Neural Basis of Functional Connectivity MRI

The brain is hierarchically organized across a range of scales. While studies based on electrophysiology and anatomy have been fruitful on the micron to millimeter scale, findings based on functional connectivity MRI (fcMRI) suggest that a higher level of brain organization has been largely overlooked. These findings show that the brain is organized into networks, and each network extends across multiple brain areas. This large-scale, across-area brain organization is functionally relevant and stable across subjects, primate species, and levels of consciousness. This dissertation addresses the neural origin of MRI functional connectivity. fcMRI relies on temporal correlation in at-rest blood oxygen level dependent (BOLD) fluctuations. Thus, understanding the neural origin of at-rest BOLD correlation is of critical significance. By shedding light on the origin of the large-scale brain organization captured by fcMRI, it will guide the design and interpretation of fcMRI studies. Prior investigations of the neural basis of BOLD have not addressed the at-rest BOLD correlation, and they have been focusing on task-related BOLD. At-rest BOLD correlation captured by fcMRI likely reflects a distinct physiological process that is different from that of task-related BOLD, since these two kinds of BOLD dynamics are different in their temporal scale, spatial spread, energy consumption, and their dependence on consciousness. To address this issue, we develop a system to simultaneously record oxygen and electrophysiology in at-rest, awake monkeys. We demonstrate that our oxygen measurement, oxygen polarography, captures the same physiological phenomenon as BOLD by showing that task-related polarographic oxygen responses and at-rest polarographic oxygen correlation are similar to those of BOLD. These results validate the use of oxygen polarography as a surrogate for BOLD to address the neural origin of MRI functional connectivity. Next, we show that at-rest oxygen correlation reflects at-rest correlation in electrophysiological signals, especially spiking activity of neurons. Using causality analysis, we show that oxygen is driven by slow changes in raw local field potential levels (slow LFP), and slow LFP itself is driven by spiking activity. These results provide critical support to the idea that oxygen correlation reflects neural activity, and pose significant challenges to the traditional view of neurohemodynamic coupling. In addition, we find that at-rest correlation does not originate from criticality, which has been the dominant hypothesis in the field. Instead, we show that at-rest correlation likely reflects a specific and potentially localized oscillatory process. We suggest that this oscillatory process could be a result of the delayed negative feedback loop between slow LFP and spiking activity. Thus, we conclude that at-rest BOLD correlation captured by fcMRI is driven by at-rest slow LFP correlation, which is itself driven by spiking activity correlation. The at-rest spiking activity correlation, itself, is likely driven by an oscillatory process. Future studies combining recording with interventional approaches, like pharmacological manipulation and microstimulation, will help to elucidate the circuitry underlying the oscillatory process and its potential functional role

Thalamo-cortical communication, glutamatergic neurotransmission and neural oscillations:a unique window into the origins of ScZ?

The thalamus has recently received renewed interest in systems-neuroscience and schizophrenia (ScZ) research because of emerging evidence highlighting its important role in coordinating functional interactions in cortical-subcortical circuits. Moreover, higher cognitive functions, such as working memory and attention, have been related to thalamo-cortical interactions, providing a novel perspective for the understanding of the neural substrate of cognition. The current review will support this perspective by summarizing evidence on the crucial role of neural oscillations in facilitating thalamo-cortical (TC) interactions during normal brain functioning and their potential impairment in ScZ. Specifically, we will focus on the relationship between NMDA-R mediated (glutamatergic) neurotransmission in TC-interactions. To this end, we will first review the functional anatomy and neurotransmitters in thalamic circuits, followed by a review of the oscillatory signatures and cognitive processes supported by TC-circuits. In the second part of the paper, data from preclinical research as well as human studies will be summarized that have implicated TC-interactions as a crucial target for NMDA-receptor hypofunctioning. Finally, we will compare these neural signatures with current evidence from ScZ-research, suggesting a potential overlap between alterations in TC-circuits as the result of NMDA-R deficits and stage-specific alterations in large-scale networks in ScZ

Neural correlates of visual awareness

openL'elaborato si propone di esporre le attuali evidenze riguardanti il modo in cui i contenuti soggettivi di consapevolezza visiva sono codificati a livello neurale. Sebbene i meccanismi neurali della percezione visiva siano ampiamente conosciuti, rimane ancora da chiarire come l'informazione visiva entri a far parte dei contenuti della coscienza. Per identificare i correlati neurali della coscienza (CNC), che rappresentano la minima attività neurale per una specifica esperienza conscia, vengono messe in relazione misure comportamentali di consapevolezza, limitatamente a stimoli presentati in un contesto sperimentale, con i sottostanti meccanismi neurali. Attraverso paradigmi sperimentali come la rivalità binoculare e tecniche di mascheramento visivo è possibile provare ad identificare i CNC contenuto-specifici utilizzando misure neurofisiologiche e tecniche di neuroimaging. Tali tecniche forniscono infatti utili informazioni circa le basi neuroanatomiche e funzionali dell'esperienza sotto esame. Sebbene i meccanismi che sottendono l’attenzione siano spesso associati all'esperienza cosciente, evidenze sperimentali suggeriscono una separazione tra i due processi. Le ricerche sui correlati neurali della consapevolezza visiva indicano come l’attività di una singola area cerebrale non possa essere necessaria e sufficiente a spiegare le qualità dei contenuti coscienti. Sembrerebbe invece essere necessaria una rappresentazione della scena visiva distribuita nella corteccia visiva primaria (V1) e nelle aree visive ventrali con attivazione di regioni temporo-parietali. Misure elettrofisiologiche come la visual awareness negativity (VAN) sono state correlate alla consapevolezza visiva mentre altri indicatori sembrerebbero essere maggiormente legati a processi attentivi. Diversi modelli teorici offrono spiegazioni empiriche sull’emergenza della coscienza dall’attività cerebrale. Nel caso della consapevolezza visiva, alcuni modelli teorici rilevanti sono la teoria dello spazio di lavoro neurale globale, la quale sottolinea la necessità di condivisione dell'informazione tra ampie aree cerebrali e la teoria dell'elaborazione ricorrente che si concentra invece sul feedback proveniente a V1 dalle aree extrastriate. Inoltre, il modello dell’”elaborazione predittiva” descrive la percezione cosciente come il risultato di un processo attivo in cui il cervello crea costantemente previsioni sull’ambiente circostante. Allo stato attuale, la ricerca sui correlati neurali della consapevolezza visiva evidenzia dunque come un network di regioni cerebrali posteriori sia fondamentale per avere esperienze visive coscienti. Inoltre, i segnali di feedback sembrano svolgere un ruolo cruciale, evidenziando le complesse interazioni tra dinamiche neurali e percezione cosciente.The paper aims to present the current evidence regarding how subjective contents of visual awareness are encoded at the neural level. While the neural mechanisms of visual perception are well understood, it remains unclear how visual information becomes part of consciousness. To identify the neural correlates of consciousness (NCC), representing the minimum neural activity for a specific conscious experience, behavioral measures of awareness are related to underlying neural mechanisms, limited to stimuli presented in an experimental context. Through experimental paradigms such as binocular rivalry and visual masking techniques, it is possible to attempt to identify content-specific NCC using neurophysiological measures and neuroimaging techniques. These techniques indeed provide valuable information about the neuroanatomical and functional basis of the examined experience. Although mechanisms underlying attention are often associated with conscious experience, experimental evidence suggests a separation between the two processes. Research on the neural correlates of visual awareness indicates that the activity of a single brain area may not be necessary and sufficient to explain the qualities of conscious contents. Instead, a distributed representation of the visual scene in the primary visual cortex (V1) and ventral visual areas with activation of temporo-parietal regions seems to be necessary. Electrophysiological measures such as Visual Awareness Negativity (VAN) have been correlated with visual awareness, while other indicators appear to be more related to attentional processes. Various theoretical models offer empirical explanations of the emergence of consciousness from brain activity. In the case of visual awareness, some relevant theoretical models include the global neural workspace theory, which emphasizes the need for information sharing among extensive brain areas, and the recurrent processing theory, which focuses on feedback from extrastriate areas to V1. Additionally, the predictive processing model describes conscious perception as the result of an active process in which the brain constantly generates predictions about the surrounding environment. Currently, research on the neural correlates of visual awareness highlights the importance of a network of posterior brain regions for conscious visual experiences. Furthermore, feedback signals appear to play a crucial role, highlighting the complex interactions between neural dynamics and conscious perception

Modeling biophysical and neural circuit bases for core cognitive abilities evident in neuroimaging patterns: hippocampal mismatch, mismatch negativity, repetition positivity, and alpha suppression of distractors

This dissertation develops computational models to address outstanding problems in the domain of expectation-related cognitive processes and their neuroimaging markers in functional MRI or EEG. The new models reveal a way to unite diverse phenomena within a common framework focused on dynamic neural encoding shifts, which can arise from robust interactive effects of M-currents and chloride currents in pyramidal neurons. By specifying efficient, biologically realistic circuits that achieve predictive coding (e.g., Friston, 2005), these models bridge among neuronal biophysics, systems neuroscience, and theories of cognition. Chapter one surveys data types and neural processes to be examined, and outlines the Dynamically Labeled Predictive Coding (DLPC) framework developed during the research. Chapter two models hippocampal prediction and mismatch, using the DLPC framework. Chapter three presents extensions to the model that allow its application for modeling neocortical EEG genesis. Simulations of this extended model illustrate how dynamic encoding shifts can produce Mismatch Negativity (MMN) phenomena, including pharmacological effects on MMN reported for humans or animals. Chapters four and five describe new modeling studies of possible neural bases for alpha-induced information suppression, a phenomenon associated with active ignoring of stimuli. Two models explore the hypothesis that in simple rate-based circuits, information suppression might be a robust effect of neural saturation states arising near peaks of resonant alpha oscillations. A new proposal is also introduced for how the basal ganglia may control onset and offset of alpha-induced information suppression. Although these rate models could reproduce many experimental findings, they fell short of reproducing a key electrophysiological finding: phase-dependent reduction in spiking activity correlated with power in the alpha frequency band. Therefore, chapter five also specifies how a DLPC model, adapted from the neocortical model developed in chapter three, can provide an expectation-based model of alpha-induced information suppression that exhibits phase-dependent spike reduction during alpha-band oscillations. The model thus can explain experimental findings that were not reproduced by the rate models. The final chapter summarizes main theses, results, and basic research implications, then suggests future directions, including expanded models of neocortical mismatch, applications to artificial neural networks, and the introduction of reward circuitry

State Regulation and Executive Function in Traumatic Brain Injury: EEG Correlates of Impairment and Intervention

Executive dysfunction is a common and persistent consequence of Traumatic Brain Injury (TBI) and has a significant detrimental impact on social, emotional, and occupational functioning. Abnormalities in EEG measures reflecting the energetic state of the brain are also common following TBI, and rehabilitation approaches such as cognitive and neurofeedback training aim to improve executive function (EF) by facilitating changes in brain state and function. However, the field is lacking a parsimonious and clinically applicable theory of the relationship between brain energetic state and cognition in TBI. The Cognitive Energetic Model (CEM; Sanders, 1983) may address this gap. The CEM provides an explanation of how two aspects of energetic state - arousal (baseline energetic state) and activation (mobilisation of arousal in response to processing demands) - interact with computational factors, effort, and evaluative processes to produce efficient cognitive performance. EEG measures of arousal (eyes-closed global alpha) and activation (changes in delta, theta, alpha, and beta bands between resting or task conditions) provide an empirical basis for investigating the applicability of this model to TBI sequelae and intervention. The aims of this thesis were: 1) to investigate the applicability of the CEM arousal and activation concepts to understanding energetic state abnormalities and their relationship to EF impairment in TBI; and 2) to investigate the effectiveness of a CEM-based neurocognitive training program for improving EF in TBI. Study 1 investigated EEG measures of arousal and activation recorded during eyes-closed and eyes-open resting conditions. Results showed intact arousal, but impaired activation for the TBI group, compared to healthy controls. The TBI group were characterised by reduced resting theta activation and a trend toward increased resting delta activation. Furthermore, enhanced resting delta and alpha activation and reduced resting theta activation were associated with impaired performance on a response inhibition task across groups. Together, the results suggested that it is not baseline resting state, but rather the ability to mobilise energetic state, that is impaired in TBI, and that this is associated with impaired EF

EEG-based neurophysiological indices for expert psychomotor performance – a review

A primary objective of current human neuropsychological performance research is to define the physiological correlates of adaptive knowledge utilization, in order to support the enhanced execution of both simple and complex tasks. Within the present article, electroencephalography-based neurophysiological indices characterizing expert psychomotor performance, will be explored. As a means of characterizing fundamental processes underlying efficient psychometric performance, the neural efficiency model will be evaluated in terms of alpha-wave-based selective cortical processes. Cognitive and motor domains will initially be explored independently, which will act to encapsulate the task-related neuronal adaptive requirements for enhanced psychomotor performance associating with the neural efficiency model. Moderating variables impacting the practical application of such neuropsychological model, will also be investigated. As a result, the aim of this review is to provide insight into detectable task-related modulation involved in developed neurocognitive strategies which support heightened psychomotor performance, for the implementation within practical settings requiring a high degree of expert performance (such as sports or military operational settings)

The neural bases of event monitoring across domains: a simultaneous ERP-fMRI study.

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, these transient processes rely on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts