Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left–right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems—e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

Daniel Tranel , Hanna Damasio , Natalie L. Denburg , and Antoine Bechara
Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?
Brain Advance Access published on December 1, 2005, DOI 10.1093/brain/awh643.
Brain 128: 2872-2881.

http://brain.oxfordjournals.org/cgi/content/full/128/12/2872

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7 s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Seiki Konishi , Kyoichi Nakajima , Idai Uchida , Hideyuki Kikyo , Masashi Kameyama , and Yasushi Miyashita
Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI
Bain 122: 981-991.

http://brain.oxfordjournals.org/cgi/content/full/122/5/981

Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli

Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 ± 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 ± 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 ± 11.6 years), we monitored HR as R–R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR and BP during pleasant and not quite significant HR increases (P = 0.06) with only slight BP increase during unpleasant VES. Other biosignals remained unchanged during VES in all groups. Our results show that VMPFC has no major influence on autonomic modulation at rest and during non-emotional, physical stimulation. The paradoxical HR and BP responses in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right VMPFC. Valence of non-stressful stimuli has a limited effect with more prominent left VMPFC modulation of pleasant and more right VMPFC modulation of unpleasant stimuli. The paradoxical sympathetic disinhibition in VMPFC-R patients may increase their risk of sympathetic hyperexcitability with negative consequences such as anxiety, hypertension or cardiac arrhythmias.

Max J. Hilz , Orrin Devinsky , Hanna Szczepanska , Joan C. Borod , Harald Marthol , and Marcin Tutaj
Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli
Brain Advance Access published on December 1, 2006, DOI 10.1093/brain/awl299.
Brain 129: 3343-3355.

http://brain.oxfordjournals.org/cgi/content/full/129/12/3343

Prefrontal regions involved in keeping information in and out of mind

Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain–behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.



Fig. 3 Rendering of group-averaged brain activations. (A) Load-related activations identified by the contrast Load 4 > Load 1 (P <>B) Load-related activations identified by the contrast Load 6 > Load 4 (P <>P <>C) Interference-related activations identified by the contrast Load 4 High Recency > Load 4 (P <>P < 0.05). Liberal thresholds were chosen to illustrate the overlap between regions activated by each contrast. The level of significance of activation at each voxel (T value) is colour-coded according to the scale on the right of each figure. Silvia A. Bunge , Kevin N. Ochsner , John E. Desmond , Gary H. Glover , and John D. E. Gabrieli Prefrontal regions involved in keeping information in and out of mind Brain 124: 2074-2086. Silvia A. Bunge , Kevin N. Ochsner , John E. Desmond , Gary H. Glover , and John D. E. Gabrieli Prefrontal regions involved in keeping information in and out of mind Brain 124: 2074-2086.

Silvia A. Bunge , Kevin N. Ochsner , John E. Desmond , Gary H. Glover , and John D. E. Gabrieli
Prefrontal regions involved in keeping information in and out of mind
Brain 124: 2074-2086.

http://brain.oxfordjournals.org/cgi/content/full/124/10/2074

Right prefrontal cortex and episodic memory retrieval: a functional MRI test of the monitoring hypothesis

Though the right prefrontal cortex is often activated in neuroimaging studies of episodic memory retrieval, the functional significance of this activation remains unresolved. In this functional MRI study of 12 healthy volunteers, we tested the hypothesis that one role of the right prefrontal cortex is to monitor the information retrieved from episodic memory in order to make an appropriate response. The critical comparison was between two word recognition tasks that differed only in whether correct responses did or did not require reference to the spatiotemporal context of words presented during a previous study episode. Activation in a dorsal midlateral region of the right prefrontal cortex was associated with increased contextual monitoring demands, whereas a more ventral region of the right prefrontal cortex showed retrieval-related activation that was independent of task instructions. This functional dissociation of dorsal and ventral right prefrontal regions is discussed in relation to a theoretical framework for the control of episodic memory retrieval.



Fig. 2 Lateral areas showing BOLD signal increases (red) and decreases (blue) in comparisons of (A) the Encoding condition relative to the Control condition, (B) the Inclusion condition relative to the Control condition, (C) the Exclusion condition relative to the Control condition and (D) the Exclusion condition relative to the Inclusion condition. For the purpose of illustration the threshold is slightly lower (P < 0.0001 uncorrected) than in Tables 2–5.

R. N. A. Henson , T. Shallice , and R. J. Dolan
Right prefrontal cortex and episodic memory retrieval: a functional MRI test of the monitoring hypothesis
Brain 122: 1367-1381.

http://brain.oxfordjournals.org/cgi/content/full/122/7/1367

Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes

Functional neuroimaging studies of episodic recognition memory consistently demonstrate retrieval-associated activation in right prefrontal regions, including the right anterior and right dorsolateral prefrontal cortices. In theory, these activations could reflect processes associated with retrieval success, retrieval effort or retrieval attempt; each of these hypotheses has some support from previous studies. In Experiment 1, we examined these functional interpretations using functional MRI to measure prefrontal activation across multiple levels of recognition performance. Results revealed similar patterns of right prefrontal activation across varying levels of retrieval success and retrieval effort, suggesting that these activations reflect retrieval attempt. Retrieval attempt may include initiation of retrieval search or evaluation of the products of retrieval, such as scrutiny of specific attributes of the test item in an effort to determine whether it was encountered previously. In Experiment 2, we examined whether engagement of retrieval attempt is context-dependent by varying the context in which retrieval was performed; this was done by changing test instructions. Importantly, study and test stimuli were held constant, with only the test instructions varying across conditions. Results revealed that the pattern of right prefrontal activation varied across retrieval contexts. Collectively, these experiments suggest that right prefrontal regions mediate processes associated with retrieval attempt, with the probability of engaging these regions depending upon the retrieval context. Conflicting results across previous studies may be reconciled if the influence of retrieval context on the adopted retrieval strategy is considered. Finally, these results suggest that right prefrontal regions activated during recognition are not critical for successful performance as similar magnitudes of activation were present across multiple levels of performance. These findings reconcile imaging results with the selective effects of prefrontal lesions on retrieval- intensive episodic memory tests.

AD Wagner , JE Desmond , GH Glover , and JD Gabrieli.
Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes.
Brain 121: 1985-2002.

http://brain.oxfordjournals.org/cgi/content/abstract/121/10/1985

Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour

Three patients with a unilateral cortical lesion affecting the dorsolateral prefrontal cortex (DLPFC), i.e. Brodmann area 46, were tested using different paradigms of reflexive saccades (gap and overlap tasks), intentional saccades (antisaccades, memory-guided and predictive saccades) and smooth pursuit movements. Visually guided saccades with gap and overlap, latency of correct antisaccades and memory-guided saccades and the gain of smooth pursuit were normal, compared with controls. These results confirm our anatomical data showing that the adjacent frontal eye field (FEF) was unimpaired in these patients. The specific pattern of abnormalities after a unilateral DLPFC lesion, compared with that of the FEF lesions previously reported, consists mainly of: (i) a bilateral increase in the percentage of errors in the antisaccade task (misdirected reflexive saccades); (ii) a bilateral increase in the variable error in amplitude, without significant decrease in the gain, in the memory-guided saccade task; and (iii) a bilateral decrease in the percentage of anticipatory saccades in the predictive task. Taken together, these results suggest that the DLPFC plays a crucial role in the decisional processes, preparing saccades by inhibiting unwanted reflexive saccades (inhibition), maintaining memorized information for ongoing intentional saccades (short-term spatial memory) or facilitating anticipatory saccades (prediction), depending upon current external environmental and internal circumstances.




Fig. 6 Cortical areas involved in saccades. After receiving visual information in the occipital lobe and after visuospatial integration in the PPC, a saccade may be either triggered reflexively, mainly by the PEF, or triggered intentionally by the FEF, an area which also appears to be involved in active visual fixation. If a reflexive saccade must be inhibited, the DLPFC appears to play a crucial role (1). This area is also involved in short-term spatial memory (2) and prediction (3) when anticipatory saccades must be performed. With these three different actions, the DLPFC could play an important role in the decisional processes controlling ocular motor behaviour. The SEF could be involved in motor programmes including several successive saccades, or saccades combined with other body movements, whereas the CEF appears to activate all the areas controlling intentional saccades via a motivation process. ACC = anterior cingulate cortex; CEF = cingulate eye field; cs = central sulcus; DLPFC = dorsolateral prefrontal cortex; FEF = frontal eye field; ips = intraparietal sulcus; ls = lateral sulcus; pcs = precentral sulcus; PEF = parietal eye field; PPC = posterior parietal cortex; RF = brainstem reticular formation; SC = superior colliculus; SEF = supplementary eye field; 1, 2, 3 = the main actions of the DLPFC; + = saccade triggering; – = saccade inhibition.

C. Pierrot-Deseilligny , R. M. Müri , C. J. Ploner , B. Gaymard , S. Demeret , and S. Rivaud-Pechoux .
Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour.
Brain Advance Access published on June 1, 2003, DOI 10.1093/brain/awg148.
Brain 126: 1460-1473.

http://brain.oxfordjournals.org/cgi/content/full/126/6/1460