Neural correlates of rumination in adolescents with remitted major depressive disorder and healthy controls

The aim of the present study was to use fMRI to examine the neural correlates of engaging in rumination among a sample of remitted depressed adolescents, a population at high risk for future depressive relapse. A rumination induction task was used to assess differences in the patterns of neural activation during rumination versus a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and in 15 healthy control adolescents. Self-report depression and rumination, as well as clinician-rated depression, were also assessed among all participants. All of the participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobe, and medial temporal gyrus, during rumination. Increased activation in these regions during rumination was correlated with increased self-report rumination and symptoms of depression across all participants. Adolescents with rMDD also exhibited greater activation in regions involved in visual, somatosensory, and emotion processing than did healthy peers. The present findings suggest that during ruminative thought, adolescents with rMDD are characterized by increased recruitment of regions within the DMN and in areas involved in visual, somatosensory, and emotion processing.     

The effect of motivation on working memory: an fMRI and SEM study

This study investigated the effective connectivity between prefrontal regions of human brain supporting motivational influence on working memory. Functional magnetic resonance imaging (fMRI) and structural equation modeling (SEM) were used to examine the interaction between the lateral orbitofrontal (OFC), medial OFC, and dorsolateral prefrontal (DLPFC) regions in the left and right hemisphere during performance of the verbal 2-back working memory task under two reinforcement conditions. The "low-motivation" condition was not associated with monetary reinforcement, while the "high-motivation" condition involved the probability of winning a certain amount of money. In the "low-motivation" condition, the OFC regions in both hemispheres positively influenced the left DLPFC activity. In the "high-motivation" condition, the connectivity in the network including the right OFC regions and left DLPFC changed from positive to negative, whereas the positive connectivity in the network composed of the left OFC and left DLPFC became slightly enhanced compared with the "low-motivation" condition. However, only the connection between the right lateral OFC and left DLPFC showed a significant condition-dependent change in the strength of influence conveyed through the pathway. This change appears to be the functional correlate of motivational influence on verbal working memory.     

抑郁症的脑结构与功能异常:来自静息态下多模态脑影像的研究证据

传统单一模态、单一分析方法在揭示抑郁症脑机制上存在较多局限;而新近多种模态、多种分析方法的结合可在一定程度上较好地促进对抑郁症脑功能和结构的全面探索、挖掘,可以更加有效地运用和实施于早期辅助诊断、干预治疗当中。因此,本文首先简要介绍了多种模态下的脑影像指标及其分析技术,而后分别从结构及功能神经影像数据融合等方面,概述了抑郁症脑结构和功能的研究现状,发现抑郁症患者存在诸多脑区及相关环路结构及功能的异常。同时,通过对抑郁症多模态研究现状的梳理和总结,结合我们已有的相关前期研究工作,对未来抑郁症等情感障碍的进一步研究工作提出了一些思考和展望。     

A preliminary study of medial temporal lobe function in youths with a history of caregiver deprivation and emotional neglect

Previous research findings have linked caregiver deprivation and emotional neglect with sensitivity to threatening cues. The present preliminary study investigated whether dysfunctions of the medial temporal lobe could underlie these associations. Using fMRI, we measured medial temporal lobe responses to emotional faces (angry, fearful, happy, neutral) among 30 youths. Eleven of the youths had a history of caregiver deprivation and emotional neglect. Attention states (i.e., attention to anger, fear, or physical attributes, or passive viewing) were systematically manipulated. Relative to comparison youths, youths with a history of caregiver deprivation and emotional neglect showed significantly greater left amygdala and left anterior hippocampus activation during the processing of threatening information. To our knowledge, these findings are the first to demonstrate altered medial temporal lobe function during the processing of threat cues in youths with a history of caregiver deprivation and emotional neglect.     

rTMS stimulation on left DLPFC increases the correct recognition of memories for emotional target and distractor words

According to a recent hypothesis, the prefrontal cortex has been proposed as the site of emotional memory integration, because it is sensitive to the recognition of emotional contents. In the present research, we explored the role of the dorsolateral prefrontal cortex (DLPFC) in memory recognition processes for positive versus negative emotional stimuli when old (target) and new (distractor, either semantically related or unrelated to the target) stimuli were presented. The role of the DLPFC was analysed using an rTMS (repeated transcranial magnetic stimulation) paradigm that induced increased cortical activation of the left DLPFC. The subjects were required to perform a task that consisted of two experimental phases (i.e., an encoding and a recognition phase) in which the targets and the distractors were presented and recognition performance was measured. rTMS stimulation was provided over the left DLPFC during the recognition phase. We found that the rTMS stimulation affected the memory recognition of positive emotional material. Moreover, related and unrelated distractors were discarded better when they were positively valenced, and a more significant effect (i.e., increased performance) was produced in response to related distractors. This result suggests that the activation of the left DLPFC favours the memory recognition of positive emotional information, and that such activation is able to induce a more appropriate selective process to distinguish target from distractor stimuli in the presence of more complex processes (related distractors). The valence model of emotional cue processing may explain this increased performance by demonstrating the distinct role of the left hemisphere in the retrieval of positive emotional information.     

The effect of bicephalic stimulation of the dorsolateral prefrontal cortex on the attentional bias for threat: A transcranial direct current stimulation study

Previous stimulation studies demonstrated that the dorsolateral prefrontal cortex (DLPFC) is involved in threat processing. According to a model of emotional processing, an unbalance between the two DLPFCs, with a hyperactivation of right frontal areas, is involved in the processing of negative emotions and genesis of anxiety. In the present study, we investigated the role of the right and left DLPFC in threat processing in healthy women who also completed the State-Trait Anxiety Inventory (STAI). We simultaneously modulated the activity of the right and left dorsolateral prefrontal cortex by applying bicephalic transcranial direct current stimulation (tDCS) before participants completed a modified version of the classic Posner task using threatening and nonthreatening stimuli as spatial cues. Anodal stimulation on the right DLPFC with a simultaneous cathodal stimulation over the left side induced a disengagement bias in individuals with low STAI scores and a facilitation bias in individuals with high STAI scores. Anodal stimulation on the left DLPFC with the simultaneous cathodal stimulation over the right side did not affect threat processing. The findings of the present study provided specific support to the hypothesis that unbalanced activation between left and right hemispheres with enhanced activation of the right DLPFC is critical in early top-down threat processing in healthy individuals.     

Alertness in young healthy subjects: An fMRI study of brain region interactivity enhanced by a warning signal

An effective connectivity study was carried out on 16 young, healthy subjects performing an alertness task. The objective of this study was to develop and to evaluate a putative network model of alertness by adapting structural equation modeling to fMRI data. This study was designed to evaluate the directed interactivity of an attentional network during intrinsic and phasic alerting tasks. On the basis of theoretical hypotheses, clinical observations, behavioral data and neuroimaging studies, it was hypothesized that neural circuits in the right hemisphere including the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex, inferior parietal cortex and the thalamus were involved. The results of this study support the existence of a common network of activated areas with significant path coefficient differences between intrinsic and phasic alertness. Functional interactivity was significantly reinforced during the phasic alertness task and appeared to preferentially involve activity in the DLPFC region, whereas the path coefficients of the model were well-balanced during intrinsic alertness. This study highlights the predominant role of the DLPFC region in maintenance of a state of alertness and in temporal preparation during an alertness task.     

Emotion-modulated performance and activity in left dorsolateral prefrontal cortex

Functional MRI (fMRI) was used to examine the relationship between processing of pleasant and unpleasant stimuli and activity in prefrontal cortex. Twenty volunteers identified the colors in which pleasant, neutral, and unpleasant words were printed. Pleasant words prompted more activity bilaterally in dorsolateral prefrontal cortex (DLPFC) than did unpleasant words. In addition, pleasant words prompted more activity in left than in right DLPFC. Response speed to pleasant words was correlated with DLPFC activity. These data directly link positive affect, enhanced performance, and prefrontal activity, providing some of the first fMRI evidence supporting models of emotional valence and frontal brain asymmetry based on electroencephalography (EEG).     

认知重评和表达抑制情绪调节策略的脑网络分析：来自EEG和ERP的证据

本文旨在对认知重评和表达抑制两种常用情绪调节策略的自发脑网络特征及认知神经活动进行深入探讨。研究采集36名在校大学生的静息态和任务态脑电数据, 经过源定位和图论分析发现节点效率与两种情绪调节显著相关的脑区, 以及脑区之间的功能连接。研究结果表明, 在使用认知重评进行情绪调节时会激活前额叶皮质、前扣带回、顶叶、海马旁回和枕叶等多个脑区, 在使用表达抑制进行情绪调节时会激活前额叶皮质、顶叶、海马旁回、枕叶、颞叶和脑岛等多个脑区。因此, 这些脑区的节点效率或功能连接强度可能成为评估个体使用认知重评和表达抑制调节情绪效果的指标。     

Near-death experiences and the temporal lobe

Abstract— Many studies in humans suggest that altered temporal lobe functioning, especially functioning in the right temporal lobe, is involved in mystical and religious experiences. We investigated temporal lobe functioning in individuals who reported having transcendental "near-death experiences" during life-threatening events. These individuals were found to have more temporal lobe epileptiform electroencephalographic activity than control subjects and also reported significantly more temporal lobe epileptic symptoms. Contrary to predictions, epileptiform activity was nearly completely lateralized to the left hemisphere. The near-death experience was not associated with dysfunctional stress reactions such as dissociation, posttraumatic stress disorder, and substance abuse, but rather was associated with positive coping styles. Additional analyses revealed that near-death experiencers had altered sleep patterns, specifically, a shorter duration of sleep and delayed REM sleep relative to the control group. These results suggest that altered temporal lobe functioning may be involved in the near-death experience and that individuals who have had such experiences are physiologically distinct from the general population.     

The role of frontal lobe functioning in the development of infant self-regulatory behavior.

In the last two decades, there has been tremendous growth in two fields of study related to human infant development: (1) the development of neural processes during the early postnatal years and (2) the development of self-regulatory behavior. In an attempt to stimulate research on the relation between early brain development and self-regulatory processes, several hypotheses pertaining to the role of frontal lobe functioning in the development of emotion regulation during infancy are proposed. The results of a study of the relation between frontal electroencephalographic (EEG) activity and emotional behavior of 21-month-old infants are reported. It was found that increases in frontal lobe activation were associated with increases in emotional arousal, while EEG activity recorded from the parietal region showed either a reciprocal pattern of activation or did not change as a function of level of emotional arousal. These results provide evidence for the specialized role of the frontal lobe in mediating emotional behavior during infancy.     

Functional and connectivity changes during working memory in Huntington’s disease: 18 month longitudinal data from the IMAGE-HD study

Background

This study aimed to characterize, for the first time, 18 month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington’s disease (pre-HD) and symptomatic HD (symp-HD).

Methods

Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18 months follow-up.

Results

Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18 months only in the pre-HD group.

Conclusions

Longitudinal reductions in connectivity over 18 months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.     

What else do you feel when you feel sad? Emotional overproduction, neuroticism and rumination

Numerous experimental and naturalistic studies have shown the relevant role of ruminative styles in the onset, duration and severity of depressive episodes. Recent research has increasingly focused on the precursors of these ruminative responses. Neuroticism has been found to be closely related to ruminative styles, but the nature of this relationship is unknown. Across three studies, we explored the role of emotional overproduction, conceptualized as the tendency to simultaneously experience an elevated number of negative emotions and feelings during sad episodes. Study 1 showed that emotional overproduction is independently and strongly associated with ruminative styles. Furthermore, emotional overproduction was found to mediate the relationship between neuroticism and ruminative styles. Study 2 replicated these findings in a large community sample even after controlling for mood, personality, and other emotion-related variables. In Study 3, we conducted a laboratory study to increase the internal and external validity of our findings. Implications for personality, for coping and stress literature, and for clinical research and treatment are suggested.     

Developing connections for affective regulation: age-related changes in emotional brain connectivity

The regulation of affective arousal is a critical aspect of children’s social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of “hot” executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional magnetic resonance imaging (fMRI), we investigated the brain mechanisms involved in the development of affective regulation in typically developing 5- to 11-year-olds and an adult comparison sample. Children and adults displayed differing patterns of increased anterior cingulate cortex and decreased amygdala activation during episodes in which emotion regulation was required. Specifically, amygdala activation increased in adults but decreased in children during recovery from a frustrating episode. In addition, we used effective connectivity analyses to investigate differential correlations between key emotional brain areas in response to the regulatory task demands. We found reliable increases in effective connectivity between the anterior cingulate cortex and the amygdala during periods of increased demand for emotion regulation. This effective connectivity increased with age.     

Co-occurring anxiety influences patterns of brain activity in depression

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in the dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in the right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in the anterior cingulate cortex (dorsal ACC and rostral ACC) and the bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala).     

Focused and Nonfocused Attention in Verbal and Emotional Dichotic Listening: An FMRI Study

Functional magnetic resonance imaging (fMRI) was used to identify cortical regions which are involved in two dichotic listening tasks. During one task the subjects were required to allocate attention to both ears and to detect a specific target word (phonetic task), while during a second task the subjects were required to detect a specific emotional tone (emotional task). During three attentional conditions of each task, the subjects were required to focus attention to the right (FR) or left ear (FL), while during a third condition subjects were required to allocate attention to both ears simultaneously. In 11 right-handed male subjects, these dichotic listening tasks evoked strong activations in a temporofrontal network involving auditory cortices located in the temporal lobe and prefrontal brain regions. Hemodynamic responses were measured in the following regions of interest: Heschl's gyrus (HG), the planum polare (PP), the planum temporale (PT), the anterior superior temporal sulcus (aSTS), the posterior superior temporal sulcus (pSTS), and the inferior frontal gyrus region (IFG) of both hemispheres. The following findings were obtained: (1) the degree of activation in HG and PP depends on the direction of attention. In particular it was found that selectively attending to right-ear input led to increased activity specifically in the left HG and PP and attention to left ear input increased right-sided activity in these structures; (2) hemodynamic responses in the PT, aSTS, pSTS, and IFG were not modulated by the different focused-attention conditions; (3) hemodynamic responses in HG and PP in the nonforced conditions were the sum activation of the forced conditions; (4) there was no general difference between the phonetic and emotion tasks in terms of hemodynamic responses; (5) hemodynamic responses in the PT and pSTS were strongly left-lateralized, reflecting the specialization of these brain regions for language processing. These findings are discussed in the context of current theories of hemispheric specialization.     

Recognition memory for text and melody of songs after unilateral temporal lobe lesion: evidence for dual encoding.

The role of left and right temporal lobes in memory for songs (words sung to a tune) was investigated. Patients who had undergone focal cerebral excision for the relief of intractable epilepsy along with normal control subjects were tested in 2 recognition memory tasks. The goal of Experiment 1 was to examine recognition of words and of tunes when they were presented together in an unfamiliar song. In Experiment 2, memory for spoken words and tunes sung without words was independently tested in 2 separate recognition tasks. The results clearly showed (a) a deficit after left temporal lobectomy in recognition of text whether sung to a tune or spoken without musical accompaniment, (b) impaired melody recognition when the tune was sung with new words following left or right temporal lobectomy and (c) impaired melody recognition in the absence of lyrics following right but not left temporal lobectomy. The different role of each temporal lobe in memorizing songs provides evidence for the use of dual memory codes. The verbal code is consistently related to left temporal lobe structures, whereas the melodie code my depend on either or both temporal lobe mechanisms, according to the type of encoding involved.     

Neurodevelopmental differences in emotional prosody in normal children and children with left and right temporal lobe epilepsy

Emotional prosody, which has been defined as the emotional aspects of speech which communicate pleasure, fear, sorrow, anger, etc., has been demonstrated to be primarily a function of the nondominant hemisphere (typically, the right hemisphere) in adult populations. However, few researchers have addressed the developmental or lateralized nature of emotional prosody in children. In this study, an instrument was developed to measure the receptive aspects of emotional prosody in pediatric populations and administered to normal children ages 6 to 11 years old. An analysis of variance revealed significant age-related differences. Additionally, the instrument was administered to 12 children with right temporal lobe epilepsy and 11 children with left temporal lobe epilepsy. Analysis of variance indicated that there was no significant difference in scores between the left temporal and right temporal lobe groups. However, right temporal epileptic patients scored significantly lower than normal children on all sections of the instrument, suggesting that in children like adults, the right temporal lobe may be dominant with respect to the receptive aspects of emotional prosody.     

Neurocognitive mechanisms behind emotional attention: Inverse effects of anodal tDCS over the left and right DLPFC on gaze disengagement from emotional faces

Background

Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted.

Methods

A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions).

Results

Compared to sham, active tDCS over the left DLPFC led to faster gaze disengagement, whereas active tDCS over the right DLPFC led to slower gaze disengagement from emotional faces. Between-group comparisons showed that such inverse change patterns were significantly different and generalized for all types of emotion.

Conclusions

Our findings support a lateralized role of left and right DLPFC activity in enhancing/worsening the top-down regulation of emotional attention processing. These results support the rationale of new therapies for affective disorders aimed to increase the activation of the left over the right DLPFC in combination with attentional control training, and identify specific target attention mechanisms to be trained.