FMRI resting slow fluctuations correlate with the activity of fast cortico-cortical physiological connections

Recording of slow spontaneous fluctuations at rest using functional magnetic resonance imaging (fMRI) allows distinct long-range cortical networks to be identified. The neuronal basis of connectivity as assessed by resting-state fMRI still needs to be fully clarified, considering that these signals are an indirect measure of neuronal activity, reflecting slow local variations in de-oxyhaemoglobin concentration. Here, we combined fMRI with multifocal transcranial magnetic stimulation (TMS), a technique that allows the investigation of the causal neurophysiological interactions occurring in specific cortico-cortical connections. We investigated whether the physiological properties of parieto-frontal circuits mapped with short-latency multifocal TMS at rest may have some relationship with the resting-state fMRI measures of specific resting-state functional networks (RSNs). Results showed that the activity of fast cortico-cortical physiological interactions occurring in the millisecond range correlated selectively with the coupling of fMRI slow oscillations within the same cortical areas that form part of the dorsal attention network, i.e., the attention system believed to be involved in reorientation of attention. We conclude that resting-state fMRI ongoing slow fluctuations likely reflect the interaction of underlying physiological cortico-cortical connections

The mechanisms of tinnitus: perspectives from human functional neuroimaging

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power

Distilling the neural correlates of conscious somatosensory perception

The ability to consciously perceive the world profoundly defines our lives as human beings. Somehow, our brains process information in a way that allows us to become aware of the images, sounds, touches, smells, and tastes surrounding us. Yet our understanding of the neurobiological processes that generate perceptual awareness is very limited. One of the most contested questions in the neuroscientific study of conscious perception is whether awareness arises from the activity of early sensory brain regions, or instead requires later processing in widespread supramodal networks. It has been suggested that the conflicting evidence supporting these two perspectives may be the result of methodological confounds in classical experimental tasks. In order to infer participants’ perceptual awareness in these tasks, they need to report the contents of their perception. This means that the neural signals underlying the emergence of perceptual awareness often cannot be dissociated from pre- and postperceptual processes. Consequently, some of the previously observed effects may not be correlates of awareness after all but instead may have resulted from task requirements. In this thesis, I investigate this possibility in the somatosensory modality. To scrutinise the task dependence of the neural correlates of somatosensory awareness, I developed an experimental paradigm that controls for the most common experimental confounds. In a somatosensory-visual matching task, participants were required to detect electrical target stimuli at ten different intensity levels. Instead of reporting their perception directly, they compared their somatosensory percepts to simultaneously presented visual cues that signalled stimulus presence or absence and then reported a match or mismatch accordingly. As a result, target detection was decorrelated from working memory and reports, the behavioural relevance of detected and undetected stimuli was equated, the influence of attentional processes was mitigated, and perceptual uncertainty was varied in a controlled manner. Results from a functional magnetic resonance imaging (fMRI) study and an electroencephalography (EEG) study showed that, when controlled for task demands, the neural correlates of somatosensory awareness were restricted to relatively early activity (~150 ms) in secondary somatosensory regions. In contrast, late activity (>300 ms) indicative of processing in frontoparietal networks occurred irrespective of stimulus awareness, and activity in anterior insular, anterior cingulate, and supplementary motor cortex was associated with processing perceptual uncertainty and reports. These results add novel evidence to the early-local vs. late-global debate and favour the view that perceptual awareness emerges at the level of modality-specific sensory cortices.Die Fähigkeit zur bewussten Wahrnehmung bestimmt maßgeblich unser Selbstbild als Menschen. Unser Gehirn verarbeitet Informationen auf eine Weise, die es uns ermöglicht, uns der Bilder, Töne, Berührungen, Gerüche und Geschmäcker, die uns umgeben, bewusst zu werden. Unser Verständnis davon, wie neurobiologische Prozesse diese bewusste Wahrnehmung erzeugen, ist jedoch noch sehr begrenzt. Eine der umstrittensten Fragen in der neurowissenschaftlichen Erforschung des perzeptuellen Bewusstseins besteht darin, ob die bewusste Wahrnehmung aus der Aktivität früher sensorischer Hirnregionen entsteht, oder aber die spätere Prozessierung in ausgedehnten supramodalen Netzwerken erfordert. Eine mögliche Erklärung für die widersprüchlichen Ergebnisse, die diesen beiden Perspektiven zugrunde liegen, wird in methodologischen Störfaktoren vermutet, die in klassischen experimentellen Paradigmen auftreten können. Um auf die Wahrnehmung der Versuchspersonen schließen zu können, müssen diese den Inhalt ihrer Wahrnehmung berichten. Das führt dazu, dass neuronale Korrelate bewusster Wahrnehmung häufig nicht sauber von prä- und postperzeptuellen Prozessen getrennt werden können. Folglich könnten einige der zuvor beobachteten Effekte, anstatt tatsächlich bewusste Wahrnehmung widerzuspiegeln, aus den Anforderungen experimenteller Paradigmen entstanden sein. In dieser Arbeit untersuche ich diese Möglichkeit in der somatosensorischen Modalität. Um zu überprüfen, inwiefern neuronale Korrelate bewusster somatosensorischer Wahrnehmung von den Anforderungen experimenteller Aufgaben abhängen, habe ich ein Paradigma entwickelt, dass die häufigsten experimentellen Störfaktoren kontrolliert. In einer somatosensorisch-visuellen Vergleichsaufgabe mussten die Versuchspersonen elektrische Zielreize in zehn verschiedenen Intensitätsstufen detektieren. Anstatt diese jedoch direkt zu berichten, sollten sie ihre somatosensorischen Perzepte mit gleichzeitig präsentierten visuellen Symbolen vergleichen, die entweder Reizanwesenheit oder -abwesenheit signalisierten. Entsprechend wurde dann eine Übereinstimmung oder Nichtübereinstimmung berichtet. Dadurch wurde die Reizwahrnehmung von Arbeitsgedächtnis und Berichterstattung dekorreliert, die Verhaltensrelevanz detektierter und nicht detektierter Reize gleichgesetzt, der Einfluss von Aufmerksamkeitsprozessen reduziert und die mit der Detektion verbundene Unsicherheit auf kontrollierte Weise variiert. Die Ergebnisse aus einer funktionellen Magnetresonanztomographie (fMRT)-Studie und einer Elektroenzephalographie (EEG)-Studie zeigen, dass die neuronalen Korrelate bewusster somatosensorischer Wahrnehmung auf relativ frühe Aktivität (~150 ms) in sekundären somatosensorischen Regionen beschränkt sind, wenn experimentelle Störfaktoren kontrolliert werden. Im Gegensatz dazu trat späte Aktivität (>300 ms), die auf die Verarbeitung in frontoparietalen Netzwerken hindeutet, unabhängig von der Reizwahrnehmung auf, und Aktivität im anterioren insulären, anterioren cingulären und supplementär-motorischen Kortex war mit der Verarbeitung von Detektionsunsicherheit und der Berichterstattung verbunden. Diese Ergebnisse liefern neue Erkenntnisse zur Debatte um die Relevanz früher, lokaler vs. später, globaler Hirnaktivität und unterstützen die Ansicht, dass perzeptuelles Bewusstsein in modalitätsspezifischen sensorischen Kortizes entsteht

Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

EEG and fMRI are important tools in cognitive and clinical neuroscience. Combined EEGfMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological-haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals, and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (“EEG-fMRI mapping”), or exploring a range of EEGderived quantities to determine which best explain co-localised BOLD fluctuations (“local EEG-fMRI coupling”). While reviewing studies of different forms of brain activity (epileptic and non-epileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG-fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations

Exposing Internal Attentional Brain States using Single-Trial EEG Analysis with Combined Imaging Modalities

The goal of this dissertation is to explore the neural correlates of endogenous task-related attentional modulations. Natural fluctuations in task engagement are challenging to study, primarily because they are by nature not event related and thus cannot be controlled experimentally. Here we exploit well-accepted links between attention and various measures of neural activity while subjects perform simple target detection tasks that leave their minds free to wander. We use multimodal neuroimaging, specifically simultaneous electroencephalograpy and functional magnetic resonance imaging (EEG-fMRI) and EEG-pupillometry, with data-driven machine learning methods and study activity across the whole brain. We investigate BOLD fMRI correlates of EEG variability spanning each trial, enabling us to unravel a cascade of attention-related activations and determine their temporal ordering. We study activity during auditory and visual paradigms independently, and we also combine data to investigate supra modal attention systems. Without aiming to study known attention-related functional brain networks, we found correlates of attentional modulations in areas representative of the default mode network (DMN), ventral attention network (VAN), locus coeruleus norepinephrine (LC-NE) system, and regions implicated in generation of the extensively-studied P300 EEG response to target stimuli. Our results reveal complex interactions between known attentional systems, and do so non-invasively to study normal fluctuations of task engagement in the human brain

When Is Simultaneous Recording Necessary? A Guide for Researchers Considering Combined EEG-fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provide non-invasive measures of brain activity at varying spatial and temporal scales, offering different views on brain function for both clinical and experimental applications. Simultaneous recording of these measures attempts to maximize the respective strengths of each method, while compensating for their weaknesses. However, combined recording is not necessary to address all research questions of interest, and experiments may have greater statistical power to detect effects by maximizing the signal-to-noise ratio in separate recording sessions. While several existing papers discuss the reasons for or against combined recording, this article aims to synthesize these arguments into a flow chart of questions that researchers can consider when deciding whether to record EEG and fMRI separately or simultaneously. Given the potential advantages of simultaneous EEG-fMRI, the aim is to provide an initial overview of the most important concepts and to direct readers to relevant literature that will aid them in this decision

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG–BOLD–CBF study in humans

Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n = 0.91 ± 0.04, M = 10.45%) than in the contralateral S1/M1 (n = 0.65 ± 0.03, M = 10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8–13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR