Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n = 8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70–250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2–5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands.
Attention, a critical component of perception and goal-directed behavior, allows the brain to allocate its limited resources depending on current task demands. A number of areas located in frontal and posterior parietal cortex (PPC), often referred to collectively as the fronto-parietal attention network, are crucial for controlling the attentional selection process in both humans and non-human primates [1]–[5]. These areas include the intraparietal sulcus (IPS) and superior parietal lobule (SPL) in PPC as well as portions of superior-lateral precentral cortex, also known as the frontal eye fields (FEF), and dorsal medial frontal cortex, also known as the supplementary eye field (SEF) [1], [4]. In the human brain, the temporal-parietal junction (TPJ) and portions of the inferior, middle, and superior frontal gyri are also involved during attentional allocation [1]. Attentional control is often investigated in these regions using functional magnetic resonance imaging (fMRI) methods (i. e. , investigating BOLD time courses in each region) or electrophysiological methods (single-unit, multi-unit, or local field potential [LFP] recordings in macaques or with electroencephalography [EEG] in humans). fMRI has excellent spatial resolution and can identify functionally active networks, but is constrained by the low temporal resolution of the blood-oxygen-level dependent (BOLD) signal. Electrophysiological recordings in monkeys provide excellent temporal resolution, but cannot easily be used to simultaneously investigate an entire network of areas. Scalp EEG studies (see [6], [7] for reviews) have provided important insights into the understanding of attention, but EEG has spatial limitations due to the inverse problem. A handful of studies have attempted to solve the inverse problem using EEG or magnetoencephalography (MEG) combined with source localization techniques to investigate the spatial attention network in greater detail [8], [9], but relatively little knowledge exists about how fronto-parietal areas support attentional behavior on a fine spatiotemporal scale in the human brain. Populations of neurons oscillate together and synchronize their firing and post-synaptic potentials in a rhythmic fashion [10]. These oscillations emerge in multiple frequency bands: delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), and low gamma (30–60 Hz). It is also possible to capture neuronal activity by sampling power fluctuations in a broadband high-frequency range, known as high gamma (HG; 60–250 Hz), as studies have shown that HG activity correlates with local spiking activity [11], [12]. Interactions within or between these bands and/or broadband HG have been proposed to serve as mechanisms for coordination within and between brain networks engaged in cognitive processing [13]–[15]. Phase-amplitude cross-frequency coupling (PAC) is a mechanism that has been proposed to coordinate the timing of neuronal firing within local neural networks (see [16] for a review). PAC, the statistical dependence between the phase of a low-frequency rhythm and the amplitude (or power) of the high-frequency component of electrical brain activity, is proposed to operate through a physiologically plausible mechanism: low-frequency phase controls neuronal excitability through fluctuations in membrane potentials, while increases in high-frequency power reflect increases in local neuronal spiking activity [11], [12]. Previous studies have demonstrated that the probability of neuronal spiking changes with the phase of the lower frequency rhythm and can define time windows during which neurons are more or less likely to fire [16]–[18]. Thus, it has been hypothesized that these lower-frequency oscillations (i. e. , in the delta, theta, alpha, or beta bands) coordinate information among areas by modulating the excitability within local neuronal ensembles [14], [17], [18]. Canolty and colleagues [19] first demonstrated that the phase of the ongoing theta oscillation is coupled to increases in HG (>70 Hz) power across a range of motor and language tasks in humans. PAC has since been reported between numerous different frequency bands within human cortex and subcortical structures [20]–[23]. To our knowledge, no study to date has investigated if PAC may serve as a mechanism for visuospatial attention control within human fronto-parietal cortex. We measured the neural dynamics and frequency-band interactions within regions of the human fronto-parietal attention network during allocation of spatial attention using a dynamic spatial-cuing task [24]. We collected electrocorticography (ECoG) recordings, measured directly from subdural electrode arrays implanted in patients undergoing intracranial monitoring for localization of epileptic foci, in order to examine the role of PAC as a mechanism for coordination within the fronto-parietal network, which adjusts parameters on a millisecond basis depending on momentary attentional demands.
To determine which electrodes were responsive to spatial attention, we first investigated changes in power across a wide range of frequencies in response to attentional allocation to either the contralateral or the ipsilateral visual field (i. e. , the visual field contralateral or ipsilateral to the implanted hemisphere). In a number of electrodes (263 out of 875 electrodes; 30. 06%) across eight subjects, we found significant increases in broadband HG power (70–250 Hz; all p<0. 05, corrected) that were time-locked to trial onset (following each cue). HG power remained elevated throughout the period when subjects were allocating their spatial attention in wait for the target appearance (0–1000 ms post-trial onset). These HG power increases were observed in electrodes covering PPC, lateral, and medial frontal cortex, occipital cortex, and posterior ventral temporal cortex (see Figure 2 for event-related spectral perturbations [ERSPs] and vertically stacked single-trial HG traces in two example electrodes across two separate subjects [S4, S7]). A subset of these electrodes (47 of 263; 17. 87%; in seven subjects) exhibited greater HG power increases when subjects allocated attention to the contralateral than to the ipsilateral visual field (all p<0. 05, corrected). In comparison, only three out of 263 electrodes (1. 14%; in one subject) exhibited greater HG power increases when subjects allocated attention to the ipsilateral than to the contralateral visual field (all p<0. 05, corrected). Increases in HG power were sometimes accompanied by power increases in lower frequencies (delta/theta: 2–5 Hz, all p<0. 05, corrected; Figure 2a) and sometimes not (Figure 2b). 59. 32% (156 of 263; in eight subjects) of the electrodes with significant HG power increases also had significant power increases in this lower frequency range. Of the 156 electrodes with significant delta/theta power increases, 17 (10. 90%) overlapped with the set of 47 electrodes that showed visual field-dependent attentional increases in HG power. A number of electrodes (119 out of 875 electrodes; 13. 60%; in eight subjects) also exhibited significant decreases in alpha and beta power (10–30 Hz; all p<0. 05, corrected) compared to baseline. This alpha and beta suppression was sustained for 500 ms (e. g. , Figure 2a) to 1000 ms or longer (e. g. , Figure 2b) following trial onset. All electrodes with sustained alpha/beta suppression were located either in parietal or visual cortex. A subset of these electrodes (21 of 119; 17. 65%; in seven subjects) exhibited larger decreases in alpha/beta power when subjects allocated attention to the contralateral than to the ipsilateral visual field (all p<0. 05, corrected). In comparison, 2 out of 119 electrodes (1. 68%; in one subject) exhibited larger decreases in alpha/beta power when subjects allocated attention to the ipsilateral than to the contralateral visual field (all p<0. 05, corrected). These results are consistent with the notion that decreases in alpha power, which are strongest in the hemisphere contralateral to a stimulus, represent a release from functional inhibition within the visual system [26]. Taken together, the results suggest that power increases in broadband HG and the delta/theta bands, as well as power decreases in the alpha/beta bands, track the allocation of visuospatial attention in human frontal, posterior parietal, and visual cortex. Because previous studies have demonstrated that frequency bands can interact in behaviorally meaningful ways [19], [27], we assessed whether any relationships existed among the different frequency bands (delta, theta, HG) during attentional allocation. We examined PAC between a wide range of frequencies for phase data (2–20 Hz) and for amplitude data (5–250 Hz) (Figure 3a, b) in all of the electrodes that had significant increases in HG power (70–250 Hz) following attentional allocation compared to baseline. In many of these electrodes (123 of 273; 45. 05%; in eight subjects), we found significant coupling between the phase of the delta/theta signal (2–5 Hz) and HG amplitude (80–250 Hz) during attention to the cued visual field while awaiting target appearance (0–1000 ms post-trial onset). The coupling values averaged across all attention trials, as measured by the phase-locking value (PLV), ranged between 0. 16 and 0. 57 for all electrodes showing this significant PAC. We observed delta/theta phase-HG amplitude coupling in electrodes over PPC, especially those surrounding the IPS, lateral and medial frontal cortex, occipital cortex, and posterior ventral temporal cortex (see Figure 3 for examples from three individual subjects (S3–S5) and Figure S1 for the group results plotted on the Montreal Neurological Institute [MNI] brain). Furthermore, this PAC remained significant after controlling for eye movements (S8 was eye-tracked during recording and all trials during which a saccade of 0. 50° or larger was made were excluded from further analyses; see Materials and Methods for details). Although a higher percentage of RH electrodes (51. 56%; 66 out of 128) exhibited significant delta/theta-HG PAC during attentional allocation than LH electrodes (39. 31%; 57 out of 145), this difference was not significant between hemispheres (U = 3. 00, p>0. 20). However, interhemispheric differences in electrode coverage and density preclude a strong conclusion regarding left vs. right differences. Many of the electrodes with significant delta/theta-HG PAC (55 of 123; 44. 71%; in seven subjects) had significantly higher coupling when subjects were attending to the contralateral, as compared to the ipsilateral, visual field (all p<0. 01, corrected). Figure 3a, b shows examples of four electrodes (two surrounding IPS and two over lateral frontal cortex) that have higher PAC in contralateral than in ipsilateral trials. Eighteen of the 55 electrodes with higher PAC in contralateral than in ipsilateral trials also had higher HG power in contralateral than in ipsilateral trials. Although the magnitude of the PAC decreased when subjects attended ipsilaterally, it did not disappear completely, which is likely due to the bilateral receptive field properties of the neuronal populations over which we recorded [28]. None of the electrodes exhibited higher PAC when subjects allocated attention to the ipsilateral than to the contralateral visual field (all p>0. 10, corrected). Because power increases, and thus the signal-to-noise ratio, can affect PLVs [29], we compared the magnitudes of delta/theta power between attend contralateral and attend ipsilateral trials during the same time period analyzed above. Out of the 55 electrodes in which higher PAC was present when subjects attended contralaterally than when they attended ipsilaterally, only two electrodes in one subject had significantly higher delta/theta power in attend contralateral than attend ipsilateral trials (p<0. 05, corrected). Thus, power differences between conditions cannot account for the PAC differences that we observed between these same conditions. To address the possibility that the observed PAC was being driven by an event-related potential (ERP) at trial onset, we repeated the analyses using only the longer trials (i. e. , target appearance 1500–2000 ms after trial onset). Only the last 1000 ms prior to the target onset were analyzed, so the first 500 ms, when the ERP was generated, was excluded from every trial. This analysis produced similar PAC results: 107 of 273 electrodes (39. 19%; in eight subjects) had significant coupling between delta/theta phase and HG amplitude (Figure S2). All 107 of these electrodes were in the original set of 123 electrodes showing significant delta/theta-HG PAC. This demonstrates that the observed PAC was sustained throughout the trial, rather than driven by a single cycle created by a transient ERP. Additionally, a number of these electrodes maintained significantly higher delta/theta-HG PAC (42 of 123; 34. 15%; in seven subjects) when subjects were attending to the contralateral, as compared to the ipsilateral, visual field (all p<0. 01, corrected) and none of these electrodes showed significant delta/theta power differences between attend contralateral and attend ipsilateral trials (all p>0. 10, corrected), further demonstrating that the observed laterality effects were not solely driven by transient ERPs. We next examined to which part of the delta/theta phase signal the HG amplitude was locking by calculating the trough-locked spectrogram for each electrode with significant delta/theta phase-HG amplitude coupling. In a large percentage of electrodes (117 of 123; 95. 12%; in eight subjects), the HG power was locked to the trough of the delta/theta signal (see Figure 3c for an example from one electrode in S4). Our results are in agreement with previous studies that found HG locks to the trough of the theta signal [19], [27]. Furthermore, this trough-locking of the HG power was significant for at least three phase cycles of the delta/theta signal (∼600–1500 ms; see Figure 3c for example of three cycles), providing additional evidence that the observed PAC was not solely driven by ERPs. Critically, changes in delta/theta phase-HG amplitude coupling were correlated with attentional behavior. Twenty-eight of the 123 electrodes with significant delta/theta-HG PAC also demonstrated significant correlations of PAC with behavior across trials, in which faster RTs were associated with stronger delta/theta-HG coupling, and slower RTs with weaker delta/theta-HG coupling, during the attentional delay period (examples from two subjects, S3 and S5, are shown in Figure 4). The electrodes with significant PAC-behavioral correlations were dispersed throughout frontal (42. 86%), parietal (32. 14%), and visual cortex (25. 00%) across seven subjects. Only the PAC values from trials when subjects attended to the visual field contralateral to electrode implantation correlated with behavior (all p<0. 05, corrected; Figure 4, S3: r (41) = −0. 51, p<0. 01, corrected; S5: r (47) = −0. 37, p<0. 05, corrected), whereas the PAC values from trials when subjects attended to the ipsilateral visual field did not reach significance in any of the electrodes (all p>0. 10, corrected; Figure 4, S3: r (40) = −0. 11, p>0. 6, corrected; S5: r (47) = −0. 10, p>0. 7, corrected). RTs also did not significantly correlate with mean amplitude of the delta/theta signal (all p>0. 05, corrected) or with mean amplitude of the HG signal (all p>0. 10, corrected) across the same time period for either attentional condition in any of these electrodes, suggesting that amplitude changes alone are not driving the results. These findings provide evidence that momentary changes in the strength of delta/theta-HG PAC predict attentional behavior in humans. We next examined the relationship between visually evoked ERPs and delta/theta-HG PAC in electrodes across frontal, parietal, and visual cortex, as previous studies have suggested a complex relationship between ERPs and the broadband HG response over visual cortex [30]. We found ERP responses time-locked to the beginning of each trial in 77 of 875 electrodes (8. 80%; in eight subjects) and time-locked to the target onset of each trial in 29 electrodes (3. 31%; in seven subjects). Each of these ERP responses consisted of the classic visual P1-N1 complex and subsequent P3b [31]–[34]. The P1, N1, and P3b components peaked around 100 ms, 200 ms, and 300 ms post-trial onset, respectively, which is consistent with previous reports of visual responses from ECoG recordings [35], [36]. Figure 5 provides an example of the visual ERPs averaged across trials (attended/cued vs. unattended/uncued; Figure 5a, top) and single-trial ERPs (attended trials only; Figure 5a, bottom) time-locked to trial onset (Figure 5a, left) and target onset (Figure 5a, right) from one electrode in a single subject (S8). The majority of electrodes with visually evoked ERP responses were located over visual cortex and PPC (Figure 6 depicts the electrodes with significant delta/theta-HG PAC [circled in red], ERP responses [circled in black], or both [circled in yellow] for each subject). Thirty-four electrodes across the group of eight patients had both ERP responses at trial onset and significant delta/theta-HG PAC (Figure 6, electrodes circled in yellow). Thus, 44. 16% (34/77) of electrodes with an ERP response also had significant increases in delta/theta-HG PAC, while 27. 64% (34/123) of electrodes with significant increases in delta/theta-HG PAC also had an ERP response. Electrodes with a visually evoked ERP time-locked to trial onset were more likely to also have significant PAC throughout the attentional allocation period, while electrodes with significant PAC throughout the attentional allocation period were not as likely to be accompanied by ERP responses at trial onset. The small percentage of parietal and extrastriate electrodes with both an ERP and significant delta/theta-HG PAC throughout the attentional allocation period provides further evidence that the PAC results were not solely driven by trial onset ERPs. Next, we averaged the signals from all electrodes that exhibited individual ERPs at trial onset (n = 77) and target onset (n = 29). There were no significant differences between the attended and unattended conditions in the P1, N1, or P3b components of the ERP time-locked to trial onset across the group (all p>0. 10, corrected; Figure 5b, top left). The P1 and N1 components of the ERP time-locked to target onset were not significantly different between the attended and unattended conditions across the group, although attended trials evoked a marginally significantly higher P1 than unattended trials (all p>0. 05, corrected; Figure 5b, top right). However, the P3b amplitude was significantly higher in the attended condition than the unattended condition 280–580 ms following target appearance (all p<0. 05, corrected; Figure 5b, top right, blue shaded area), which is consistent with previous studies [31], [34]. The individual electrode example reflects the group results (Figure 5a, top right). These results suggest that the ERPs generated at trial onset were due to the onset of the display, and did not differentiate between stimulus conditions, while the target responses were modulated by spatial attention. We next examined the ERPs from the same conditions (attended/cued vs. unattended/uncued, time-locked to trial and target onsets) averaged across all of the electrodes with significant delta/theta-HG PAC (n = 123; Figure 5b, bottom). These ERPs were diminished (in the case of the trial onset ERP) or nearly absent (in the case of the target onset ERP). The lack of an ERP at target onset in these electrodes suggests that the significant increases in delta/theta-HG PAC are not always accompanied by the presence of a visually evoked ERP, indicating that the target onset ERP does not contribute to the observed PAC increases in the pre-target interval. We also examined separate ERP responses for trials when attention was directed to either the contralateral or ipsilateral visual field averaged across all electrodes that exhibited individual trial-locked (n = 77) or stimulus-locked (n = 29) ERPs. Again, there were no significant differences between the contralateral and ipsilateral attentional conditions for any of the ERP components time-locked to trial onset (all p>0. 05, corrected; Figure 7, left), while N1 and P3b amplitudes were enhanced when the attended target appeared in the contralateral visual field in comparison to when it appeared in the ipsilateral visual field (all p<0. 05, corrected; Figure 7, right). These results are consistent with previous studies showing enhanced N1 and P3 amplitudes following allocation of spatial attention to the contralateral visual field [33], [34] and provide electrophysiological evidence that subjects were allocating spatial attention during the task. Taken together, these results suggest that the relationship between the visually evoked ERPs that are generated over PPC and visual cortex and the observed increases in PAC over these same areas is complex. Many electrodes had significant PAC without an ERP and vice versa, providing evidence that PAC and ERPs result from distinct cortical mechanisms, with ERPs reflecting post-synaptic potentials and HG power reflecting neuronal firing rates and the synaptic currents induced by this firing [12], [37].
We used ECoG recordings in humans to provide insight into the neural mechanisms supporting visual attention. We found increases in broadband HG power (70–250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. Attention modulated broadband HG power in two distinct patterns. First, ∼20% of these electrodes exhibited visual field-dependent attentional increases in HG (stronger in the contralateral than ipsilateral visual field), which is consistent with visual field-dependent attentional increases in single-unit activity observed in primates [2], [3]. Second, the remaining electrodes exhibited task-dependent HG increases that were independent of attended visual field, which is consistent with the broadly tuned, bilateral receptive field properties of the neurons over which we recorded [28]. The phase of the ongoing delta/theta (2–5 Hz) oscillation modulated these HG power changes during attentional allocation and, importantly, the strength of the delta/theta phase-HG amplitude coupling predicted RTs to detected targets on a trial-by-trial basis. The current study provides evidence that coupling between HG amplitude and the phase of the delta/theta signal serves as a mechanism to facilitate processing within frontal, parietal, and visual areas during allocation of visuospatial attention. Based upon evidence from animal neurophysiology, we hypothesize that the PAC identified in the current study may serve to coordinate spiking activity in local regions of the network [38]. Phase coherence, in comparison, has been hypothesized as a potential mechanism through which distant brain areas are engaged across task-relevant networks. This synchronization of neuronal oscillations between areas may provide a mechanism for attentional selection of relevant sensory stimuli [14]. Numerous studies in humans and macaque monkeys have reported coherence increases across a wide range of band-limited frequencies, including delta, theta, alpha, beta, and low gamma, within and between frontal, parietal, and visual cortex during visual attentional allocation [6], [7], [9], [23], [39]–[46]. Thus, we hypothesize delta/theta-HG PAC increases that we observe in local regions of the fronto-parietal attention network may be modulated by neural synchrony across the network using one or more of these frequency bands [47], perhaps through a series of nested oscillations [48]. Our results are compatible with those reported by Lakatos and colleagues [43], who investigated PAC in V1 while monkeys were trained to attend to either visual or auditory stimuli presented in a rhythmic stream. They found that neural activity entrained to the stimulus rhythm (1. 55 Hz) and that the amplitude of the multi-unit responses, and LFPs were systemically related to the phase of this delta oscillation during attention to both modalities. A study using a similar rhythmic attentional paradigm found coupling between delta phase (1–3 Hz) and alpha amplitude in human auditory cortex using ECoG, but amplitudes at higher frequencies were not significantly coupled to delta phase [23]. Several recent studies have also reported increases in coupling between gamma power and alpha phase in visual areas V4 and TEO while monkeys performed a flanker task [46], and between broadband HG power and beta phase over occipital cortex while humans performed a visual search task with free viewing [30]. A number of factors may contribute to differences in the observed results among the aforementioned studies. First, it is not clear whether attention operates using a mechanism at similar frequencies across modalities. For instance, oscillatory mechanisms underlying auditory attention (i. e. , [23]) might be different from those underlying visual attention. Second, it is not clear whether PAC would operate at similar frequencies over fronto-parietal and visual cortex in the monkey and the human during attentional allocation. Although gamma oscillations are associated with attentive aspects of visual processing in monkey [39], [40] and human [49]–[51] cortex, considerably less evidence exists to support functional similarities among lower frequency oscillations between species. Given the size difference between the monkey and the human brain, interactions within and between lower frequency bands may differ between species. Third, each of these studies investigated attention using different types of tasks (detection vs. flanker vs. spatial cuing) and different trial structures. Many previous studies were not designed to investigate lower-frequency rhythms (i. e. , 2–5 Hz), since the cue-target time (the attentional allocation period) was not sufficiently long enough to include 2–3 cycles. We purposely designed our experiment with a long interval between cue and target, so that we could investigate effects at lower frequencies. Furthermore, some experiments have investigated synchronization and PAC using entrainment to rhythmically presented stimuli [23], [43], [45] or using a fixed interval [30], while others, including the current study, have used temporally jittered target presentations. Thus, many of the previous studies have focused on how networks can be entrained by the cadence of a task, whereas the slower rhythms that we report here appear to be endogenous and are most likely determined by the local neurophysiology. It was previously suggested that lower-frequency oscillations might be suppressed when attention is utilized to detect unpredictable target appearances, since this requires a mode of operation with continuously high excitability and vigilance [52]. The results from the current study suggest that this is not the case; lower-frequency oscillations are utilized for sensory processing and attentional control, even in the absence of any obvious task-relevant temporal structure. Finally, the recording locations are different between studies. Most of these studies have investigated neuronal oscillations over sensory cortex during attentional allocation. The current study investigates how frontal and parietal association cortices utilize PAC during attentional allocation in the human brain. In summary, it is evident based upon these studies, that no single frequency band is solely responsible for attentional processes, in accord with the notion that attention is not a unitary function [53]. ERP responses at trial or target onset cannot explain these PAC results. First, there were few electrodes that had both visually evoked ERPs time-locked to trial onset and increases in delta/theta-HG PAC during the attentional allocation period (Figure 6). Many of the electrodes that were responsive to the Starry Night Test showed independent ERP responses or PAC increases. This suggests that ERPs and PAC convey different types of informational content and are dependent upon distinct underlying cortical dynamics. These results support previous studies that have reported a separation between ERPs, broadband HG, and PAC across multiple cortical regions [30], [54], [55]. Secondly, we did not observe any systematic signal changes immediately preceding target appearance in the single trial ERPs (Figure 5a) or in the average ERPs, in any electrode. Thus, it is unlikely that ERPs at target onset were responsible for the observed PAC increases in the pre-target interval. Lastly, delta/theta-HG PAC remained significantly elevated in nearly all electrodes after eliminating the initial 500 ms (when the ERP was generated) from the longest (>1500 ms) trials (Figure S2). Together, these results suggest that the observed increases in delta/theta-HG PAC are due to the allocation of visuospatial attention, rather than an artifact of analysis procedures. A recent study in macaque monkeys reported that microsaccades occur at a frequency of ∼3. 3 Hz and are followed by characteristic increases and decreases in gamma band synchronization [56]. We cannot completely rule out the possibility that the increases in delta/theta-HG PAC were a result of microsaccadic activity, since our eye-tracker did not have sufficient sensitivity to measure microsaccades and hospital protocols did not allow patient head stabilization in the epilepsy ICU environment. We think this case is unlikely, since microsaccades induce bilateral cortical effects [57], while many of the electrodes exhibited strongly lateralized increases in delta/theta-HG PAC. Furthermore, microsaccades were shown to modulate spike-field coherence at lower gamma frequencies, 40–60 Hz [56], while our PAC results were strongest above 70 Hz. Microsaccades are present during most tasks that require sustained fixation [58] and several studies have indicated a close relationship between microsaccades and shifts in visuospatial attention [59], [60]. Several recent studies have provided behavioral evidence that attentional switching occurs between visual field locations or objects at ∼4 Hz rhythm [61], [62]. We propose that delta/theta-HG PAC may reflect an underlying neural mechanism that regulates the timing of such rhythmic sampling across the visual field or across objects. The current study demonstrates a functional relationship between PAC and behavioral performance in the SNT: the strength of delta/theta phase-HG amplitude coupling predicted RTs on a trial-by-trial basis, wherein high PAC predicted faster RTs and low PAC predicted slower RTs during attentional allocation. Similar coupling between theta phase and gamma amplitude has been tied to learning in the rodent hippocampus [63]: the strength of theta-gamma PAC increases as a rodent' s performance increases, both plateauing together, over time. These studies are important, since they provide evidence that PAC serves a functional role in the brain. The current study demonstrates that delta/theta phase-HG amplitude coupling also serves a functional role by indexing the overall level of engagement within human frontal and parietal cortex during the allocation of visuospatial attention.
Eight subjects (S1–S8), undergoing pre-surgical epilepsy evaluation, provided written and oral informed consent to participate in the study. The institutional review board of each institution approved the research that was conducted at each respective location. Anti-epileptic medications were discontinued for 2–3 days beforehand, and patients were seizure free for at least five hours before testing. Subjects had normal or corrected-to-normal vision. Subjects were implanted with 74–128 electrodes (1 cm spacing; grids and strips), covering extensive portions of lateral and medial frontal, parietal, occipital, and temporal cortex in the RH and LH (see Figure 1a for overlap of electrodes from all subjects and Table 1 for specific coverage information for each subject). Visual displays were generated on a Dell Precision M4600 laptop (Dell, Inc.) using EPrime software (Psychology Software Tools, Inc.). Subjects were seated 50–60 cm from the computer screen. Electrophysiological and the peripheral (photodiode) channels were acquired using a 128-channel Stellate Harmonie recording system (Natus Medical, Inc. ; 1000 Hz digitization) at Johns Hopkins, a 128-channel Nihon Kohden recording system (Nihon Kohden Corporation; 1000 Hz digitization) at Children' s Hospital, and 128-channel Tucker Davis Technologies recording system at Stanford (3052 Hz digitization). Data were recorded using a subdural electrode reference and a scalp ground. Postoperative computed tomography (CT) scans were aligned to the preoperative MRI anatomical brain volume [64]. Electrodes were visualized on the 3D cortical surface using MATLAB (MathWorks, Inc. ; Figures 2–5). Brains and electrodes were transformed into MNI space across subjects (Figure 1a, Figure S1). A neurologist manually inspected all ECoG channels to identify those with interictal or ictal epileptiform activity and artifacts. Channels and epochs contaminated by epileptiform activity or abnormal signal (e. g. , poor contact, excess drift, high frequency noise) and those located over tissue that was later resected were removed from analysis. Data processing used custom functions written in MATLAB and the EEGLAB toolbox [65]. Raw, continuous data were filtered with a 60 Hz notch filter and re-referenced to a common average reference (mean of remaining channels). Single channels of this ECoG data are referred to as “raw signal. ” Trials were classified based upon attention condition (attended target in cued visual field; or unattended target appearing in the uncued visual field). Contralateral and ipsilateral attention conditions refer to the cued visual field with respect to the implanted ECoG electrodes. All trials were designated by response type (hits, misses, correct rejections, and false alarms). Correctly attended trials were designated hits and correctly unattended trials were designated rejections.
The frontal and parietal areas of the cortex control the ability to focus visuospatial attention, and damage to these areas results in profound attentional disturbances. Although much research has concentrated on where these areas are located, little is known about how these areas may function in humans. Previous studies have demonstrated that neuronal spiking is more likely to occur in specific time windows based upon the phase of lower frequency neural oscillations – rhythmic or repetitive neuronal activity. These low-frequency rhythms are hypothesized to coordinate the timing of neuronal firing within local and across network regions. Here, we investigated how human frontal and parietal cortices use neural oscillations to control visuospatial attention. We identified a high-frequency component of electrical brain activity, broadband high gamma (70–250 Hz) amplitude, that became phase-locked to a slower rhythm, delta/theta (2–5 Hz), over frontal, parietal, and visual areas while the study subjects paid attention to the peripheral visual field. Changes in the strength of the coupling between delta/theta phase and high gamma amplitude predicted the attentional behavior of the subjects across single trials. From these results, we conclude that coupling between delta/theta phase and high gamma amplitude serves to coordinate information within – and perhaps between – frontal and parietal areas during allocation of visuospatial attention.
cognitive neuroscience
cognitive psychology
neural networks
biology and life sciences
vision
brain electrophysiology
evoked potentials
sensory perception
cognitive science
neuroscience
neurophysiology
attention
Dynamic Changes in Phase-Amplitude Coupling Facilitate Spatial Attention Control in Fronto-Parietal Cortex