DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT): research protocol for a cross-sectional pilot study.

INTRODUCTION: Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance. METHODS AND ANALYSIS: The cross-sectional 'DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia' (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood-brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media. TRIAL REGISTRATION NUMBER: NCT02347540.

Neural Correlates of Tooth Clenching in Patients with Bruxism and Temporomandibular Disorder-Related Pain.

AIMS: To measure brain activity in patients with bruxism and temporomandibular disorder (TMD)-related pain in comparison to controls using functional magnetic resonance imaging (fMRI) and to investigate whether modulations in jaw clenching led to different pain reports and/or changes in neural activity in motor and pain processing areas within and between both groups. METHODS: A total of 40 participants (21 patients with bruxism and TMD-related pain and 19 healthy controls) performed a tooth-clenching task while lying inside a 3T MRI scanner. Participants were instructed to mildly or strongly clench their teeth for brief periods of 12 seconds and to subsequently rate their clenching intensity and pain experience after each clenching period. RESULTS: Patients reported significantly more pain during strong clenching compared to mild clenching. Further results showed significant differences between patients and controls in activity in areas of brain networks commonly associated with pain processing, which were also correlated with reported pain intensity. There was no evidence for differences in activity in motor-related areas between groups, which contrasts with findings of previous research. CONCLUSIONS: Brain activity in patients with bruxism and TMD-related pain is correlated more with pain processing than with motoric differences.

Attenuated cognitive functioning decades after preeclampsia.

BACKGROUND: Preeclampsia, a hypertensive pregnancy disorder, is a leading cause of maternal and fetal morbidity and mortality, with remote cardio- and cerebrovascular implications. After preeclampsia, women may report serious disabling cognitive complaints, especially involving executive function, but the extent and time course of these complaints are unknown. OBJECTIVE: This study aimed to determine the impact of preeclampsia on perceived maternal cognitive functioning decades after pregnancy. STUDY DESIGN: This study is part of a cross-sectional case-control study named Queen of Hearts (ClinicalTrials.gov Identifier: NCT02347540), a collaboration study of 5 tertiary referral centers within the Netherlands investigating long-term effects of preeclampsia. Eligible participants were female patients aged ≥18 years after preeclampsia and after normotensive pregnancy between 6 months and 30 years after their first (complicated) pregnancy. Preeclampsia was defined as new-onset hypertension after 20 weeks of gestation along with proteinuria, fetal growth restriction, or other maternal organ dysfunction. Women with a history of hypertension, autoimmune disease, or kidney disease before their first pregnancy were excluded. Attenuation of higher-order cognitive functions, that is, executive function, was measured with the Behavior Rating Inventory of Executive Function for Adults. Crude and covariate-adjusted absolute and relative risks of clinical attenuation over time after (complicated) pregnancy were determined with moderated logistic and log-binomial regression. RESULTS: This study included 1036 women with a history of preeclampsia and 527 women with normotensive pregnancies. Regarding overall executive function, 23.2% (95% confidence interval, 19.0-28.1) of women experienced clinically relevant attenuation after preeclampsia, as opposed to 2.2% (95% confidence interval, 0.8-6.0) of controls immediately after childbirth (adjusted relative risk, 9.20 [95% confidence interval, 3.33-25.38]). Group differences diminished yet remained statistically significant (P < .05) at least 19 years postpartum. Regardless of history of preeclampsia, women with lower educational attainment, mood or anxiety disorders, or obesity were especially at risk. Neither severity of preeclampsia, multiple gestation, method of delivery, preterm birth, nor perinatal death was related to overall executive function. CONCLUSION: After preeclampsia, women were 9 times more likely to experience clinical attenuation of higher-order cognitive functions as opposed to after normotensive pregnancy. Despite overall steady improvement, elevated risks persisted over decades after childbirth.

Multisensory synchrony of contextual boundaries affects temporal order memory, but not encoding or recognition.

We memorize our daily life experiences, which are often multisensory in nature, by segmenting them into distinct event models, in accordance with perceived contextual or situational changes. However, very little is known about how multisensory boundaries affect segmentation, as most studies have focused on unisensory (visual or audio) segmentation. In three experiments, we investigated the effect of multisensory boundaries on segmentation in memory and perception. In Experiment 1, participants encoded lists of pictures while audio and visual contexts changed synchronously or asynchronously. After each list, we tested recognition and temporal associative memory for pictures that were encoded in the same audio-visual context or that crossed a synchronous or an asynchronous multisensory change. We found no effect of multisensory synchrony for recognition memory: synchronous and asynchronous changes similarly impaired recognition for pictures encoded at those changes, compared to pictures encoded further away from those changes. Multisensory synchrony did affect temporal associative memory, which was worse for pictures encoded at synchronous than at asynchronous changes. Follow up experiments showed that this effect was not due to the higher dimensionality of multisensory over unisensory contexts (Experiment 2), nor that it was due to the temporal unpredictability of contextual changes inherent to Experiment 1 (Experiment 3). We argue that participants formed situational expectations through multisensory synchronicity, such that synchronous multisensory changes deviated more strongly from those expectations than asynchronous changes. We discuss our findings in light of supportive and conflicting findings of uni- and multi-sensory segmentation.

Time changes: Timing contexts support event segmentation in associative memory.

We tend to mentally segment a series of events according to perceptual contextual changes, such that items from a shared context are more strongly associated in memory than items from different contexts. It is also known that timing context provides a scaffold to structure experiences in memory, but its role in event segmentation has not been investigated. We adapted a previous paradigm, which was used to investigate event segmentation using visual contexts, to study the effects of changes in timing contexts on event segmentation in associative memory. In two experiments, we presented lists of 36 items in which the interstimulus intervals (ISIs) changed after a series of six items ranging between 0.5 and 4 s in 0.5 s steps. After each list, participants judged which one of two test items were shown first (temporal order judgment) for items that were either drawn from the same context (within an ISI) or from consecutive contexts (across ISIs). Further, participants judged from memory whether the ISI associated to an item lasted longer than a standard interval (2.25 s) that was not previously shown (temporal source memory). Experiment 2 further included a time-item encoding task. Results revealed an effect of timing context changes in temporal order judgments, with faster responses (Experiment 1) or higher accuracy (Experiment 2) when items were drawn from the same context, as opposed to items drawn from across contexts. Further, in both experiments, we found that participants were well able to provide temporal source memory judgments based on recalled durations. Finally, replicated across experiments, we found subjective duration bias, as estimated by psychometric curve fitting parameters of the recalled durations, correlated negatively with within-context temporal order judgments. These findings show that changes in timing context support event segmentation in associative memory.

7T dynamic contrast-enhanced MRI for the detection of subtle blood-brain barrier leakage.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage. METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2* degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack. RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue. CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

Transcranial alternating current stimulation at theta frequency to left parietal cortex impairs associative, but not perceptual, memory encoding.

Neural oscillations in the theta range (4-8 Hz) are thought to underlie associative memory function in the hippocampal-cortical network. While there is ample evidence supporting a role of theta oscillations in animal and human memory, most evidence is correlational. Non-invasive brain stimulation (NIBS) can be employed to modulate cortical oscillatory activity to influence brain activity, and possibly modulate deeper brain regions, such as hippocampus, through strong and reliable cortico-hippocampal functional connections. We applied focal transcranial alternating current stimulation (tACS) at 6 Hz over left parietal cortex to modulate brain activity in the putative cortico-hippocampal network to influence associative memory encoding. After encoding and brain stimulation, participants completed an associative memory and a perceptual recognition task. Results showed that theta tACS significantly decreased associative memory performance but did not affect perceptual memory performance. These results show that parietal theta tACS modulates associative processing separately from perceptual processing, and further substantiate the hypothesis that theta oscillations are implicated in the cortico-hippocampal network and associative encoding.

Corticolimbic Circuitry in Chronic Pain Tracks Pain Intensity Relief Following Exposure In Vivo.

Background: A subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief. Methods: Resting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens. Results: Pain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus. Conclusions: While changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.

Hippocampus plays a role in speech feedback processing.

There is increasing evidence that the hippocampus is involved in language production and verbal communication, although little is known about its possible role. According to one view, hippocampus contributes semantic memory to spoken language. Alternatively, hippocampus is involved in the processing the (mis)match between expected sensory consequences of speaking and the perceived speech feedback. In the current study, we re-analysed functional magnetic resonance (fMRI) data of two overt picture-naming studies to test whether hippocampus is involved in speech production and, if so, whether the results can distinguish between a "pure memory" versus a "prediction" account of hippocampal involvement. In both studies, participants overtly named pictures during scanning while hearing their own speech feedback unimpededly or impaired by a superimposed noise mask. Results showed decreased hippocampal activity when speech feedback was impaired, compared to when feedback was unimpeded. Further, we found increased functional coupling between auditory cortex and hippocampus during unimpeded speech feedback, compared to impaired feedback. Finally, we found significant functional coupling between a hippocampal/supplementary motor area (SMA) interaction term and auditory cortex, anterior cingulate cortex and cerebellum during overt picture naming, but not during listening to one's own pre-recorded voice. These findings indicate that hippocampus plays a role in speech production that is in accordance with a "prediction" view of hippocampal functioning.

Hippocampal-striatal functional connectivity supports processing of temporal expectations from associative memory.

The hippocampus and dorsal striatum are both associated with temporal processing, but they are thought to play distinct roles. The hippocampus has been reported to contribute to storing temporal structure of events in memory, whereas the striatum contributes to temporal motor preparation and reward anticipation. Here, we asked whether the striatum cooperates with the hippocampus in processing the temporal context of memorized visual associations. In our task, participants were trained to implicitly form temporal expectations for one of two possible time intervals associated to specific cue-target associations, and subsequently were scanned using ultra-high-field 7T functional magnetic resonance imaging. During scanning, learned temporal expectations could be violated when the pairs were presented at either the associated or not-associated time intervals. When temporal expectations were met during testing trials, activity in left and right hippocampal subfields and right putamen decreased, compared to when temporal expectations were not met. Further, psycho-physiological interactions showed that functional connectivity between left hippocampal subfields and caudate decreased when temporal expectations were not met. Our results indicate that the hippocampus and striatum cooperate to process implicit temporal expectation from mnemonic associations. Our findings provide further support for a hippocampal-striatal network in temporal associative processing.

Contributions of Cerebro-Cerebellar Default Mode Connectivity Patterns to Memory Performance in Mild Cognitive Impairment.

BACKGROUND: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients. OBJECTIVE: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance. METHODS: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the cerebellar DMN seeds and the cerebral DMN. RESULTS: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients. CONCLUSION: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases.

Physical exploration of a virtual reality environment: Effects on spatiotemporal associative recognition of episodic memory.

Associative memory has been increasingly investigated in immersive virtual reality (VR) environments, but conditions that enable physical exploration remain heavily under-investigated. To address this issue, we designed two museum rooms in VR throughout which participants could physically walk (i.e., high immersive and interactive fidelity). Participants were instructed to memorize all room details, which each contained nine paintings and two stone sculptures. On a subsequent old/new recognition task, we examined to what extent shared associated context (i.e., spatial boundaries, ordinal proximity) and physically travelled distance between paintings facilitated recognition of paintings from the museum rooms. Participants more often correctly recognized a sequentially probed old painting when the directly preceding painting was encoded within the same room or in a proximal position, relative to those encoded across rooms or in a distal position. A novel finding was that sequentially probed paintings from the same room were also recognized better when the physically travelled spatial or temporal distance between the probed paintings was shorter, as compared with longer distances. Taken together, our results in highly immersive VR support the notion that spatiotemporal context facilitates recognition of associated event content.

Hemifield-specific Correlations between Cue-related Blood Oxygen Level Dependent Activity in Bilateral Nodes of the Dorsal Attention Network and Attentional Benefits in a Spatial Orienting Paradigm.

The dorsal attention network (DAN) is known to be involved in shifts of spatial attention or in orienting. However, the involvement of each hemisphere in shifts to either hemifield is still a matter of debate. In this study, interindividual hemifield-specific attentional benefits in RTs were correlated with cue-related BOLD responses specific to directive cues in the left and right frontal and posterior nodes of the DAN, measured in a Spatial Orienting Paradigm. The pattern of correlations was analyzed with respect to its fit with three existing hypotheses of spatial attention control: the contralateral, right dominance, and hybrid hypotheses. Results showed that activation in frontal and parietal nodes of the DAN could explain a significant proportion of the interindividual variance in attentional benefits. Although we found that benefits in the right hemifield correlated with cue-related activity in the left, as well as the right, DAN and that the pattern of correlations fit best with the right dominance hypothesis, there were no significant correlations between left benefits and activation in the right (as well as left) DAN, which precludes the conclusion that our data support the right dominance hypothesis and might instead point toward a potential qualitative difference between leftward and rightward shifts of attention. In conclusion, this study demonstrates that behavioral effects of orienting can be linked to activation changes in the DAN, and it raises new questions with respect to the involvement of the frontal and parietal nodes in each hemisphere in hemifield-specific orienting.

Anger provocation increases limbic and decreases medial prefrontal cortex connectivity with the left amygdala in reactive aggressive violent offenders.

Neurobiological models propose reactive aggression as a failure in emotion regulation, caused by an imbalance between prefrontal cortical control and excessive bottom-up signals of negative affect by limbic regions, including the amygdala. Therefore, we hypothesize a negative correlation between PFC and amygdala activity (pre/post resting-state scans) in violent offenders. In this study resting-state fMRI was administered before and after an emotion (anger and happiness) provocation or engagement task within 18 male violent offenders scoring high on reactive aggression, and 18 male non-offender controls. Research in emotional pre/post resting-state showed altered connectivity by task performance. Therefore, bilateral amygdala region of interest (ROI) whole brain functional connectivity analysis tested dynamic change differences between pre and post resting-state connectivity between groups. Self-reported anger showed a positive significant relationship with medial prefrontal cortex activity in the pre-task scan and significantly increased during the emotion task in both the violent and control group. Imaging results showed a significant decrease in amygdala - medial prefrontal functional connectivity in the violent offenders and an increase in the non-offender controls after the emotion task. The opposite pattern was found for amygdala connectivity with the (para) limbic regions: violent offenders showed increased connectivity and non-offender controls showed decreased connectivity. The present results indicate that reactive aggression might stem from a focus on emotion processing, as indicated by an increase in limbic functional connectivity. The combination of a focus on emotion, along with a lack of medial prefrontal cortex regulation, has the potential to grow out of control e.g. in reactive aggression.

Single-trial log transformation is optimal in frequency analysis of resting EEG alpha.

The appropriate definition and scaling of the magnitude of electroencephalogram (EEG) oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and nonlinear transformation of alpha power. A family of nonlinear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs within each participant, or across participants. The transformations were performed either at the single epoch level or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in 2 min of eyes-closed and 2 min of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12 Hz) alpha band. The log-transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed conditions when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log-transform on single epochs to achieve appropriate scaling of alpha magnitude.

Reduced intrinsic visual cortical connectivity is associated with impaired perceptual closure in schizophrenia.

Sensory perceptual processing deficits, such as impaired visual object identification and perceptual closure, have been reported in schizophrenia. These perceptual impairments may be associated with neural deficits in visual association areas, including lateral occipital cortex and inferior temporal areas. However, it remains unknown if such deficits can be found in the intrinsic architecture of the visual system. In the current study, we measured perceptual closure performance and resting-state functional connectivity using functional magnetic resonance imaging (FMRI) in 16 schizophrenia patients and 16 matched healthy controls. We estimated intrinsic functional connectivity using self-organized grouping spatial ICA, which clusters component maps in the subject space according to spatial similarity. Patients performed worse than controls in the perceptual closure task. This impaired closure performance of patients was correlated with increased severity of psychotic symptoms. We also found that intrinsic connectivity of the visual processing system was diminished in patients compared to controls. Lower perceptual closure performance was correlated to lower visual cortical intrinsic connectivity overall. We suggest that schizophrenia is associated with impaired intrinsic connectivity of the visual system, and that it is a potential mechanism leading to impaired visual object perception. These findings contribute to increasing evidence for impairments of higher visual functions in schizophrenia.

The impact of early visual cortex transcranial magnetic stimulation on visual working memory precision and guess rate.

Neuroimaging studies have demonstrated that activity patterns in early visual areas predict stimulus properties actively maintained in visual working memory. Yet, the mechanisms by which such information is represented remain largely unknown. In this study, observers remembered the orientations of 4 briefly presented gratings, one in each quadrant of the visual field. A 10Hz Transcranial Magnetic Stimulation (TMS) triplet was applied directly at stimulus offset, or midway through a 2-second delay, targeting early visual cortex corresponding retinotopically to a sample item in the lower hemifield. Memory for one of the four gratings was probed at random, and participants reported this orientation via method of adjustment. Recall errors were smaller when the visual field location targeted by TMS overlapped with that of the cued memory item, compared to errors for stimuli probed diagonally to TMS. This implied topographic storage of orientation information, and a memory-enhancing effect at the targeted location. Furthermore, early pulses impaired performance at all four locations, compared to late pulses. Next, response errors were fit empirically using a mixture model to characterize memory precision and guess rates. Memory was more precise for items proximal to the pulse location, irrespective of pulse timing. Guesses were more probable with early TMS pulses, regardless of stimulus location. Thus, while TMS administered at the offset of the stimulus array might disrupt early-phase consolidation in a non-topographic manner, TMS also boosts the precise representation of an item at its targeted retinotopic location, possibly by increasing attentional resources or by injecting a beneficial amount of noise.

Learned interval time facilitates associate memory retrieval.

The extent to which time is represented in memory remains underinvestigated. We designed a time paired associate task (TPAT) in which participants implicitly learned cue-time-target associations between cue-target pairs and specific cue-target intervals. During subsequent memory testing, participants showed increased accuracy of identifying matching cue-target pairs if the time interval during testing matched the implicitly learned interval. A control experiment showed that participants had no explicit knowledge about the cue-time associations. We suggest that "elapsed time" can act as a temporal mnemonic associate that can facilitate retrieval of events associated in memory.

Deficient amygdala-prefrontal intrinsic connectivity after effortful emotion regulation in borderline personality disorder.

Emotion instability in borderline personality disorder (BPD) has been associated with an impaired fronto-limbic inhibitory network. However, functional connectivity (FC) underlying altered emotion regulation in BPD has yet to be established. Here, we used resting-state fMRI to investigate enduring effects of effortful emotion regulation on the amygdala intrinsic FC in BPD. In this multicenter study, resting-state fMRI was acquired before and after an emotion regulation task in 48 BPD patients and 39 non-patient comparison individuals. The bilateral amygdalae were used as a seed in the whole-brain FC analysis and two-way mixed ANOVA to test whether BPD patients exhibited weaker post-task increase in the amygdala intrinsic FC with the prefrontal cortex (PFC), compared to non-patients. Subsequently, we explored whether the results are common for personality disorders characterized by emotional problems, using additional data of 21 cluster-C personality disorder patients. In contrast to non-patients, BPD patients failed to show increased post-task amygdala resting-state FC with the medial, dorsolateral, ventrolateral PFC, and superior temporal gyrus, but surprisingly exhibited decreased FC with the posterior cingulate cortex and increased FC with the superior parietal lobule. In BPD patients, the emotion regulation task failed to increase resting-state amygdala FC with brain regions essential for effortful emotion regulation, which suggests: (a) altered cognitive control typically used to indirectly alleviate distress by reinterpreting the meaning of emotional stimuli; (b) impaired direct regulation of emotional responses, which might be common for personality disorders;

Negative mood-induction modulates default mode network resting-state functional connectivity in chronic depression.

BACKGROUND: The aim of this study was to investigate the effects of sad mood on default mode network (DMN) resting-state connectivity in persons with chronic major depressive disorder (cMDD). METHODS: Participants with a diagnosis of cMDD (n=18) and age, gender and education level matched participants without a diagnosis of depression (n=18) underwent a resting-state fMRI scan, before and after a sad mood induction. The posterior cingulate cortex (PCC) was used as a seed for DMN functional connectivity across the two resting-state measurements. RESULTS: Mood ratings decreased in both groups following the sad mood induction procedure. PCC connectivity with the parahippocampal gyrus, the superior temporal gyrus and the anterior inferior temporal cortex increased in cMDD patients following the sad mood induction, whereas it decreased in non-patient controls. PCC connectivity with the anterior prefrontal cortex and the precuneus decreased in cMDD patients following the sad mood induction, whereas it increased in non-patient controls. LIMITATIONS: Limitations of this study include the relatively small sample size and lack of a clinical control group. CONCLUSIONS: These findings are in line with neurobiological models of depression suggesting that the observed changes in DMN connectivity following the sad mood induction might reflect a failure to exert cognitive control over negative memory retrieval in patients with cMDD.