René Scheeringa

Spatial Remapping of Cortico-striatal Connectivity in Parkinson's Disease

Parkinsons disease (PD) is characterized by striatal dopamine depletion, especially in the posterior putamen. The dense connectivity profile of the striatum suggests that these local impairments may propagate throughout the whole cortico-striatal network. Here we test the effect of striatal dopamine depletion on cortico-striatal network properties by comparing the functional connectivity profile of the posterior putamen, the anterior putamen, and the caudate nucleus between 41 PD patients and 36 matched controls. We used multiple regression analyses of resting-state functional magnetic resonance imaging data to quantify functional connectivity across different networks. Each region had a distinct connectivity profile that was similarly expressed in patients and controls: the posterior putamen was uniquely coupled to cortical motor areas, the anterior putamen to the pre-supplementary motor area and anterior cingulate cortex, and the caudate nucleus to the dorsal prefrontal cortex. Differences between groups were specific to the putamen: although PD patients showed decreased coupling between the posterior putamen and the inferior parietal cortex, this region showed increased functional connectivity with the anterior putamen. We conclude that dopamine depletion in PD leads to a remapping of cerebral connectivity that reduces the spatial segregation between different cortico-striatal loops. These alterations of network properties may underlie abnormal sensorimotor integration in PD.

Intrinsic Connectivity Networks, Alpha Oscillations, and Tonic Alertness: A Simultaneous Electroencephalography/Functional Magnetic Resonance Imaging Study

Trial-by-trial variability in perceptual performance on identical stimuli has been related to spontaneous fluctuations in ongoing activity of intrinsic functional connectivity networks (ICNs). In a paradigm requiring sustained vigilance for instance, we previously observed that higher prestimulus activity in a cingulo-insular-thalamic network facilitated subsequent perception. Here, we test our proposed interpretation that this network underpins maintenance of tonic alertness. We used simultaneous acquisition of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) in the absence of any paradigm to test an ensuing hypothesis, namely that spontaneous fluctuations in this ICN′s activity (as measured by fMRI) should show a positive correlation with the electrical signatures of tonic alertness (as recorded by concurrent EEG). We found in human subjects (19 male, 7 female) that activity in a network comprising dorsal anterior cingulate cortex, anterior insula, anterior prefrontal cortex and thalamus is positively correlated with global field power (GFP) of upper alpha band (10–12 Hz) oscillations, the most consistent electrical index of tonic alertness. Conversely, and in line with earlier findings, alpha band power was negatively correlated with activity in another ICN, the so-called dorsal attention network which is most prominently involved in selective spatial attention. We propose that the cingulo-insular-thalamic network serves maintaining tonic alertness through generalized expression of cortical alpha oscillations. Attention is mediated by activity in other systems, e.g., the dorsal attention network for space, selectively disrupts alertness-related suppression and hence manifests as local attenuation of alpha activity.

Neuronal Dynamics Underlying High- and Low-Frequency EEG Oscillations Contribute Independently to the Human BOLD Signal

Work on animals indicates that BOLD is preferentially sensitive to local field potentials, and that it correlates most strongly with gamma band neuronal synchronization. Here we investigate how the BOLD signal in humans performing a cognitive task is related to neuronal synchronization across different frequency bands. We simultaneously recorded EEG and BOLD while subjects engaged in a visual attention task known to induce sustained changes in neuronal synchronization across a wide range of frequencies. Trial-by-trial BOLD fluctuations correlated positively with trial-by-trial fluctuations in high-EEG gamma power (60-80 Hz) and negatively with alpha and beta power. Gamma power on the one hand, and alpha and beta power on the other hand, independently contributed to explaining BOLD variance. These results indicate that the BOLD-gamma coupling observed in animals can be extrapolated to humans performing a task and that neuronal dynamics underlying high- and low-frequency synchronization contribute independently to the BOLD signal.

Trial-by-trial coupling between EEG and BOLD identifies networks related to alpha and theta EEG power increases during working memory maintenance

PET and fMRI experiments have previously shown that several brain regions in the frontal and parietal lobe are involved in working memory maintenance. MEG and EEG experiments have shown parametric increases with load for oscillatory activity in posterior alpha and frontal theta power. In the current study we investigated whether the areas found with fMRI can be associated with these alpha and theta effects by measuring simultaneous EEG and fMRI during a modified Sternberg task This allowed us to correlate EEG at the single trial level with the fMRI BOLD signal by forming a regressor based on single trial alpha and theta power estimates. We observed a right posterior, parametric alpha power increase, which was functionally related to decreases in BOLD in the primary visual cortex and in the posterior part of the right middle temporal gyrus. We relate this finding to the inhibition of neuronal activity that may interfere with WM maintenance. An observed parametric increase in frontal theta power was correlated to a decrease in BOLD in regions that together form the default mode network. We did not observe correlations between oscillatory EEG phenomena and BOLD in the traditional WM areas. In conclusion, the study shows that simultaneous EEG-fMRI recordings can be successfully used to identify the emergence of functional networks in the brain during the execution of a cognitive task.

Cerebral correlates of motor imagery of normal and precision gait.

We have examined the cerebral structures involved in motor imagery of normal and precision gait (i.e., gait requiring precise foot placement and increased postural control). We recorded cerebral activity with functional magnetic resonance imaging while subjects imagined walking along paths of two different widths (broad, narrow) that required either normal gait, or exact foot placement and increased postural control. We used a matched visual imagery (VI) task to assess the motor specificity of the effects, and monitored task performance by recording imagery times, eye movements, and electromyography during scanning. In addition, we assessed the effector specificity of MI of gait by comparing our results with those of a previous study on MI of hand movements. We found that imagery times were longer for the narrow path during MI, but not during VI, suggesting that MI was sensitive to the constraints imposed by a narrow walking path. Moreover, MI of precision gait resulted in increased cerebral activity and effective connectivity within a network involving the superior parietal lobules, the dorsal precentral gyri, and the right middle occipital gyrus. Finally, the cerebral responses to MI of gait were contiguous to but spatially distinct from regions involved in MI of hand movements. These results emphasize the role of cortical structures outside primary motor regions in imagining locomotion movements when accurate foot positioning and increased postural control is required.

Alpha-Band Phase Synchrony Is Related to Activity in the Fronto-Parietal Adaptive Control Network

Neural oscillations in the alpha band (8–12 Hz) are increasingly viewed as an active inhibitory mechanism that gates and controls sensory information processing as a function of cognitive relevance. Extending this view, phase synchronization of alpha oscillations across distant cortical regions could regulate integration of information. Here, we investigated whether such long-range cross-region coupling in the alpha band is intrinsically and selectively linked to activity in a distinct functionally specialized brain network. If so, this would provide new insight into the functional role of alpha band phase synchrony. We adapted the phase-locking value to assess fluctuations in synchrony that occur over time in ongoing activity. Concurrent EEG and functional magnetic resonance imaging (fMRI) were recorded during resting wakefulness in 26 human subjects. Fluctuations in global synchrony in the upper alpha band correlated positively with activity in several prefrontal and parietal regions (as measured by fMRI). fMRI intrinsic connectivity analysis confirmed that these regions correspond to the well known fronto-parietal (FP) network. Spectral correlations with this networks activity confirmed that no other frequency band showed equivalent results. This selective association supports an intrinsic relation between large-scale alpha phase synchrony and cognitive functions associated with the FP network. This network has been suggested to implement phasic aspects of top-down modulation such as initiation and change in moment-to-moment control. Mechanistically, long-range upper alpha band synchrony is well suited to support these functions. Complementing our previous findings that related alpha oscillation power to neural structures serving tonic control, the current findings link alpha phase synchrony to neural structures underpinning phasic control of alertness and task requirements.

Modulation of Visually Evoked Cortical fMRI Responses by Phase of Ongoing Occipital Alpha Oscillations

Using simultaneous electroencephalography as a measure of ongoing activity and functional magnetic resonance imaging (fMRI) as a measure of the stimulus-driven neural response, we examined whether the amplitude and phase of occipital alpha oscillations at the onset of a brief visual stimulus affects the amplitude of the visually evoked fMRI response. When accounting for intrinsic coupling of alpha amplitude and occipital fMRI signal by modeling and subtracting pseudo-trials, no significant effect of prestimulus alpha amplitude on the evoked fMRI response could be demonstrated. Regarding the effect of alpha phase, we found that stimuli arriving at the peak of the alpha cycle yielded a lower blood oxygenation level-dependent (BOLD) fMRI response in early visual cortex (V1/V2) than stimuli presented at the trough of the cycle. Our results therefore show that phase of occipital alpha oscillations impacts the overall strength of a visually evoked response, as indexed by the BOLD signal. This observation complements existing evidence that alpha oscillations reflect periodic variations in cortical excitability and suggests that the phase of oscillations in postsynaptic potentials can serve as a mechanism of gain control for incoming neural activity. Finally, our findings provide a putative neural basis for observations of alpha phase dependence of visual perceptual performance.

EEG Alpha Power Modulation of fMRI Resting-State Connectivity

In the past decade, the fast and transient coupling and uncoupling of functionally related brain regions into networks has received much attention in cognitive neuroscience. Empirical tools to study network coupling include functional magnetic resonance imaging (fMRI)-based functional and/or effective connectivity, and electroencephalography (EEG)/magnetoencephalography-based measures of neuronal synchronization. Here we use simultaneously recorded EEG and fMRI to assess whether fMRI-based connectivity and frequency-specific EEG power are related. Using data collected during resting state, we studied whether posterior EEG alpha power fluctuations are correlated with connectivity within the visual network and between the visual cortex and the rest of the brain. The results show that when alpha power increases, BOLD connectivity between the primary visual cortex and occipital brain regions decreases and that the negative relation of the visual cortex with the anterior/medial thalamus decreases and the ventral-medial prefrontal cortex is reduced in strength. These effects were specific for the alpha band, and not observed in other frequency bands. The decreased connectivity within the visual system may indicate an enhanced functional inhibition during a higher alpha activity. This higher inhibition level also attenuates long-range intrinsic functional antagonism between the visual cortex and the other thalamic and cortical regions. Together, these results illustrate that power fluctuations in posterior alpha oscillations result in local and long-range neural connectivity changes.

When elephants fly: Differential sensitivity of right and left inferior frontal gyri to discourse and world knowledge

Both local discourse and world knowledge are known to influence sentence processing. We investigated how these two sources of information conspire in language comprehension. Two types of critical sentences, correct and world knowledge anomalies, were preceded by either a neutral or a local context. The latter made the world knowledge anomalies more acceptable or plausible. We predicted that the effect of world knowledge anomalies would be weaker for the local context. World knowledge effects have previously been observed in the left inferior frontal region (Brodmanns area 45/47). In the current study, an effect of world knowledge was present in this region in the neutral context. We also observed an effect in the right inferior frontal gyrus, which was more sensitive to the discourse manipulation than the left inferior frontal gyrus. In addition, the left angular gyrus reacted strongly to the degree of discourse coherence between the context and critical sentence. Overall, both world knowledge and the discourse context affect the process of meaning unification, but do so by recruiting partly different sets of brain areas.

Occipital alpha activity during stimulus processing gates the information flow to object-selective cortex

A simultaneous EEG-fMRI study demonstrates that alpha-band activity in early visual cortex is associated with gating visual information to downstream regions, boosting attended information and suppressing distraction.