Inhibition processes are dissociable and lateralized in human prefrontal cortex

Abstract

The prefrontal cortex (PFC) is known to make fundamental contributions to executive functions. However, the precise nature of these contributions is incompletely understood. We focused on a specific executive function, inhibition, the ability to suppress a pre-potent response. Functional imaging and animal studies have studied inhibition. However, there are only few lesion studies, typically reporting discrepant findings. For the first time, we conducted cognitive and neuroimaging investigations on patients with focal unilateral PFC lesions across two widely used inhibitory tasks requiring a verbal response: The Hayling Part 2 and Stroop Colour-Word Tests. We systematically explored the relationship between inhibition, fluid intelligence and lesion location using voxel-based lesion symptom mapping (VLSM). We found that PFC patients were significantly impaired compared with healthy comparison group (HC) on both suppression measures of the Hayling and on the Stroop, even when performance on a fluid intelligence test was covaried. No significant relationship was found between patients' performance on each Hayling suppression measure and the Stroop, once fluid intelligence was partialled out, suggesting that the two tests may involve different kinds of inhibition. After accounting for fluid intelligence, we found a significant interaction between tests, Hayling or Stroop, and site, left or right, of PFC damage. This finding suggesting lateralized functional organization was complemented and extended by our VLSM results. We found that performance on both Hayling suppression measures significantly relied on the integrity of a similar and relatively circumscribed region within the right lateral PFC, in the right lateral superior and middle frontal gyri. In stark contrast, performance on the Stroop relies on the integrity of left lateral superior and middle frontal gyri. Thus, lesion location, right or left PFC, is critical in producing impairments on two inhibitory tasks loading similarly on verbal control. This suggests that the two suppression measures of the Hayling and the Stroop are likely to assess dissociable components of executive functions, related to anatomically defined and lateralized PFC circuits. Our findings also suggest that inhibition may actually comprise qualitatively different forms with different neural substrates. This has clinical implications for the diagnosis and treatment of disinhibition impairments, a common behavioural problem caused by PFC lesions. Our results highlight the need to assess inhibition using a variety of tasks and to develop different types of treatments.

Tempering Proactive Cognitive Control by Transcranial Direct Current Stimulation of the Right (but Not the Left) Lateral Prefrontal Cortex

“…From this perspective, the increased rate of “yes responses” to BX trials in our cathode right DLPFC group could be interpreted as a consequence of an impairment in modulating the influence of dominant, integrated stimulus-response representations (“X-yes response”). It is worth noting here that while the two above-mentioned interpretations attribute distinct roles to the right DLPFC, both fit well with the general assumption that this region is a core component of the inhibitory control network (i.e., Kelly et al, 2004; Shackman et al, 2009; Gagnepain et al, 2014; Zmigrod et al, 2014; Cipolotti et al, 2016), which could have been compromised by cathodal tDCS in the present experiment.…”

“…The right DLPFC, along with other prefrontal and subcortical regions, is typically considered a part of an inhibitory network (Kelly et al, 2004; Beeli et al, 2008; Shackman et al, 2009; Gagnepain et al, 2014; Cipolotti et al, 2016; but see Aron et al, 2014). Thus, for example, this region is thought to play a role in the distributed neural system underpinning behavioral inhibition in response to threat, with more behaviorally inhibited individuals showing more EEG activity in the right DLPFC (McNaughton and Corr, 2004; Shackman et al, 2009).…”

Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

“…Similar increases in inhibitory control, revealed as faster responses to incongruent word-color conditions, have also been encountered after high-frequency rTMS over left dlPFC (Vanderhasselt et al, 2006 ; Kim et al, 2012 ). The left dlPFC is directly involved in inhibitory control processes (Miller and Cohen, 2001 ; Cipolotti et al, 2016 ), thus the increased excitability of this region can lead to a better performance. Nonetheless, in our study, the excitability decrease hypothetically caused by cTBS (Tupak et al, 2013 ) did not hinder the capacity for inhibitory control, unlike in a previous study (Lowe et al, 2014 ).…”

“…This “paradoxical facilitation” after decreasing cortical excitability could be explained by a disruption of a competing process localized in the left hemisphere, probably causing a transcallosal facilitation in the contralateral region. Indeed, different studies show the involvement of the right dlPFC in planning abilities, visuospatial memory, and/or response inhibition, the three main processes measured by the Tower of Hanoi (Epstein et al, 2002 ; Fincham et al, 2002 ; Sack et al, 2005 ; Srovnalova et al, 2012 ; Kaller et al, 2013 ; Fried et al, 2014 ; Cipolotti et al, 2016 ).…”

Intra- and Inter-individual Variability of Executive Functions: Determinant and Modulating Factors in Healthy and Pathological Conditions

“…Roca et al (2010) demonstrated that impaired performance in frontal patients on EF tests such as the Wisconsin Card Sorting Test, verbal fluency and the Iowa Gambling Task can be explained by fluid intelligence impairments, although Robinson et al (2012) showed the opposite for verbal fluency. However, for other EF tasks such as the Hayling Sentence Completion test and the Stroop test, frontal patients' impairments could not be accounted for by reduced fluid abilities (Roca et al, 2010;Cipolotti et al, 2016: for a similar finding in schizophrenia see Martin et al, 2015). Moreover, although Barbey et al (2012) identified shared neural substrates in the frontal and parietal cortex for EF and general intelligence (g), there were additional brain regions specific to EF (e.g., the left anterior pole) and brain regions specific to g (e.g., the left inferior occipital gyrus and the right superior and inferior parietal lobe).…”