Trait anxiety and the neural efficiency of manipulation in working memory

The present study investigates the effects of trait anxiety on the neural efficiency of working memory component functions (manipulation vs. maintenance) in the absence of threat-related stimuli. For the manipulation of affectively neutral verbal information held in working memory, high- and low-anxious individuals (N = 46) did not differ in their behavioral performance, yet trait anxiety was positively related to the neural effort expended on task processing, as measured by BOLD signal changes in fMRI. Higher levels of anxiety were associated with stronger activation in two regions implicated in the goal-directed control of attention--that is, right dorsolateral prefrontal cortex (DLPFC) and left inferior frontal sulcus--and with stronger deactivation in a region assigned to the brain's default-mode network--that is, rostral-ventral anterior cingulate cortex. Furthermore, anxiety was associated with a stronger functional coupling of right DLPFC with ventrolateral prefrontal cortex. We interpret our findings as reflecting reduced processing efficiency in high-anxious individuals and point out the need to consider measures of functional integration in addition to measures of regional activation strength when investigating individual differences in neural efficiency. With respect to the functions of working memory, we conclude that anxiety specifically impairs the processing efficiency of (control-demanding) manipulation processes (as opposed to mere maintenance). Notably, this study contributes to an accumulating body of evidence showing that anxiety also affects cognitive processing in the absence of threat-related stimuli

Neural mechanisms of reactivation-induced updating that enhance and distort memory

We remember a considerable number of personal experiences because we are frequently reminded of them, a process known as memory reactivation. Although memory reactivation helps to stabilize and update memories, reactivation may also introduce distortions if novel information becomes incorporated with memory. Here we used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms mediating reactivation-induced updating in memory for events experienced during a museum tour. During scanning, participants were shown target photographs to reactivate memories from the museum tour followed by a novel lure photograph from an alternate tour. Later, participants were presented with target and lure photographs and asked to determine whether the photographs showed a stop they visited during the tour. We used a subsequent memory analysis to examine neural recruitment during reactivation that was associated with later true and false memories. We predicted that the quality of reactivation, as determined by online ratings of subjective recollection, would increase subsequent true memories but also facilitate incorporation of the lure photograph, thereby increasing subsequent false memories. The fMRI results revealed that the quality of reactivation modulated subsequent true and false memories via recruitment of left posterior parahippocampal, bilateral retrosplenial, and bilateral posterior inferior parietal cortices. However, the timing of neural recruitment and the way in which memories were reactivated contributed to differences in whether memory reactivation led to distortions or not. These data reveal the neural mechanisms recruited during memory reactivation that modify how memories will be subsequently retrieved, supporting the flexible and dynamic aspects of memory

Exercise Training and Functional Connectivity Changes in Mild Cognitive Empairment and Healthy Elders

Background: Effective interventions are needed to improve brain function in mild cognitive impairment (MCI), an early stage of Alzheimer’s disease (AD). The posterior cingulate cortex (PCC)/precuneus is a hub of the default mode network (DMN) and is preferentially vulnerable to disruption of functional connectivity in MCI and AD. Objective: We investigated whether 12 weeks of aerobic exercise could enhance functional connectivity of the PCC/precuneus in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders (age range = 60–88) engaged in a supervised 12-week walking exercise intervention. Functional MRI was acquired at rest; the PCC/precuneus was used as a seed for correlated brain activity maps. Results: A linear mixed effects model revealed a significant interaction in the right parietal lobe: the MCI group showed increased connectivity while the healthy elders showed decreased connectivity. In addition, both groups showed increased connectivity with the left postcentral gyrus. Comparing pre to post intervention changes within each group, the MCI group showed increased connectivity in 10 regions spanning frontal, parietal, temporal and insular lobes, and the cerebellum. Healthy elders did not demonstrate any significant connectivity changes. Conclusion: The observed results show increased functional connectivity of the PCC/precuneus in individuals with MCI after 12 weeks of moderate intensity walking exercise training. The protective effects of exercise training on cognition may be realized through the enhancement of neural recruitment mechanisms, which may possibly increase cognitive reserve. Whether these effects of exercise training may delay further cognitive decline in patients diagnosed with MCI remains to be demonstrated

The Effect Of Abstinence From Smoking On Stress Reactivity

Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by the reliability of current available measures of stress. Functional magnetic reasoning imaging (fMRI) could provide a much-needed objective measure of stress reactivity. The goal of this dissertation is to contribute to the understanding of abstinence-induced changes in stress reactivity by examining neural, neuroendocrine (cortisol), and subjective measures of stress response during abstinence. In addition, this study investigated the influence of individual variation in nicotine metabolism rates on these measures of stress reactivity. Seventy-five treatment-seeking smokers underwent blood oxygen level dependent (BOLD) fMRI during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counter-balanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST. Neural stress reactivity during abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus (IFG), a brain region previously associated with inhibitory control. Greater abstinence-induced change in brain response to stress was associated with greater abstinence-induced change in subjective stress. However, there was no association with abstinence-induced change in cortisol response. In addition, higher rates of nicotine metabolism were associated with increased abstinence-induced change in self-reported stress, but not with brain or cortisol response. This study provides novel evidence that the brain response to stress is altered during the first 24 hours of a quit attempt compared to smoking satiety. These results underscore the importance of stress response during abstinence, and suggest that neuroimaging may provide a useful biomarker of stress response during the early smoking cessation, a period when smokers are most vulnerable to relapse

Investigating the neural basis of self-awareness deficits following traumatic brain injury

Self-awareness deficits are a common and disabling consequence of traumatic brain injury (TBI). ‘On-line’ awareness is one facet of self-awareness that can be studied by examining how people monitor their performance and respond to their errors. Performance monitoring, like many of the cognitive functions disrupted after TBI, is believed to depend on the coordinated activity of neural networks. The fronto-parietal control network (FPCN) is one such network that contains a sub-network called the salience network (SN). The SN consists of the dorsal anterior cingulate (dACC) and bilateral insulae cortex and is thought to monitor salient events (e.g. errors). I used advanced structure and function MRI techniques to investigate these networks and test two overarching hypotheses: first, performance monitoring is regulated by regions within the FPCN; and second, dysfunction of the FPCN leads to impaired self-awareness after TBI. My first study demonstrated two distinct frontal networks that respond to different error types. Predictable/internally signalled errors caused SN activation; whereas unpredictable/externally signalled errors caused activation of the ventral attentional network, a network thought to respond to unexpected events. This suggested the presence of parallel performance monitoring systems within the FPCN. My second study established that the ‘driving’ input into the SN originated in right anterior insula and subsequent behavioural adaptation was regulated by enhanced effective connectivity from the dACC to the left anterior insula. In my third study I identified a large group of TBI patients with impaired performance monitoring. These patients had additional metacognitive evidence of impaired self-awareness and demonstrated reduced functional connectivity between the dACC and the remainder of the FPCN at ‘rest’, and abnormally large insulae activation in response to errors. These studies clarified how the brain monitors and responds to salient events; and, provided evidence that self-awareness deficits after TBI are due to FPCN dysfunction, identifying this network as a potential target for future treatments.Open Acces

Network Dynamics Underlying Speed-Accuracy Trade-Offs in Response to Errors

The ability to dynamically and rapidly adjust task performance based on its outcome is fundamental to adaptive, flexible behavior. Over trials of a task, responses speed up until an error is committed and after the error responses slow down. These dynamic adjustments serve to optimize performance and are well-described by the speed-accuracy trade-off (SATO) function. We hypothesized that SATOs based on outcomes reflect reciprocal changes in the allocation of attention between the internal milieu and the task-at-hand, as indexed by reciprocal changes in activity between the default and dorsal attention brain networks. We tested this hypothesis using functional MRI to examine the pattern of network activation over a series of trials surrounding and including an error. We further hypothesized that these reciprocal changes in network activity are coordinated by the posterior cingulate cortex (PCC) and would rely on the structural integrity of its white matter connections. Using diffusion tensor imaging, we examined whether fractional anisotropy of the posterior cingulum bundle correlated with the magnitude of reciprocal changes in network activation around errors. As expected, reaction time (RT) in trials surrounding errors was consistent with predictions from the SATO function. Activation in the default network was: (i) inversely correlated with RT, (ii) greater on trials before than after an error and (iii) maximal at the error. In contrast, activation in the right intraparietal sulcus of the dorsal attention network was (i) positively correlated with RT and showed the opposite pattern: (ii) less activation before than after an error and (iii) the least activation on the error. Greater integrity of the posterior cingulum bundle was associated with greater reciprocity in network activation around errors. These findings suggest that dynamic changes in attention to the internal versus external milieu in response to errors underlie SATOs in RT and are mediated by the PCC

Social working memory: neurocognitive networks and directions for future research.

Navigating the social world requires the ability to maintain and manipulate information about people's beliefs, traits, and mental states. We characterize this capacity as social working memory (SWM). To date, very little research has explored this phenomenon, in part because of the assumption that general working memory systems would support working memory for social information. Various lines of research, however, suggest that social cognitive processing relies on a neurocognitive network (i.e., the "mentalizing network") that is functionally distinct from, and considered antagonistic with, the canonical working memory network. Here, we review evidence suggesting that demanding social cognition requires SWM and that both the mentalizing and canonical working memory neurocognitive networks support SWM. The neural data run counter to the common finding of parametric decreases in mentalizing regions as a function of working memory demand and suggest that the mentalizing network can support demanding cognition, when it is demanding social cognition. Implications for individual differences in social cognition and pathologies of social cognition are discussed

Early error detection predicted by reduced pre-response control process: an ERP topographic mapping study

Advanced ERP topographic mapping techniques were used to study error monitoring functions in human adult participants, and test whether proactive attentional effects during the pre-response time period could later influence early error detection mechanisms (as measured by the ERN component) or not. Participants performed a speeded go/nogo task, and made a substantial number of false alarms that did not differ from correct hits as a function of behavioral speed or actual motor response. While errors clearly elicited an ERN component generated within the dACC following the onset of these incorrect responses, I also found that correct hits were associated with a different sequence of topographic events during the pre-response baseline time-period, relative to errors. A main topographic transition from occipital to posterior parietal regions (including primarily the precuneus) was evidenced for correct hits similar to 170-150 ms before the response, whereas this topographic change was markedly reduced for errors. The same topographic transition was found for correct hits that were eventually performed slower than either errors or fast (correct) hits, confirming the involvement of this distinctive posterior parietal activity in top-down attentional control rather than motor preparation. Control analyses further ensured that this pre-response topographic effect was not related to differences in stimulus processing. Furthermore, I found a reliable association between the magnitude of the ERN following errors and the duration of this differential precuneus activity during the pre-response baseline, suggesting a functional link between an anticipatory attentional control component subserved by the precuneus and early error detection mechanisms within the dACC. These results suggest reciprocal links between proactive attention control and decision making processes during error monitoring

반응 억제의 개인차와 관련한 대규모 휴지기 뇌네트워크의 특성

학위논문 (박사) -- 서울대학교 대학원 : 인문대학 협동과정 인지과학전공, 2020. 8. 이동수.Response inhibition is one of the essential cognitive functions and suppresses inappropriate responses for goal-directed behavior. When a brain is cognitively engaged, it enters a cognitive state that task-positive regions are activated, and the default mode network is deactivated (DMN). In contrast, DMN is activated, and task-positive regions are deactivated at rest. The transition between the states is important for the cognitive function, and recent studies have found that the salience network (SN) plays a crucial role in detecting and processing a salient signal and suppressing DMN at rest. It can be assumed that there exists optimized connectivity to perform response inhibition successfully and that it will also appear in resting-state requiring no cognitive effort. It was hypothesized that lower functional connectivity within SN and higher functional connectivity within DMN and greater anti-correlation between then is related to better response inhibition. The response inhibition of individuals was measured by the stop-signal task and the Stroop task. The correlation between intra-/inter-component functional connectivity derived from independent component analysis with dual regression and task performances were examined to test the hypothesis. The intra-/inter-component structural connectivity analysis using diffusion tensor imaging was conducted to provide a deeper understanding of functional connectivity. Topological characteristics of inter-component functional connectivity were also examined using the minimum spanning tree (MST) of each individual to provide a heuristic insight from the topological view. The results indicate that the functional connectivity within SN, but not DMN components, and the functional and structural connectivity between SN and DMN components are critical to elucidate individual differences in response inhibition. Higher structural connectivity but low functional connectivity of SN at rest was an important feature for superior response inhibition. The stronger structural connectivity and stronger anti-correlation between SN and DMN components were also indicative of better response inhibition. MST of a subject with the best performance showed direct connections between SN and anterior DMN/pDMN, whereas the MST of the one with the worst performance does not. These intra-/inter components connectivities reflect the organization of the brain that enables competent response inhibition and account for individual differences. This study might suggest that the individuals characteristics of large-scale network components at rest provide evidence to illustrate response inhibition of an individual without any experimental scan.반응 억제는 가장 주요한 인지 기능 중 하나이며 이상행동을 동반하는 다양한 정신 질환과도 깊은 관련이 있다. 따라서 이와 관련된 신경적 특성을 탐구하는 것은 매우 중요하다. 우리의 뇌는 어떠한 인지 기능을 수행할 때, 작업 관련 영역들을 활성화하고 자기 참조적 처리를 하는 디폴트 모드 네트워크 영역들은 비활성화한다. 휴지기에는 반대로 작업 관련 영역들은 비활성화하고 디폴트 모드 네트워크 영역은 활성화한다. 이처럼 인지 기능을 수행하기 위해서는 상태를 효율적으로 전환하는 것이 중요하다. 현출성 네트워크 (salience network)는 어떠한 과제를 할 때 중요한 자극을 탐지하여 처리하며 또한 디폴트 모드 네트워크의 활성을 억제하기 때문에 상태 간 전환에 핵심적인 역할을 하는 대규모 뇌네트워크이다. 따라서 이와 관련된 연결적 특성이 인지 기능과 밀접한 관련이 있으며, 그러한 특성은 휴지기의 연결성에도 반영되어 있을 것이라 가정하였다. 즉, 본 연구에서는 반응 억제의 개인차를 휴지기 대규모 뇌네트워크들의 특성을 통해 설명할 수 있을 것이며, 특히 현출성 네트워크의 낮은 기능적 연결성, 디폴트 모드 네트워크의 높은 기능적 연결성, 그리고 그 둘 간의 높은 기능적 역 상관 (anti-correlation)이 반응 억제에 우수한 사람들의 특징적인 휴지기 연결성일 것이라 가설을 세웠다. 개인의 반응 억제는 정지 신호 과제와 스트룹 과제를 통해 측정하였으며, 휴지기 대규모 뇌네트워크들의 특성들과 어떠한 상관을 갖는지 알아보았다. 즉, 기능적 뇌네트워크 내의 연결성과 두 뇌네트워크 간 연결성이 과제 수행과 어떠한 상관을 보이는지를 알아보았다. 또한 기능적 연결성에 대한 보다 깊은 이해를 위해 확산 텐서 영상과 트랙토그래피 기법을 사용하여 구조적 연결성과 반응 억제와의 상관을 알아보았다. 반응 억제와 관련된 토폴로지 특성 역시 함께 알아보기 위해 참여자들의 미니멈 스패닝 트리(MST: minimum spanning tree)를 계산하였다. 분석 결과, 현출성 네트워크, 그리고 현출성 네트워크와 디폴트 모드 네트워크 간의 연결성을 통해 반응 억제의 개인차를 설명할 수 있었다. 현출성 네트워크의 성분 내 구조적 연결성은 강하지만 휴지기의 기능적 연결성이 약한 참여자들일수록 반응 억제 수행이 우수했다. 현출성 네트워크와 디폴트 모드 네트워크 간의 구조적 연결성과 기능적 역 상관은 모두 높을수록 우수한 반응 억제를 보였다. 또한 두 네트워크 간 구조적 연결성이 높을수록 기능적 역 상관이 높은 것으로 나타났다. 토폴로지 분석에서는 가장 수행이 좋은 참여자의 MST는 현출성 네트워크와 디폴트 모드 네트워크들 간에 직접적인 연결이 관찰되었으나 수행이 가장 나쁜 참여자에서는 그러한 직접적인 연결이 관찰되지 않았다. 분석 결과, 휴지기의 현출성 네트워크 내 연결성, 그리고 현출성 네트워크와 디폴트 모드 네트워크 간의 기능적 역 상관과 구조적 연결성이 반응 억제의 개인 차이를 설명하였으나, 디폴트 모드 네트워크 내의 연결성은 그렇지 못했다. 이 연구는 과제 수행 중이 아닌 휴지기 동안의 뇌네트워크의 특성들을 통해 반응 억제의 개인차를 설명할 수 있음을 보여준다.1. Introduction 1 1.1. Response inhibition and its neural correlates 1 1.1.1. Cognitive tasks to measure response inhibition 1 1.1.2. The neural correlates of response inhibition 2 1.1.3. Response inhibition and resting-state brain 3 1.2. Investigations on large-scale networks underlying response inhibition 4 1.2.1. Resting-state networks and response inhibition 4 1.2.2. Structural connectivity 6 1.2.3. Topological characteristics 7 1.2.4. The aim of the present study 8 2. Methods 9 2.1. Subjects 9 2.2. Behavioral tasks to assess response inhibition 11 2.3. Brain imaging data acquisition and preprocessing 14 2.3.1. Resting-state fMRI 14 2.3.2. Diffusion tensor imaging 15 2.4. Resting-state networks and functional connectivity analysis 16 2.4.1. Group independent component analysis to identify resting-state networks 16 2.4.2. Dual regression to obtain subject-specific data of components 17 2.4.3. Estimation of subject-specific intra-/inter-component functional connectivity 21 2.5. Structural connectivity analysis 21 2.5.1. Structural connectivity and response inhibition 21 2.5.2. Relationship between functional connectivity and structural connectivity 22 2.6. Topological data analysis 25 2.6.1. Minimum spanning tree 25 3. Results 27 3.1. The performances of behavioral tasks 27 3.2. Intra-component connectivity and response inhibition 30 3.3. Inter-component connectivity and response inhibition 35 3.4. Relationship between functional connectivity and structural connectivity 41 3.5. Minimum spanning tree 43 4. Discussion 46 4.1. Resting-state network and cognition 46 4.2. Salience network and response inhibition 47 4.3. Connectivity and structural connectivity between SN and DMN 50 4.3.1. Functional connectivity between SN and DMN 50 4.3.2. Structural connectivity between SN and DMN 51 4.3.3. Topological characteristics between SN and DMN 53 4.4. Limitations of the study 54 5. Conclusion 56 References 57 국문 초록 70Docto

Functional organisation of behavioural inhibitory control mechanisms in cortico-basal ganglia circuitry: implications for stimulant use disorder.

The neural and psychological mechanisms of inhibitory control processes were investigated, focusing on the cortico-basal ganglia circuits in rats and humans. These included behavioural flexibility, ‘waiting’ and ‘stopping’ impulsivity and involved serial spatial reversal learning task in rodents, and in humans, premature responses in the Monetary Incentive Delay (MID) task and the stop-signal reaction time task. Chapter 2 and Chapter 3 focus on individual differences in behavioural flexibility in rats while Chapter 4, Chapter 5 and Chapter 6 consider how inhibitory control mechanisms are affected by the psychostimulant drug cocaine in both rats and humans. As reported in Chapter 2, systemic modulation of monoaminergic transmission by monoamine oxidase A (MAO-A) inhibitors enhanced reversal learning performance, selectively by decreasing the lose-shift probability, thereby implicating a role for dopamine, serotonin and noradrenaline in facilitating learning from negative feedback. Resting state functional magnetic resonance imaging (fMRI) revealed enhanced functional connectivity of the orbitofrontal and motor cortices as a correlate of flexible reversal learning performance, consistent with elevated levels of monoamines in these region (Chapter 3). Having clarified the mechanisms underlying behavioural flexibility in rats, Chapter 4 reports that escalation of intravenous cocaine self-administration induces behavioural inflexibility in rats even after a relatively short period of cocaine intake. Computational models, including a reinforced and Bayesian learner, revealed a lack of exploitation of the learned response-outcome relationships in cocaine-exposed rats. Chapter 5 focused on impulse control in human volunteers, identifying the striatal and cingulo-opercular networks as substrates of impulsive, premature responding in healthy 4 volunteers, stimulant-dependent individuals and their unaffected siblings. Loss of impulse control was elicited by different incentives for drug-free participants as opposed to drug users. Drug cues elicited striatal activation and increased premature responses in the stimulant-dependent group compared with the control group. In contrast, the ventral striatum was linked to incentive specific activation to reward anticipation. Task-based fMRI demonstrated that interactions between dorsal striatum and cingulo-opercular “cold cognition” networks underlie failures of impulse control in the control, at-risk and stimulant-dependent groups. However, whereas the cingulo-opercular networks were associated with premature responding in all groups, the reward system was activated specifically by the drug incentive cues in the stimulant group, and by monetary incentive cues in the drug-free groups. Chapter 6 presents evidence that corticostriatal functional and effective connectivity in an overlapping network that includes the anterior cingulate and inferior frontal cortices as well as motor cortex, the subthalamic nucleus and dorsal striatum, is critical to stopping impulse control in both control and cocaine individuals. No stopping efficiency impairments were observed in the cocaine-dependent group. Nevertheless, lower structural corticostriatal connectivity measured using diffusion MRI was associated with response execution impairments in cocaine participants performing a stop-signal reaction time task. Further, response execution was rescued by the selective noradrenaline reuptake inhibitor atomoxetine, which also increased corticostriatal effective connectivity. Finally, increased impulsivity and behavioural inflexibility seen in stimulant use disorder in Chapter 5 and Chapter 4, respectively, were not observed in the endophenotype at risk for developing stimulant abuse but were rather a consequence of stimulant abuse. These results further clarify the monoaminergic substrates of behavioural flexibility and specify the neural and computational impairments in inhibitory control induced by stimulant dependence.Pinsent Darwin Studentship from the Dept of Physiology, Development and Neuroscienc