Neurophysiological biomarkers of response inhibition and the familial risk for borderline personality disorder.

Understanding of the biological factors that run in families affected with borderline personality disorder (BPD) is limited. The authors investigated the familial aggregation of neurophysiological biomarkers of response inhibition in the first-degree biological relatives of probands with BPD and associations with psychiatric diagnosis and impulsive traits. In the present study, psychiatric diagnoses and impulsive traits were measured in BPD probands (n = 86), psychiatrically affected and non-affected relatives (n = 60) and controls (n = 83). While undergoing neuroimaging using functional near-infrared spectroscopy, prefrontal cortex (PFC) activation was measured during a go/no-go response inhibition task and compared between probands, relatives and controls. Additionally, non-psychiatrically affected relatives and controls were contrasted to examine the potential impact of familial risk for BPD on response inhibition-related PFC activation in the absence of confounding psychiatric morbidity. Probands showed bilateral decreases in PFC activation during response inhibition compared to relatives and controls. Conversely, both affected and non-affected relatives displayed higher activation than controls and probands in left lateral/medial and right medial PFC, although non-affected relatives showed a lesser extent of activation than affected relatives. Probands and controls reporting greater impulsive traits displayed deactivation across the PFC during response inhibition, whereas relatives showed increased activation. In this first family study of neuroimaging biomarkers in BPD, we show that the familial risk for BPD is reflected in activation of the PFC during response inhibition, with lifetime psychiatric diagnosis and higher impulsive traits in relatives associated with larger increases in PFC activity. Higher PFC activity during response inhibition including among non-affected relatives could reflect a neurophysiological compensatory mechanism.

Inhibit, switch, and update: A within-subject fMRI investigation of executive control.

An influential model of executive control suggests that it comprises three dissociable processes: working memory, inhibition, and task switching. Multiple studies have investigated how these processes are individually implemented in the human brain. However, few have directly investigated this question using a common task architecture and a within-subject design. Here, healthy adult humans (N = 22) performed a novel executive control task during fMRI scanning. The paradigm independently manipulated working memory updating, inhibition, and task switching demands, while keeping all other task features constant. Direct contrasts of each executive task with a closely matched control condition revealed a differentiated pattern of recruitment across control tasks: working memory was associated with activity in dorsolateral prefrontal, lateral parietal and insular cortices bilaterally; Inhibition engaged right lateral and superior medial prefrontal cortex, inferior parietal lobules bilaterally, right middle and inferior temporal cortex, and ventral visual processing regions; Task switching was associated with bilateral activity in medial prefrontal cortex, posterior cingulate cortex and precuneus, as well as left inferior parietal lobule, lateral temporal cortex and right thalamus. A conjunction of all executive versus control task activations revealed common areas of activation overlapping regions of canonical frontoparietal control and dorsal attention networks. Further, multivariate analyses suggest that working memory may be a putative common factor supporting executive functioning. Taken together, these results are consistent with a hybrid model of executive control in the human brain.

Intrinsic default-executive coupling of the creative aging brain.

Creativity refers to the ability to generate novel associations and has been linked to better problem-solving and real-world functional abilities. In younger adults, creative cognition has been associated with functional connectivity among brain networks implicated in executive control [fronto-parietal network (FPN) and salience network (SN)] and associative or elaborative processing default network (DN). Here, we investigate whether creativity is associated with the intrinsic network architecture of the brain and how these associations may differ for younger and older adults. Young (mean age: 24.76, n = 22) and older (mean age: 70.03, n = 44) adults underwent multi-echo functional magnetic resonance image scanning at rest and completed a divergent-thinking task to assess creative cognition outside the scanner. Divergent thinking in older adults, compared to young adults, was associated with functional connectivity between the default and both executive control networks (FPN and SN) as well as more widespread default-executive coupling. Finally, the ventromedial prefrontal cortex appears to be a critical node involved in within- and between-network connectivity associated with creative cognition in older adulthood. Patterns of intrinsic network coupling revealed here suggest a putative neural mechanism underlying a greater role for mnemonic processes in creative cognition in older adulthood.

Clinical, personality, and neurodevelopmental phenotypes in borderline personality disorder: a family study.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a heterogeneous clinical phenotype that emerges from interactions among genetic, biological, neurodevelopmental, and psychosocial factors. In the present family study, we evaluated the familial aggregation of key clinical, personality, and neurodevelopmental phenotypes in probands with BPD (n = 103), first-degree biological relatives (n = 74; 43% without a history of psychiatric disorder), and non-psychiatric controls (n = 99). METHODS: Participants were assessed on DSM-IV psychiatric diagnoses, symptom dimensions of emotion dysregulation and impulsivity, 'big five' personality traits, and neurodevelopmental characteristics, as part of a larger family study on neurocognitive, biological, and genetic markers in BPD. RESULTS: The most common psychiatric diagnoses in probands and relatives were major depression, substance use disorders, post-traumatic stress disorder, anxiety disorders, and avoidant personality disorder. There was evidence of familial aggregation for specific dimensions of impulsivity and emotion dysregulation, and the big five traits neuroticism and conscientiousness. Both probands and relatives reported an elevated neurodevelopmental history of attentional and behavioral difficulties. CONCLUSIONS: These results support the validity of negative affectivity- and impulse-spectrum phenotypes associated with BPD and its familial risk. Further research is needed to investigate the aggregation of neurocognitive, neural and genetic factors in families with BPD and their associations with core phenotypes underlying the disorder.

Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control.

Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control.

Subjective cognitive complaints and functional disability in patients with borderline personality disorder and their nonaffected first-degree relatives.

OBJECTIVE: To examine the contributions of subjective cognitive complaints to functional disability in patients with borderline personality disorder (BPD) and their nonaffected relatives. METHOD: Patients with BPD (n = 26), their first-degree biological relatives (n = 17), and nonpsychiatric control subjects (n = 31) completed a self-report measure of cognitive difficulties and rated the severity of their functional disability on the World Health Organization Disability Assessment Schedule 2.0. RESULTS: After accounting for group differences in age and severity of depressive symptoms, patients and relatives endorsed more inattention and memory problems than control subjects. Whereas probands reported greater disability than relatives and control subjects across all functional domains, relatives described more difficulties than control subjects in managing multiple life activities, including domestic activities and occupational and academic functioning, and participating in society. For both probands and relatives, inattention and memory problems were linked primarily to difficulties with life activities, independent of depression and other comorbid psychiatric disorders. CONCLUSIONS: Problems with inattention and forgetfulness may lead to difficulties carrying out activities of daily living and occupational or academic problems in patients with BPD, as well as their nonaffected first-degree relatives.

A problem-solving task specialized for functional neuroimaging: validation of the Scarborough adaptation of the Tower of London (S-TOL) using near-infrared spectroscopy.

Problem-solving is an executive function subserved by a network of neural structures of which the dorsolateral prefrontal cortex (DLPFC) is central. Whereas several studies have evaluated the role of the DLPFC in problem-solving, few standardized tasks have been developed specifically for use with functional neuroimaging. The current study adapted a measure with established validity for the assessment of problem-solving abilities to design a test more suitable for functional neuroimaging protocols. The Scarborough adaptation of the Tower of London (S-TOL) was administered to 38 healthy adults while hemodynamic oxygenation of the PFC was measured using 16-channel continuous-wave functional near-infrared spectroscopy (fNIRS). Compared to a baseline condition, problems that required two or three steps to achieve a goal configuration were associated with higher activation in the left DLPFC and deactivation in the medial PFC. Individuals scoring higher in trait deliberation showed consistently higher activation in the left DLPFC regardless of task difficulty, whereas individuals lower in this trait displayed less activation when solving simple problems. Based on these results, the S-TOL may serve as a standardized task to evaluate problem-solving abilities in functional neuroimaging studies.

Differentiating functions of the lateral and medial prefrontal cortex in motor response inhibition.

The right inferior frontal gyrus is generally considered a critical region for motor response inhibition. Recent studies, however, suggest that the role of this cortical area in response inhibition may be overstated and that the contributions of other aspects of the prefrontal cortex are often overlooked. The current study used optical imaging to identify regions of the prefrontal cortex beyond the right inferior frontal gyrus which may serve to support motor response inhibition. Forty-three right-handed healthy adults completed a manual Go/No-Go task while evoked oxygenation of the prefrontal cortex was measured using 16-channel functional near-infrared spectroscopy. During motor response inhibition, the right inferior frontal gyrus, and to a lesser extent the homologous contralateral region, showed increased activation relative to a baseline task. Conversely, the medial prefrontal cortex was significantly deactivated, and the extent of reduced activity in this region was associated with fewer errors on the response inhibition task. These findings suggest a more substantial role of the left inferior frontal gyrus in response inhibition and possibly a distinct function of the middle frontal gyrus subserving error detection on manual motor control tasks.