An exploratory study of functional brain activation underlying response inhibition in major depressive disorder and borderline personality disorder.

Cognitive control is associated with impulsive and harmful behaviours, such as substance abuse and suicidal behaviours, as well as major depressive disorder (MDD) and borderline personality disorder (BPD). The association between MDD and BPD is partially explained by shared pathological personality traits, which may be underpinned by aspects of cognitive control, such as response inhibition. The neural basis of response inhibition in MDD and BPD is not fully understood and could illuminate factors that differentiate between the disorders and that underlie individual differences in cross-cutting pathological traits. In this study, we sought to explore the neural correlates of response inhibition in MDD and BPD, as well as the pathological personality trait domains contained in the ICD-11 personality disorder model. We measured functional brain activity underlying response inhibition on a Go/No-Go task using functional magnetic resonance imaging in 55 female participants recruited into three groups: MDD without comorbid BPD (n = 16), MDD and comorbid BPD (n = 18), and controls with neither disorder (n = 21). Whereas response-inhibition-related activation was observed bilaterally in frontoparietal cognitive control regions across groups, there were no group differences in activation or significant associations between activation in regions-of-interest and pathological personality traits. The findings highlight potential shared neurobiological substrates across diagnoses and suggest that the associations between individual differences in neural activation and pathological personality traits may be small in magnitude. Sufficiently powered studies are needed to elucidate the associations between the functional neural correlates of response inhibition and pathological personality trait domains.

The transdiagnostic relationship of cumulative lifetime stress with memory, the hippocampus, and personality psychopathology.

Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function.

Stressed, sick, and sad: Neuroendoimmune pathways between subjective lifetime stress and depression.

Disruptions in stress-sensitive biological systems, notably the immune system and hypothalamic-pituitary-adrenal axis, are strongly implicated in depression, and disturbances in these neuroendoimmune systems could reflect potential pathways through which experiences of stress are translated into depression. To characterize the links between stress and depression, the present study investigated whether neuroendoimmune activity mediates the relationship between perceived stress and depressive symptoms in 59 medically healthy adult females with varying levels of depression. Consistent with hypotheses, both greater perceived stress and higher concentrations of the proinflammatory immune marker, interleukin-6 (IL-6), were associated with greater depressive symptoms. Although neuroendoimmune activity did not significantly mediate the relationship between lifetime perceived stress and depressive symptoms, when considered together, elevated concentrations of IL-6 and lower free cortisol mediated the relationship between severity of childhood stress and current depressive symptoms. These findings shed light on how early life stress may be translated into adulthood depression.

Facial Emotion Perception in Borderline Personality Disorder: Differential Neural Activation to Ambiguous and Threatening Expressions and Links to Impairments in Self and Interpersonal Functioning.

BACKGROUND: Many individuals with borderline personality disorder (BPD) perceive emotional expressions in faces intended to convey no emotion and display a heightened sensitivity to facial expressions conveying threat, such as fear. In BPD, the amygdala activates in response to ambiguous and threatening facial expressions, although the differential sensitivity of this brain region to higher and lower intensities of fearful expressions and the relationship of this neural activity to personality impairments have not yet been investigated. METHODS: In the present study, we examined brain activation during an implicit facial emotion task with neutral faces and fearful expressions displayed at 50% and 100% intensity in patients with BPD (n=45) and healthy controls (HC; n=25). RESULTS: On neutral faces, higher brain activation was found in BPD compared to HC in the right temporal pole, amygdala, hippocampus, pallidum, and orbitofrontal cortex, whereas no significant whole-brain group differences were observed for either intensity of fearful expressions. A region-of-interest analysis focused on the amygdala-hippocampal complex showed greater activation for neutral and 50%-intensity fearful faces in BPD. Severity of personality impairment in the domains of empathy and identity were associated with higher precuneus activity during neutral and 100%-fearful face processing. LIMITATIONS: Brain activation differences of this naturalistic severely ill inpatient sample may be influenced by comorbid Axis-I disorders often seen in samples of BPD. CONCLUSIONS: These findings suggest a heightened amygdala-hippocampal response to neutral faces and moderate-intensity fearful expressions in BPD, while self and interpersonal impairments are associated with task-based activations in regions implicated in self-referential processes.

Disrupted Relationship between Hippocampal Activation and Subsequent Memory Performance in Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is associated with subjective reports of forgetfulness and deficits on tests of memory performance. However, it is not yet known whether individuals with BPD show different patterns of activation in the hippocampus during episodic memory encoding, especially for materials that are not emotionally-valenced. METHODS: Participants with BPD (n = 20) and non-psychiatric controls (n = 21) completed a memory encoding task in which they viewed scenes without emotional content during functional magnetic resonance imaging scans. Subsequently, they completed a recognition memory test outside of the scanner and neural activation during the presentation of successfully remembered scenes was contrasted with scenes that were subsequently forgotten. RESULTS: Controls exhibited significant left hippocampal activation during successful memory encoding, displaying greater activity during the presentation of subsequently remembered versus forgotten scenes, and the strength of this activation was related to their recognition memory performance. Although hippocampal activation was observed for the BPD group during successful memory encoding, it did not reach significance when implementing a non-parametric statistical approach. Additionally, individual hippocampal recruitment was not significantly correlated with recognition memory performance in the BPD group. The strength of this correlation, but not the overall magnitude of hippocampal activation, was significantly different between the groups. LIMITATIONS: Participants with BPD had comorbid psychiatric diagnoses and varied treatment histories. Whether patients and controls differentially perceived emotional content in the neutral scene memoranda was not tested. CONCLUSIONS: Memory problems in BPD may be partially explained by a disrupted relationship between hippocampal activation and successful memory encoding.

The NIMH Research Domain Criteria (RDoC) Initiative and Its Implications for Research on Personality Disorder.

PURPOSE OF REVIEW: We discuss the implications of the Research Domain Criteria (RDoC) initiative for neuroscience research on personality disorder (PD). To organize our review, we construct a preliminary conceptual mapping of PD symptom criteria onto RDoC constructs. We then highlight recent neuroscience research, often built around concepts that correspond to RDoC elements, and discuss the findings in reference to the constructs we consider most pertinent to PD. RECENT FINDINGS: PD symptoms were strongly conceptually tied to RDoC constructs within the Social Processes domain, implicating brain systems involved in interpersonal rejection, facial emotion perception, and self-referential processes. Negative and Positive Valence Systems were conceptually associated with many PD symptoms, with particular relevance ascribed to the latter's Reward Valuation construct, which could reflect a more widespread disruption of computational processes involved in estimating the probability and benefits of a future outcome. Within the Cognitive Systems domain, the Cognitive Control construct mainly related to PD symptoms associated with impulse control, suggesting a connection to neural circuits that underlie goal selection and behavioral control. Arousal and Regulatory Systems could only be conceptually mapped onto PD symptoms through the Arousal construct, with different symptoms reflecting either a higher or lower biological sensitivity to internal and external stimuli. The RDoC framework has promise to advance neuroscience research on PD. The Social Processes domain is especially relevant to PD, although constructs falling within the other RDoC domains could also yield important insights into the neurobiology of PD and its connections with other forms of psychopathology. Identifying RDoC constructs (e.g., habit formation) that subserve more fundamental processes relevant to personality functioning warrants further investigation.

Toward an Open-Ended BCI: A User-Centered Coadaptive Design.

Brain-computer interfaces (BCIs) allow users to control a device by interpreting their brain activity. For simplicity, these devices are designed to be operated by purposefully modulating specific predetermined neurophysiological signals, such as the sensorimotor rhythm. However, the ability to modulate a given neurophysiological signal is highly variable across individuals, contributing to the inconsistent performance of BCIs for different users. These differences suggest that individuals who experience poor BCI performance with one class of brain signals might have good results with another. In order to take advantage of individual abilities as they relate to BCI control, we need to move beyond the current approaches. In this letter, we explore a new BCI design aimed at a more individualized and user-focused experience, which we call open-ended BCI. Individual users were given the freedom to discover their own mental strategies as opposed to being trained to modulate a given brain signal. They then underwent multiple coadaptive training sessions with the BCI. Our first open-ended BCI performed similarly to comparable BCIs while accommodating a wider variety of mental strategies without a priori knowledge of the specific brain signals any individual might use. Post hoc analysis revealed individual differences in terms of which sensory modality yielded optimal performance. We found a large and significant effect of individual differences in background training and expertise, such as in musical training, on BCI performance. Future research should be focused on finding more generalized solutions to user training and brain state decoding methods to fully utilize the abilities of different individuals in an open-ended BCI. Accounting for each individual's areas of expertise could have important implications on BCI training and BCI application design.

Six Years of Research on the National Institute of Mental Health's Research Domain Criteria (RDoC) Initiative: A Systematic Review.

Six years have passed since the National Institute of Mental Health (NIMH) in the United States launched the Research Domain Criteria (RDoC) initiative. The RDoC introduces a framework for research on the biology of mental illness that integrates research findings across multiple levels of information. The framework outlines constructs that represent specific quantifiable dimensions of behavior (e.g., responses to acute threat, cognitive control) and corresponding units of analysis that can be used to study the constructs, beginning at the levels of genes, molecules, cells, circuits and physiology, and moving up to behaviors and self-reports. In this systematic review, a literature search was conducted to synthesize empirical research published since the proposal of the framework that incorporated the RDoC. Forty-eight peer-reviewed scholarly articles met eligibility criteria for the review. Studies differed according to whether they analyzed RDoC constructs and units of analysis within vs. between clinically-diagnosed and non-psychiatric samples. The most commonly studied constructs were subsumed within the domains of Negative Valence Systems, Positive Valence Systems and Cognitive Systems, providing initial results which primarily connected genetics, brain circuits and physiology research findings with behavior and self-reports. Prospects for future research adopting the RDoC matrix and utilizing a dimensional approach to studying the biology of mental illness are discussed.

Neurocognitive Deficits in Borderline Personality Disorder: Associations With Childhood Trauma and Dimensions of Personality Psychopathology.

The present study evaluates the severity of neurocognitive deficits and assesses their relations with self-reported childhood trauma and dimensions of personality psychopathology in 45 outpatients with borderline personality disorder (BPD) matched to 56 non-psychiatric controls. Participants completed a comprehensive battery of neurocognitive tests, a retrospective questionnaire on early life trauma and a dimensional measure of personality psychopathology. Patients with BPD primarily showed deficits in verbal comprehension, sustained visual attention, working memory and processing speed. Comorbid posttraumatic stress disorder (PTSD) and an elevated childhood history of physical trauma were each accompanied by more severe neurocognitive deficits. There were no statistically significant associations between neurocognitive function and dimensions of personality psychopathology. These results suggest that patients with BPD display deficits mainly in higher-order thinking abilities that may be exacerbated by PTSD and substantial early life trauma. Potential relationships between neurocognitive deficits and dimensions of personality psychopathology in BPD need further examination.

A Neurobiological Model of Borderline Personality Disorder: Systematic and Integrative Review.

Borderline personality disorder (BPD) is a severe mental disorder with a multifactorial etiology. The development and maintenance of BPD is sustained by diverse neurobiological factors that contribute to the disorder's complex clinical phenotype. These factors may be identified using a range of techniques to probe alterations in brain systems that underlie BPD. We systematically searched the scientific literature for empirical studies on the neurobiology of BPD, identifying 146 articles in three broad research areas: neuroendocrinology and biological specimens; structural neuroimaging; and functional neuroimaging. We consolidate the results of these studies and provide an integrative model that attempts to incorporate the heterogeneous findings. The model specifies interactions among endogenous stress hormones, neurometabolism, and brain structures and circuits involved in emotion and cognition. The role of the amygdala in BPD is expanded to consider its functions in coordinating the brain's dynamic evaluation of the relevance of emotional stimuli in the context of an individual's goals and motivations. Future directions for neurobiological research on BPD are discussed, including implications for the Research Domain Criteria framework, accelerating genetics research by incorporating endophenotypes and gene × environment interactions, and exploring novel applications of neuroscience findings to treatment research.

Tryptophan hydroxylase 1 gene polymorphisms alter prefrontal cortex activation during response inhibition.

OBJECTIVE: The tryptophan hydroxylase 1 gene (TPH1) catalyzes the formation of 5-hydroxytryptophan, a precursor to the neurotransmitter serotonin. Variations in the gene encoding this enzyme may underlie difficulties in impulse control; however, the proximate relationship between risk alleles for polymorphisms in the TPH1 gene and the neural correlates of response inhibition remain poorly understood. The present study examined the relationship of 2 single nucleotide polymorphisms in the TPH1 gene (rs1799913 and rs4537731) to prefrontal cortex (PFC) activation on a response inhibition task. METHOD: Evoked hemodynamic oxygenation in the PFC was measured in 30 unrelated healthy adult women using 16-channel continuous-wave functional near-infrared spectroscopy while they completed a manual go/no-go task. RESULTS: TPH1 alleles showed no association with demographic characteristics, general intelligence, impulsive personality traits, or accuracy and response latency indices on the go/no-go task. Participants carrying the risk alleles, however, showed less activity primarily in bilateral inferior frontal gyri and medial PFC under conditions of response inhibition. CONCLUSIONS: Polymorphisms in the TPH1 gene may be represented by diminished activity in lateral areas of the PFC underlying response inhibition. Reduced activity in medial PFC might represent altered self-monitoring of performances on the response inhibition task.