healthy old subjects participated in the study and performed a battery of neuropsychological tests including the TMT, the Digit Symbol subtest [Wechsler Adult Intelligence Scale (Third Version) (WAIS-III)], a Finger Tapping Test, the Digits Forward and Backward subtests (WAIS-III), Stroop Test, and a task-switching paradigm inspired in the Wisconsin Card Sorting Test. Correlation and regression analyses were used in order to clarify the joint and unique contributions from different cognitive factors to the prediction of TMT scores. The results suggest that TMT-A requires mainly visuoperceptual abilities, TMT-B reflects primarily working memory and secondarily task-switching ability, while B-A minimizes visuoperceptual and working memory demands, providing a relatively pure indicator of executive control abilities.

Prefrontal modulation of visual processing in humans

Single neuron, evoked potential and metabolic techniques show that attention influences visual processing in extrastriate cortex. We provide anatomical, electrophysiological and behavioral evidence that prefrontal cortex regulates neuronal activity in extrastriate cortex during visual discrimination. Event-related potentials (ERPs) were recorded during a visual detection task in patients with damage in dorsolateral prefrontal cortex. Prefrontal damage reduced neuronal activity in extrastriate cortex of the lesioned hemisphere. These electrophysiological abnormalities, beginning 125 ms after stimulation and lasting for another 500 ms, were accompanied by behavioral deficits in detection ability in the contralesional hemifield. The results provide evidence for intrahemispheric prefrontal modulation of visual processing.

The Wisconsin Card Sorting Test and the Cognitive Assessment of Prefrontal Executive Functions: A Critical Update.

For over four decades the Wisconsin Card Sorting Test (WCST) has been one of the most distinctive tests of prefrontal function. Clinical research and recent brain imaging have brought into question the validity and specificity of this test as a marker of frontal dysfunction. Clinical studies with neurological patients have confirmed that, in its traditional form, the WCST fails to discriminate between frontal and non-frontal lesions. In addition, functional brain imaging studies show rapid and widespread activation across frontal and non-frontal brain regions during WCST performance. These studies suggest that the concept of an anatomically pure test of prefrontal function is not only empirically unattainable, but also theoretically inaccurate. The aim of the present review is to examine the causes of these criticisms and to resolve them by incorporating new methodological and conceptual advances in order to improve the construct validity of WCST scores and their relationship to prefrontal executive functions. We conclude that these objectives can be achieved by drawing on theory-guided experimental design, and on precise spatial and temporal sampling of brain activity, and then exemplify this using an integrative model of prefrontal function [i.e., Miller, E. K. (2000). The prefrontal cortex and cognitive control. Nature Reviews Neuroscience, 1, 59-65.] combined with the formal information theoretical approach to cognitive control [Koechlin, E., & Summerfield, C. (2007). An information theoretical approach to prefrontal executive function. Trends in Cognitive Sciences, 11, 229-235.].

Think differently: a brain orienting response to task novelty.

Cognitive flexibility hinges on a readiness to direct attention to novel events, and on an ability to change ones mental set to find new solutions for old problems. Human event-related potential (ERP) studies have described a brain ‘orienting’ response to discrete novel events, marked by a frontally distributed positive potential peaking 300–400 ms post-stimulus (P3a). This brain potential has been typically related to bottom-up processing of novel non-targets under a fixed task-set (i.e., press a button to coloured targets), but had never been related to top-down attention control in dual-task paradigms. In this study, 27 subjects had their ERPs measured while they performed a version of the Wisconsin card sorting test (WCST), a dual-task paradigm where the same feedback cue signalled unpredictable shifts to a new task set (i.e., from ‘sort by colour’ to ‘sort by shape’). Feedback cues that directed a shift in the subjects mental set to a new task-set elicited frontally distributed P3a activity, thus suggesting a role of the P3a response system in task-set shifting. Feedback cues also evoked a longer latency positive potential (350–600 ms; P3b), that was larger the more task rules were held in memory. In line with current models of prefrontal function in the executive control of attention, this P3a/P3b response system appears to reflect the co-ordinated action of prefrontal and posterior association cortices during the switching and updating of task sets in working memory.

Task Switching and Novelty Processing Activate a Common Neural Network for Cognitive Control

The abrupt onset of a novel event captures attention away from, and disrupts, ongoing task performance. Less obvious is that intentional task switching compares with novelty-induced behavioral distraction. Here we explore the hypothesis that intentional task switching and attentional capture by a novel distracter both activate a common neural network involved in processing contextual novelty [Barcelo, F., Periez, J. A., & Knight, R. T. Think differently: A brain orienting response to task novelty. NeuroReport, 13, 18871892, 2002.]. Event-related potentials were recorded in two task-cueing paradigms while 16 subjects sorted cards following either two (color or shape; two-task condition) or three (color, shape, or number; three-task condition) rules of action. Each card was preceded by a familiar tone cueing the subject either to switch or to repeat the previous rule. Novel sound distracters were interspersed in one of two blocks of trials in each condition. Both novel sounds and task-switch cues impaired responses to the following visual target. Novel sounds elicited novelty P3 potentials with their usual peak latency and frontal-central scalp distribution. Familiar tonal switch cues in the three- and two-task conditions elicited brain potentials with a similar latency and morphology as the novelty P3, but with relatively smaller amplitudes over frontal scalp regions. Covariance and principal component analyses revealed a sustained frontal negative potential that was distorting concurrent novelty P3 activity to the tonal switch cues. When this frontal negativity was statistically removed, P3 potentials to novel sounds and task-switch cues showed similar scalp topographies. The degree of activation in the novelty P3 network seemed to be a function of the information (entropy) conveyed by the eliciting stimulus for response selection, over and above its relative novelty, probability of occurrence, task relevance, or feedback value. We conclude that novelty P3 reflects transient activation in a neural network involved in updating task set information for goal-directed action selection and might thus constitute one key element in a central bottleneck for attentional control.

Attentional set shifting modulates the target P3b Response in the Wisconsin card sorting test

For years the Wisconsin card sorting test (WCST) has been used as a test of frontal lobe function. Recent event-related potential (ERP) research has shown large differences in the amplitude of P3b responses evoked by early and late trials within each WCST series ([8]: Barceló F., Sanz M., Molina V., Rubia FJ. The Wisconsin Card Sorting Test and the assessment of frontal function: A validation study with event-related potentials. Neuropsychologia 1997;35:399-408). In this study, 16 normal subjects performed a WCST adaptation to investigate the role of attentional set shifting in these WCST P3b effects. Two control tasks were designed to examine whether early-late WCST P3b changes reflect category selection (attention) or category storage (memory) operations. Results suggest both a sharp P3b attenuation during shift WCST trials, followed by a gradual P3b build-up during post-shift trials. This P3b modulation could not be attributed to selection or storage of simple sensory stimulus dimensions, nor was it observed when the new rule was externally prompted by the first card in the WCST series. Instead, WCST P3b changes seem related to the endogenously generated shift in the perceptual rule used to sort the cards (i.e., the shift in set). The gradual build-up in P3b amplitude paralleled a progressive improvement in sorting efficiency over several post-shift WCST trials. A model based on formal theories of visual attention and attentional set shifting is proposed to account for these effects. The model offers firm grounds for prediction and bridges the gap between related clinical and experimental evidence.

The Wisconsin Card Sorting Test and the assessment of frontal function: A validation study with event-related potentials

The Wisconsin Card Sorting Test (WCST) is generally regarded as the prototype of abstract reasoning task and has been routinely used to assess frontal lobe function in a variety of clinical and research contexts. However, there are growing concerns that the WCST fails to discriminate frontal patients from those with lesions in other brain regions or from normals. Event-related potentials (ERP) from frontal, fronto-temporal, temporal, parietal and occipital areas were recorded during the performance of a computerized version of the WCST in order to explore frontal versus non-frontal ERP indexes during WCST activation. The task protocol was contrived to focus on the differences between early and late trials of each WCST series. Cognitive processes underlying these two task conditions have been described as extradimensional and intradimensional shifts in attention, respectively. Differences between early and late WCST trials appeared as soon as 120 msec poststimulus and were associated with a negative field potential centred at the fronto-temporal region of the left hemisphere. Significantly larger amplitudes of the posterior P3b wave for late as compared with early WCST trials also lent support to claims of a strong involvement of working memory mechanisms during WCST performance. Results are discussed in terms of the implications for the utility of ERP measures in clinical neuropsychology.

Dynamic Neuroplasticity after Human Prefrontal Cortex Damage

Memory and attention deficits are common after prefrontal cortex (PFC) damage, yet people generally recover some function over time. Recovery is thought to be dependent upon undamaged brain regions, but the temporal dynamics underlying cognitive recovery are poorly understood. Here, we provide evidence that the intact PFC compensates for damage in the lesioned PFC on a trial-by-trial basis dependent on cognitive load. The extent of this rapid functional compensation is indexed by transient increases in electrophysiological measures of attention and memory in the intact PFC, detectable within a second after stimulus presentation and only when the lesioned hemisphere is challenged. These observations provide evidence supporting a dynamic and flexible model of compensatory neural plasticity.

Electrophysiological evidence of two different types of error in the Wisconsin Card Sorting Test.

The specificity of the Wisconsin Card Sorting Test (WCST) for assessing frontal lobe pathology remains controversial, although lesion and cerebral blood flow studies continue to suggest a role for the dorsolateral prefrontal cortex in WCST performance. Inconsistencies might derive from the extended use of various WCST scores as equivalent indicators of frontal pathology. In this study, event-related potentials (ERPs) were recorded from 32 normal subjects who committed perseverative and non-perseverative errors. Both types of WCST errors evoked anomalous but distinct ERP patterns over frontal lobe regions. Perseverative errors were also associated with a dysfunctional extrastriate response to stimulation. This evidence suggests that perseverative and non-perseverative errors result from disruptions in two different prefrontal neural networks engaged during card sorting.

An information theoretical approach to task-switching: evidence from cognitive brain potentials in humans

This study aimed to clarify the neural substrates of behavioral switch and restart costs in intermittently instructed task-switching paradigms. Event-related potentials (ERPs) were recorded while participants were intermittently cued to switch or repeat their categorization rule (Switch task), or else they performed two perceptually identical control conditions (NoGo and Oddball). The three tasks involved different task-sets with distinct stimulus-response associations in each, but identical visual stimulation, consisting of frequent colored shapes (p = 0.9) and randomly interspersed infrequent black shapes (p = 0.1; ‘+’ and ‘x’ symbols). Behavioral restart costs were observed in the first target responses following all black shapes in the Switch and NoGo tasks – but not in the Oddball task – and corresponded with enhanced fronto-centrally distributed early cue-locked P3 activity (peak latency 325–375 ms post-cue onset at the vertex). In turn, behavioral switch costs were associated with larger late cue-locked P3 amplitudes in the Switch task only (peak latency 400–450 ms post-cue onset at mid-parietal sites). Together with our information theoretical estimations, ERP results suggested that restart and switch costs indexed two neural mechanisms related to the preparatory resolution of uncertainty: (1) the intermittent re-activation of task-set information, and (2) the updating of stimulus-response mappings within an active task set, as indexed by early and late cue-locked P3 activations, respectively. In contrast, target-locked P3 activations reflected a functionally distinct mechanism related to the implementation of task-set information. We conclude that task-switching costs consist of both switch-specific and switch-unspecific processes during the preparation and execution stages of task performance.