Errors on the Trail Making Test Are Associated with Right Hemispheric Frontal Lobe Damage in Stroke Patients.

Measures of performance on the Trail Making Test (TMT) are among the most popular neuropsychological assessment techniques. Completion time on TMT-A is considered to provide a measure of processing speed, whereas completion time on TMT-B is considered to constitute a behavioral measure of the ability to shift between cognitive sets (cognitive flexibility), commonly attributed to the frontal lobes. However, empirical evidence linking performance on the TMT-B to localized frontal lesions is mostly lacking. Here, we examined the association of frontal lesions following stroke with TMT-B performance measures (i.e., completion time and completion accuracy measures) using voxel-based lesion-behavior mapping, with a focus on right hemispheric frontal lobe lesions. Our results suggest that the number of errors, but not completion time on the TMT-B, is associated with right hemispheric frontal lesions. This finding contradicts common clinical practice-the use of completion time on the TMT-B to measure cognitive flexibility, and it underscores the need for additional research on the association between cognitive flexibility and the frontal lobes. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether our observation is specific for right frontal lesions.

Disorganized behavior on Link's cube test is sensitive to right hemispheric frontal lobe damage in stroke patients.

One of Luria's favorite neuropsychological tasks for challenging frontal lobe functions was Link's cube test (LCT). The LCT is a cube construction task in which the subject must assemble 27 small cubes into one large cube in such a manner that only the painted surfaces of the small cubes are visible. We computed two new LCT composite scores, the constructive plan composite score, reflecting the capability to envisage a cubical-shaped volume, and the behavioral (dis-) organization composite score, reflecting the goal-directedness of cube construction. Voxel-based lesion-behavior mapping (VLBM) was used to test the relationship between performance on the LCT and brain injury in a sample of stroke patients with right hemisphere damage (N = 32), concentrated in the frontal lobe. We observed a relationship between the measure of behavioral (dis-) organization on the LCT and right frontal lesions. Further work in a larger sample, including left frontal lobe damage and with more power to detect effects of right posterior brain injury, is necessary to determine whether this observation is specific for right frontal lesions.

Age-related changes in neural recruitment for cognitive control.

The dual mechanisms of control (DMC; Braver, Gray, & Burgess, 2007) framework postulates a distinction between proactive and reactive modes of cognitive control. Event-related brain potentials (ERPs) were used to examine age differences in the neural correlates of proactive and reactive control for task-switching. Whereas proactive control is associated with brain activity for anticipatory task preparation, reactive control is accompanied by reduced preparatory activity, but increased activation during task execution. Switching between tasks was based on feedback-based transition cueing which places particularly high demands on mechanisms for cognitive control. Older adults maintained good performance accuracy at the expense of slower response times. No age-related increase in behavioral switching costs was observed. The cue-locked ERP (P3a) data revealed an age-related decrease in neural activity related to the processing of switch cues. In the target-locked ERPs, there was an increased frontal focus of the P3b in older adults. These ERP data indicate an age-related neural under-recruitment for proactive cognitive control and an age-related neural over-recruitment for reactive cognitive control. They are consistent with the idea that older adults may not fully implement task settings before target onset, after which they need to catch up on the omitted preparatory task settings.

Performance on the Frontal Assessment Battery is sensitive to frontal lobe damage in stroke patients.

BACKGROUND: The Frontal Assessment Battery (FAB) is a brief battery of six neuropsychological tasks designed to assess frontal lobe function at bedside [Neurology 55:1621-1626, 2000]. The six FAB tasks explore cognitive and behavioral domains that are thought to be under the control of the frontal lobes, most notably conceptualization and abstract reasoning, lexical verbal fluency and mental flexibility, motor programming and executive control of action, self-regulation and resistance to interference, inhibitory control, and environmental autonomy. METHODS: We examined the sensitivity of performance on the FAB to frontal lobe damage in right-hemisphere-damaged first-ever stroke patients based on voxel-based lesion-behavior mapping. RESULTS: Voxel-based lesion-behavior mapping of FAB performance revealed that the integrity of the right anterior insula (BA13) is crucial for the FAB global composite score, for the FAB conceptualization score, as well as for the FAB inhibitory control score. Furthermore, the FAB conceptualization and mental flexibility scores were sensitive to damage of the right middle frontal gyrus (MFG; BA9). Finally, the FAB inhibitory control score was sensitive to damage of the right inferior frontal gyrus (IFG; BA44/45). CONCLUSIONS: These findings indicate that several FAB scores (including composite and item scores) provide valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the MFG and in the IFG.

A model-based approach to trial-by-trial p300 amplitude fluctuations.

It has long been recognized that the amplitude of the P300 component of event-related brain potentials is sensitive to the degree to which eliciting stimuli are surprising to the observers (Donchin, 1981). While Squires et al. (1976) showed and modeled dependencies of P300 amplitudes from observed stimuli on various time scales, Mars et al. (2008) proposed a computational model keeping track of stimulus probabilities on a long-term time scale. We suggest here a computational model which integrates prior information with short-term, long-term, and alternation-based experiential influences on P300 amplitude fluctuations. To evaluate the new model, we measured trial-by-trial P300 amplitude fluctuations in a simple two-choice response time task, and tested the computational models of trial-by-trial P300 amplitudes using Bayesian model evaluation. The results reveal that the new digital filtering (DIF) model provides a superior account of the trial-by-trial P300 amplitudes when compared to both Squires et al.'s (1976) model, and Mars et al.'s (2008) model. We show that the P300-generating system can be described as two parallel first-order infinite impulse response (IIR) low-pass filters and an additional fourth-order finite impulse response (FIR) high-pass filter. Implications of the acquired data are discussed with regard to the neurobiological distinction between short-term, long-term, and working memory as well as from the point of view of predictive coding models and Bayesian learning theories of cortical function.

A hypothesis of local intrinsic cortical signal processing.

Nearly a century ago, Ramón y Cajal [1] speculated that cortical interneurones underlie specific functions that are fundamental to human thought. Here we develop a computational analysis of the function of local cortical loops and their synaptic connections. Specifically, we propose that the function of cortical interneurones is to reduce redundancy and to contribute to compute saliency of information represented in neurones by implementing divisive normalization and multiplicative filtering functions. This contextual filtering by cortical interneurones reduces the energy of locally homogeneous information flowing between different cortical areas, in a non-linear manner and along various event spaces, thereby ensuring a homeostatic level of informational selectivity. Dysregulations of the synaptic transmission in this ubiquitous basic building block of the functional architecture of the brain are correspondingly associated with disturbances of informational selectivity. Perturbations of synaptic transmission in local intrinsic connections of the cerebral cortex consequently lead to various kinds of cognitive and/or affective disorders, depending on the exact nature, the extension and the specific localization of the distortion.

Event-related brain potentials and the efficiency of visual search for vertically and horizontally oriented stimuli.

Reports that visual search is more efficient for vertically than for horizontally shaded objects suggested that search is influenced by a priori knowledge about the source of light. In this study, we examined search for targets defined by the orientation of luminance gradients and measured event-related brain potentials (ERPs). In Experiment 1, we examined search for stimuli that comprised gradual luminance differences. Response times showed the expected orientation anisotropy effect. ERP amplitudes in the P1 latency range were slightly more positive in response to horizontally oriented stimuli, whereas P3 amplitudes were more positive in response to nonsingleton vertically oriented stimuli. Experiment 2 compared search for stimuli that comprised gradual versus step differences in luminance. All the anisotropies that we observed in Experiment 1 could be replicated in Experiment 2. Moreover, these anisotropies were not dependent on the type of the luminance gradient. This finding is inconsistent with the view that search efficiency is influenced by a priori knowledge about the source of light. The behavioral and electrophysiological data are consistent with a context model of visual search. We propose that contextual modulation reduces redundancy and contributes to computing the saliency of visual information by implementing divisive normalization and multiplicative filtering.

Event-related brain potentials and cognitive processes related to perceptual-motor information transmission.

In the present study, event-related potentials (ERPs) were recorded to investigate cognitive processes related to the partial transmission of information from stimulus recognition to response preparation. Participants classified two-dimensional visual stimuli with dimensions size and form. One feature combination was designated as the go-target, whereas the other three feature combinations served as no-go distractors. Size discriminability was manipulated across three experimental conditions. N2c and P3a amplitudes were enhanced in response to those distractors that shared the feature from the faster dimension with the target. Moreover, N2c and P3a amplitudes showed a crossover effect: Size distractors evoked more pronounced ERPs under high size discriminability, but form distractors elicited enhanced ERPs under low size discriminability. These results suggest that partial perceptual-motor transmission of information is accompanied by acts of cognitive control and by shifts of attention between the sources of conflicting information. Selection negativity findings imply adaptive allocation of visual feature-based attention across the two stimulus dimensions.

Psychometric characteristics and practice effects of the Brunswick Trail Making Test.

Three trail-making tasks were designed to yield measures of visuomotor speed, efficiency of visual search, and cognitive flexibility (attentional switching). Scores on paper-and-pencil trail-making performance tasks were analyzed in 54 neurologically nonimpaired participants (21 men, 33 women; M=40 yr., SD=15 yr.). In Study 1, a 5-item 3-task format of the new trail-making test was developed by selecting items based on psychometric characteristics. The tasks were visuomotor trail-making (one item), visual search (two items), and cognitive flexibility (two items). Estimates of internal consistency of the resulting test scores of the Brunswick Trail Making Test yielded acceptable values (.91 and .90). In Study 2, the effects of repeated practice on trail-making tasks were analyzed. Task repetition affected the performance in the three trail-making tasks differentially. On the visuomotor task, effects of repeated task practice were completely carried over to similar trails. Evidence for transfer of learning was obtained neither for the visual search task nor for the cognitive flexibility task. It is concluded that training effects of perceptual-motor and cognitive skills are highly specific. Implications of these findings for cognitive neurorehabilitation are discussed.

Temporal dynamics of selective attention and conflict resolution during cross-dimensional Go-NoGo decisions.

BACKGROUND: Decision-making is a fundamental capacity which is crucial to many higher-order psychological functions. We recorded event-related potentials (ERPs) during a visual target-identification task that required go-nogo choices. Targets were identified on the basis of cross-dimensional conjunctions of particular colors and forms. Color discriminability was manipulated in three conditions to determine the effects of color distinctiveness on component processes of decision-making. RESULTS: Target identification was accompanied by the emergence of prefrontal P2a and P3b. Selection negativity (SN) revealed that target-compatible features captured attention more than target-incompatible features, suggesting that intra-dimensional attentional capture was goal-contingent. No changes of cross-dimensional selection priorities were measurable when color discriminability was altered. Peak latencies of the color-related SN provided a chronometric measure of the duration of attention-related neural processing. ERPs recorded over the frontocentral scalp (N2c, P3a) revealed that color-overlap distractors, more than form-overlap distractors, required additional late selection. The need for additional response selection induced by color-overlap distractors was severely reduced when color discriminability decreased. CONCLUSION: We propose a simple model of cross-dimensional perceptual decision-making. The temporal synchrony of separate color-related and form-related choices determines whether or not distractor processing includes post-perceptual stages. ERP measures contribute to a comprehensive explanation of the temporal dynamics of component processes of perceptual decision-making.

Fractionating the neural mechanisms of cognitive control.

Modifications of the Wisconsin Card Sorting Test were established. In these new task variants, participants were asked to exert sequential control over attentional sets or over intentional sets (task domain factor). Attentional set shifting requires changing the priorities by which sensory stimuli are selected, whereas intentional set shifting requires changing the priorities by which motor responses are selected. Auditory stimuli that signaled to maintain or shift set were presented immediately before (precuing) or after (postcuing) the selection of cards (cue timing factor). Twenty-four healthy young individuals participated. Performance data (response times, error percentages) indicated that intentional tasks were easier to perform than attentional tasks. The electroencephalogram was recorded during task performance, and the N1, medial frontal negativity (MFN), P3a, and sustained potential (SP) components of the cue event-related brain potentials (ERPs) were analyzed. Irrespective of the task domain, shift precues led to increased N1 amplitudes compared to shift postcues. When intentional sets had to be shifted, the MFNs in the postcuing condition were more pronounced than in the precuing condition. On the other hand, shifts of attentional sets resulted in a more prominent P3a in response to postcues compared to precues. Irrespective of the task domain, the shift effect that was evident in SPs was more pronounced in precue ERPs compared to postcue ERPs. We conclude that ERPs provide valid measures to empirically constrain theories about the neural mechanisms of cognitive control. The domain hypothesis of the fractionation of the neural mechanisms of cognitive control is introduced.

On the role of the cerebellum in exploiting temporal contingencies:; evidence from response times and preparatory EEG potentials in patients with cerebellar atrophy.

Patients with degenerative cerebellar disease were compared to healthy controls in their ability to adapt behaviour to temporal contingencies, both according to instructions and according to acquired experience. Participants had to press the cued key whenever the inside of a clock face changed its colour, which could occur when the pointer, rotating once every 4s, was at "10h" or at "12h" or at "2h". Probabilities varied between blocks at which of these three time points the colour change occurred, with participants being instructed accordingly. Response times correlated intraindividually with these instructed "a priori" probabilities in control participants only. Subjectively, at any moment, probabilities of occurrence depend on whether the imperative colour change had occurred before, thus may be better described by conditional ("a posteriori") probabilities. Indeed, when response times were correlated to a posteriori rather than a priori probabilities, correlations increased in both groups equally from their different a priori levels. The amplitudes of preparatory EEG negativity before responding tended to obey to the same relationships, suggesting that the difference between groups was not due to pure motor impairment. Thus, these data suggest that patients with cerebellar atrophy are more impaired in implementing and using task-relevant information in a top-down manner than in learning to modify task-relevant contingencies.

Modulation of cerebellar activation by predictive and non-predictive sequential finger movements.

We investigated the modulation of cerebellar activation by predictive and non-predictive sequential finger movements. It is hypothesized that the prediction of desired movement sequences and adaptation to new movement parameters is mediated by the cerebellum. Using functional MRI at 1.5 T, seven normal subjects performed sequential finger to thumb opposition movements, either in predictive (repeatedly 2,3,4,5) or non-predictive (randomized) fashion at a constant frequency of 1 Hz. Performance and error rates were monitored by simultaneous recording of the finger movements. Predictive sequential finger opposition movements activated a cerebellar network including the lobuli IV-VI ipsilateral to the movements, the contralateral lobuli IV-VI, the vermis, and lobuli VIIB-VIII ipsilaterally. Non-predictive compared to predictive finger opposition movements activated a broader area within the ipsi- and contralateral anterior cerebellum, lobuli IV-VI, the vermis, and the ipsilateral lobuli VIIB-VIII. Additional activation foci were found in the contralateral lobuli VIIA and VIIB-VIII. Our study demonstrates a modulated information processing within the cerebellar network dependent on the predictability of movement sequences.