Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

Fifty Years of Prefrontal Cortex Research: Impact on Assessment

Our knowledge of the functions of the prefrontal cortex, often called executive, supervisory, or control, has been transformed over the past 50 years. After operationally defining terms for clarification, we review the impact of advances in functional, structural, and theoretical levels of understanding upon neuropsychological assessment practice as a means of identifying 11 principles/challenges relating to assessment of executive function. Three of these were already known 50 years ago, and 8 have been confirmed or emerged since. Key themes over this period have been the emergence of the use of naturalistic tests to address issues of "ecological validity"; discovery of the complexity of the frontal lobe control system; invention of new tests for clinical use; development of key theoretical frameworks that address the issue of the role of prefrontal cortex systems in the organization of human cognition; the move toward considering brain systems rather than brain regions; the advent of functional neuroimaging, and its emerging integration into clinical practice. Despite these huge advances, however, practicing neuropsychologists are still desperately in need of new ways of measuring executive function. We discuss pathways by which this might happen, including decoupling the two levels of explanation (information processing; brain structure) and integrating very recent technological advances into the neuropsychologist's toolbox. (JINS, 2017, 23, 755-767)

Ventral tegmental area deep brain stimulation for chronic cluster headache: Effects on cognition, mood, pain report behaviour and quality of life

BACKGROUND: Deep brain stimulation in the ventral tegmental area (VTA-DBS) has provided remarkable therapeutic benefits in decreasing headache frequency and severity in patients with medically refractory chronic cluster headache (CH). However, to date the effects of VTA-DBS on cognition, mood and quality of life have not been examined in detail. METHODS: The aim of the present study was to do so in a case series of 18 consecutive patients with cluster headache who underwent implantation of deep brain stimulation electrodes in the ventral tegmental area. The patients were evaluated preoperatively and after a mean of 14 months of VTA-DBS on tests of global cognition (Mini Mental State Examination), intelligence (Wechsler Abbreviated Scale of Intelligence), verbal memory (California Verbal Learning Test-II), executive function (Delis-Kaplan Executive Function System), and attention (Paced Auditory Serial Addition Test). Depression (Beck Depression Inventory and Hospital Anxiety and Depression Rating Scale-D), anxiety (Hospital Anxiety and Depression Rating Scale-A), apathy (Starkstein Apathy Scale), and hopelessness (Beck Hopelessness Scale) were also assessed. Subjective pain experience (McGill Pain Questionnaire), behaviour (Pain Behaviour Checklist) and quality of life (Short Form-36) were also evaluated at the same time points. RESULTS: VTA-DBS resulted in significant improvement of headache frequency (from a mean of five to two attacks daily, p < .001) and severity (from mean Verbal Rating Scale [VRS] of 10 to 7, p < .001) which was associated with significant reduction of anxiety (from mean HADS-A of 11.94 to 8.00, p < .001) and help-seeking behaviours (from mean PBC of 4.00 to 2.61, p < .001). VTA-DBS did not produce any significant change to any tests of cognitive function and any other outcome measures (BDI, HADS-D, SAS, BHS, McGill Pain Questionnaire, Short Form-36). CONCLUSION: We confirm the efficacy of VTA-DBS in the treatment of medically refractory chronic cluster headache. The reduction of headache frequency and severity was associated with a significant reduction of anxiety. Furthermore, the result suggests that VTA-DBS for chronic cluster headache improves pain-related help-seeking behaviours and does not produce any change in cognition

Neuro-cognitive architecture of executive functions: A latent variable analysis

Executive functions refer to high-level cognitive processes that, by operating on lower-level mental processes, flexibly regulate and control our thoughts and goal-directed behavior. Despite their crucial role, the study of the nature and organization of executive functions still faces inherent difficulties. Moreover, most executive function models put under test until now are brain-free models: they are defined and discussed without assumptions regarding the neural bases of executive functions. By using a latent variable approach, here we tested a brain-centered model of executive function organization proposing that two distinct domain-general executive functions, namely, criterion setting and monitoring, may be dissociable both functionally and anatomically, with a left vs. right hemispheric preference of prefrontal cortex and related neural networks, respectively. To this end, we tested a sample of healthy participants on a battery of computerized tasks assessing criterion setting and monitoring processes and involving diverse task domains, including the verbal and visuospatial ones, which are well-known to be lateralized. By doing this, we were able to specifically assess the influence of these task domains on the organization of executive functions and to directly contrast a process-based model of EF organization versus both a purely domain-based model and a process-based, but domain-dependent one. The results of confirmatory factor analyses showed that a purely process-based model reliably provided a better fit to the observed data as compared to alternative models, supporting the specific theoretical model that fractionates a subset of executive functions into criterion setting and monitoring with hemispheric specializations emerging regardless of the task domain

FMRI evidence of a functional network setting the criteria for withholding a response

That the left prefrontal cortex has a critical role setting response criteria for numerous tasks has been well established, but gaps remain in our understanding of the brain mechanisms of task-setting. We aimed at (i) testing the involvement of this region in setting the criteria for a non-response and (ii) assessing functional connectivity between this and other brain regions involved in task-setting. Fourteen young participants performed a go/nogo task during functional magnetic resonance imaging. The task included two nogo visual stimuli which elicit a high (distractor) or a low (other) tendency to respond, respectively. Two task blocks were examined to assess learning the criteria. First, a multivariate Partial Least Squares (PLS) analysis identified brain regions that co-varied with task conditions, as expressed by two significant Latent Variables (LVs). One LV distinguished go and nogo stimuli. The other LV identified regions involved in the first block when the criteria not to respond to distractors were established. The left prefrontal region was prominently involved. Second, a left ventrolateral prefrontal area was selected from this LV as a seed region to perform functional connectivity using a multi-block PLS analysis. Results showed a distributed network functionally connected with the seed, including superior medial prefrontal and left superior parietal regions. These findings extend our understanding of task-setting along the following dimensions: 1) even when a task requires withholding a response, the left prefrontal cortex has a critical role in setting criteria, and 2) this region responds to the task demands within a distinctive functional network

Tracing the boundaries of executive function fractionation: evidence from lesion-symptom mapping in brain tumor patients

The purpose of the present research project was to investigate, by means of different lesion-symptom mapping techniques, the behavioral consequences of focal frontal lobe injuries in order to tackle the currently debated issues regarding the PFC organization. In particular, in the first two studies we aimed at delineating the observed impairments as possible disruptions of common and/or distinct processes in order to test the dissociability of putatively distinct cognitive control processes. We focused on switching and response inhibition abilities, which according to the literature rely on left and right prefrontal areas, and tested whether their impairments could be accounted for by more general task-setting and/or sustained attention impairments. In particular, we tested brain tumor patients with left and right prefrontal damage, and compared their performance with non-prefrontal patients and healthy controls. Critically, in order to exclude eventual lower-level processing difficulties known to emerge after lateralized brain lesions, verbal and spatial features of the employed tasks were mostly balanced. The results from both studies suggest that there is probably no specialized inhibitory or switching module hosted by a particular brain area; instead they show how performance on tasks requiring both inhibitory and switching abilities can be disrupted by a more general task-setting impairment supported by left prefrontal areas and their connections with posterior regions. Furthermore, inhibitory impairments, previously observed in patients with right prefrontal lesion, might alternatively be explained by sustained attention impairments. In the last study, instead, we focused on finding out whether lesions in specific prefrontal areas could account for a general cognitive decline, as supported by unitary models of the PFC organization. In particular, we applied a latent variable analysis on distinct neuropsychological test scores in order to minimize the influence of low-level processing requirements and thus obtain a more pure measure of general cognitive functioning. Additionally, we examined the impact of surgical tumor removal on general cognitive functioning across different tumor histological types. The results confirmed previous findings on the impact of surgery on low-grade glioma. However, they also extend them by showing that surgery in left dorsolateral frontal areas causes a more prominent cognitive decline, regardless of the tumor histology. Taken together, the findings across all the three studies have highlighted a critical involvement of left- lateralized prefrontal areas in most of the high-level cognitive tasks we employed, event though the precise localization was somewhat different. However, the involvement of right prefrontal areas seemed critical in more sustained type of processing required to maintain attention to task-relevant events. This observation is in line with a more integrative, albeit lateralized, view of the PFC organization according to which higher, associative types of processes rely on the interaction between frontal and posterior brain regions, but their left and right lateralizations reflect separate, specialized type of processing probably involved in more phasic type of processing, necessary to form and flexibly implement task-relevant associations, and sustained type of processing, needed to maintain the relevant features of the task in an active state

Cortical oscillatory changes associated with cognitive effort, value of effort, and incentive.

Cognitive effort is conceptualised as being deployed relative to the SV of its associated outcomes. The SV of incentives should therefore directly modulate effortful performance, as well as cortical processes associated with effortful engagement. However, the relationship between incentive value and modality, and effortful engagement remains unclear. The current thesis aimed to elaborate on the deployment of cognitive effort in response to incentives of differing magnitude and valence using preparatory ERD/ERS measures in tandem with discounting procedures. ERD/ERS in the alpha and beta bands was used to untangle cortical activation from inhibition during effortful engagement, as well as separating anticipatory attention from approach/avoidance motor responses under rewards of differing magnitudes and valence. Further, a COGED discounting task was used to estimate effort discounting rates, and to compare the SV of gains and losses. The results presented in the three experimental chapters showed that rewards lead to different modulations in pre-movement ERD/ERS depending on the task-structure used. Losses were more motivating than gains, but were associated with slower RTs, as well as deteriorations in alpha-band ERD. Further, individual SVs of effort were not significantly associated with changes in RT or ERD under differing incentives. The current thesis showed that cognitive effort is deployed through patterns of strategic cortical activation and inhibition, rather than a sustained increase in cortical activation. Further, the divergent effect of losses and gains was revealed to likely be due to attentional effects not the previously hypothesised approach/avoidance associations. Finally, the SV of effort does not appear to directly inform effortful engagement