Prestimulus EEG alpha oscillations modulate task-related fMRI BOLD responses to auditory stimuli.

EEG alpha-band activity is generally thought to represent an inhibitory state related to decreased attention and play a role in suppression of task-irrelevant stimulus processing, but a competing hypothesis suggests an active role in processing task-relevant information - one in which phase dynamics are involved. Here we used simultaneous EEG-fMRI and a whole-brain analysis to investigate the effects of prestimulus alpha activity on the event-related BOLD response during an auditory oddball task. We separately investigated the effects of the posterior alpha rhythm's power and phase on activity related to task-relevant stimulus processing and also investigated higher-level decision-related processing. We found stronger decision-related BOLD activity in areas late in the processing stream when subjects were in the high alpha power state prior to stimulus onset, but did not detect any effect in primary sensory regions. Our phase analysis revealed correlates in the bilateral thalamus, providing support for a thalamo-cortical loop in attentional modulations and suggesting that the cortical alpha rhythm acts as a cyclic modulator of task-related responses very early in the processing stream. Our results help to reconcile the competing inhibition and active-processing hypotheses for ongoing alpha oscillations and begin to tease apart the distinct roles and mechanisms underlying their power and phase.

Simultaneous EEG-fMRI reveals temporal evolution of coupling between supramodal cortical attention networks and the brainstem.

Cortical and subcortical networks have been identified that are commonly associated with attention and task engagement, along with theories regarding their functional interaction. However, a link between these systems has not yet been demonstrated in healthy humans, primarily because of data acquisition and analysis limitations. We recorded simultaneous EEG-fMRI while subjects performed auditory and visual oddball tasks and used these data to investigate the BOLD correlates of single-trial EEG variability at latencies spanning the trial. We focused on variability along task-relevant dimensions in the EEG for identical stimuli and then combined auditory and visual data at the subject level to spatially and temporally localize brain regions involved in endogenous attentional modulations. Specifically, we found that anterior cingulate cortex (ACC) correlates strongly with both early and late EEG components, whereas brainstem, right middle frontal gyrus (rMFG), and right orbitofrontal cortex (rOFC) correlate significantly only with late components. By orthogonalizing with respect to event-related activity, we found that variability in insula and temporoparietal junction is reflected in reaction time variability, rOFC and brainstem correlate with residual EEG variability, and ACC and rMFG are significantly correlated with both. To investigate interactions between these correlates of temporally specific EEG variability, we performed dynamic causal modeling (DCM) on the fMRI data. We found strong evidence for reciprocal effective connections between the brainstem and cortical regions. Our results support the adaptive gain theory of locus ceruleus-norepinephrine (LC-NE) function and the proposed functional relationship between the LC-NE system, right-hemisphere ventral attention network, and P300 EEG response.

Simultaneous EEG-fMRI reveals a temporal cascade of task-related and default-mode activations during a simple target detection task.

Focused attention continuously and inevitably fluctuates, and to completely understand the mechanisms responsible for these modulations it is necessary to localize the brain regions involved. During a simple visual oddball task, neural responses measured by electroencephalography (EEG) modulate primarily with attention, but source localization of the correlates is a challenge. In this study we use single-trial analysis of simultaneously-acquired scalp EEG and functional magnetic resonance image (fMRI) data to investigate the blood oxygen level dependent (BOLD) correlates of modulations in task-related attention, and we unravel the temporal cascade of these transient activations. We hypothesize that activity in brain regions associated with various task-related cognitive processes modulates with attention, and that their involvements occur transiently in a specific order. We analyze the fMRI BOLD signal by first regressing out the variance linked to observed stimulus and behavioral events. We then correlate the residual variance with the trial-to-trial variation of EEG discriminating components for identical stimuli, estimated at a sequence of times during a trial. Post-stimulus and early in the trial, we find activations in right-lateralized frontal regions and lateral occipital cortex, areas that are often linked to task-dependent processes, such as attentional orienting, and decision certainty. After the behavioral response we see correlates in areas often associated with the default-mode network and introspective processing, including precuneus, angular gyri, and posterior cingulate cortex. Our results demonstrate that during simple tasks both task-dependent and default-mode networks are transiently engaged, with a distinct temporal ordering and millisecond timescale.

The path of a click stimulus from ear canal to umbo.

The tympanic membrane (TM) has a key role in transmitting sounds to the inner ear, but a concise description of how the TM performs this function remains elusive. This paper probes TM operation by applying a free field click stimulus to the gerbil ear and exploring the consequent motions of the TM and umbo. Motions of the TM were measured both on radial tracks starting close to the umbo and on a grid distal and adjacent to the umbo. The experimental results confirmed the high fidelity of sound transmission from the ear canal to the umbo. A delay of 5-15 µs was seen in the onset of TM motion between points just adjacent to the umbo and mid-radial points. The TM responded with a ringing motion, with different locations possessing different primary ringing frequencies. A simple analytic model from the literature, treating the TM as a string, was used to explore the experimental results. The click-based experiments and analysis led to the following description of TM operation: A transient sound pressure on the TM causes a transient initial TM motion that is maximal âˆ¼ at the TM's radial midpoints. Mechanical forces generated by this initial prominent TM distortion then pull the umbo inward, leading to a delayed umbo response. The initial TM deformation also gives rise to prolonged mechanical ringing on the TM that does not result in significant umbo motion, likely due to destructive interference from the range of ringing frequencies. Thus, the umbo's response is a high-fidelity representation of the transient stimulus. Because any sound can be considered as a consecutive series of clicks, this description is applicable to any sound stimulus.

Effect of long-term osmotic loading culture on matrix synthesis from intervertebral disc cells.

The intervertebral disc is a highly hydrated tissue that acts to absorb and distribute large complex loads placed on the spine. Diurnal loading and disc degeneration causes significant changes in water volume and proteoglycan content, which alters the internal osmotic environment. Short-term osmotic loading alters disc cell gene expression; however, the long-term effect of osmotic loading on disc cell matrix synthesis is not well understood. The objective of this study was to determine the effect of long-term osmotic loading on matrix turnover and proliferation by juvenile and adult cells from the nucleus pulposus (NP) and the cartilaginous endplate (EP). Matrix synthesis was evaluated using pellets and a 3D agarose system, which has been used for developing engineered tissues. Intervertebral discs were acquired from juvenile and adult cows. Cells were acquired through enzymatic digestion and expanded in culture. Pellets were formed through centrifugation, and constructs were created by encapsulating cells within 2% w/v agarose hydrogel. Pellets and constructs were cultured up to 42 days in chemically defined medium with the osmolality adjusted to 300, 400, or 500 mOsm/kg. EP cells were evaluated as a chondrocyte comparison to chondrocyte-like NP cells. Pellet and agarose cultures of juvenile NP and EP cells demonstrated similarities with respect to cell proliferation and functional mechanical properties. Cell proliferation decreased significantly with increased osmotic loading. The final compressive Young's modulus of juvenile NP cells was 10-40× greater than initial properties (i.e., day 0) and was greater than the final Young's modulus of adult NP and juvenile EP constructs. In juvenile NP constructs, there were no significant differences in GAG content with respect to osmotic loading. However, GAG synthesis and mechanical properties were greatest for the 400 mOsm/kg group in adult NP constructs. Taken together, the results presented here suggest a tradeoff between cell proliferation and matrix production under osmotic loading conditions. In conclusion, culturing disc cells in an osmotic environment that best mimics the healthy disc environment (400 mOsm/kg) may be ideal for balancing cell proliferation, matrix production, and mechanical properties of engineered disc tissues.