Altered networks in bothersome tinnitus: a functional connectivity study

<p>Abstract</p> <p>Background</p> <p>The objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm³brain volumes in 17 patients with moderate-severe bothersome tinnitus (<it>Tinnitus Handicap Index: average </it>53.5 ± 3.6 (range 38-76)) and 17 age-matched controls.</p> <p>Results</p> <p>In bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula - executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex.</p> <p>Conclusions</p> <p>These results imply that in bothersome tinnitus there is dissociation between activity in auditory cortex and visual, attention and control networks. The reciprocal negative correlations in connectivity between these networks might be maladaptive or reflect adaptations to reduce phantom noise salience and conflict with attention to non-auditory tasks.</p

Neural bases of enhanced attentional control: Lessons from action video game players.

OBJECTIVES: The ability to resist distraction and focus on-task-relevant information while being responsive to changes in the environment is fundamental to goal-directed behavior. Such attentional control abilities are regulated by a constant interplay between previously characterized bottom-up and top-down attentional networks. Here we ask about the neural changes within these two attentional networks that may mediate enhanced attentional control. MATERIALS AND METHODS: To address this question, we contrasted action video game players (AVGPs) and nonvideo game players (NVGPs) in a Posner-cueing paradigm, building on studies documenting enhanced attentional control in AVGPs. RESULTS: Behavioral results indicated a trend for more efficient target processing in AVGPs, and better suppression in rare catch trials for which responses had to be withheld. During the cue period, AVGPs recruited the top-down network less than NVGPs, despite showing comparable validity effects, in line with a greater efficiency of that network in AVGPs. During target processing, as previously shown, recruitment of top-down areas correlated with greater processing difficulties, but only in NVGPs. AVGPs showed no such effect, but rather greater activation across the two networks. In particular, the right temporoparietal junction, middle frontal gyrus, and superior parietal cortex predicted better task performance in catch trials. A functional connectivity analysis revealed enhanced correlated activity in AVGPs compared to NVGPs between parietal and visual areas. CONCLUSIONS: These results point to dynamic functional reconfigurations of top-down and bottom-up attentional networks in AVGPs as attentional demands vary. Aspects of this functional reconfiguration that may act as key signatures of high attentional control are discussed

Modifications de la connectivité cérébrale au sein du réseau attentionnel ventral lors du vieillissement normal

Les capacités attentionnelles sont nécessaires à la plupart des tâches de la vie quotidienne. Au cours du vieillissement normal, ces habiletés se modifient. De même, les études suggèrent que l’activité neurofonctionnelle du réseau fronto-pariétal qui sous-tend les capacités attentionnelles diffère entre les individus âgés et de jeunes adultes. Par contre, les changements en contexte du vieillissement du réseau fronto-pariétal ventral, aussi appelé le réseau attentionnel ventral, ont été peu investigués. Une telle question doit être soulevée dans le contexte où les plus récents modèles décrivant les changements fonctionnels associés au vieillissement rapportent que des possibles transformations neurofonctionnelles peuvent survenir au niveau intrahémisphérique et interhémisphérique. Le but de cet ouvrage est de déterminer comment le vieillissement normal affecte le réseau attentionnel ventral et de décrire la nature des changements qui peuvent survenir sur les axes intra et interhémisphériques. Pour y parvenir, la méthode de connectivité fonctionnelle fut privilégiée puisqu’elle permet de quantifier l’interaction neurofonctionnelle entre diverses régions composant un réseau fonctionnel. La première étude de cette thèse a permis de décrire les modifications de connectivité fonctionelle intrahémisphériques du réseau attentionnel ventral en comparant des adultes jeunes et âgés lorsqu’ils réalisent une tâche d’attention sélective en imagerie par résonance magnétique. Sur le plan comportemental, les individus âgés répondaient significativement plus lentement et commettaient davantage d’erreurs que le groupe composé de jeunes adultes. Les résultats de connectivité fonctionnelle montrent que le degré d’intégration de la connectivité fonctionnelle intrahémisphérique est globalement plus élevé chez les individus âgés dans l’ensemble des régions fronto-pariétales composant ce réseau. De plus, il semble que les aires antérieures du réseau, soit les aires préfrontales et insulaires, sont moins intégrées chez les individus âgés, alors que les zones pariétales, temporales et cérébelleuses le sont davantage. Le degré d’intégration de la connectivité est également plus élevé chez les adultes âgés entre les régions postérieures et antérieures. Ainsi, les résultats de cette étude suggèrent que la dynamique des régions antérieures et postérieures du réseau attentionnel ventral est modifiée au cours du vieillissement normal et que les régions postérieures occupent au sein de ce réseau un rôle plus important avec l’âge. Cette hyperconnectivité des aires pariétales pourrait représenter une stratégie de compensation intrahémisphérique (i.e. recrutement de régions additionnelles en postérieur) qui aurait cependant atteint un certain plateau puisque bien que les âgés réussissent à réaliser la tâche, ils performent significativement plus faiblement que de jeunes adultes. La seconde étude s’est intéressée aux modifications de connectivité interhémisphériques du même réseau fonctionnel en comparant le degré de connectivité fonctionnelle entre des individus jeunes et âgés. De manière similaire à l’étude 1, sur le plan comportemental les individus âgés répondaient significativement plus lentement et commettaient plus d’erreurs que les jeunes adultes. En ce qui concerne la dimension inter-hémisphérique du réseau, les résultats des analyses de connectivité montrent que le degré d’intégration des régions hémisphériques gauches fronto-pariétales et temporales est plus faible pour les participants âgés que pour les participants jeunes. Au contraire, les régions frontales, pariétales, temporales et sous-corticales de l’hémisphère droit sont plus intégrées. Par ailleurs, les résultats montrent également que le degré d’intégration interhémisphérique est plus élevé chez les individus âgés. Ainsi, cette étude suggère que le degré de connectivité fonctionnelle entre les régions hémisphériques droites du réseau attentionnel ventral augmente au cours du vieillissement, suggérant ainsi une amplification de la latéralisation de ce réseau vers l’hémisphère droit avec l’âge. Cette étude montre également que malgré une augmentation de la latéralisation du VAN à droite, celle-ci s’accompagne d’une augmentation du degré de connectivité fonctionnelle interhémisphérique qui pourrait être envisagée comme une tentative de compensation interhémisphérique (i.e. recrutement des régions homologues) qui aurait atteint toutefois un certain plateau car même si les âgés réussissent à réaliser la tâche, leur niveau de performance reste significativement plus faible que les jeunes. En somme, ce travail a permis de contribuer à notre compréhension de l’impact du vieillissement sur le réseau attentionnel ventral sur l’axe intrahémisphérique et interhémisphérique. Cet ouvrage lance de nouvelles pistes d’investigation dans ce domaine et pourrait éventuellement mener à l’élaboration d’interventions susceptibles de promouvoir une santé cognitive optimale lors du vieillissement.Attention is necessary for most of daily life’s tasks. During aging, these cognitive abilities are changed. Studies suggest that the neurofunctional activity of the frontoparietal network, which upholds the attentional capacities, differ between young and older adults. However, age-related changes of the ventral frontoparietal network, also called the ventral attention network, have been less investigated. Such question has to be raised in context of recent models of neurofunctional changes in aging, who report possible functional transformation that could occur both at the intrahemispheric and interhemispheric levels. The goal of the present thesis is to determine how aging affects the ventral attention network and describe the nature of such changes that can occur on the intrahemispheric and interhemispheric axis. To do so, functional connectivity methods were favoured because of their capacity to measure the neurofunctional interaction between the regions of a network. The first study of the present thesis has allowed describing the age-related intrahemispheric modifications of functional connectivity in this network by comparing young and older adults while they respond on a selective attention task during a functional magnetic resonance imagery scan. On the task, aged adults performed significantly slower and made more errors than the young adults. At the functional connectivity level, the results show higher level of the functional connectivity between all frontoparietal regions of this network for the older group. Further, the integration level of functional connectivity in anterior regions of the network seems to be less integrated for the older participants, while posterior regions have more neurofunctional signal dependency. Also, the level of integration of functional connectivity is higher in older adults between anterior and posterior regions. Thus, results from this study suggest that the anterior and posterior regions of the ventral attention network interact differently during aging and that the posterior regions play a more important role with age in this network. This hyperconnectivity in the parietal regions could represent an unsuccessful intrahemispheric compensation attempt (i.e. recruitment of additional regions in posterior part of the brain) since older adults perform significantly less well than younger adults. The second study has investigated interhemispheric alterations of functional connectivity in the same functional network by comparing young and older adults. Like in the first study, younger adults were faster to respond on task and were more accurate. Regarding the neurofunctional lateralization of the network, the degree of functional connectivity is lower in older adults for the left hemisphere’s frontoparietal and temporal regions. However, older adults have a higher degree of functional connectivity in the right frontal, parietal, temporal and subcortical regions of the same network. Also, the results also show that the interhemispheric integration level is superior for the older adults. Thus, this study suggests that the level of functional connectivity with the right hemisphere’s regions of the ventral attention network increases with age, which could suggest an age-related lateralization of this network towards the right hemisphere. In this context, increased interhemispheric functional connectivity could be interpreted as a failed interhemispheric compensation attempt (i.e. recruitment of homologous regions) since the performance of older adults on task was significantly lower than younger adults. In short, this work has allowed contributing to our understanding of the impact of aging on the ventral attention network both on the intrahemispheric and interhemispheric axis. These various results bring up new hypothesis that needs to be investigated in further studies and eventually that could lead to the establishment of intervention that promote an optimal healthy cognitive aging

Anxiety and attention to threat: cognitive mechanisms and treatment with attention bias modification

Anxiety disorders are common and difficult to treat. Some cognitive models of anxiety propose that attention bias to threat causes and maintains anxiety. This view led to the development of a computer-delivered treatment: attention bias modification (ABM) which predominantly trains attention avoidance of threat. However, meta-analyses indicate disappointing effectiveness of ABM-threat-avoidance training in reducing anxiety. This article considers how ABM may be improved, based on a review of key ideas from models of anxiety, attention and cognitive control. These are combined into an integrative framework of cognitive functions which support automatic threat evaluation/detection and goal-directed thought and action, which reciprocally influence each other. It considers roles of bottom-up and top-down processes involved in threat-evaluation, orienting and inhibitory control in different manifestations of attention bias (initial orienting, attention maintenance, threat avoidance, threat-distractor interference) and different ABM methods (e.g., ABM-threat-avoidance, ABM-positive-search). The framework has implications for computer-delivered treatments for anxiety. ABM methods which encourage active goal-focused attention-search for positive/nonthreat information and flexible cognitive control across multiple processes (particularly inhibitory control, which supports a positive goal-engagement mode over processing of minor threat cues) may prove more effective in reducing anxiety than ABM-threat-avoidance training which targets a specific bias in spatial orienting to threat

Effective connectivity during visual processing is affected by emotional state

The limitations of our cognitive resources necessitate the selection of relevant information from the incoming visual stream. This selection and prioritizing of stimuli allows the organism to adapt to the current conditions. However, the characteristics of this process vary with time and depend on numerous external and internal factors. The present study was aimed at determining how the emotional state affects effective connectivity between visual, attentional and control brain areas during the perception of affective visual stimuli. The Directed Transfer Function was applied on a 32-electrode EEG recording to quantify the direction and intensity of the information flow during two sessions: positive and negative. These data were correlated with a self-report of the emotional state. We demonstrated that the current mood, as measured by self-report, is a factor which affects the patterns of effective cortical connectivity. An increase in prefrontal top-down control over the visual and attentional areas was revealed in a state of tension. It was accompanied by increased outflow within and from the areas recognized as the ventral attentional network. By contrast, a positive emotional state was associated with heightened flow from the parietal to the occipital area. The functional significance of the revealed effects is discussed

Investigation of the multiple-demand network at multiple spatial scales

This dissertation investigates the frontoparietal ‘multiple-demand’ (MD) network that is involved in the processing of diverse cognitive demands. This network is active when the task at hand is made more demanding, in a variety of different tasks including working memory, task switching, inhibition, math, language etc. While the different MD regions have partly different functions, they are highly interconnected allowing them to function together as a network. The experiment in Chapter 2 looked at the interplay between functional differences as well as co-recruitment within this multiple-demand network. Quantitative differences between regions were more prominent in simple tasks. A strong co-recruitment was seen with increased challenge or incentive. In Chapter 3, task preferences were studied at the voxel level. MD regions were equally well localised in single-subjects using any of three task demands. Voxels localised by all three tasks also captured the underlying neural representations to a similar level in a separate criterion task. Chapter 4 investigated if task representations, as measured by multi-voxel patterns, were modified due to external motivation. The effect was limited to the cue phase and did not extend to the stimulus processing phase where the stimulus is integrated with the cue to arrive at the response. Chapter 5 examined neural representations in frontal and parietal regions more directly through single unit activity and local field potentials (LFPs), during a spatial working memory task. While single neurons showed dynamic coding of target information rather than persistent coding, LFPs held this information constant through time. The impact of reference voltages on LFP data was further investigated. Together, these results explore the functional differences between and within the MD regions, and provide evidence for flexible task representations at the voxel and neuronal level.Funded by Gates Cambridg

Neural Circuitry Underlying the Intrusion of Task-irrelevant Threat into Working Memory in Anxiety

Dispositional anxiety is an important risk factor for the development of anxiety and other psychological disorders. Symptoms commonly expressed by highly anxious individuals include intrusive memories, uncertainty, and worry — all occurring in the absence of immediate threat. This raises the possibility that anxious individuals have difficulty governing threat’s access to working memory, the mental workspace where goal-related information is actively retained for guiding on-going behavior. Using functional magnetic resonance imaging (fMRI) while 81 subjects completed a well-validated working memory task, I show that threat-related and neutral distracters unnecessarily gain access to working memory, as evidenced by increased neural activity in the fusiform face area and the posterior parietal cortex. Critically, this pattern was exaggerated in individuals with high levels of self-reported dispositional anxiety. Moreover, an amygdala-based circuit mediated this anxiety-related unnecessary storage. These results provide evidence for a novel neural circuit that subserves impaired working memory filtering of threat-related distracters, and sets the stage for understanding the maladaptive cognitive profile characteristic of extreme anxiety

Examining the Transient Neural Dynamics Underlying Working Memory Maintenance for Complex Visual Stimuli

Working memory (WM) is the temporary storage of information to accomplish a future goal. The WM delay period is the time after encoding but before retrieval when information is being maintained, typically in the absence of relevant stimuli. Understanding how the brain supports maintenance during the delay period, and how neural activity and connectivity are related to memory is critical for advancing both basic knowledge as well as informing declines in memory and cognition related to neurodegenerative diseases and healthy aging. An open question in the field of WM research is how information is stored during this delay period. One theory suggests persistent neural activity supports the storage of information while another theory suggests rapid synaptic weight changes (i.e., an activity-silent mechanism). While support exists for both theories, numerous confounds complicate the experiments designed to distinguish between these two theories. Most notably, studies typically use simple stimuli with short, predictable, unfilled delay periods, with few studies examining this open question using complex visual stimuli. For this dissertation four EEG experiments were conducted to answer three questions: 1) Does the type of maintenance technique used during the delay period modulate the neural activity for complex visual stimuli? 2) What are the load-dependent delay activity and connectivity patterns associated with maintenance of complex visual stimuli? And 3) How do patterns of delay activity and connectivity change when attention is sustained during unpredictable delay period durations? In the first set of experiments, we examined the role of rehearsal in maintaining complex visual stimuli. We looked at the impact of rehearsal versus suppression of rehearsal using novel naturalistic scenes that contained semantic content and phase-scrambled scenes that lacked semantic content. The benefit of rehearsal was associated with increases in theta and alpha band amplitude, but only when the stimuli lacked semantic content. The overall pattern of change in amplitude was similar for rehearsal and suppression of rehearsal, regardless of the type of stimulus. In the second set of experiments, we examined the role of attention in maintaining complex visual stimuli. We used a similar set of stimuli to the first experiments, employing a load manipulation (low load-2 images, high load-5 images) while perceptual interference was present. While increasing the WM load, particularly with complex stimuli, places a greater demand on attentional resources, interfering stimuli may compete for the available resources. This was confirmed in the examination of theta and alpha amplitude, as amplitude was reduced for the high WM load as compared with the low WM load. We also analyzed functional connectivity to identify the underlying brain networks that facilitated performance for the low load condition and identified three supporting networks, including a frontal- posterior temporal network that is responsible for filtering the interfering stimuli. Additionally, in a separate experiment using similar stimuli, we randomly varied the delay interval (short-2 sec, medium-5 sec, and long-9 sec) from trial to trial, which ensured sustained attention throughout the delay period because participants did not know when the delay period would end and the probe would appear. The delay activity associated with complex visual stimuli suggests a pattern of transient delay activity for medium and long delay periods, regardless of load, with an early increase in event-related synchronous activity (ERS) in alpha and lower beta activity (until 2-3 secs) followed by an extended period of event-related desynchronous (ERD) in alpha and beta band activity, in parietal and parieto-occipital regions. Sustained delay activity (i.e., ERS in alpha activity followed by a return to baseline) was only observed for the short delay interval (~2 sec). Our results suggest that the pattern of ERS reflects an early period of goal setting, in which attention is focused inward to prevent interference. As the delay interval increases, the pattern of ERD reflects ongoing maintenance and associations with stored semantic knowledge. Finally, we compared the underlying brain networks that supported maintenance across all experiments using connectivity measures. This comparison identified a different frontoparietal network that is implicated in cognitive control and was found to be involved in both effortful maintenance (i.e., for stimuli lacking semantic content) as well as maintenance that places an increased demand on attentional resources (e.g., interference present or increased intervals). These results provide some support for the persistent delay activity hypothesis, as there were changes in delay activity from baseline throughout the delay period in all experiments, regardless of maintenance technique, WM load or delay period interval. Furthermore, the delay period connectivity analyses for all experiments implicate fronto-parietal and temporal networks in supporting maintenance and suggest a flexible role of attention (e.g., filtering of interfering stimuli, control over attention) that varies based on task demands. Together, these delay activity and connectivity findings inform the ongoing debate about the neural dynamics that support visual WM