Dorsolateral Prefrontal Cortex Lesions Research Articles

Patients with dorsolateral prefrontal cortex lesions are capable of discriminatory threat learning but appear impaired in cognitive regulation of subjective fear.

Humans are able to cognitively regulate emotions by changing their thoughts. Neuroimaging studies show correlations between dorsolateral prefrontal cortex (dlPFC) activity and cognitive regulation of emotions. Here our objective was to investigate whether dlPFC damage is associated with impaired cognitive regulation of emotion. We therefore tested the ability of patients with dlPFC lesions (N = 6) and matched control participants (N = 19) to utilize a laboratory version of cognitive regulation training (CRT) to regulate subjective fear and autonomic threat responses following Pavlovian threat conditioning. We found that patients with dlPFC lesions were able to acquire conditioned threat but seemed impaired in their ability to utilize CRT to cognitively regulate subjective fear to a threatening stimulus. Despite inclusion of a limited number of lesion patients, our results suggest that the dlPFC is important for the cognitive regulation of subjective fear.

Discourse production following injury to the dorsolateral prefrontal cortex

Individuals with damage to the prefrontal cortex, and the dorsolateral prefrontal cortex (DLPFC) in particular, often demonstrate difficulties with the formulation of complex language not attributable to aphasia. The present study employed a discourse analysis procedure to characterize the language of individuals with left (L) or right (R) DLPFC lesions. All participants were 30–35 years post-onset of injury and presented with persistent discourse impairments. The discourse performance of the R DLPFC group was not significantly different from either the L DLPFC group or the non-injured comparison group. Individuals from the L DLPFC group demonstrated specific difficulties with narrative coherence and inclusion of critical story components. Both measures were significantly different from the comparison group. The discourse ability of the DLPFC groups was significantly correlated with measures of working memory. Findings support the use of discourse analysis for examining language impairments in individuals with PFC lesions.

BDNF Polymorphism–Dependent OFC and DLPFC Plasticity Differentially Moderates Implicit and Explicit Bias

This study examined the role of orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) plasticity in controlling implicit and explicit social biases. Normal controls and patients with varied OFC and DLPFC lesion size and single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor (BDNF) gene, which promotes (methionine-valine [Met/Val] SNP) or stifles (valine-valine [Val/Val] SNP) plasticity in damaged PFC regions, completed measures of implicit and explicit social bias. Patients and controls demonstrated comparable levels of implicit bias, but patients with Met/Val SNPs exhibited less implicit bias when they had smaller OFC lesions compared with Val/Val patients with similar size lesions and those with large OFC lesions. Both patients and controls demonstrated patterns of explicit bias consistent with hypotheses. Patients with Met/Val SNPs exhibited less explicit bias when they had smaller DLPFC lesions sizes compared with Val/Val patients with similar size lesions and those with large DLPFC lesions. OFC lesion size and BDNF SNP type did not moderate explicit bias; DLPFC lesion size and BDNF SNP type did not moderate implicit bias (nor did other medial or lateral regions). Findings suggest that plasticity within specific PFC regions modulates the type and degree of social bias that individuals' exhibit.

Deficits in Subprocesses of Visual Feature Search after Frontal, Parietal, and Temporal Brain Lesions—A Modeling Approach

Deficits in visuospatial attention are commonly observed after different kinds of brain lesions. However, the structure-function relationships are not well understood. We investigated whether our response time (RT) model, strategies of visual search (STRAVIS), combined with a linear model of brain lesions, enables us to relate specific impairments in cognitive processes to specific sites of focal brain lesions. In STRAVIS, RTs in overt visual feature search with graded target-distractor similarity are decomposed into the durations of successive search steps. Fitting the model to an observer's RTs yields individual estimates of the parameters "attentional focus size," "attentional dwell time," and "movement time of attention or the eyes." In 28 patients with various focal lesions to the frontal, parietal, and/or temporal cortex and 28 matched controls, we determined with the help of linear models which lesions were most predictive for each parameter. Predictions were validated with a second sample of 12 patients and 12 controls. Critical lesion areas for the STRAVIS focus size were the dorsolateral prefrontal cortex and the temporal lobe, with dorsolateral prefrontal cortex lesions reducing the focus and temporal lesions enlarging it. The STRAVIS dwell time was reduced in patients with lesions to the anterior insula and the superior parietal lobe. Lesions to the frontal eye fields, the superior parietal lobe, and the parieto-occipital cortex were most detrimental to the STRAVIS movement time. Applying linear models to a patient sample with heterogeneous lesions may be a promising new method for investigating how different brain areas interplay in a complex task.

Dorsolateral prefrontal cortex lesions impair goal-directed modulation of representations within visual association cortex

Dorsolateral prefrontal cortex lesions impair goal-directed modulation of representations within visual association cortex

Prefrontal cortex and rule abstraction: Where and whether? Theoretical comment on Moore et al. (2009).

The primate dorsolateral prefrontal cortex is implicated in diverse aspects of behavioral regulation, cognitive control, and memory. However, direct neuropsychological evidence supporting a requirement of this area in functions other than spatial working memory has been scarce. T. L. Moore, S. P. Schettler, R. J. Killiany, D. L. Rosene, and M. B. Moss have shown, for the first time, that lesions of dorsolateral prefrontal cortex in the rhesus monkey (including areas 9 and 46) substantially impair performance in a test of executive function modeled on the Wisconsin Card Sorting Task. The pattern of impairment is consistent with a role for dorsolateral prefrontal areas in rule abstraction but may relate to a role for this area in rule maintenance as well. Interestingly, monkeys with dorsolateral prefrontal lesions do not appear to perseverate in their use of particular rules in the task, different from the common impairment associated with frontal lobe damage in humans. These findings indicate that dorsolateral prefrontal cortex is necessary for some aspects of rule-guided behavior in the primate brain and help illuminate the involvement of different prefrontal areas in different aspects of executive function and rule-guided behavior.

Rhinal and dorsolateral prefrontal cortex lesions produce selective impairments in object and spatial learning and memory in canines

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed nonmatching to sample, or DNMS) and a spatial (delayed nonmatching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-second delay, suggesting disrupted retention of the general task rules; however, this impairment was transient, and long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a nonmatching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals.

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal-temporal interaction.

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure.

Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions.

Damage to the orbitofrontal cortex (OFC) in humans has been associated with disinhibited or socially inappropriate behaviour and emotional changes. Some of the changes may be related to difficulty in responding correctly to rewards and punishers, in that these patients have difficulty in learning to correct their choice of a visual stimulus when it is no longer associated with reward. We extend this fundamental approach by investigating the relationship between frontal dysfunction and impulsive behaviour, the behavioural, emotional and personality changes seen in patients with prefrontal cortex damage, and thus in addition illuminate the cognitive and biological processes that are impaired in impulsive people. OFC patients (n = 23) performed more impulsively on both self-report and cognitive/behavioural tests of impulsivity, reported more inappropriate 'frontal' behaviours, and performed worse on a stimulus-reinforcement association reversal task, than non-OFC prefrontal cortex lesion control (n = 20) and normal control (n = 39) participants. Further, OFC patients experienced more subjective anger than non-OFC and normal participants, and less subjective happiness than normals; and had a faster subjective sense of time (overestimated and underproduced time intervals) than normal controls, while non-OFC patients did not differ from normals. Finally, both OFC and non-OFC patients were less open to experience than normal participants. There were no differences between OFC patients, non-OFC lesion patients and normal controls on all other personality traits, most notably extraversion. In a spatial working memory task, the non-OFC group, most of whom had dorsolateral prefrontal cortex lesions, were impaired in that they repeatedly returned to previously chosen empty locations ('within errors'), whereas OFC patients were not impaired on this measure. Thus there is a dissociation between the effects of OFC damage which does not affect this measure of spatial working memory but does affect impulsive and inappropriate behaviour, reversal, personality, time perception and emotion; and dorsolateral prefrontal cortex damage which does affect this measure of spatial working memory, but not impulsive and inappropriate behaviour, reversal, personality, time perception and emotion. The effects of OFC damage on impulsive and related behaviours described here have implications for understanding impulsive behaviour.

Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices.

To analyse the functions of different parts of the prefrontal cortex in emotion, patients with different prefrontal surgical excisions were compared on four measures of emotion: voice and face emotional expression identification, social behaviour, and the subjective experience of emotion. Some patients with bilateral lesions of the orbitofrontal cortex (OFC) had deficits in voice and face expression identification, and the group had impairments in social behaviour and significant changes in their subjective emotional state. Some patients with unilateral damage restricted to the OFC also had deficits in voice expression identification, and the group did not have significant changes in social behaviour or in their subjective emotional state. Patients with unilateral lesions of the antero-ventral part of the anterior cingulate cortex (ACC) and/or medial Brodmann area (BA) 9 were, in some cases, impaired on voice and face expression identification, had some change in social behaviour, and had significant changes in their subjective emotional state. Patients with unilateral lesions of the OFC and of the ACC and/or medial BA 9 were, in some cases, impaired on voice and face expression identification, had some changes in social behaviour, and had significant changes in their subjective emotional state. Patients with dorsolateral prefrontal cortex lesions or with medial lesions outside ACC and medial BA 9 areas (dorsolateral/other medial group) were unimpaired on any of these measures of emotion. In all cases in which voice expression identification was impaired, there were no deficits in control tests of the discrimination of unfamiliar voices and the recognition of environmental sounds. Thus bilateral or unilateral lesions circumscribed surgically within the OFC can impair emotional voice and/or face expression identification, but significant changes in social behaviour and in subjective emotional state are related to bilateral lesions. Importantly, unilateral lesions of the ACC (including some of medial BA 9) can produce voice and/or face expression identification deficits, and marked changes in subjective emotional state. These findings with surgically circumscribed lesions show that within the prefrontal cortex, both the OFC and the ACC/medial BA 9 region are involved in a number of aspects of emotion in humans including emotion identification, social behaviour and subjective emotional state, and that the dorsolateral prefrontal areas are not involved in emotion in these ways.

The effects of frontal lobe lesions on goal achievement in the water jug task.

Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water Jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities with other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST). Our results demonstrate that the Water Jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required "counterintuitive moves" not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found that poor performance was linked to left dorsolateral prefrontal cortex damage. We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal.

Spatio-Temporal Working Memory and Frontal Lesions in Man

The delayed-response paradigm is thought to be a marker of the activity of the dorsolateral convexity of primates' prefrontal cortex, as this procedure requires the activation of working memory processes. Although the role of the dorsolateral prefrontal cortex (DLPC) in working memory seems to be well established, much remains to be understood about the processes this structure actually controls: encoding domain-specific information, its retention in short-term memory, its monitoring in working memory, or its selection and retrieval when a specific response program is required. To clarify the role of the DLPC in delayed-response tasks in humans, a set of sequencing paradigms was designed which incorporates the dissociation of (1) spatial and temporal parameters, (2) recall and recognition processes, and (3) the presence or absence of a delay. Performance of a group of patients with DLPC lesions (n = 8) was compared to that of age-matched normal subjects (n = 8). To verify the specificity of the results obtained for the DLPC lesioned patients, the performance of patients with a temporal lobotomy was also studied (n = 10). A significant effect of the delay was observed only in patients with DLPC lesions, affecting both their spatial and spatio-temporal recall, whereas their spatio-temporal recognition was normal. These findings suggest that the DLPC plays a role in the retrieval of visuospatial information for guiding a response program.

Abnormal saccadic distractibility in patients with schizophrenia: a 99mTc-HMPAO SPET study.

Recent research has shown that some patients with schizophrenia have a severe impairment in the suppression of reflexive saccadic eye movements in the ANTI-saccade task. This saccadic distractibility has previously been found in patients with lesions of dorsolateral prefrontal cortex, implicating an abnormality of prefrontal cortex. The objective of the present study was to determine the contribution of these and other areas to the ANTI-saccadic abnormality in schizophrenia by functional neuroimaging. Using 99mtechnetium-HMPAO high resolution multidetector single-photon emission tomography, regional cerebral blood flow (rCBF) during performance of the ANTI-saccade eye-movement task was compared, by statistical parametric mapping, in ten male schizophrenic patients on stable antipsychotic medication who had a high distractibility error rate on the task, and eight similar patients who had normal distractibility error rates. Compared with the normal error group, the patients with high error rates showed significantly decreased rCBF bilaterally, in the anterior cingulate, insula, and in left striatum. These same patients also had increased perseverative errors on the Wisconsin Card Sort Test.

Gating of somatosensory input by human prefrontal cortex

Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded in controls and in patients with focal lesions in dorsolateral prefrontal cortex (PFCx). Unilateral PFCx lesions increased the amplitude of the P26 component generated in postcentral areas 1 and 2. The amplitudes of the N28, P45 and N67 SEP components recorded over post-rolandic and frontal electrodes were also enhanced by PFCx damage. In contrast, the N19 component generated in postcentral area 3b was unaffected by PFCx lesions. The results indicate that PFCx exerts inhibitory modulation on sensory processing that may be mediated by corticocortical PFCx-parietal connections.

The performance of human infants on a measure of frontal cortex function, the delayed response task.

The Delayed Response task is the best-established marker of frontal lobe function in nonhuman primates. This article reports the developmental progression of human infants on that task. It is proposed that maturation of prefrontal cortex may make possible these age-related improvements in Delayed Response performance. This would suggest the importance of prefrontal cortex functioning very early in life. Twelve infants (6 male, 6 female) were tested longitudinally every two weeks from 6-12 months of age. Another 36 infants (18 male, 18 female) were tested only once: 12 each at 8, 10, and 12 months. We predicted that infants would improve on Delayed Response over these ages because infants' performance on AB improves during this time, and Delayed Response is very similar to AB. The AB task, devised by Piaget, is used to study cognitive development in infants. The ages over which AB performance improves are well established. In both AB and Delayed Response, the subject watches as the experimenter hides a desired object in one of two identical wells. After a brief delay, the subject is allowed to reach. In AB, the object is hidden in the same well on subsequent trials until the subject reaches to the correct well; then side of hiding is reversed and the procedure repeated. In Delayed Response, side of hiding is varied randomly over trials. In the present study of Delayed Response each testing session consisted of 16 trials (eight to the right, eight to the left). We found: (1) the developmental progression for Delayed Response is almost identical to that for AB. (2) Infants of 7 1/2-9 months fail Delayed Response under the same conditions and in the same ways as do monkeys with lesions of dorsolateral prefrontal cortex. It is therefore suggested that AB and Delayed Response require the same cognitive abilities, and that improved performance on these tasks provides an index of maturation of frontal cortex function.

Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys.

Visual recognition in monkeys appears to involve the participation of two limbothalamic pathways, one including the amygdala and the magnocellular portion of the medial dorsal nucleus (MDmc) and the other, the hippocampus and the anterior nuclei of the thalamus (Ant N). Both MDmc and Ant N project, in turn, to the prefrontal cortex, mainly to its ventral and medial portions. To test whether the prefrontal projection targets of the two limbothalamic pathways also participate in memory functions, performance on a variety of learning and memory tasks was assessed in monkeys with lesions of the ventromedial prefrontal cortex (Group VM). Normal monkeys and monkeys with lesions of dorsolateral prefrontal cortex (Group DL) served as controls. Group VM was severely impaired on a test of object recognition, whereas Group DL did not differ appreciably from normal animals. Conversely, the animals in Group VM were able to learn a spatial delayed response task, whereas 2 of the 3 animals in Group DL could not. Neither group was impaired in the acquisition of visual discrimination habits, even though the successive trials on a given discrimination were separated by 24-h intervals. The patterns of deficit suggest that ventromedial prefrontal cortex constitutes another station in the limbothalamic system underlying cognitive memory processes, whereas the dorsolateral prefrontal cortex lies outside this system. The results support the view that the classical delayed-response deficit observed after dorsolateral prefrontal lesions represents a perceptuo-mnemonic impairment in spatial functions selectively rather than a memory loss of a more general nature.

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, re-inforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.

The effects of dorsolateral-frontal and ventrolateral-orbitofrontal lesions on spatial discrimination learning and delayed response in two modalities

Thirteen Rhesus monkeys were trained pre- and post-operatively on classical direct-method delayed-response problems, on automated successive visual and auditory discriminations, and on automated indirect-method delayed-response problems with the same visual or auditory cues as those used in discrimination learning. Four subjects sustained lesions in dorsolateral prefrontal cortex, five subjects received lesions of the ventrolateral-orbitofrontal region, and four subjects remained as unoperated controls. On classical and on visual indirect-method delayed-response problems, dorsolaterals were inferior to ventrolateral-orbitals, and ventrolateral-orbitals were inferior to normals; on the successive visual discrimination, ventrolateral-orbitals were inferior to dorsolaterals; and on the auditory discrimination and the auditory delayed-response problems, the operates as a group were somewhat worse than normals.