W.R. Fulham

The spatial and temporal dynamics of anticipatory preparation and response inhibition in task-switching

We investigated ERP and fMRI correlates of anticipatory preparation and response inhibition in a cued task-switching paradigm with informatively cued, non-informatively cued and no-go trials. Cue-locked ERPs showed evidence for a multicomponent preparation process. An early cue-locked differential positivity was larger for informative vs. non-informative cues and its amplitude correlated with differential activity for informatively vs. non-informatively cued trials in the dorsolateral prefrontal cortex (DLPFC), consistent with a goal activation process. A later differential positivity was larger for informatively cued switch vs. repeat trials and its amplitude correlated with informatively cued switch vs. repeat activity in the posterior parietal cortex (PPC), compatible with a category-response (C-R) rule activation process. No-go trials elicited a frontal P3, whose amplitude was negatively correlated with activity in the ventrolateral prefrontal cortex (VLPFC) and basal ganglia motor network, suggesting that a network responsible for response execution was inhibited in the course of a no-go trial. These findings indicate that anticipatory preparation in task-switching is comprised of at least two processes: goal activation and C-R rule activation. They also support a functional dissociation between DLPFC and VLPFC, with the former involved in top-down biasing and the latter involved in response inhibition.

Stop-signal response inhibition in schizophrenia: behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Epidural Auditory Event-Related Potentials in the Rat to Frequency and duration Deviants: Evidence of Mismatch Negativity?

The capacity of the human brain to detect deviance in the acoustic environment pre-attentively is reflected in a brain event-related potential (ERP), mismatch negativity (MMN). MMN is observed in response to the presentation of rare oddball sounds that deviate from an otherwise regular pattern of frequent background standard sounds. While the primate and cat auditory cortex (AC) exhibit MMN-like activity, it is unclear whether the rodent AC produces a deviant response that reflects deviance detection in a background of regularities evident in recent auditory stimulus history or differential adaptation of neuronal responses due to rarity of the deviant sound. We examined whether MMN-like activity occurs in epidural AC potentials in awake and anesthetized rats to high and low frequency and long and short duration deviant sounds. ERPs to deviants were compared with ERPs to common standards and also with ERPs to deviants when interspersed with many different standards to control for background regularity effects. High frequency (HF) and long duration deviant ERPs in the awake rat showed evidence of deviance detection, consisting of negative displacements of the deviant ERP relative to ERPs to both common standards and deviants with many standards. The HF deviant MMN-like response was also sensitive to the extent of regularity in recent acoustic stimulation. Anesthesia in contrast resulted in positive displacements of deviant ERPs. Our results suggest that epidural MMN-like potentials to HF sounds in awake rats encode deviance in an analogous manner to the human MMN, laying the foundation for animal models of disorders characterized by disrupted MMN generation, such as schizophrenia.

Sustained brain activation supporting stop-signal task performance

Stop‐signal paradigms operationalize a basic test of goal‐directed behaviour whereby an overarching stop goal that is performed intermittently must be maintained throughout ongoing performance of a reaction time go task (go goal). Previous studies of sustained brain activation during stop‐signal task performance in humans did not observe activation of the dorsolateral prefrontal cortex (DLPFC) that, in concert with the parietal cortex, is known to subserve goal maintenance. Here we explored the hypothesis that a DLPFC and parietal network has a key role in supporting ongoing stop‐signal task performance. We used a blocked functional magnetic resonance imaging design that included blocks of trials containing typical stop‐signal paradigm stimuli that were performed under three conditions: Stop condition, which required reaction time responding to go stimuli and inhibition of cued responses upon presentation of a stop signal; Go condition, identical except that the tone was ignored; and Passive condition, which required only quiescent attention to stimuli. We found that, whereas a distributed corticothalamic network was more active in Stop compared with Go, only the right DLPFC and bilateral parietal cortex survived after masking that contrast with Stop compared with Passive. These findings indicate that sustained activation of a right dominant frontoparietal network supports stop goal processes during ongoing performance of the stop‐signal task.

Repetition suppression of the rat auditory evoked potential at brief stimulus intervals

An important prerequisite for the development of animal models of human auditory evoked potentials (AEP) is the accurate identification of homology. Prior research has revealed some remarkably similar response properties between rat and human AEPs, although there remains little consensus regarding the nature or validity of this correspondence. In the present study we seek to extend this research by examining the response properties of rat AEP as a function of stimulus repetition and interval. The aim being to determine whether rat AEP components show the same paradoxical reversal of repetition suppression observed for the human N100 AEP component at brief stimulus intervals. To achieve this, AEPs were recorded epidurally at the vertex in the freely moving rat in response to acoustic stimuli presented at random stimulus intervals between 50 and 5,000 ms. Using stimulation and analysis techniques to remove AEP waveform distortion due to overlapping AEP responses, the present results show that rat AEP components can be successfully resolved at intervals as brief as 50 ms. The results also demonstrate several fundamental types of correspondence between human and rat AEP components in terms of the sensitivity to stimulus interval and acoustic stimulus type. However the results found no evidence that rat AEP components show the reversal of repetition suppression at brief, relative to long, stimulus intervals as demonstrated for the N100 component in humans. The results are discussed in terms of EEG recording and AEP analysis procedures that provide promising avenues for future research.

Event-related potential response to attended and unattended locations in an interference task

Event-related potentials were measured in response to an interference task in which unattended stimulus items were compatible, incompatible a neutral with regard to the attended stimulus items. Two stimulus items were presented simultaneously and bilaterally--one in each visual field. This allowed examination of the event-related potential waveform according to whether recording sites were contralateral to the attended or unattended location. The first experiment used sustained cueing with 3.5 degrees separation between attended and unattended locations. Attentional modulation of the N1 was observed but not for the P1. In the second experiment, separation between attended and unattended locations was increased to 11.5 degrees. In both experiments, the hemisphere contralateral to the unattended material (unattended hemisphere) showed a greater negativity in the N2 latency range in the temporal regions to compatible and incompatible conditions compared to a neutral condition. These data are inconsistent with findings suggesting the filtering of material early in visual processing.

Late deviance detection in rats is reduced, while early deviance detection is augmented by the NMDA receptor antagonist MK-801

One of the most robust electrophysiological features of schizophrenia is reduced mismatch negativity, a component of the event related potential (ERP) induced by rare and unexpected stimuli in an otherwise regular pattern. Emerging evidence suggests that mismatch negativity (MMN) is not the only ERP index of deviance detection in the mammalian brain and that sensitivity to deviant sounds in a regular background can be observed at earlier latencies in both the human and rodent brain. Pharmacological studies in humans and rodents have previously found that MMN reductions similar to those seen in schizophrenia can be elicited by N-methyl-d-aspartate (NMDA) receptor antagonism, an observation in agreement with the hypothesised role of NMDA receptor hypofunction in schizophrenia pathogenesis. However, it is not known how NMDA receptor antagonism affects early deviance detection responses. Here, we show that NMDA antagonism impacts both early and late deviance detection responses. By recording EEG in awake, freely-moving rats in a drug-free condition and after varying doses of NMDA receptor antagonist MK-801, we found the hypothesised reduction of deviance detection for a late, negative potential (N55). However, the amplitude of an early component, P13, as well as deviance detection evident in the same component, were increased by NMDA receptor antagonism. These findings indicate that late deviance detection in rats is similar to human MMN, but the surprising effect of MK-801 in increasing ERP amplitudes as well as deviance detection at earlier latencies suggests that future studies in humans should examine ERPs over early latencies in schizophrenia and after NMDA antagonism.

The Potential for New Understandings of Normal and Abnormal Cognition by Integration of Neuroimaging and Behavioral Data: Not an Exercise in Carrying Coals to Newcastle

Discovering the means to prevent and cure schizophrenia is a vision that motivates many scientists. But in order to achieve this goal, we need to understand its neurobiological basis. The emergent metadiscipline of cognitive neuroscience fields an impressive array of tools that can be marshaled towards achieving this goal, including powerful new methods of imaging the brain (both structural and functional) as well as assessments of perceptual and cognitive capacities based on psychophysical procedures, experimental tasks and models developed by cognitive science. We believe that the integration of data from this array of tools offers the greatest possibilities and potential for advancing understanding of the neural basis of not only normal cognition but also the cognitive impairments that are fundamental to schizophrenia. Since sufficient expertise in the application of these tools and methods rarely reside in a single individual, or even a single laboratory, collaboration is a key element in this endeavor. Here, we review some of the products of our integrative efforts in collaboration with our colleagues on the East Coast of Australia and Pacific Rim. This research focuses on the neural basis of executive function deficits and impairments in early auditory processing in patients using various combinations of performance indices (from perceptual and cognitive paradigms), ERPs, fMRI and sMRI. In each case, integration of two or more sources of information provides more information than any one source alone by revealing new insights into structure-function relationships. Furthermore, the addition of other imaging methodologies (such as DTI) and approaches (such as computational models of cognition) offers new horizons in human brain imaging research and in understanding human behavior.

No Effect of Anodal Transcranial Direct Current Stimulation Over the Motor Cortex on Response-Related ERPs during a Conflict Task

Anodal transcranial direct current stimulation (tDCS) over the motor cortex is considered a potential treatment for motor rehabilitation following stroke and other neurological pathologies. However, both the context under which this stimulation is effective and the underlying mechanisms remain to be determined. In this study, we examined the mechanisms by which anodal tDCS may affect motor performance by recording event-related potentials (ERPs) during a cued go/nogo task after anodal tDCS over dominant primary motor cortex (M1) in young adults (Experiment 1) and both dominant and non-dominant M1 in older adults (Experiment 2). In both experiments, anodal tDCS had no effect on either response time (RT) or response-related ERPs, including the cue-locked contingent negative variation (CNV) and both target-locked and response-locked lateralized readiness potentials (LRP). Bayesian model selection analyses showed that, for all measures, the null effects model was stronger than a model including anodal tDCS vs. sham. We conclude that anodal tDCS has no effect on RT or response-related ERPs during a cued go/nogo task in either young or older adults.