Brain functional abnormality in drug naïve adolescents with borderline personality disorder during self- and other-reflection

doi:10.21203/rs.3.rs-4885886/v1

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Brain functional abnormality in drug naïve adolescents with borderline personality disorder during self- and other-reflection

https://doi.org/10.21203/rs.3.rs-4885886/v1

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A disturbed sense of identity is one of the major features of borderline personality disorder (BPD), which manifests early in the course of the disorder, and is potentially examinable using functional imaging during tasks involving self-reflection. Twenty-seven medication-naïve adolescent female patients with BPD, who had no psychiatric comorbidities, and 28 matched healthy female controls underwent fMRI while answering questions about themselves or an acquaintance. Control conditions consisted of answering questions involving factual knowledge and a low-level baseline (cross-fixation). When self-reflection was compared to fact processing, BPD patients exhibited reduced activation in the right dorsolateral prefrontal cortex (DLPFC), as well as in the left parietal and calcarine cortex and the right precuneus. In contrast, other-reflection was associated with relatively lower activation in the medial frontal cortex in BPD patients, with further analysis revealing that this change reflected a failure of de-activation during the fact processing condition. There were no differences between the BPD patients and controls when self- and other-processing was examined against low-level baseline. This study provides evidence of reduced DLPFC activation during self-reflection in adolescent females with BPD, which may reflect diminished top-down cognitive control of this process in the disorder.

Biological sciences/Neuroscience

Health sciences/Diseases/Psychiatric disorders

Borderline personality disorder (BPD), characterized by emotional dysregulation, impulsive behaviors, instability in interpersonal relationships, and a disturbed sense of self, affects 1.5–5.5% of the adult population and is often disabling ¹. Although it has traditionally been considered an adult disorder, there is increasing evidence to support its reliable diagnosed in adolescence ^2–4. However, the presentation of BPD in at this age may not always be stable ^1,5, with changes in clinical expression from adolescence to adulthood being argued to depend on the transactional interaction between environmental and biological variables throughout development ⁶.

The importance of biological factors in BPD is widely recognized and have been examined in genetic, structural imaging and functional imaging studies ^7–15. With respect to the last of these, the focus to date has been on the affective dysregulation component of the disorder, and studies have identified a range of changes. Thus, a meta-analysis of 19 studies examining brain functional responses to negative emotional stimuli compared to neutral stimuli in BPD patients found reduced activation in the dorsolateral prefrontal cortex (DLPFC), the left lingual gyrus, and the left superior parietal gyrus bilaterally, and also increased activation in the posterior cingulate gyrus, the left middle temporal gyrus, and left amygdala and hippocampus ¹⁵.

Less investigated from the functional imaging point of view has been the disturbed sense of identity that is a feature of BPD ¹; see also ^16,17, and, along with affective instability, has been argued to be one of the two predominant features of the disorder when it presents in adolescence ¹⁸. One way to investigate BPD-associated identity disturbance is by means of autobiographical recall, which has been argued to be central to the creation and maintenance of one’s sense of self, forming links between disparate elements of our lives ¹⁹. Autobiographical recall is well-established as being associated with activation in the medial frontal cortex and the posterior cingulate cortex/precuneus (Svoboda et al, 2006, meta-analysis). Studies of autobiographical memory in patients with BPD have not had fully consistent findings. During the recall of unresolved versus resolved life events, Beblo et al ²⁰ reported higher activation in 21 adult BPD patients than in 21 healthy controls in the anterior and posterior cingulate cortex, ie the two midline cortical regions of the default mode network, as well as the amygdala and insula. Increased activation in the anterior cingulate and medial prefrontal cortex during the recall of both resolved and unresolved events compared to neutral events was also reported by Bozzatello et al ²¹ in adult BPD patients with disturbed sense of self. However, Metz et al ²² found no differences between BPD and healthy controls using a paradigm in which participants were told to recall a specific event from their past in response to a specific cue word. Most recently, our group ²³ found increased lingual/occipital cortex and hippocampal activity in a sample of drug-naïve adolescent females with BPD during recall of all types of personal events.

A second approach to the investigation of identity disturbance in BPD would be to examine brain activity during the processing of self-related information. In the healthy population this process, often referred to as self-reflection, is associated with activation in the medial frontal cortex, though more rostrally than the region activated by autobiographical recall; other regions activated include the posterior cingulate cortex and precuneus and the angular gyrus and the temporoparietal junction (TPJ) (meta-analyses ^24–26; see also ²⁷). Interestingly, processing of information about other people, eg their characteristics and attitudes (‘other-reflection’), activates essentially the same neural network (meta-analyses ^24–26; see also ²⁷), although with overlapping but discernibly different localizations in the medial frontal cortex according to one meta-analysis ²⁴. To date only one functional imaging studies has examined self-reflection in BPD. Scherpiet et al ²⁸ found increased activation in 19 adult female BPD patients compared to 19 healthy controls in a task where participants were instructed to think about themselves, reflect who they were and their goals, compared to a task where they were asked to be aware of their current emotions and bodily feelings;

the regions affected included the right dorsomedial prefrontal cortex (superior, medial, and middle frontal areas, as well as the anterior supplementary motor area). When self-reflection was compared to a condition requiring neither self-reflection nor emotional reflection, the regions affected were also in the right cortex and included the precentral, postcentral, supramarginal, and superior temporal gyri.

The present study aimed to examine brain functional changes during self– and other-reflection tasks in a sample of drug-naïve adolescent patients diagnosed with BPD. We compared activations during these tasks to a low-level baseline (a fixation cross) and also to an active control task commonly used in self-reflection studies, processing of impersonal factual information.

2.1. Participants

The initial clinical sample consisted of 37 treatment-naïve female adolescent patients with a DSM-5 diagnosis of BPD. Patients were recruited from two outpatient mental health services for children and adolescents in Barcelona with expertise in BPD in adolescents and young adults, (Vall d’Hebron University Hospital and the Orienta Foundation). Exclusion criteria included left-handedness, age below 12 or above 18 years, alcohol or substance abuse or dependence (excluding nicotine) in the last year, head trauma with loss of consciousness, and general exclusion criteria for MRI such as the presence of metals within the body. We also excluded patients with any comorbid psychiatric disorder according to DSM-5 diagnostic criteria. All the patients were drug-naïve at the time of examination, as confirmed by questioning.

The diagnosis of BPD was based on the Spanish version of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) ²⁹. The Spanish version of Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime version ³⁰ was used to assess psychiatric disorders other than BPD in patients and controls under 16 years old. The Spanish version of the Structured Clinical Interview for DSM-IV Axis I Disorders ³¹ was used to assess psychiatric disorders other than BPD in those who were between 16 and 18 years old.

Healthy controls (HC) were selected from an initial sample of 40 female adolescents recruited from the community on the basis that they were similar to the patients in age and estimated IQ, as assessed using the Word Accentuation Test (Test de Acentuación de Palabras, TAP ³²). Exclusion criteria were the same as for the patients. HC were also excluded if they reported having a first-degree relative with a psychiatric diagnosis.

All participants gave written informed consent prior to participation in accordance to the Declaration of Helsinki. This was obtained from participants aged 18 years and from parents/legal guardians for participants aged under 18. All the study procedures had been previously approved by the Clinical Research Ethics Committee of Vall d’Hebron University Hospital [PR(AG)353/2015] and the Clinical Research Ethics Committee of Germanes Hospitalàries [PI15/02025].

2.2. Self-other fMRI task

Participants performed a self- and other-reflection task previously used by our group ²⁷. Before scanning, participants were asked to choose an acquaintance to think about inside the scanner. The chosen individual had to be familiar with the participant but not too close to avoid eliciting strong feelings towards them (for example, a classmate). During the task, participants viewed a series of statements about themselves (‘self” condition), the acquaintance (‘other’ condition), or concerning general knowledge (‘facts’, the control condition). They had to respond with a button press indicating whether they considered the sentence to be true or false. Stimuli were presented on VisualSystem goggles mounted on the head coil, and responses were made and registered with the MRI-compatible response device Response-grip (NordicNeuroLab).

The task consisted of 54 trials (18 per condition) arranged in a block design. Each block started with an instruction screen indicating the condition that corresponded to the block (‘Sentences about me’, ‘Sentences about other’, ‘Sentences about facts’), which lasted 3s. After a 1s delay, three trials were presented, each lasting 9s, were the sentence appeared in the centre of the screen and the options “Yes” and “No” appeared at the bottom-right and bottom-left corners, respectively, to act as a reminder of the required response (“Yes” with the right index finger, and “No” with the left index finger). The trials were separated by a 1s blank screen. After three trials, the next block started, with a total of 6 blocks per condition. Every 3 blocks there was a baseline period of 16s in which a fixation cross was presented (‘low-level baseline’). Block order was pseudorandomized, with each of the three conditions occurring once between baseline periods.

2. 3. Image acquisition

Images were acquired with a 3T Philips Achieva scanner (Philips Medical Systems, Best, The Netherlands). Functional data were acquired using a T2*-weighted echo-planar imaging (EPI) sequence with the following acquisition parameters: TR = 2000 ms, TE = 30 ms, Flip angle = 78^O, in-plane resolution = 3 × 3 mm, FOV = 240 mm, slice thickness = 3mm, inter-slice gap = 1 mm. Slices (32 per volume; 364 volumes) were acquired with an interleaved order parallel to the anterior-posterior commissure plane. The first 10 volumes were discarded to avoid T1 saturation effects. Before the functional sequence, a high-resolution anatomical 3D volume was acquired using a TFE (Turbo Field Echo) sequence for anatomical reference and inspection (TR = 8.15 ms; TE = 3.73 ms; flip angle = 8º; voxel-size = 0.9735 x 0.9735 mm; slice thickness = 1mm; slice number = 160; FOV = 240 mm).

2. 4. Image pre-processing and analysis

Pre-processing and analyses of the fMRI data were carried out with the FEAT module included in FSL (FMRIB Software Library) ³³. Preprocessing included motion correction (using the MCFLIRT algorithm with 6 degrees of freedom) and co-registration and normalization to a common stereotactic space, for accurate registration, a two-step process was used; first, brain extraction was applied to the structural image, and the functional sequence was registered to it; then the structural image was registered to a standard asymmetric age-appropriate template (for ages 13.0 to 18.5) ^34,35); these two transformations were used to finally register the functional sequence to the standard space. Before group analyses, normalized images were spatially filtered with a Gaussian filter (FWHM = 5 mm). Individuals with an estimated maximum absolute movement > 3.0 mm or an average absolute movement > 0.3 mm were excluded from analyses to minimize unwanted movement-related effects.

Statistical analyses were performed by means of General Linear Models (GLMs). At the single-subject level, three regressors of interest were defined in the GLM corresponding to the three task conditions (Self, Other and Facts). Instructions screens were modelled by an additional nuisance regressor. Fixation periods were not modelled and thus acted as an implicit baseline. GLMs were fitted to generate 1) activation and de-activations maps for the self- and another- reflection conditions compared to low level baseline and 2) activations maps comparing the experimental and control conditions (Self vs. Facts and Other vs. Facts).

Temporal derivatives for each regressor of interest, as well as movement parameters (six in total, three rotations and three translations) were included as additional regressors. Images were high-pass filtered with a 130 s cut-off.

At the intra-group level, task-related activations and /or de-activations were assessed with one-sample t-tests on the contrasts defined at the subject level with mixed-effects models ³⁶ within the FEAT module. Comparisons between groups were run to evaluate differences between BPD and healthy controls. All statistical tests were carried out at the cluster level with a corrected p < 0.05 using Gaussian random field methods. A threshold of z > 3.1 (p < 0.001) at the voxel level was used to define the initial set of clusters.

3.1 Demographic and clinical data

From the initial samples, 10 patients and 12 controls were excluded due to excessive head movement giving a final sample of 27 patients and 28 HC. As shown in Table 1, the remaining subjects were matched for age and estimated IQ.

Table 1

Demographic data for the BPD patients and healthy controls.
	BPD patients N = 27	Healthy controls N = 28	Statistics
Age (mean ± SD) [range]	16.22 ± 1.24 [14–18]	16.46 ± 1.10 [13–18]	t = 0.10 p = 0.92
TAP-estimated IQ (mean ± SD) [range]	95.41 ± 7.76 [79–110]	95.21 ± 7.19 [79–112]	t = 0.75 p = 0.46
Socioeconomic level*(median) [range]	3 [1–5]	3[2–5]	Z = 0.71 p = 0.56
Years of education (mean ± SD) [range]	10.65 ± 1.56	10.69 ± 1.05	t = 0.12 p = 0.90
* Socioeconomic level was categorized as follows: 1(high); 2(medium-high); 3(medium); 4(medium-low); 5(low); 6(severe socioeconomics deficiencies)

3.2. fMRI Results

3.2.1. Self- and other- reflection versus low level baseline

As shown in Fig. 1, clusters of significant activation in the healthy controls were similar for both self- and other-reflection and encompassed bilaterally the cerebellum, the inferior, middle, superior occipital and lingual gyrus, the calcarine, the cuneus, and the fusiform cortex, the anterior insula, the angular gyrus and supramarginal areas, as well as the inferior and dorsolateral frontal cortex, and the medial superior frontal cortex, including the supragenual anterior cingulate. Activations were also seen in the left temporal cortex (middle temporal gyrus and temporal pole) and in the pallidum, the putamen, the amygdala and the hippocampus and parahippocampal nuclei. The TPJ was also activated, with the left side being involved in both tasks, and the right side specifically in the other-reflection task (see Fig. 1).

Areas of de-activation during both self- and other-reflection were seen in the subgenual anterior medial frontal cortex, the posterior cingulate cortex, the cuneus and precuneus. The right middle/superior temporal and inferior parietal/supramarginal cortex were two other regions showing de-activation.

In the patients, the pattern of activations was similar to that of the healthy controls in both self- and other-reflection. De-activations were also similar, but whereas the anterior medial frontal subgenual cortex was de-activated during performance of both tasks in the controls, this was only the case for other-reflection in patients.

-Figure 1 abaout here-

There were no clusters of difference between the patients and the controls in either the self- or other-reflection tasks.

3.2.2. Self-reflection vs facts

Activations in the self-reflection condition compared to fact processing are shown in Fig. 2A and 2B (for full details see Supplementary Table S1). The healthy controls showed greater activation in former task in the medial frontal cortex including the pregenual anterior cingulate cortex and the middle/posterior cingulate cortex involving the cuneus and precuneus. Greater activation was also seen in occipital, lingual, fusiform, and temporal polar regions, and in the left angular gyrus and middle temporal cortex and the TPJ, more markedly on the left. Activation was also seen in the left anterior insular and inferior and dorsolateral frontal cortex.

-Figure 2 about here-

The pattern was broadly similar though visually less marked in the BPD patients. Greater activation during self-reflection compared to fact processing was seen in a small cluster in the pregenual anterior cingulate cortex and a larger cluster in the middle/posterior cingulate cortex extending to precuneus and cuneus. There was also a small cluster in the left TPJ. Greater self-related activation was also seen bilaterally in temporal polar regions.

In the comparison between groups (Fig. 2C, see also Supplementary Table S1), the BPD patients showed significantly reduced activation in four clusters. One was in the right DLPFC, (1590 voxels; MNI coordinates: 29 50 15; z-value = 4.63; p = 0.003), a second was in the left calcarine cortex (1176 voxels; MNI: -11 -79 15; z = 3.92; p = 0.016), a third was in the left superior parietal cortex (1115 voxels; MNI: -22 -70 64; z = 4.72, p = 0.02) and finally there was a cluster in the right precentral gyrus (1010 voxels; MNI: 30 − 10 50; z = 4.63; p = 0.031).

Because, as pointed out by Gusnard and Raichle (2001), relative changes between two active tasks can be difficult to interpret – specifically both reduced activation and increased de-activation will give the same appearances – we further explored the findings in regions of interest (ROIs) based on these clusters, examining the changes for both self-reflection and fact processing with respect to low level baseline. Boxplots are shown in Fig. 3. It can be seen that the healthy controls showed greater activation during self-reflection than during facts processing (left calcarine and right precentral clusters), or similar activation levels in both conditions (right DLPFC and left superior parietal clusters). In contrast, activation in the BPD patients was lower during self-reflection than fact processing in all clusters apart from the one in the left calcarine cortex. For the right DLPFC, where controls showed moderate activation, the BPD patients showed de-activation.

-Figure 3 about here-

3.2.3. Other-reflection vs fact processing

The contrast other-reflection vs fact processing yielded a similar pattern of activation to the corresponding self-reflection vs fact processing comparison (see Fig. 4 and Supplementary Table S3). In the healthy controls clusters of greater activation during other-reflection were seen in the medial frontal cortex including the pregenual anterior cingulate, in this case also including the subgenual region, and in the middle/posterior cingulate cortex and the cuneus/precuneus. Greater activation was also seen in lingual, calcarine and temporal polar regions, and bilaterally in a region including the TPJ ; on the left this cluster minimally included the the inferior frontal cortex and insula, but minimally.

-Figure 4 about here-

In the patients, activations were visually less marked, particularly in the medial frontal cortex and the lingual/calcarine cortex, but otherwise similar to those of the controls in the cingulate. Activations were also seen bilaterally in the angular and middle temporal cortex including the TPJ and the temporal pole region.

The between groups comparison (Fig. 4C) revealed two clusters of decreased activation for BPD patients in the medial frontal cortex, one affecting the subgenual anterior cingulate cortex, with a peak in the left hemisphere (3033 voxels; MNI: -13 34 − 4; z-value = 4.24; p < 0.001), and another in a corresponding position on the right (1053 voxels; MNI: 16 41 − 1; z-value = 4.21; p = 0.03).

Figure 5 shows mean activations in a ROI based on these two clusters combined, examining the changes for both other-reflection and fact processing with respect to low level baseline It can be seen that this area was de-activated in both groups during both other-reflection and facts processing, with greater de-activation by the controls during the latter task. Accordingly, the differences between the BPD patients and the HC reflected a failure of de-activation in the fact processing task by the patients.

-Figure 5 about here-

Our goal in this study was to identify, through a self- and other-reflection task, brain functional abnormalities potentially relevant to the identity disturbance of BPD, while avoiding confounding factors such as drug treatment, the clinical course of the disease or comorbidity. The main finding was that adolescent patients with BPD showed reduced activation in the right DLPFC during a self-reflection task compared to healthy controls, albeit among other areas including the parietal cortex, the occipital cortex and the precentral cortex. Between-group differences were also seen during other-reflection, but this time the location was in the subgenual anterior cingulate cortex and took the form of failure of de-activation. Both findings were seen when the experimental condition, ie self- or other-reflection, was contrasted with a control condition, involving general knowledge, and there were no differences between the groups when activations and de-activations were measured against a low-level baseline.

Our finding of reduced DLPFC activation (to the point of deactivation) in patients with BPD during self-reflection was unexpected given that, in healthy adults, self-related cognition appears to be primarily associated with activation in default mode network regions, i.e., the medial frontal cortex, the posterior cingulate cortex/precuneus, the angular gyrus, and the TPJ ^24–26. However, it should be noted that three meta-analyses also found activation in frontal regions, although primarily involving the left hemisphere. Murray et al. ²⁵ revealed activation in the left inferior frontal cortex in the contrast between self versus control tasks, while the contrast between self- versus other-referencing reported activation in the right inferior frontal cortex. In the meta-analysis conducted by van der Meer et al. ²⁶, activations in the left inferior frontal cortex were reported in the contrast between self-reflection and a baseline condition; however, in the comparison between self and other, they reported a dorsolateral frontal region similar to the cluster of differences found in our study, but on the left. In Denny et al. ²⁴, the comparison between self- and other-related judgments also included the left inferior frontal cortex.

At a theoretical level, it also seems plausible to speculate that reduced activation in this region during self-reflection in patients with BPD might reflect difficulties in top-down cognitive regulation of emotional processes during tasks with significant emotional load.

It should be noted that our findings differ from the study by Scherpiet et al.²⁸ on adult BPD patients, described in the introduction. Instead of reduced activation, they found increased activation in BPD patients compared to healthy controls in the right motor and somatosensory cortex, the right supramarginal gyrus, and the superior temporal gyrus during a self-reflection task compared to a task with no cognitive or emotional demands. Additionally, when they compared a task where participants were asked to be aware of their current emotions and bodily feelings to the self-reflection task, they observed decreased activation in the right frontal cortex in BPD patients compared to healthy controls.

The only other possibly relevant study in this context is that of Beeney et al. ³⁷, although this did not employ anything clearly recognizable as a control condition. they scanned 17 adult females with BPD and 21 healthy controls while they answered questions about their own personality characteristics (eg ‘Are you kind?’) and the personality characteristics of a close friend (eg ‘Is Julie kind? ); there were also two ‘third-person’ conditions where the participants carried out cognitive operations perhaps best understandable as involving theory of mind (eg ‘According to Julie, are you kind?’ and ‘According to Julie, is she kind?’). Contrasting the self-and other-reflection conditions with the ‘third person’ conditions revealed clusters of significantly lower activation in the lingual gyrus, occipital cortex, precuneus, and angular gyrus in both groups. However, there were no differences between the BPD patients and the healthy controls for this (or any other contrasts).

During other-reflection, we found reduced activation in the ventral medial frontal cortex in the BPD patients when contrasted with the active control task. Further analysis indicated that this reduced activation in fact reflected failure of de-activation in the BPD group during fact processing. While a finding of changes in the processing of self-related information in BPD would be in line with identity disturbance in the disorder, why there should be differences in other processing in patients with BPD is less easy to explain. Nor is it easy to explain why the changes were seen in a different region from those found during self-reflection – the medial frontal cortex as opposed to the DLPFC – and why they were in the opposite direction – failure of de-activation (during fact processing) as opposed to hypoactivation (during self-processing. However, it may be relevant here that failure of de-activation of the ventral medial frontal cortex was found in our previous study of adult BPD patients ³⁸, as well as in a sample of 30 female adolescent BPD (that included the patients evaluated in the present work) ³⁹, during performance of the n-back working memory task, which like fact processing, requires externally directed attention.

During both self-reflection and other-reflection, both BPD patients and healthy controls showed activation of the left TPJ. This was observed in both the comparison against the active control condition and the low-level baseline. The right TPJ was activated in the other > self-reflection contrast but was not activated in the self-reflection versus low-level baseline comparison in either group. Unlike the controls, BPD patients did not show right TPJ activity in the other-reflection versus baseline nor in the self > other comparison. However, there were no differences between the groups in this region either compared to an active control or to the low-level baseline. The TPJ is known to be implicated in social cognition, having been argued to play a crucial role in understanding the beliefs of others ⁴⁰ and possibly other social cognitive processes as well ^41,42. Given that social interactions are central to BPD, the lack of activation differences between BPD patients and healthy individuals represents a significant negative finding, one that could point to a dissociation between processes underlying social cognition and identity disturbance in the disorder.

In summary, our study finds evidence of reduced activity in cortical region of the right DLPFC during self-reflection in adolescent females with BPD, which might be indicative of reduced top-down cognitive control of this process in the disorder. We also observed a failure in deactivation in the ventral mPFC, a core region of the default mode network, which is more difficult to account for, but which fits with existing findings with other tasks in the disorder Some limitations need to be acknowledged. First, this study has been conducted only in adolescent females; while BPD is almost certainly more prevalent in females, it also affects males and so our findings may not be generalizable to the latter. Secondly, a larger sample size may have yielded clearer results, particular with respect to resolving the activity differences we found between self- and other-reflection. Also, it is important to keep in mind that, as mentioned in the introduction, the stability of BPD diagnosis from adolescence to adulthood appears to be moderate to low, and therefore a follow-up longitudinal study of these patients would be desirable to determine whether and to what extent the fMRI changes we found alter with development. Finally, we used a fact verification task as an active control for self- and other-processing, as this externally oriented, attention-demanding task deactivates the default mode network, whereas self- and other-reflection activate it. This discrepancy may rise concerns about its suitability as a control task, so comparisons of the conditions of interest against a low-level baseline were used to aid in the interpretation of the results.

Conflict of Interest

Authors have no conflict of interest to declare

Acknowledgments

This work was supported by the Instituto de Salud Carlos III and CIBERSAM-ISCIII, and co-funded by the European Union (ERDF/ESF "A way to make Europe"/"Investing in your future"): project PI15/02025 to MF and grant CD19/00149 to PF-C. Support was also received from the Catalonian Government (2017SGR1271, 2021SGR01475 to EP-C). PF-C is currently funded by a “la Caixa” Junior Leader Fellowship (LCF/BQ/PR22/11920017).

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Brain functional abnormality in drug naïve adolescents with borderline personality disorder during self- and other-reflection

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Abstract

Figures

1. Introduction

2. Methods

2.1. Participants

2.2. Self-other fMRI task

2. 3. Image acquisition

2. 4. Image pre-processing and analysis

3. Results

3.1 Demographic and clinical data

3.2. fMRI Results

3.2.1. Self- and other- reflection versus low level baseline

3.2.2. Self-reflection vs facts

3.2.3. Other-reflection vs fact processing

4. Discussion

Declarations

Conflict of Interest

Acknowledgments

References

Additional Declarations

Supplementary Files

Status:

Version 1