Facial emotion processing in patients with borderline personality disorder as compared with healthy controls: an fMRI and ECG study.

BACKGROUND: Maladaptive behaviors and interpersonal difficulties in patients with borderline personality disorder (BPD) seem connected to biased facial emotion processing. This bias is often accompanied by heightened amygdala activity in patients with BPD as compared to healthy controls. However, functional magnetic resonance imaging (fMRI) studies exploring differences between patients and healthy controls in facial emotion processing have produced divergent results. The current study explored fMRI and heart rate variability (HRV) correlates of negative facial emotion processing in patients with BPD and healthy controls. METHODS: The study included 30 patients with BPD (29 females; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 females; M = 24.66, SD = 5.28). All participants underwent the "faces" task, an emotional face perception task, in an fMRI session simultaneously with ECG. In this task, participants are presented with emotional expressions of disgust, sadness, and fear (as a negative condition) and with the same pictures in a scrambled version (as a neutral condition). RESULTS: We found no differences in brain activity between patients with BPD and healthy controls when processing negative facial expressions as compared to neutral condition. We observed activation in large-scale brain areas in both groups when presented with negative facial expressions as compared to neutral condition. Patients with BPD displayed lower HRV than healthy controls in both conditions. However, there were no significant associations between HRV and amygdala activity and BPD symptoms. CONCLUSION: The results of this study indicate no abnormal brain activity during emotional facial processing in patients with BPD. This result contrasts with previous studies and more studies are needed to clarify the relationship between facial emotion processing and brain activity in patients with BPD. Possible reasons for the absence of brain activity differences are discussed in the study. Consistent with previous findings, patients showed lower HRV than healthy controls. However, HRV was not associated with amygdala activity and BPD symptoms.

EEG Microstates in Mood and Anxiety Disorders: A Meta-analysis.

To reduce the psycho-social burden increasing attention has focused on brain abnormalities in the most prevalent and highly co-occurring neuropsychiatric disorders, such as mood and anxiety. However, high inter-study variability in these patients results in inconsistent and contradictory alterations in the fast temporal dynamics of large-scale networks as measured by EEG microstates. Thus, in this meta-analysis, we aim to investigate the consistency of these changes to better understand possible common neuro-dynamical mechanisms of these disorders.In the systematic search, twelve studies investigating EEG microstate changes in participants with mood and anxiety disorders and individuals with subclinical depression were included in this meta-analysis, adding up to 787 participants.The results suggest that EEG microstates consistently discriminate mood and anxiety impairments from the general population in patients and subclinical states. Specifically, we found a small significant effect size for B microstates in patients compared to healthy controls, with larger effect sizes for increased B presence in unmedicated patients with comorbidity. In a subgroup meta-analysis of ten mood disorder studies, microstate D showed a significant effect size for decreased presence. When investigating only the two anxiety disorder studies, we found a significantly small effect size for the increased microstate A and a medium effect size for decreased microstate E (one study). However, more studies are needed to elucidate whether these findings are diagnostic-specific markers.Results are discussed in relation to the functional meaning of microstates and possible contribution to an explanatory mechanism of overlapping symptomatology of mood and anxiety disorders.

EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Neural correlates of social exclusion and overinclusion in patients with borderline personality disorder: an fMRI study.

BACKGROUND: Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion. METHODS: The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions. RESULTS: Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation. CONCLUSIONS: The results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.

Osteocalcin levels decrease during the treatment of an acute depressive episode.

Objectives: Osteocalcin is a protein secreted by osteoblasts with a versatile endocrine role. Several domains in which it plays a role-stress response, monoamine synthesis, and cognitive functioning-are implicated also in the pathophysiology of major depressive disorder. In search of possible objective biomarkers of depression, the aim of the study was to assess the relationship between osteocalcin and depressive symptoms during the treatment of depressive episode. Methods: The study included female inpatients with at least moderate depressive episode. In these patients, depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), and osteocalcin levels were assessed before the stabilization of antidepressive treatment and after 6 weeks. Relationships between osteocalcin levels and symptoms were analyzed with mixed-effect and linear models, taking into account age, menopausal status, and body mass index. Results: In 11 out of 13 enrolled inpatients, osteocalcin levels decreased during the first 6 weeks of treatment; this decrease was significant according to the mixed-effects model (t = -2.345, p = 0.019). According to the linear model, this decrease was significantly associated with reduction in depressive symptom severity (t = 2.673, p = 0.028). Osteocalcin was not associated with initial depressive symptom severity, and initial osteocalcin levels did not predict response to treatment. Limitations of the study include low sample size and inclusion of both pre- and postmenopausal women of various ages. Conclusions: This preliminary study suggests that osteocalcin may be a candidate biomarker of antidepressive treatment response and that this topic warrants further investigation.

Resting-State Phase-Amplitude Coupling Between the Human Subthalamic Nucleus and Cortical Activity: A Simultaneous Intracranial and Scalp EEG Study.

It has been suggested that slow oscillations in the subthalamic nucleus (STN) reflect top-down inputs from the medial prefrontal cortex, thus implementing behavior control. It is unclear, however, whether the STN oscillations are related to cortical activity in a bottom-up manner. To assess resting-state subcortico-cortical interactions, we recorded simultaneous scalp electroencephalographic activity and local field potentials in the STN (LFP-STN) in 11 patients with Parkinson's disease implanted with deep brain stimulation electrodes in the on-medication state during rest. We assessed the cross-structural phase-amplitude coupling (PAC) between the STN and cortical activity within a wide frequency range of 1 to 100 Hz. The PAC was dominant between the δ/θ STN phase and ß/γ cortical amplitude in most investigated scalp regions and between the δ cortical phase and θ/α STN amplitude in the frontal and temporal regions. The cross-frequency linkage between the slow oscillations of the LFP-STN activity and the amplitude of the scalp-recorded cortical activity at rest was demonstrated, and similar involvement of the left and right STNs in the coupling was observed. Our results suggest that the STN plays a role in both bottom-up and top-down processes within the subcortico-cortical circuitries of the human brain during the resting state. A relative left-right symmetry in the STN-cortex functional linkage was suggested. Practical treatment studies would be necessary to assess whether unilateral stimulation of the STN might be sufficient for treatment of Parkinson's disease.

Altered directed functional connectivity of the right amygdala in depression: high-density EEG study.

The cortico-striatal-pallidal-thalamic and limbic circuits are suggested to play a crucial role in the pathophysiology of depression. Stimulation of deep brain targets might improve symptoms in treatment-resistant depression. However, a better understanding of connectivity properties of deep brain structures potentially implicated in deep brain stimulation (DBS) treatment is needed. Using high-density EEG, we explored the directed functional connectivity at rest in 25 healthy subjects and 26 patients with moderate to severe depression within the bipolar affective disorder, depressive episode, and recurrent depressive disorder. We computed the Partial Directed Coherence on the source EEG signals focusing on the amygdala, anterior cingulate, putamen, pallidum, caudate, and thalamus. The global efficiency for the whole brain and the local efficiency, clustering coefficient, outflow, and strength for the selected structures were calculated. In the right amygdala, all the network metrics were significantly higher (p < 0.001) in patients than in controls. The global efficiency was significantly higher (p < 0.05) in patients than in controls, showed no correlation with status of depression, but decreased with increasing medication intake ([Formula: see text]). The amygdala seems to play an important role in neurobiology of depression. Practical treatment studies would be necessary to assess the amygdala as a potential future DBS target for treating depression.

Altered Electroencephalographic Resting-State Large-Scale Brain Network Dynamics in Euthymic Bipolar Disorder Patients.

Background: Neuroimaging studies provided evidence for disrupted resting-state functional brain network activity in bipolar disorder (BD). Electroencephalographic (EEG) studies found altered temporal characteristics of functional EEG microstates during depressive episode within different affective disorders. Here we investigated whether euthymic patients with BD show deviant resting-state large-scale brain network dynamics as reflected by altered temporal characteristics of EEG microstates. Methods: We used high-density EEG to explore between-group differences in duration, coverage, and occurrence of the resting-state functional EEG microstates in 17 euthymic adults with BD in on-medication state and 17 age- and gender-matched healthy controls. Two types of anxiety, state and trait, were assessed separately with scores ranging from 20 to 80. Results: Microstate analysis revealed five microstates (A-E) in global clustering across all subjects. In patients compared to controls, we found increased occurrence and coverage of microstate A that did not significantly correlate with anxiety scores. Conclusion: Our results provide neurophysiological evidence for altered large-scale brain network dynamics in BD patients and suggest the increased presence of A microstate to be an electrophysiological trait characteristic of BD.

EEG Resting-State Large-Scale Brain Network Dynamics Are Related to Depressive Symptoms.

Background: The few previous studies on resting-state electroencephalography (EEG) microstates in depressive patients suggest altered temporal characteristics of microstates compared to those of healthy subjects. We tested whether resting-state microstate temporal characteristics could capture large-scale brain network dynamic activity relevant to depressive symptomatology. Methods: To evaluate a possible relationship between the resting-state large-scale brain network dynamics and depressive symptoms, we performed EEG microstate analysis in 19 patients with moderate to severe depression in bipolar affective disorder, depressive episode, and recurrent depressive disorder and in 19 healthy controls. Results: Microstate analysis revealed six classes of microstates (A-F) in global clustering across all subjects. There were no between-group differences in the temporal characteristics of microstates. In the patient group, higher depressive symptomatology on the Montgomery-Åsberg Depression Rating Scale correlated with higher occurrence of microstate A (Spearman's rank correlation, r = 0.70, p < 0.01). Conclusion: Our results suggest that the observed interindividual differences in resting-state EEG microstate parameters could reflect altered large-scale brain network dynamics relevant to depressive symptomatology during depressive episodes. Replication in larger cohort is needed to assess the utility of the microstate analysis approach in an objective depression assessment at the individual level.

Deep brain stimulation targets for treating depression.

Deep brain stimulation (DBS) is a new therapeutic approach for treatment-resistant depression (TRD). There is a preliminary evidence of the efficacy and safety of DBS for TRD in the subgenual anterior cingulate cortex, the ventral capsule/ventral striatum, the nucleus accumbens, the lateral habenula, the inferior thalamic peduncle, the medial forebrain bundle, and the bed nucleus of the stria terminalis. Optimal stimulation targets, however, have not yet been determined. Here we provide updated knowledge substantiating the suitability of each of the current and potential future DBS targets for treating depression. In this review, we discuss the future outlook for DBS treatment of depression in light of the fact that antidepressant effects of DBS can be achieved using different targets.

Evoked potentials in final epoch of self-initiated hand movement: A study in patients with depth electrodes.

Comparison between the intended and performed motor action can be expected to occur in the final epoch of a voluntary movement. In search for electrophysiological correlates of this mental process the purpose of the current study was to identify intracerebral sites activated in final epoch of self-paced voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42 epileptic patients who performed self-paced voluntary movement task. Evoked potentials starting at 0 to 243ms after the peak of averaged, rectified electromyogram were identified in 21 regions of 13 subjects. The mean amplitude value of these late movement potentials (LMP) was 56.4±27.5µV. LMPs were observed in remote regions of mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices. Closely before the LMP onset, a significant increase of phase synchronization was observed in all EEG record pairs in 9 of 10 examined subjects; p<0.001, Mann-Whitney U test. In conclusion, mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices seem to represent integral functionally linked parts of network activated in final epoch of self-paced voluntary movement. Activation of this large-scale neuronal network was suggested to reflect a comparison process between the intended and actually performed motor action. Our results contribute to better understanding of neural mechanisms underlying goal-directed behavior crucial for creation of agentive experience.

Post-movement processing in visual oddball task - Evidence from intracerebral recording.

OBJECTIVE: To identify intracerebral sites activated after correct motor response during cognitive task and to assess associations of this activity with mental processes. METHODS: Intracerebral EEG was recorded from 205 sites of frontal, temporal and parietal lobes in 18 epileptic patients, who responded by button pressing together with mental counting to target stimuli in visual oddball task. RESULTS: Post-movement event-related potentials (ERPs) with mean latency 295 ± 184 ms after movement were found in all subjects in 64% of sites investigated. Generators were consistently observed in mesiotemporal structures, anterior midcingulate, prefrontal, and temporal cortices. Task-variant nonspecific and target specific post-movement ERPs were identified, displaying no significant differences in distribution among generating structures. Both after correct and incorrect performances the post-performance ERPs were observed in frontal and temporal cortices with latency sensitive to error commission in several frontal regions. CONCLUSION: Mesiotemporal structures and regions in anterior midcingulate, prefrontal and temporal cortices seem to represent integral parts of network activated after correct motor response in visual oddball task with mental counting. Our results imply equivalent involvement of these structures in task-variant nonspecific and target specific processes, and suggest existence of common nodes for correct and incorrect responses. SIGNIFICANCE: Our results contribute to better understanding of neural mechanisms underlying goal-directed behavior.

The primary motor cortex is involved in the control of a non-motor cognitive action.

OBJECTIVE: Adaptive interactions with the outer world necessitate effective connections between cognitive and executive functions. The primary motor cortex (M1) with its control of the spinal cord motor apparatus and its involvement in the processing of cognitive information related to motor functions is one of the best suited structures of this cognition-action connection. The question arose whether M1 might be involved also in situations where no overt or covered motor action is present. METHODS: The EEG data analyzed were recorded during an oddball task in one epileptic patient (19 years) with depth multilead electrodes implanted for diagnostic reasons into the M1 and several prefrontal areas. RESULTS: The main result was the finding of an evoked response to non-target stimuli with a pronounced late component in all frontal areas explored, including three loci of the M1. The late component was implicated in the evaluation of predicted and actual action and was synchronized in all three precentral loci and in the majority of prefrontal loci. CONCLUSION: The finding is considered as direct evidence of functional involvement of the M1 in cognitive activity not related to motor function. SIGNIFICANCE: Our results contribute to better understanding of neural mechanisms underlying cognition.

Hippocampal negative event-related potential recorded in humans during a simple sensorimotor task occurs independently of motor execution.

A hippocampal-prominent event-related potential (ERP) with a peak latency at around 450 ms is consistently observed as a correlate of hippocampal activity during various cognitive tasks. Some intracranial EEG studies demonstrated that the amplitude of this hippocampal potential was greater in response to stimuli requiring an overt motor response, in comparison with stimuli for which no motor response is required. These findings could indicate that hippocampal-evoked activity is related to movement execution as well as stimulus evaluation and associated memory processes. The aim of the present study was to investigate the temporal relationship between the hippocampal negative potential latency and motor responses. We analyzed ERPs recorded with 22 depth electrodes implanted into the hippocampi of 11 epileptic patients. Subjects were instructed to press a button after the presentation of a tone. All investigated hippocampi generated a prominent negative ERP peaking at ~420 ms. In 16 from 22 cases, we found that the ERP latency did not correlate with the reaction time; in different subjects, this potential could either precede or follow the motor response. Our results indicate that the hippocampal negative ERP occurs independently of motor execution. We suggest that hippocampal-evoked activity, recorded in a simple sensorimotor task, is related to the evaluation of stimulus meaning within the context of situation.