This study represents the first demonstration of neural networks associated with executive inhibitory control of generic information in PTSD. We found that PTSD involves both inhibitory deficits and reduced activation of brain areas normally associated with successful inhibition (particularly the right IFC, which may be an important locus of inhibitory control27–29
). Consistent with previous studies in healthy individuals, control participants activated a mostly right-lateralized fronto-parietal cortical network during inhibitory processing.27–30
In contrast, patients with PTSD activated mostly the left VLPFC and showed reduced activation of a right-lateralized frontotemporoparietal cortical inhibitory network, relative to control participants. We also found that inhibitory responding in PTSD was associated with the recruitment of areas related to sensory processing (somatosensory cortex, parahippocampus and visual cortex) and higher inhibitory task demand (striatal regions30
We found that there was an increase in inhibitory error with increased PTSD severity. Appropriately, our findings suggest not only that there is an increase in inhibitory error with increased PTSD severity but also that more severe PTSD may be related to the diminished recruitment of inhibitory control networks. Successful inhibition (reduced commission error) in patients with PTSD recruited a bilateral inferior frontal and striatal (putamen) inhibition network. We found that decreased PTSD severity related to the enhanced recruitment of inhibitory control areas (right IFC and DLPFC) and to additional recruitment of the mPFC/left supplementary motor area (which has been implicated in motor response planning and inhibition27
). That is, patients with less severe PTSD recruited inhibitory control areas to a greater extent during inhibitory responding than did those with more severe PTSD. One possible explanation for this reduction in executive control with increased PTSD severity is that PTSD disrupts cortical control systems; participants with PTSD are able to recruit inhibitory control networks, but these control systems may be deficient or “overwhelmed” with increasing PTSD severity. Alternatively, it is possible that individuals with a diminished ability to recruit these executive areas are at greater risk for developing more severe PTSD symptoms. Importantly, our findings argue against the possibility that the diminished cortical recruitment observed in PTSD is adaptive or reflects an enhanced cortical efficiency because increased PTSD severity was associated with both increased inhibitory error and a diminished recruitment of inhibitory control systems.
PTSD involves generalized hypervigilence, excessive arousal-related processing and enhanced response to salient stimuli2
as well as cortical hyperexcitability.24
Adrenergic, arousal-related processing stimulates the cortex and contributes to deficits in prefrontal function and executive control.41
As such, inhibitory deficits in PTSD may be explained by increased stimulus processing that stimulates and places a demand on the cortex. Our finding of increased somatosensory cortical (postcentral gyrus), parahippocampal and visual cortical activation in patients with PTSD relative to control participants is consistent with a state of enhanced sensory processing during inhibitory control.2,42
The increased activation in the putamen in patients with PTSD relative to control participants during inhibitory processing suggests that there may be an increased demand placed on inhibitory control systems in PTSD. The striatum is recruited during Go/No-Go performance when the task requires more urgent inhibition and therefore involves an increased demand on inhibitory control.30
Animal models also show that differential activation of the frontal cortex and striatal network is involved in behavioural flexibility, with the frontal cortex supporting the inhibition of a previous choice to generate a new behavioural choice, whereas the striatum maintains a behavioural strategy once it is selected.43
Disruptions in this corticostriatal pathway possibly underlie the lack of both cognitive and behavioural flexibility and the repetitive, stereotyped behaviour that is characteristic of certain neuropsychiatric conditions (such as obsessive–compulsive disorder44
). The striatum is also important for learning to predict aversive and rewarding outcomes,45
and it is suggested that the striatum plays a role in regulating attention to predict danger.46
Considering this role of the striatum, an increase in striatal activation in PTSD is particularly relevant to the enhanced attentional bias to threat and novelty shown to be characteristic of PTSD.2
Taken together, the increased activation of sensory-related areas and the striatum in PTSD during No-Go responding may reflect enhanced sensory processing, an increased demand on control systems and a possible dysregulation in the substrates of behavioural flexibility.
Notably, we found diminished mPFC and dorsal ACC (dACC) activation in patients with PTSD relative to control participants during inhibitory control in our Go/No-Go task. This stands in contrast to previous studies showing increased dACC/mPFC activation in patients with PTSD relative to control participants during target-related responding in an auditory oddball task.2
Similar to the auditory oddball task, the Go/No-Go task involves both selective attention and response selection, but in addition, it involves executive inhibitory control. These convergent findings suggest that processing related to attention and response selection may be heightened in PTSD, whereas an additional demand on executive inhibition may involve a breakdown in cortical control. That is, our findings of reduced mPFC/dACC in patients with PTSD during inhibitory responding may indicate that our emotionally neutral inhibitory control task involves a sufficient demand on cortical control to overwhelm this regulatory structure.6
This suggestion is further supported by our observation that decreased PTSD severity was related to increased activation of the mPFC during inhibitory control. The mPFC, ACC and orbitofrontal cortex may have a critical role in coordinating the networks involved in alerting and processing significant stimuli with those involved in more detailed, controlled contextual processing (hippocampus and lateral prefrontal cortex).47
Our findings of reduced dACC/mPFC and orbitofrontal cortex activation in PTSD during inhibitory control may suggest a disruption of “significance processing” networks in PTSD.
Previous trauma exposure in the control participants did not significantly influence our main findings; both trauma-exposed and healthy control participants activated the right orbitofrontal/VLPFC during inhibitory control and also activated this area to a greater extent than participants with PTSD. However, whereas those with PTSD differed in their inhibitory performance relative to healthy control participants, our behavioural findings indicated that participants with PTSD did not differ in inhibition-related performance relative to trauma-exposed control participants. This may reflect a possible floor effect, since our Go/No-Go task was relatively simple (commission errors: PTSD mean 3.5; trauma-exposed control mean 2.3; healthy control mean 1.4). It is interesting, however, that even this simple inhibitory task was associated with a significant reduction in cortical activation in participants with PTSD.
Limitations of this study include the possible effects on our findings of comorbid diagnoses, possible axis II disorder (DSM-IV36
) or the use of medication. Comorbid depressive symptoms did not significantly affect inhibition-related frontal cortical activation in patients with PTSD; those having PTSD both with and without depression showed diminished activation of the orbitofrontal/VLPFC and mPFC inhibition areas as well as increased activation of somatosensory areas (postcentral cortex) and areas related to increased inhibitory demand (striatum), relative to control participants. Further, depression severity did not significantly influence frontal cortical activation in participants with PTSD during No-Go inhibition. Another limitation of the current study is the possible effect of sex or handedness on our findings (considering that inhibitory control networks showed right lateralization). This possibility should be explored in future studies.
In conclusion, our findings not only support previous models of PTSD suggesting that PTSD is accompanied by enhanced stimulus processing2
and reduced cortical control,3–22
they also extend these models to show that PTSD involves unique neural alterations during the executive inhibitory control of emotionally neutral information processing. Our findings indicate that increasing PTSD severity may be related to a greater disruption of cortical control networks. Additional research should be undertaken to explore further the mechanisms associated with these PTSD-related changes in inhibitory processing, and particularly the ways in which autonomic arousal may modulate these changes.