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Working memory load-dependent brain response predicts behavioral training gains in older adults
(2014)
In the domain of working memory (WM), a sigmoid-shaped relationship between WM load and brain activation patterns has been demonstrated in younger adults. It has been suggested that age-related alterations of this pattern are associated with changes in neural efficiency and capacity. At the same time, WM training studies have shown that some older adults are able to increase their WM performance through training. In this study, functional magnetic resonance imaging during an n-back WM task at different WM load levels was applied to compare blood oxygen level-dependent (BOLD) responses between younger and older participants and to predict gains in WM performance after a subsequent 12-session WM training procedure in older adults. We show that increased neural efficiency and capacity, as reflected by more "youth-like" brain response patterns in regions of interest of the frontoparietal WM network, were associated with better behavioral training outcome beyond the effects of age, sex, education, gray matter volume, and baseline WM performance. Furthermore, at low difficulty levels, decreases in BOLD response were found after WM training. Results indicate that both neural efficiency (i. e., decreased activation at comparable performance levels) and capacity (i. e., increasing activation with increasing WM load) of a WM-related network predict plasticity of the WM system, whereas WM training may specifically increase neural efficiency in older adults.
Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder
(2017)
Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).
CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors.
Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.
Working memory (WM) performance declines with age. However, several studies have shown that WM training may lead to performance increases not only in the trained task, but also in untrained cognitive transfer tasks. It has been suggested that transfer effects occur if training task and transfer task share specific processing components that are supposedly processed in the same brain areas. In the current study, we investigated whether single-task WM training and training-related alterations in neural activity might support performance in a dual-task setting, thus assessing transfer effects to higher-order control processes in the context of dual-task coordination. A sample of older adults (age 60–72) was assigned to either a training or control group. The training group participated in 12 sessions of an adaptive n-back training. At pre and post-measurement, a multimodal dual-task was performed in all participants to assess transfer effects. This task consisted of two simultaneous delayed match to sample WM tasks using two different stimulus modalities (visual and auditory) that were performed either in isolation (single-task) or in conjunction (dual-task). A subgroup also participated in functional magnetic resonance imaging (fMRI) during the performance of the n-back task before and after training. While no transfer to single-task performance was found, dual-task costs in both the visual modality (p < 0.05) and the auditory modality (p < 0.05) decreased at post-measurement in the training but not in the control group. In the fMRI subgroup of the training participants, neural activity changes in left dorsolateral prefrontal cortex (DLPFC) during one-back predicted post-training auditory dual-task costs, while neural activity changes in right DLPFC during three-back predicted visual dual-task costs. Results might indicate an improvement in central executive processing that could facilitate both WM and dual-task coordination.
Conceptual knowledge about objects, people and events in the world is central to human cognition, underlying core cognitive abilities such as object recognition and use, and word comprehension. Previous research indicates that concepts consist of perceptual and motor features represented in modality-specific perceptual-motor brain regions. In addition, cross-modal convergence zones integrate modality-specific features into more abstract conceptual representations.
However, several questions remain open: First, to what extent does the retrieval of perceptual-motor features depend on the concurrent task? Second, how do modality-specific and cross-modal regions interact during conceptual knowledge retrieval? Third, which brain regions are causally relevant for conceptually-guided behavior? This thesis addresses these three key issues using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in the healthy human brain.
Study 1 - an fMRI activation study - tested to what extent the retrieval of sound and action features of concepts, and the resulting engagement of auditory and somatomotor brain regions depend on the concurrent task. 40 healthy human participants performed three different tasks - lexical decision, sound judgment, and action judgment - on words with a high or low association to sounds and actions. We found that modality-specific regions selectively respond to task-relevant features: Auditory regions selectively responded to sound features during sound judgments, and somatomotor regions selectively responded to action features during action judgments. Unexpectedly, several regions (e.g. the left posterior parietal cortex; PPC) exhibited a task-dependent response to both sound and action features. We propose these regions to be "multimodal", and not "amodal", convergence zones which retain modality-specific information.
Study 2 - an fMRI connectivity study - investigated the functional interaction between modality-specific and multimodal areas during conceptual knowledge retrieval. Using the above fMRI data, we asked (1) whether modality-specific and multimodal regions are functionally coupled during sound and action feature retrieval, (2) whether their coupling depends on the task, (3) whether information flows bottom-up, top-down, or bidirectionally, and (4) whether their coupling is behaviorally relevant. We found that functional coupling between multimodal and modality-specific areas is task-dependent, bidirectional, and relevant for conceptually-guided behavior. Left PPC acted as a connectivity "switchboard" that flexibly adapted its coupling to task-relevant modality-specific nodes.
Hence, neuroimaging studies 1 and 2 suggested a key role of left PPC as a multimodal convergence zone for conceptual knowledge. However, as neuroimaging is correlational, it remained unknown whether left PPC plays a causal role as a multimodal conceptual hub. Therefore, study 3 - a TMS study - tested the causal relevance of left PPC for sound and action feature retrieval. We found that TMS over left PPC selectively impaired action judgments on low sound-low action words, as compared to sham stimulation. Computational simulations of the TMS-induced electrical field revealed that stronger stimulation of left PPC was associated with worse performance on action, but not sound, judgments. These results indicate that left PPC causally supports conceptual processing when action knowledge is task-relevant and cannot be compensated by sound knowledge. Our findings suggest that left PPC is specialized for action knowledge, challenging the view of left PPC as a multimodal conceptual hub.
Overall, our studies support "hybrid theories" which posit that conceptual processing involves both modality-specific perceptual-motor regions and cross-modal convergence zones. In our new model of the conceptual system, we propose conceptual processing to rely on a representational hierarchy from modality-specific to multimodal up to amodal brain regions. Crucially, this hierarchical system is flexible, with different regions and connections being engaged in a task-dependent fashion. Our model not only reconciles the seemingly opposing grounded cognition and amodal theories, it also incorporates task dependency of conceptually-related brain activity and connectivity, thereby resolving several current issues on the neural basis of conceptual knowledge retrieval.
It has frequently been observed that single emotional events are not only more efficiently processed, but also better remembered, and form longer-lasting memory traces than neutral material. However, when emotional information is perceived as a part of a complex event, such as in the context of or in relation to other events and/or source details, the modulatory effects of emotion are less clear. The present work aims to investigate how emotional, contextual source information modulates the initial encoding and subsequent long-term retrieval of associated neutral material (item memory) and contextual source details (contextual source memory). To do so, a two-task experiment was used, consisting of an incidental encoding task in which neutral objects were displayed over different contextual background scenes which varied in emotional content (unpleasant, pleasant, and neutral), and a delayed retrieval task (1 week), in which previously-encoded objects and new ones were presented. In a series of studies, behavioral indices (Studies 2, 3, and 5), event-related potentials (ERPs; Studies 1-4), and functional magnetic resonance imaging (Study 5) were used to investigate whether emotional contexts can rapidly tune the visual processing of associated neutral information (Study 1) and modulate long-term item memory (Study 2), how different recognition memory processes (familiarity vs. recollection) contribute to these emotion effects on item and contextual source memory (Study 3), whether the emotional effects of item memory can also be observed during spontaneous retrieval (Sstudy 4), and which brain regions underpin the modulatory effects of emotional contexts on item and contextual source memory (Study 5). In Study 1, it was observed that emotional contexts by means of emotional associative learning, can rapidly alter the processing of associated neutral information. Neutral items associated with emotional contexts (i.e. emotional associates) compared to neutral ones, showed enhanced perceptual and more elaborate processing after one single pairing, as indexed by larger amplitudes in the P100 and LPP components, respectively. Study 2 showed that emotional contexts produce longer-lasting memory effects, as evidenced by better item memory performance and larger ERP Old/New differences for emotional associates. In Study 3, a mnemonic differentiation was observed between item and contextual source memory which was modulated by emotion. Item memory was driven by familiarity, independently of emotional contexts during encoding, whereas contextual source memory was driven by recollection, and better for emotional material. As in Study 2, enhancing effects of emotional contexts for item memory were observed in ERPs associated with recollection processes. Likewise, for contextual source memory, a pronounced recollection-related ERP enhancement was observed for exclusively emotional contexts. Study 4 showed that the long-term recollection enhancement of emotional contexts on item memory can be observed even when retrieval is not explicitly attempted, as measured with ERPs, suggesting that the emotion enhancing effects on memory are not related to the task embedded during recognition, but to the motivational relevance of the triggering event. In Study 5, it was observed that enhancing effects of emotional contexts on item and contextual source memory involve stronger engagement of the brain's regions which are associated with memory recollection, including areas of the medial temporal lobe, posterior parietal cortex, and prefrontal cortex.
Taken together, these findings suggest that emotional contexts rapidly modulate the initial processing of associated neutral information and the subsequent, long-term item and contextual source memories. The enhanced memory effects of emotional contexts are strongly supported by recollection rather than familiarity processes, and are shown to be triggered when retrieval is both explicitly and spontaneously attempted. These results provide new insights into the modulatory role of emotional information on the visual processing and the long-term recognition memory of complex events. The present findings are integrated into the current theoretical models and future ventures are discussed.
Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.
Reward expectation and affective responses across psychiatric disorders - A dimensional approach
(2014)
Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U-shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J-shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition-related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan-related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age-specific effects in fronto-parietal regions. Hum Brain Mapp 35:5153-5165, 2014. (c) 2014 Wiley Periodicals, Inc.
Mental health problems remain among the main generators of costs within and beyond the health care system. Psychotherapy, the tool of choice in their treatment, is qualified by social interaction, and cooperation within the therapist-patient-dyad. Research into the factors influencing therapy success to date is neither exhaustive nor conclusive. Among many others, the quality of the relationship between therapist and patient stands out regardless of the followed psychotherapy school. Emerging research points to a connection between interpersonal synchronization within the sessions and therapy outcome. Consequently, it can be considered significant for the shaping of this relationship. The framework of Embodied Cognition assumes bodily and neuronal correlates of thinking. Therefore, the present paper reviews investigations on interpersonal, non-verbal synchrony in two domains: firstly, studies on interpersonal synchrony in psychotherapy are reviewed (synchronization of movement). Secondly, findings on neurological correlates of interpersonal synchrony (assessed with EEG, fMRI, fNIRS) are summarized in a narrative manner. In addition, the question is asked whether interpersonal synchrony can be achieved voluntarily on an individual level. It is concluded that there might be mechanisms which could give more insights into therapy success, but as of yet remain uninvestigated. Further, the framework of embodied cognition applies more to the current body of evidence than classical cognitivist views. Nevertheless, deeper research into interpersonal physical and neurological processes utilizing the framework of Embodied Cognition emerges as a possible route of investigation on the road to lower drop-out rates, improved and quality-controlled therapeutic interventions, thereby significantly reducing healthcare costs.