this is my research paper i did... the formatting is kinda screwy bc i copy and pasted it from a Word.doc. enjoy :)
Frontolimbic Circuit and Ventromedial Prefrontal Cortex Pathology inBorderline Personality Disorder
Patients with a borderline personality disorder (BPD) often experience a recurring pattern of disorganization and instability in self-image, mood, behavior and personal relationships. The main feature of BPD is a pervasive pattern of instability in interpersonal relationships, self-image and emotions. The affective instability and impulsivity are most prevalent in social relationships. A person with BPD sees things in black and white, and their relationships with family, loved ones, and friends can fluctuate from ideation to devaluation after a small conflict. Borderline patients exhibit other impulsive behaviors such as excessive spending, binge eating, self mutilation and risky sex. Impulsivity and/or impulsive aggression is considered to best predict the persistence of borderline psychopathology across time (5). Disturbances of higher cognition and social behavior, as seen in BPD, have long been recognized as common result of dysfunctions of the prefrontal cortex.
Early studies using computed tomographic (CT) imaging have ruled out gross abnormalities, significant differences in ventricle-brain ratio, and found no evidence of frontal lobe atrophy in borderline patients compared with healthy subjects (4). Current research is focusing specifically on pathology of the ventromedial prefrontal cortex (VMPFC) and the frontolimbic circuits; as they have been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals (4). Dysfunctions in these and other prefrontal regions have been linked to other disorders including depression, bipolar disorder and schizophrenia. The orbitofrontal cortex (OFC) makes up a part of the VMPFC and deficits in these areas have been correlated to lesions and a decreased of myelination in experimental animals. In humans, fMRI imaging studies have shown the VMPFC to be linked with their action evaluation, and the orbitofrontal frontal cortex is a specific point of reward punishment processing (1). The frontolimbic circuit includes the amygdala, hippocampus and anterior cingulate cortex (ACC). The sublingual (ACC) has higher levels of activation when errors are likely in the subjects’ decision making (8).
Evidence from previous brain imaging studies on borderline patients suggests VMPFC dysfunction in the disorder; specifically hypometabolism, and smaller volume, of the OFC (8). Negative emotional states exacerbate borderline patients’ difficulty in modulating their behavior. Silbersweig et al. (2007) hypothesized that reduced activation in borderline patients’ VMPFC and associated regions of the frontolimbic system were responsible for this characteristic. They designed a study to specifically probe the interaction between behavioral inhibition and negative emotion in sixteen patients with BPD compared to fourteen healthy controls. Functional magnetic resonance imaging (fMRI) of the medial OFC and the subgenual ACC was used to test for the presence of decreased prefrontal inhibitory function and examine the neurocircuitry underlying the interaction between emotions and motor inhibition with verbal stimuli (7). The participants performed an emotional linguistic go/no-go task which utilized themes prominent for individuals with borderline personality disorder. Behavioral response was based on orthographically based cues: participants were instructed to perform a right-index-finger button press immediately after silently reading a word to themselves that appeared in normal font (go trial) and to inhibit this response after reading a word in italicized font (no-go trial). Button-press responses and reaction times were recorded (7).
Behavioral data categorized as response times, error rates, recognition rates, and valence ratings was recorded. The data was analyzed using repeated measures analysis of variance and subsequent Wilcox on signed rank-sum tests to focus on performance differences across groups and conditions (7). Behavioral measures showed significant between-group differences and trends where borderline patients rate negative words more negative, have longer reaction times for no-go conditions, and make more errors of omission and commission during the negative no-go conditions. Negative emotional stimuli comparatively decreased activity level in borderline patients in the VMPFC, specifically within the medial OFC and subgenual ACC, and in the dorsal ACC suggesting these neural substrates are associated with core clinical features of emotional and behavioral dyscontrol in BPD (7). These results are consistent with a model of domain-specific mapping of prefrontal function, with more dorsal regions involved in more cognitive, conscious, and effortful controlled tasks and more ventral regions involved in more social-emotional, unconscious control tasks (7). Similarly, Grant et al. (2007) (MRI) volumetric study of ten borderline patients and ten healthy controls produced evidence of decreased white matter microstructural integrity in inferior frontal brain regions of borderline patients, including components of orbitofrontal circuitry (3).
Comparing the psychiatric population of patients with borderline personality disorder to neurological patients with OFC brain lesions is a fairly new approach to studying brain physiology in psychiatric patients. Iverson, Berlin and Rolls (2005) hypothesized that frontolimbic circuit dysfunction (involving both the OFC and amygdala regions) may be involved in BPD related impulsivity (4). Iverson et al. administered questionnaires on personality, emotion, and impulsivity as well as a number of computer-based tasks that are sensitive to frontal lobe dysfunction to assess possible underlying factors related to impulsivity in their participants. Four different groups of people were used; twenty-three patients with OFC lesions, twenty patients with lesions in the prefrontal cortex but not in the OFC, nineteen patients with borderline personality disorder and a history of self-harm, and thirty-nine healthy comparison subjects.
Both the OFC lesion group and the borderline personality disorder group showed significant impairment (regardless of whether they differed significantly from each other), compared to the healthy group (4). On some measures the BPD patients differed significantly as being more impulsive than the patients with OFC lesions. However when compared to the control group or the patients with lesions outside of the OFC, both the BPD and the orbitofrontal lesion patients show significantly higher levels of impulsivity, reported more inappropriate behaviors, more borderline personality disorder traits, more anger, and less happiness than subjects in both of the comparison groups (patients with prefrontal lesions outside the OFC and healthy comparison subjects). In support of Iverson et al.’s main hypothesis, the patients with borderline personality disorder had deficits that were similar to those of the patients with OFC lesions and dissimilar to those of the patients with lesions outside the OFC.
These findings suggest that the OFC is involved with impulsivity and affect instability in borderline patients. One implication of this finding is that some of the core characteristics of borderline personality disorder, in particular impulsivity, are similar to the effects of OFC damage. The OFC, with its extensive reciprocal connections with the amygdala (which is implicated in emotional behavior), may play a role in regulating emotional and behavioral responses. This supports the hypothesis that patients with borderline personality disorder have some deficits that can be related to the functions performed by the OFC. These deficits might be related to smaller volume of the OFC or to lower levels of activity in the OFC. However there was one variation in Berlin et al.’s study where the BPD patients and the patients with OFC lesions performed differently on a few of the tasks. This suggests that other characteristics of borderline personality disorder (e.g. high levels of emotionality, neuroticism and introversion and a low level of conscientiousness) may be caused by a neurochemical imbalance or dysfunction of the ACC and/or the amygdala. There isn’t evidence of ACC and amygdala pathology in the patients with OFC lesions, therefore abnormalities in these areas in borderline patients would account for the variations between subject groups on some measures.
Not surprisingly amygdala pathology, dysfunction and chemical imbalances have been recorded in borderline patients. The amygdala has been shown to have greater activation in borderline patients in response to fear stimuli (6).Blair et al. (2006) performed magnetic resonance imaging volumetric measurements of the frontolimbic regions, temporal lobes, and prosencephalon, and the borderline patients had nearly eight percent smaller volumes of the amygdala (1).Measures of cerebral N -acetylaspartate (NAA) concentration (which is regarded as an indicator of cerebral neuronal integrity and density) revealed a significant nineteen percent reduction of dorsolateral prefrontal (NAA) concentration in patients with BPD (8). Significantly lower levels of activation responding to fear in borderline patients relative to healthy controls have been recorded in the subgenual ACC (6).Minzenberg,Fan,New,Tang,and Siever’s (2007) research provides evidence that adult borderline patients have changes in frontolimbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity (6). These functional changes may represent an expression of the volumetric deficits observed in these brain areas by in borderline patients (6).
Iverson et al. performed analyses of covariance across all variables, which discounted any confounding effects of age or gender on the results; but the level of impulsivity (such as measured by the Minnesota Multiphasic Personality Inventory-2) was not included. Impulsivity is a personality trait that can exist independently from BPD and should be included in the covariance analyses. Without impulsivity being ruled out as a confounding variable, low impulsivity in the healthy subjects could account for the variations of brain pathology between groups. It is not made clear if the brain pathology in borderline patients is strictly limited to the disorder, or if otherwise healthy controls that are high on impulsivity will also have similar pathology.
Future studies should treat the level of impulsivity as a quasi-independent variable. Three subject groups used for this hypothetical study include a group of borderline patients, of healthy controls with low scores of impulsivity, and healthy controls with high scores of impulsivity. The healthy controls should have their levels of impulsivity evaluated by the MMPI-2 and sorted into the high and low level groups based on their scores. A second study suggestion is to administer the MMPI-2 to all participants in the study (borderline patients and healthy control) and then perform covariance analyses across the impulsivity variable (along with age and gender variables) to rule out any confounding effects the trait may have.
All referenced studies between borderline patients and healthy controls had post hoc least significant difference analyses that were significant at least at p <0.05,>
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