Pinning down response inhibition in the brain--conjunction analyses of the Stop-signal task.

Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA.
NeuroImage (Impact Factor: 6.13). 05/2010; 52(4):1621-32. DOI: 10.1016/j.neuroimage.2010.04.276
Source: PubMed

ABSTRACT Successful behavior requires a finely-tuned interplay of initiating and inhibiting motor programs to react effectively to constantly changing environmental demands. One particularly useful paradigm for investigating inhibitory motor control is the Stop-signal task, where already-initiated responses to Go-stimuli are to be inhibited upon the rapid subsequent presentation of a Stop-stimulus (yielding successful and unsuccessful Stop-trials). Despite the extensive use of this paradigm in functional neuroimaging, there is no consensus on which functional comparison to use to characterize response-inhibition-related brain activity. Here, we utilize conjunction analyses of successful and unsuccessful Stop-trials that are each contrasted against a reference condition. This conjunction approach identifies processes common to both Stop-trial types while excluding processes specific to either, thereby capitalizing on the presence of some response-inhibition-related activity in both conditions. Using this approach on fMRI data from human subjects, we identify a network of brain structures that was linked to both types of Stop-trials, including lateral-inferior frontal and medial frontal cortical areas and the caudate nucleus. In addition, comparisons with a reference condition matched for visual stimulation identified additional activity in the right inferior parietal cortex that may play a role in enhancing the processing of the Stop-stimuli. Finally, differences in stopping efficacy across subjects were associated with variations in activity in the left anterior insula. However, this region was also associated with general task accuracy (which furthermore correlated directly with stopping efficacy), suggesting that it might actually reflect a more general mechanism of performance control that supports response inhibition in a relatively nonspecific way.

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    ABSTRACT: Clinical signs of traumatic brain injury (TBI) such as altered- or complete loss of consciousness, other neurological signs, and findings based on conventional neuroimaging, represents important information for initial treatment and further follow-up of TBI survivors. However, not all real-life problems after TBI are easily detected by conventional imaging methods or neurological exams. This is particularly evident when trying to assess the more subtle effects of TBI, such as cognitive and emotional problems, that are often experienced in the chronic stage, after the initial recovery period has passed. The main aim for this thesis was to extend current knowledge on functional and structural changes in the brain after moderate-to-severe TBI by means of advanced neuroimaging methods, and to relate these findings to injury-related variables and functional measures known to be important for outcome. A particular focus was on investigating cognitive control function, as this has been demonstrated to play an especially important role for functional outcome after TBI. In order to reach this aim, several studies with different but related perspectives were performed, and four papers (Paper I – IV) based on these studies are included in this thesis. In Paper I, a large group of healthy participants was included in a study in order to validate a clinically relevant task protocol that could measure both adaptive and stable cognitive control processes in the brain by means of blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Results from this study gave further support for a core network of cognitive control, with overlapping activations for both stable and adaptive processes, comprised by brain regions bilaterally in the insula (and adjacent cortices) and dorsal medial frontal cortex. It was also established that in this particular task, adaptive cognitive control processes by and large were distributed in more anterior regions of the prefrontal cortex as compared to stable cognitive control processes. Another novel and important finding, was that only stable cognitive control processes were affected by time on task (TOT), indicating that this contrast might be particularly sensitive for detecting adaptive changes in the brain. In Paper II, it was demonstrated that executive, emotional and behavioral problems were more frequently reported in chronic moderate-to-severe TBI survivors as compared to healthy controls. The results also indicated that identification of traumatic axonal injury (TAI) and symptoms of depression in an earlier phase after injury, might give a warning of later problems. Furthermore, self-report measures of cognitive control seemed to extend the information obtained from performance-based measures. In Paper III, it was shown that neuronal correlates of adaptive and stable cognitive control processes were differently affected by moderate-to severe TBI. Moreover, TBI survivors exhibited increased TOT related BOLD activation related to stable cognitive control processes in the right inferior parietal lobe and right prefrontal cortex. Increases in BOLD activations had a dose-dependent relationship with injury severity, with increased activation with more severe injury. Interestingly, increased BOLD activations after TBI were related to better self-reported cognitive control function in everyday-life situations, indicating a compensatory role for these activations. In paper IV, it was shown that more severe injury based on clinical signs, and findings on conventional MRI evaluations, was related to more pronounced alterations of white matter microstructure in a wide range of tracts as measured with diffusion tensor imaging (DTI). Reduced white matter integrity in TBI survivors was also associated with worse global outcome, and poorer cognitive control function as measured by performance-based measures. No association was found between any of the DTI measures and self-reported cognitive control function. The findings presented in this thesis demonstrated that a broad assessment is warranted in order to optimize our understanding and follow-up of TBI patients. Also, it was shown that subtle changes in brain structure and function, not necessarily detectable with conventional imaging tools, might still have an important impact on how TBI survivors are able to cope with every-day life. A particularly interesting finding with possible clinical implications was that performance-based cognitive control function in chronic TBI was related to subtle structural changes in the brain as measured with DTI, whereas selfreported problems were exclusively related to functional adaptations as measured with fMRI. In general, knowing that self-reported cognitive control function in chronic moderate- to-severe TBI survivors is associated with functional changes in the brain, gives an important perspective when seeing patients where such problems are not easily explained by conventional neuropsychological measures. More than that, as these functional changes were shown to play a potential compensatory role, this might indicate a potential target for neuro-rehabilitation.
    12/2014, Degree: PhD, Supervisor: Asta Kristine Håberg, Co Supervisor: Nils Inge Landrø
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    ABSTRACT: Previous research has shown that stimulation of the left dorsolateral prefrontal cortex (DLPFC) enhances working memory (e.g. in the n-back task), and reduces craving for cigarettes and alcohol. Stimulation of the right inferior frontal gyrus (IFG) improves response inhibition. The underlying mechanisms are not clearly understood, nor is it known whether IFG stimulation also reduces craving. Here, we compared effects of DLPFC, IFG, and sham stimulation on craving in heavy drinkers in a small sample (n=41). We also tested effects of tDCS on overcoming response biases due to associations between alcohol and valence and alcohol and approach, using Implicit Association Tests (IATs). Mild craving was reduced after DLPFC stimulation. Categorization of valence attribute words in the IAT was faster after DLPFC stimulation. We conclude that DLPFC stimulation can reduce craving in heavy drinkers, but found no evidence for tDCS induced changes in alcohol biases, although low power necessitates caution. Copyright © 2014 Elsevier B.V. All rights reserved.
    Biological Psychology 12/2014; 105. DOI:10.1016/j.biopsycho.2014.12.004 · 3.47 Impact Factor
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    ABSTRACT: Response inhibition is an essential control function necessary to adapt one's behavior. This key cognitive capacity is assumed to be dependent on the prefrontal cortex and basal ganglia. It is unresolved whether varying inhibitory demands engage different control mechanisms or whether a single motor inhibitory mechanism is involved in any situation. We addressed this question by comparing electrophysiological activity in conditions that require stopping a response to conditions that require switching to an alternate response. Analyses of electrophysiological data obtained from stop-signal tasks are complicated by overlapping stimulus-related activity that is distributed over frontal and parietal cortical recording sites. Here, we applied Laplacian transformation and independent component analysis (ICA) to overcome these difficulties. Participants were faster in switching compared to stopping a response, but we did not observe differences in neural activity between these conditions. Both stop- and change-trials Laplacian transformed ERPs revealed a comparable bilateral parieto-occipital negativity around 180ms and a frontocentral negativity around 220ms. ICA results suggested an inhibition-related frontocentral component which was characterized by a negativity around 200ms with a likely source in anterior cingulate cortex. The data provide support for the importance of posterior mediofrontal areas in inhibitory response control and are consistent with a common neural pathway underlying stopping and changing a motor response. The methodological approach proved useful to distinguish frontal and parietal sources despite similar timing and the ICA approach allowed assessment of single-trial data with respect to behavioral data. Copyright © 2015. Published by Elsevier B.V.
    International journal of psychophysiology: official journal of the International Organization of Psychophysiology 02/2015; 26. DOI:10.1016/j.ijpsycho.2015.01.012 · 2.65 Impact Factor

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