A Functional and Structural Investigation of the Human Fronto-Basal Volitional Saccade Network

Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF): a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF) were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of monkey studies favoring the caudate nucleus over the putamen in the search for oculomotor functions

The functional role of alpha-band activity in attentional processing: the current zeitgeist and future outlook

Electrophysiological activity measured at the scalp surface using electroencephalography or magnetoencephalography (EEG or MEG)contains prominent ongoing rhythmic activity across a mixture of different frequency bands. This rhythmic oscillatory activity is present during both rest and task performance. The most visible rhythm in the adult human brain is in the band between approximately 8–12 Hz, and is referred to as alpha activity. While sometimes dismissed by neurophysiologists as a nuisance biological artefact, since it often interferes with the recording of event-related potentials (ERPs), there has been an explosion of research linking it to specific functional roles in cognition and behavior over the past two decades. Here, we review some of the research into the functional significance of alpha oscillations with respect to attention and expectation. We focus our discussion on how the amplitude and phase of alpha activity might be involved in the prioritization of relevant sensory input. In addition to summarizing the literature, we also endeavor to provide a critical appraisal as well as highlight limitations and conceptual gaps in the field

Attention and temporal expectations modulate power, not phase, of ongoing alpha oscillations

The perception of near-threshold visual stimuli has been shown to depend in part on the phase (i.e., time in the cycle) of ongoing alpha (8-13 Hz) oscillations in the visual cortex relative to the onset of that stimulus. However, it is currently unknown whether the phase of the ongoing alpha activity can be manipulated by top-down factors such as attention or expectancy. Using three variants of a cross-modal attention paradigm with constant predictable stimulus onsets, we examined if cues signaling to attend to either the visual or the auditory domain influenced the phase of alpha oscillations in the associated sensory cortices. Importantly, intermixed in all three experiments, we included trials without a target to estimate the phase at target presentation without contamination from the early evoked responses. For these blank trials, at the time of expected target and distractor onset, we examined (1) the degree of the uniformity in phase angles across trials, (2) differences in phase angle uniformity compared with a pretarget baseline, and (3) phase angle differences between visual and auditory target conditions. Across all three experiments, we found that, although the cues induced a modulation in alpha power in occipital electrodes, neither the visual condition nor the auditory cue condition induced any significant phase-locking across trials during expected target or distractor presentation. These results suggest that, although alpha power can be modulated by top-down factors such as attention and expectation, the phase of the ongoing alpha oscillation is not under such contro

The Role of Alpha Activity in Spatial and Feature-Based Attention

Modulations in alpha oscillations (∼10 Hz) are typically studied in the context of anticipating upcoming stimuli. Alpha power decreases in sensory regions processing upcoming targets compared to regions processing distracting input, thereby likely facilitating processing of relevant information while suppressing irrelevant. In this electroencephalography study using healthy human volunteers, we examined whether modulations in alpha power also occur after the onset of a bilaterally presented target and distractor. Spatial attention was manipulated through spatial cues and feature-based attention through adjusting the color-similarity of distractors to the target. Consistent with previous studies, we found that informative spatial cues induced a relative decrease of pretarget alpha power at occipital electrodes contralateral to the expected target location. Interestingly, this pattern reemerged relatively late (300-750 ms) after stimulus onset, suggesting that lateralized alpha reflects not only preparatory attention, but also ongoing attentive stimulus processing. Uninformative cues (i.e., conveying no information about the spatial location of the target) resulted in an interaction between spatial attention and feature-based attention in post-target alpha lateralization. When the target was paired with a low-similarity distractor, post-target alpha was lateralized (500-900 ms). Crucially, the lateralization was absent when target selection was ambiguous because the distractor was highly similar to the target. Instead, during this condition, midfrontal theta was increased, indicative of reactive conflict resolution. Behaviorally, the degree of alpha lateralization was negatively correlated with the reaction time distraction cost induced by target-distractor similarity. These results suggest a pivotal role for poststimulus alpha lateralization in protecting sensory processing of target information

ROI activation timecourse.

<p>The average peri-stimulus-time-histograms (PSTHs; BOLD time courses) are shown for several ROIs: the clusters activated for saccades in darkness vs rest in left and right precentral sulcus/premotor cortex (‘lateral and medial FEF’) and the left and right putamen and SEF, and the left and right clusters in the FEF more active for anti as compared to prosaccades (‘antisaccade FEF’). The aforementioned group activation patterns from which the ROIs were taken are depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029517#pone-0029517-g004" target="_blank">figure 4</a>. PSTHs were averaged over voxels in the ROIs and then participants, and aligned at target stimulus onset. Saccade onset typically follows within 300 ms, therefore PSTHs aligned at saccade onset would have been largely identical. Data for the left hemisphere are given in the left panels and data for the right hemisphere in the right panels. In each panel, average PSTHs are presented for pro and antisaccades (gray squares and black circles) to the left and right (solid and dashed lines with open and solid symbols). The unit on the ordinate is global % signal change. The absolute magnitude of this unit is not directly meaningful and should not be compared over regions, as averaging took place over different numbers of voxel per region and within different brain areas. Absolute BOLD measures are known to vary considerably over regions. Differences between conditions within a region can be compared. Except the bilateral putamen, the right ‘lateral FEF’ and left SEF, peak activation in all ROIs was significantly larger for antisaccades as compared to prosaccades (p<0.05). The left SEF exhibited larger responses for antisaccades at trend level, T(12) = 1.59;p = 0.06. Further tests on single timepoints of interest are presented in the text of the results section.</p

Group activation maps.

<p>Overview of group activation patterns (T-maps) for three tasks. The figure was split into panels A and B as combining activation overlays obscured too much detail due to overlap. Panel A at the left shows event related anti vs prosaccade activation in blue and saccades in darkness activation in red. Panel B at the right shows activation for visual stimulation vs rest in green and again for saccades in darkness vs rest in red. Overlap is rendered in yellow. In the upper row of panel A and B group activation is rendered in 3D on top of a high-quality individual (MNI normalized) skull stripped brain, only to indicate the location of activation with respect to the main sulci and gyri. In the right 3D rendering in panels A and B the anterior upper right part of the brain is cut out to show activation in deeper sulci and along the medial wall of the cortex. In the lower rows activation is overlaid on selected 2D slices through the T1 weighted normalized anatomical scan averaged over all participants, providing a more realistic impression of anatomical precision after normalization. Slice MNI coordinates are given for each slice at the upper right hand side (z-coordinate for axial slices, y for coronal and x for sagittal slices). Activation for all renderings is thresholded at T = 3.5, implying that also some stronger trends are displayed for the sake of completeness. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029517#pone-0029517-t001" target="_blank">table 1</a> for an overview of statistics. Slices are displayed in neurological convention (left = left). Labels are indicating regions of interest or sulci. Lateral and medial FEF (frontal eye fields): two foci activated during saccades in darkness vs rest; antisaccade FEF: preferentially activated for antisaccades vs prosaccades (note that FEF label is only used for sake of simplicity; lateral activations are probably not part of the human FEF homologue). SEF: supplementary eye fields; PUT: Putamen; CS: central sulcus; SFS: superior frontal sulcus; CS: central sulcus.</p