Caffeine-Induced Global Reductions in Resting-State BOLD Connectivity Reflect Widespread Decreases in MEG Connectivity.

In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity

Functional connectivity in relation to motor performance and recovery after stroke.

Plasticity after stroke has traditionally been studied by observing changes only in the spatial distribution and laterality of focal brain activation during affected limb movement. However, neural reorganization is multifaceted and our understanding may be enhanced by examining dynamics of activity within large-scale networks involved in sensorimotor control of the limbs. Here, we review functional connectivity as a promising means of assessing the consequences of a stroke lesion on the transfer of activity within large-scale neural networks. We first provide a brief overview of techniques used to assess functional connectivity in subjects with stroke. Next, we review task-related and resting-state functional connectivity studies that demonstrate a lesion-induced disruption of neural networks, the relationship of the extent of this disruption with motor performance, and the potential for network reorganization in the presence of a stroke lesion. We conclude with suggestions for future research and theories that may enhance the interpretation of changing functional connectivity. Overall findings suggest that a network level assessment provides a useful framework to examine brain reorganization and to potentially better predict behavioral outcomes following stroke

Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA, revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep

Task-evoked functional connectivity does not explain functional connectivity differences between rest and task conditions

During complex tasks, patterns of functional connectivity differ from those in the resting state. However, what accounts for such differences remains unclear. Brain activity during a task reflects an unknown mixture of spontaneous and task-evoked activities. The difference in functional connectivity between a task state and the resting state may reflect not only task-evoked functional connectivity, but also changes in spontaneously emerging networks. Here, we characterized the differences in apparent functional connectivity between the resting state and when human subjects were watching a naturalistic movie. Such differences were marginally explained by the task-evoked functional connectivity involved in processing the movie content. Instead, they were mostly attributable to changes in spontaneous networks driven by ongoing activity during the task. The execution of the task reduced the correlations in ongoing activity among different cortical networks, especially between the visual and non-visual sensory or motor cortices. Our results suggest that task-evoked activity is not independent from spontaneous activity, and that engaging in a task may suppress spontaneous activity and its inter-regional correlation

Thalamo-cortical network activity between migraine attacks. Insights from MRI-based microstructural and functional resting-state network correlation analysis

BACKGROUND: Resting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks. METHODS: Eighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores. RESULTS: In comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally. CONCLUSIONS: The present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology

Dynamic BOLD functional connectivity in humans and its electrophysiological correlates

Neural oscillations subserve many human perceptual and cognitive operations. Accordingly, brain functional connectivity is not static in time, but fluctuates dynamically following the synchronization and desynchronization of neural populations. This dynamic functional connectivity has recently been demonstrated in spontaneous fluctuations of the Blood Oxygen Level-Dependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI). We analyzed temporal fluctuations in BOLD connectivity and their electrophysiological correlates, by means of long (≈50 min) joint electroencephalographic (EEG) and fMRI recordings obtained from two populations: 15 awake subjects and 13 subjects undergoing vigilance transitions. We identified positive and negative correlations between EEG spectral power (extracted from electrodes covering different scalp regions) and fMRI BOLD connectivity in a network of 90 cortical and subcortical regions (with millimeter spatial resolution). In particular, increased alpha (8-12 Hz) and beta (15-30 Hz) power were related to decreased functional connectivity, whereas gamma (30-60 Hz) power correlated positively with BOLD connectivity between specific brain regions. These patterns were altered for subjects undergoing vigilance changes, with slower oscillations being correlated with functional connectivity increases. Dynamic BOLD functional connectivity was reflected in the fluctuations of graph theoretical indices of network structure, with changes in frontal and central alpha power correlating with average path length. Our results strongly suggest that fluctuations of BOLD functional connectivity have a neurophysiological origin. Positive correlations with gamma can be interpreted as facilitating increased BOLD connectivity needed to integrate brain regions for cognitive performance. Negative correlations with alpha suggest a temporary functional weakening of local and long-range connectivity, associated with an idling state

Development of Low-Frequency Repetitive Transcranial Magnetic Stimulation as a Tool to Modulate Visual Disorders: Insights from Neuroimaging

Repetitive transcranial magnetic stimulation (rTMS) has become a popular neuromodulation technique, increasingly employed to manage several neurological and psychological conditions. Despite its popular use, the underlying mechanisms of rTMS remain largely unknown, particularly at the visual cortex. Moreover, the application of rTMS to modulate visual-related disorders is under-investigated. The goal of the present research was to address these issues. I employ a multitude of neuroimaging techniques to gain further insight into neural mechanisms underlying low-frequency (1 Hz) rTMS to the visual cortex. In addition, I begin to develop and refine clinical low-frequency rTMS protocols applicable to visual disorders as an alternative therapy where other treatment options are unsuccessful or where there are simply no existing therapies. One such visual disorder that can benefit from rTMS treatment is the perception of visual hallucinations that can occur following visual pathway damage in otherwise cognitively healthy individuals. In Chapters 23, I investigate the potential of multiday low-frequency rTMS to the visual cortex to alleviate continuous and disruptive visual hallucinations consequent to occipital injury. Combining rTMS with magnetic resonance imaging techniques reveals functional and structural cortical changes that lead to the perception of visual hallucinations; and rTMS successfully attenuates these anomalous visual perceptions. In Chapters 45, I compare the effects of alternative doses of low-frequency rTMS to the visual cortex on neurotransmitter levels and intrinsic functional connectivity to gain insight into rTMS mechanisms and establish the most effective protocol. Differential dose-dependent effects are observed on neurotransmitter levels and functional connectivity that suggest the choice of protocol critically depends on the neurophysiological target. Collectively, this work provides a basic framework for the use of low-frequency rTMS and neuroimaging in clinical application for visual disorders

A Quest for Meaning in Spontaneous Brain Activity - From fMRI to Electrophysiology to Complexity Science

The brain is not a silent, complex input/output system waiting to be driven by external stimuli; instead, it is a closed, self-referential system operating on its own with sensory information modulating rather than determining its activity. Ongoing spontaneous brain activity costs the majority of the brain\u27s energy budget, maintains the brain\u27s functional architecture, and makes predictions about the environment and the future. I have completed three separate studies on the functional significance and the organization of spontaneous brain activity. The first study showed that strokes disrupt large-scale network coherence in the spontaneous functional magnetic resonance imaging: fMRI) signals, and that the degree of such disruption predicts the behavioral impairment of the patient. This study established the functional significance of coherent patterns in the spontaneous fMRI signals. In the second study, by combining fMRI and electrophysiology in neurosurgical patients, I identified the neurophysiological signal underlying the coherent patterns in the spontaneous fMRI signal, the slow cortical potential: SCP). The SCP is a novel neural correlate of the fMRI signal, most likely underlying both spontaneous fMRI signal fluctuations and task-evoked fMRI responses. Some theoretical considerations have led me to propose a hypothesis on the involvement of the neural activity indexed by the SCP in the emergence of consciousness. In the last study I investigated the temporal organization across a wide range of frequencies in the spontaneous electrical field potentials recorded from the human brain. This study demonstrated that the arrhythmic, scale-free brain activity often discarded in human and animal electrophysiology studies in fact contains rich, complex structures, and further provided evidence supporting the functional significance of such activity

Movie-driven fMRI Reveals Network Asynchrony and Connectivity Alterations in Temporal Lobe Epilepsy

Mesial temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is often resistant to medication. Recent studies have noted brain-wide disruptions to several neural networks in so-called “focal” epilepsy, notably TLE, leading to it being recognized as a network disease. We aimed to assess the integrity of functional networks while they were simultaneously activated in an ecologically valid manner, using an actively engaging, richly stimulating audio-visual film clip. This stimulus elicits widespread, dynamic patterns of time-locked brain activity, measurable using functional magnetic resonance imaging. Thirteen persons with drug-resistant TLE (persons with epilepsy; PWE) and 10 demographically matched controls were scanned while at rest and while watching a suspenseful movie clip in a 3T MRI system. We observed idiosyncratic activation in several functional networks among PWE during movie-viewing. Activation time courses among PWE synchronized poorly with the highly stereotyped movie-driven BOLD fluctuations exhibited by controls [i.e., high inter-subject correlation (ISC)]. We also examined coupling (functional connectivity) among 10 canonical functional networks during resting-state and movie-viewing conditions. Whereas functional networks in healthy viewers segregate to support movie processing, the auditory and dorsal attention networks among PWE do not segregate as efficiently. Furthermore, we observed a robust pattern of connectivity alterations in temporal and extratemporal regions during movie viewing in PWE compared to controls. Our findings supplement evidence derived from resting-state fMRI and provide novel insight into how the cognitively engaged brain is altered in TLE