Orbitofrontal Cortex Function Research Articles

Time perception, impulsivity, emotionality, and personality in self-harming borderline personality disorder patients.

To investigate how time perception may contribute to the symptoms of self-harming Borderline Personality Disorder (BPD) patients, 19 self-harming BPD inpatients and 39 normal controls were given measures of time perception, impulsivity, personality, emotion, and BPD characteristics. A test sensitive to orbitofrontal cortex (OFC) function ("Frontal" Behavior Questionnaire) was also administered, as the OFC has been associated with impulsivity and time perception. BPD patients produced less time than controls, and this correlated with impulsiveness and other characteristics commonly associated with BPD. BPD patients were also less conscientious, extraverted, and open to experience, as well as more impulsive (self-report and behaviorally), emotional, neurotic, and reported more BPD characteristics, compared to controls. The results suggest that some of these core characteristics of BPD may be on a continuum with the normal population and, impulsivity in particular, may be related to time perception deficits (i.e., a faster subjective sense of time). Finally, BPD patients scored higher on the Frontal Behavior Questionnaire, suggesting that some symptoms of the BPD syndrome may be related to problems associated with the OFC. A control spatial working memory task (SWM) revealed that SWM deficits could not explain any of the BPD patients' poor performance. While impulsivity was correlated with time perception across all participants, emotionality, introversion, and lack of openness to experience were not. This suggests that different symptoms of the borderline personality syndrome may be separable, and therefore, related to different cognitive deficits, and potentially to different brain systems. This may have important implications for treatment strategies for BPD.

Differential involvement of orbitofrontal cortex subregions in conditioned cue-induced and cocaine-primed reinstatement of cocaine seeking in rats.

Orbitofrontal cortex (OFC) damage elicits impulsivity and perseveration, and impairments in OFC function may underlie compulsive drug seeking in cocaine users. To test this hypothesis, we assessed the effects of fiber-sparing lesions or functional inactivation of OFC subregions on cocaine seeking in rats. Rats were trained to lever press for intravenous cocaine (0.20 mg/infusion) paired with the presentations of light plus tone stimuli. Responding was then allowed to extinguish. Rats received bilateral NMDA (0.1 M) or sham lesions of the lateral OFC (lOFC) or medial OFC (mOFC) before self-administration training (experiment 1) or muscimol plus baclofen (0.1 and 1.0 mM) or vehicle infusions into the lOFC or mOFC before reinstatement testing (experiment 2). The effects of these manipulations on reinstatement of cocaine seeking (i.e., responding on the previously cocaine-paired lever) were assessed in the presence of the light plus tone stimuli or after a cocaine priming injection (10 mg/kg, i.p.). Post-training lOFC inactivation impaired conditioned cue-induced reinstatement, whereas other manipulations failed to alter this behavior. This suggests that the lOFC plays a critical role in assessing the current motivational significance of cocaine-conditioned stimuli or in using this information to guide cocaine-seeking behavior if stimulus-reward learning takes place before lOFC damage. OFC inactivation failed to alter cocaine-primed reinstatement. However, lOFC lesions augmented cocaine-primed reinstatement in a perseverative manner, whereas mOFC lesions attenuated cocaine-primed reinstatement, suggesting that prolonged cell loss in OFC subregions may modulate the propensity for cocaine seeking in a subregion-specific manner.

Age differences in orbitofrontal activation: an fMRI investigation of delayed match and nonmatch to sample

Several investigations have suggested that the orbitofrontal cortex (OFC) may be particularly vulnerable to the effects of age-related changes. We recently reported behavioral data indicating greater age differences in orbitofrontal tasks when directly compared to tasks tapping dorsolateral prefrontal functions. The present study was designed to investigate the neural underpinnings of age differences in OFC functioning. Event-related functional magnetic resonance imaging (fMRI) was performed during delayed match and nonmatch to sample tasks, previously shown to differentially activate medial and lateral OFC in young adults. Sixteen healthy younger [age = 26.7(5.6)] and 16 healthy older individuals [age = 69.1 + 5.6] with similar levels of education and general cognitive functioning participated in the experiment. Participants chose the stimulus from a pair of stimuli matching a previously viewed target (match to sample) or chose the nontarget item (nonmatch to sample) depending upon a trial-specific instruction word. Consistent with previous studies, SPM99 analyses of the younger age group revealed activation for medial OFC regions during the match task compared to the nonmatch task and lateral OFC activation during the nonmatch task compared to the match task. In contrast, older adults showed prefrontal activation only during the match relative to the nonmatch task and posterior temporal and limbic involvement during the nonmatch relative to the match task. Between-group analyses confirmed within-group results suggesting differential age-related recruitment of prefrontal regions when performing match and nonmatch tasks. Results suggest that OFC recruitment during these cognitive tasks changes with age and should be evaluated within the context of other prefrontal subregions to further define differential age effects on frontal functions.

Resistance to extinction: A measure of orbitofrontal function suitable for children?

Extinction of operantly conditioned responses, which provides a measure of the ability to adapt to changes in the reinforcement value of stimuli, has been linked to orbitofrontal cortex (OFC) in human and non-human animals. This article examines the feasibility of using extinction as a measure of the development of OFC function in preschool-age children. If extinction serves as a measure of OFC function, resistance to extinction should decrease during this age range. In Part 1, we review the literature on extinction as related to OFC, and summarize what is known regarding age-related changes in extinction in young children. In Part 2, we report results of a study assessing extinction in children between 3 and 6 years of age. Results revealed age-related increases in responding during extinction, with girls (particularly, 6-year-old girls) exhibiting stronger resistance to extinction. Some relations were found with temperament and normative compulsive-like behavior. The findings of this study question the utility of extinction of operant responding as a measure of OFC function in young children.

Alternation learning in OCD/schizophrenia patients

In continuation of our previous studies on orbitofrontal cortex function in obsessive compulsive disorder (OCD) we studied a group of OCD patients with schizophrenia in comparison with a group of schizophrenia patients. In order to test orbitofrontal cortex function we again used an alternation learning task. We found no difference between the two groups in the performance of this task. The relationship between severity of OC symptoms and alternation learning was curvilinear. Thus, in the low range of symptom severity the correlation between alternation learning and symptom severity was negative, while in the high range it was positive. The positive correlation in the severely affected patients is essentially the same as that found in severe “pure” OCD patients, which we have previously reported. We conclude that the data indicate independent orbitofrontal cortex function in OCD, irrespective of comorbidity.

Risky decisions and response reversal: is there evidence of orbitofrontal cortex dysfunction in psychopathic individuals?

This study investigates the performance of psychopathic individuals on tasks believed to be sensitive to dorsolateral prefrontal and orbitofrontal cortex (OFC) functioning. Psychopathic and non-psychopathic individuals, as defined by the Hare psychopathy checklist revised (PCL-R) [Hare, The Hare psychopathy checklist revised, Toronto, Ontario: Multi-Health Systems, 1991] completed a gambling task [Cognition 50 (1994) 7] and the intradimensional/extradimensional (ID/ED) shift task [Nature 380 (1996) 69]. On the gambling task, psychopathic participants showed a global tendency to choose disadvantageously. Specifically, they showed an impaired ability to show learning over the course of the task. On the ID/ED task, the performance of psychopathic individuals was not significantly different from incarcerated controls on attentional set-shifting, but significant impairments were found on response reversal. These results are interpreted with reference to an OFC and amygdala dysfunction explanation of psychopathy.

Decision-making heterogeneity in obsessive-compulsive disorder: ventromedial prefrontal cortex function predicts different treatment outcomes

Certain clinical aspects of patients with Obsessive-Compulsive Disorder (OCD) appear similar to those of patients with damage to the ventromedial sector of the prefrontal cortex. The hypothesis for the involvement of the frontal region in OCD is also supported by neuropsychological findings. Building on this evidence, we assessed the performance of a group of 34 OCD patients on a measure indexing with orbitofrontal cortex functioning and compared it with the performance of two other subject groups, one consisting of 34 healthy control subjects and the other 16 patients with panic disorder. All study subjects performed a neuropsychological task, which is sensitive to frontal lobe dysfunction and simulating real-life decision-making. Significant differences were found between the neuropsychological profiles of the OCD and of other groups, pointing to a possible specificity of decision-making deficit in OCD. Comparison of the performance of the OCD patients grouped according to response to antiobsessive drug treatment showed that poor neuropsychological task performance predicted poor outcome of pharmacological treatment. Task behavior did not correlate with severity of illness or demographic characteristics of the subjects. Results support the role of the ventromedial prefrontal cortex in OCD.

Somatic markers and response reversal: is there orbitofrontal cortex dysfunction in boys with psychopathic tendencies?

This study investigated the performance of boys with psychopathic tendencies and comparison boys, aged 9 to 17 years, on two tasks believed to be sensitive to amygdala and orbitofrontal cortex functioning. Fifty-one boys were divided into two groups according to the Psychopathy Screening Device (PSD, P. J. Frick & R. D. Hare, in press) and presented with two tasks. The tasks were the gambling task (A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) and the Intradimensional/Extradimensional (ID/ED) shift task (R. Dias, T. W. Robbins, & A. C. Roberts, 1996). The boys with psychopathic tendencies showed impaired performance on the gambling task. However, there were no group differences on the ID/ED task either for response reversal or extradimensional set shifting. The implications of these results for models of psychopathy are discussed.

Orbitofrontal cortex dysfunction in obsessive–compulsive disorder?: I. Alternation learning in obsessive–compulsive disorder: male–female comparisons

Background: We have previously reported a significant negative correlation between severity of symptoms and performance of an alternation learning task in female obsessive–compulsive disorder (OCD) patients. The present study was aimed at exploring this relationship between alternation learning and OCD symptom severity in male OCD patients. Methods and results: Eighteen female obsessive–compulsive disorder patients and 14 male non-depressed, drug free, OCD patients participated in the study. Measures of dorsolateral prefrontal function (Wisconsin Card Sorting Test) and orbitofrontal cortex function (object alternation learning) showed no significant differences between the sexes. The relationship between orbitofrontal cortex function and severity of OC symptoms was significantly different between the sexes ( z=2.44, P=0.007). While this correlation was negative in the females it was positive in the males. Conclusions: These results may indicate sexual dimorphism in OCD.

Orbitofrontal cortex dysfunction in obsessive-compulsive disorder?: II. Olfactory quality discrimination in obsessive-compulsive disorder

Background: Olfactory quality discrimination is a putative marker of orbitofrontal cortex function in mammals. As this portion of the cerebral cortex was repeatedly implicated in the pathophysiology of obsessive-compulsive disorder (OCD) this study was designed in an attempt to quantify this behavioural function in OCD patients. Methods and Results: Olfactory quality discrimination was compared in OCD patients and healthy controls. Thirty two subjects participated in the study: 16 (13 women and 3 men) medication free OCD outpatients and 16 sex and age matched healthy controls. Olfactory tests consisted of determination of detection thresholds to isoamyl acetate, and a three way forced choice quality discrimination task, using isoamyl acetate, citral and eugenol as stimuli. No significant differences in sensitivity and performance of the quality discrimination task between the two groups were found. Within the OCD group the more severely affected patients (Y-BOCS>29) performed significantly better than the less severely affected (Y-BOCS<30) patients on the more difficult part of the quality discrimination task. Within this subgroup of patients the correlation between performance on the olfactory task and a previously reported alternation task tended to be negative as compared to a significantly positive correlation in the control group. Conclusions: It seems that olfactory quality discrimination may prove to be a useful noninvasive marker of prefrontal cortex function in OCD. Furthermore, the organization of functional modules within the orbitofrontal cortex, rather than a simple dysfunction, may prove to characterize OCD.

The limbic system: an anatomic, phylogenetic, and clinical perspective.

The limbic system is the border zone where psychiatry meets neurology. The authors provide a model of limbic function that combines phylogenetic, anatomic, functional, and clinical data to interpret diseases relevant to neuropsychiatry. They provide evidence supporting two major divisions in the limbic system: a paleocortical division with the amygdala and orbitofrontal cortex at its center, and an archicortical division with the hippocampus and cingulate cortex at its center. The implicit integration of affect, drives, and object associations is the function of the paleocortical limbic division; explicit sensory processing, encoding, and attentional control is the function of the archicortical limbic division. The two work in concert to integrate thought, feeling, and action. Understanding their development and organization informs us about how best to care for our patients.

Preface

One dominant hypothesis about the function of the orbitofrontal cortex (OFC) is that the OFC signals the subjective values of possible outcomes to other brain areas for learning and decision making. This popular view generally neglects the fact that OFC is not necessary for simple value-based behavior (i.e. when values have been directly experienced). An alternative, emerging view suggests that OFC plays a more general role in representing structural information about the task or environment, derived from prior experience, and relevant to predicting behavioral outcomes, such as value. From this perspective, value signaling is simply one derivative of the core underlying function of OFC. New data in favor of both views have been accumulating rapidly. Here we review these new data in discussing the relative merits of these two ideas.