Linking tonic and phasic pupil responses to P300 amplitude in an emotional face-word Stroop task.

The locus coeruleus-norepinephrine (LC-NE) system, which regulates arousal levels, is important for cognitive control, including emotional conflict resolution. Additionally, the LC-NE system is implicated in P300 generation. If the P300 is mediated by the LC-NE system, and considering the established correlations between LC activity and pupil dilation, P300 amplitude should correlate with task-evoked (phasic) pupil dilation on a trial-by-trial basis. However, prior studies, predominantly utilizing oddball-type paradigms, have not demonstrated correlations between concurrently recorded task-evoked pupil dilation and P300 responses. Using a recently developed emotional face-word Stroop task that links pupil dilation to the LC-NE system, here, we examined both intra- and inter-individual correlations between task-evoked pupil dilation and P300 amplitude. We found that lower accuracy, slower reaction times, and larger task-evoked pupil dilation were obtained in the incongruent compared to the congruent condition. Furthermore, we observed intra-individual correlations between task-evoked pupil dilation and P300 amplitude, with larger pupil dilation correlating with a greater P300 amplitude. In contrast, pupil dilation did not exhibit consistent correlations with N450 and N170 amplitudes. Baseline (tonic) pupil size also showed correlations with P300 and N170 amplitudes, with smaller pupil size corresponding to larger amplitude. Moreover, inter-individual differences in task-evoked pupil dilation between the congruent and incongruent conditions correlated with differences in reaction time and P300 amplitude, though these effects only approached significance. To summarize, our study provides evidence for a connection between task-evoked pupil dilation and P300 amplitude at the single-trial level, suggesting the involvement of the LC-NE system in P300 generation.

Amplitude modulating frequency overrides carrier frequency in tACS-induced phosphene percept.

The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM-tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20-44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4 Hz) over the mid-occipital and left facial areas. We also examined the phosphene source by adopting a high-density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM-tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM-tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper-left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near-eye electrodermal activity (EDA) measured under the threshold-level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM-tACS-induced phosphene.

Critical role of rhythms in prefrontal transcranial magnetic stimulation for depression: A randomized sham-controlled study.

Repetitive transcranial magnetic stimulation (rTMS) is an alternative treatment for depression, but the neural correlates of the treatment are currently inconclusive, which might be a limit of conventional analytical methods. The present study aimed to investigate the neurophysiological evidence and potential biomarkers for rTMS and intermittent theta burst stimulation (iTBS) treatment. A total of 61 treatment-resistant depression patients were randomly assigned to receive prolonged iTBS (piTBS; N = 19), 10 Hz rTMS (N = 20), or sham stimulation (N = 22). Each participant went through a treatment phase with resting state electroencephalography (EEG) recordings before and after the treatment phase. The aftereffects of stimulation showed that theta-alpha amplitude modulation frequency (fam ) was associated with piTBS_Responder, which involves repetitive bursts delivered in the theta frequency range, whereas alpha carrier frequency (fc ) was related to 10 Hz rTMS, which uses alpha rhythmic stimulation. In addition, theta-alpha amplitude modulation frequency was positively correlated with piTBS antidepressant efficacy, whereas the alpha frequency was not associated with the 10 Hz rTMS clinical outcome. The present study showed that TMS stimulation effects might be lasting, with changes of brain oscillations associated with the delivered frequency. Additionally, theta-alpha amplitude modulation frequency may be as a function of the degree of recovery in TRD with piTBS treatment and also a potential EEG-based predictor of antidepressant efficacy of piTBS in the early treatment stage, that is, first 2 weeks.

Within-cycle instantaneous frequency profiles report oscillatory waveform dynamics.

The nonsinusoidal waveform is emerging as an important feature of neuronal oscillations. However, the role of single-cycle shape dynamics in rapidly unfolding brain activity remains unclear. Here, we develop an analytical framework that isolates oscillatory signals from time series using masked empirical mode decomposition to quantify dynamical changes in the shape of individual cycles (along with amplitude, frequency, and phase) with instantaneous frequency. We show how phase-alignment, a process of projecting cycles into a regularly sampled phase grid space, makes it possible to compare cycles of different durations and shapes. "Normalized shapes" can then be constructed with high temporal detail while accounting for differences in both duration and amplitude. We find that the instantaneous frequency tracks nonsinusoidal shapes in both simulated and real data. Notably, in local field potential recordings of mouse hippocampal CA1, we find that theta oscillations have a stereotyped slow-descending slope in the cycle-wise average yet exhibit high variability on a cycle-by-cycle basis. We show how principal component analysis allows identification of motifs of theta cycle waveform that have distinct associations to cycle amplitude, cycle duration, and animal movement speed. By allowing investigation into oscillation shape at high temporal resolution, this analytical framework will open new lines of inquiry into how neuronal oscillations support moment-by-moment information processing and integration in brain networks.NEW & NOTEWORTHY We propose a novel analysis approach quantifying nonsinusoidal waveform shape. The approach isolates oscillations with empirical mode decomposition before waveform shape is quantified using phase-aligned instantaneous frequency. This characterizes the full shape profile of individual cycles while accounting for between-cycle differences in duration, amplitude, and timing. We validated in simulations before applying to identify a range of data-driven nonsinusoidal shape motifs in hippocampal theta oscillations.

Neurophysiological signatures of hand motor response to dual-transcranial direct current stimulation in subacute stroke: a TMS and MEG study.

BACKGROUND: Dual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influencing responsiveness of dual-tDCS in subacute stroke survivors. METHODS: We conducted a randomized sham-controlled crossover study in 18 survivors with first-ever, unilateral subcortical ischaemic stroke 2-4 weeks after stroke onset and 14 matched healthy controls. Participants had real dual-tDCS (with an ipsilesional [right for controls] M1 anode and a contralesional M1 [left for controls] cathode; 2 mA for 20mins) and sham dual-tDCS on separate days, with concurrent paretic [left for controls] hand exercise. Using transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), we recorded motor evoked potentials (MEPs), the ipsilateral silent period (iSP), short-interval intracortical inhibition, and finger movement-related cortical oscillations before and immediately after tDCS. RESULTS: Stroke survivors had decreased excitability in ipsilesional M1 with a relatively excessive transcallosal inhibition from the contralesional to ipsilesional hemisphere at baseline compared with controls, as quantified by decreased MEPs and increased iSP duration. Dual-tDCS led to increased MEPs and decreased iSP duration in ipsilesional M1. The magnitude of the tDCS-induced MEP increase in stroke survivors was predicted by baseline contralesional-to-ipsilesional transcallosal inhibition (iSP) ratio. Baseline post-movement synchronization in α-band activity in ipsilesional M1 was decreased after stroke compared with controls, and its tDCS-induced increase correlated with upper limb score in stroke survivors. No significant adverse effects were observed during or after dual-tDCS. CONCLUSIONS: Task-concurrent dual-tDCS in subacute stroke can safely and effectively modulate bilateral M1 excitability and inter-hemispheric imbalance and also movement-related α-activity.

Human visual steady-state responses to amplitude-modulated flicker: Latency measurement.

The response latency of steady-state visually evoked potentials (SSVEPs) is a sensitive measurement for investigating visual functioning of the human brain, specifically in visual development and for clinical evaluation. This latency can be measured from the slope of phase versus frequency of responses by using multiple frequencies of stimuli. In an attempt to provide an alternative measurement of this latency, this study utilized an envelope response of SSVEPs elicited by amplitude-modulated visual stimulation and then compared with the envelope of the generating signal, which was recorded simultaneously with the electroencephalography recordings. The advantage of this measurement is that it successfully estimates the response latency based on the physiological envelope in the entire waveform. Results showed the response latency at the occipital lobe (Oz channel) was approximately 104.55 ms for binocular stimulation, 97.14 ms for the dominant eye, and 104.75 ms for the nondominant eye with no significant difference between these stimulations. Importantly, the response latency at frontal channels (125.84 ms) was significantly longer than that at occipital channels (104.11 ms) during binocular stimulation. Together with strong activation of the source envelope at occipital cortex, these findings support the idea of a feedforward process, with the visual stimuli propagating originally from occipital cortex to anterior cortex. In sum, these findings offer a novel method for future studies in measuring visual response latencies and also potentially shed a new light on understanding of how long collective neural activities take to travel in the human brain.

Electrophysiological and behavioral evidence reveals the effects of trait anxiety on contingent attentional capture.

Few studies have investigated the effects of anxiety on contingent attentional capture. The present study examined contingent attentional capture in trait anxiety by applying a rapid serial visual presentation (RSVP) paradigm during electroencephalographic recording. Overall, the behavioral and electrophysiological results showed a larger capture effect when a distractor was the same color as the target compared to when the distractor was not of the target color. Moreover, high-anxiety individuals showed a larger N2pc in the target colored distractor condition and nontarget colored distractor condition compared to the distractor-absent condition. In addition, the reaction time was slower when distractors were presented in the left visual field compared to when they were in the right visual field. This pattern was not seen in low-anxiety individuals. The findings may indicate that high-anxiety individuals allocate attention to the target less efficiently and have reduced suppression of distractors compared to low-anxiety individuals who could suppress attention to the distractors more efficiently. Future work could valuably investigate the consequences of such differences in terms of benefits and disruption associated with attentional capture differences in a range of anxious populations in different risk monitoring situations.

On Holo-Hilbert spectral analysis: a full informational spectral representation for nonlinear and non-stationary data.

The Holo-Hilbert spectral analysis (HHSA) method is introduced to cure the deficiencies of traditional spectral analysis and to give a full informational representation of nonlinear and non-stationary data. It uses a nested empirical mode decomposition and Hilbert-Huang transform (HHT) approach to identify intrinsic amplitude and frequency modulations often present in nonlinear systems. Comparisons are first made with traditional spectrum analysis, which usually achieved its results through convolutional integral transforms based on additive expansions of an a priori determined basis, mostly under linear and stationary assumptions. Thus, for non-stationary processes, the best one could do historically was to use the time-frequency representations, in which the amplitude (or energy density) variation is still represented in terms of time. For nonlinear processes, the data can have both amplitude and frequency modulations (intra-mode and inter-mode) generated by two different mechanisms: linear additive or nonlinear multiplicative processes. As all existing spectral analysis methods are based on additive expansions, either a priori or adaptive, none of them could possibly represent the multiplicative processes. While the earlier adaptive HHT spectral analysis approach could accommodate the intra-wave nonlinearity quite remarkably, it remained that any inter-wave nonlinear multiplicative mechanisms that include cross-scale coupling and phase-lock modulations were left untreated. To resolve the multiplicative processes issue, additional dimensions in the spectrum result are needed to account for the variations in both the amplitude and frequency modulations simultaneously. HHSA accommodates all the processes: additive and multiplicative, intra-mode and inter-mode, stationary and non-stationary, linear and nonlinear interactions. The Holo prefix in HHSA denotes a multiple dimensional representation with both additive and multiplicative capabilities.

The relationship between aerobic fitness and neural oscillations during visuo-spatial attention in young adults.

While the cognitive benefits of aerobic fitness have been widely investigated, current findings in young adults remain unclear. Specifically, little is known about how these effects are reflected in the time-frequency domain. This study thus assessed the relationship between aerobic fitness and neural oscillations during visuo-spatial attention. A between-subjects design that included 20 participants with higher aerobic fitness (age = 21.95 ± 2.24 years; VO2max = 58.98 ± 6.94 ml/kg/min) and 20 age- and gender-matched lower aerobic fitness participants (age = 23.25 ± 2.07 years; VO2max = 35.87 ± 3.41 ml/kg/min) was used to examine the fitness-related differences in performance and neuroelectric indexes during a Posner visuo-spatial attention paradigm. The results demonstrated that high-fitness participants, in comparison with their low-fitness counterparts, showed faster reaction times as well as greater modulation of oscillatory theta and beta power during target processing, regardless of cue types. Moreover, the neurocognitive correlation showed that higher theta power was related to better task performance. Collectively, these findings suggest that aerobic fitness is associated with general enhanced attentional control in relation to visuo-spatial processing, as evidenced through greater motor preparation and in particular the up-regulation of attentional processing in healthy young adults. The present study may contribute to current knowledge by revealing the relationship between aerobic fitness and modulation of brain oscillations.

Transcranial direct current stimulation over right posterior parietal cortex changes prestimulus alpha oscillation in visual short-term memory task.

Alpha band activity changes accompanied with the level attentional state, and recent studies suggest that such oscillation is associated with activities in the posterior parietal cortex. Here we show that artificially elevating parietal activity via positively-charged electric current through the skull can rapidly and effortlessly change people's prestimulus alpha power and improve subsequent performance on a visual short-term memory (VSTM) task. This modulation of alpha power and behavioral performance, however, is dependent on people's natural VSTM capability such that only the low performers benefitted from the stimulation, whereas high performers did not. This behavioral dichotomy is accounted by prestimulus alpha powers around the parieto-occipital regions: low performers showed decreased prestimulus alpha power, suggesting improvement in attention deployment in the current paradigm, whereas the high performers did not benefit from tDCS as they showed equally-low prestimulus alpha power before and after the stimulation. Together, these results suggest that prestimulus alpha power, especially in low performers, can be modulated by anodal stimulation and alter subsequent VSTM performance/capacity. Thus, measuring alpha before stimulus onset may be as important as measuring other VSTM-related electrophysiological components such as attentional allocation and memory capacity related components (i.e. N2 posterior-contralateral, N2pc, or contralateral delay activity, CDA). In addition, low VSTM performers perhaps do not suffer not only from poor VSTM capacity, but also from broad attentional mechanisms, and prestimulus alpha may be an useful tool in understanding the nature of individual differences in VSTM.

Revealing the brain's adaptability and the transcranial direct current stimulation facilitating effect in inhibitory control by multiscale entropy.

The abilities to inhibit impulses and withdraw certain responses are critical for human's survival in a fast-changing environment. These processes happen fast, in a complex manner, and sometimes are difficult to capture with fMRI or mean electrophysiological brain signal alone. Therefore, an alternative measure that can reveal the efficiency of the neural mechanism across multiple timescales is needed for the investigation of these brain functions. The present study employs a new approach to analyzing electroencephalography (EEG) signal: the multiscale entropy (MSE), which groups data points with different timescales to reveal any occurrence of repeated patterns, in order to theoretically quantify the complexity (indicating adaptability and efficiency) of neural systems during the process of inhibitory control. From this MSE perspective, EEG signals of successful stop trials are more complex and information rich than that of unsuccessful stop trials. We further applied transcranial direct current stimulation (tDCS), with anodal electrode over presupplementary motor area (preSMA), to test the relationship between behavioral modification with the complexity of EEG signals. We found that tDCS can further increase the EEG complexity of the frontal lobe. Furthermore, the MSE pattern was found to be different between high and low performers (divided by their stop-signal reaction time), where the high-performing group had higher complexity in smaller scales and less complexity in larger scales in comparison to the low-performing group. In addition, this between-group MSE difference was found to interact with the anodal tDCS, where the increase of MSE in low performers benefitted more from the anodal tDCS. Together, the current study demonstrates that participants who suffer from poor inhibitory control can efficiently improve their performance with 10min of electrical stimulation, and such cognitive improvement can be effectively traced back to the complexity within the EEG signals via MSE analysis, thereby offering a theoretical basis for clinical intervention via tDCS for deficits in inhibitory control.

The association of physical activity to neural adaptability during visuo-spatial processing in healthy elderly adults: A multiscale entropy analysis.

Physical activity has been shown to benefit brain and cognition in late adulthood. However, this effect is still unexplored in terms of brain signal complexity, which reflects the level of neural adaptability and efficiency during cognitive processing that cannot be acquired via averaged neuroelectric signals. Here we employed multiscale entropy analysis (MSE) of electroencephalography (EEG), a new approach that conveys important information related to the temporal dynamics of brain signal complexity across multiple time scales, to reveal the association of physical activity with neural adaptability and efficiency in elderly adults. A between-subjects design that included 24 participants (aged 66.63±1.31years; female=12) with high physical activity and 24 age- and gender-matched low physical activity participants (aged 67.29±1.20years) was conducted to examine differences related to physical activity in performance and MSE of EEG signals during a visuo-spatial cognition task. We observed that physically active elderly adults had better accuracy on both visuo-spatial attention and working memory conditions relative to their sedentary counterparts. Additionally, these physically active elderly adults displayed greater MSE values at larger time scales at the Fz electrode in both attention and memory conditions. The results suggest that physical activity may be beneficial for adaptability of brain systems in tasks involving visuo-spatial information. MSE thus might be a promising approach to test the effects of the benefits of exercise on cognition.

Unleashing potential: transcranial direct current stimulation over the right posterior parietal cortex improves change detection in low-performing individuals.

The limits of human visual short-term memory (VSTM) have been well documented, and recent neuroscientific studies suggest that VSTM performance is associated with activity in the posterior parietal cortex. Here we show that artificially elevating parietal activity via positively charged electric current through the skull can rapidly and effortlessly improve people's VSTM performance. This artificial improvement, however, comes with an interesting twist: it interacts with people's natural VSTM capability such that low performers who tend to remember less information benefitted from the stimulation, whereas high performers did not. This behavioral dichotomy is explained by event-related potentials around the parietal regions: low performers showed increased waveforms in N2pc and contralateral delay activity (CDA), which implies improvement in attention deployment and memory access in the current paradigm, respectively. Interestingly, these components are found during the presentation of the test array instead of the retention interval, from the parietal sites ipsilateral to the target location, thus suggesting that transcranial direct current stimulation (tDCS) was mainly improving one's ability to suppress no-change distractors located on the irrelevant side of the display during the comparison stage. The high performers, however, did not benefit from tDCS as they showed equally large waveforms in N2pc and CDA, or SPCN (sustained parietal contralateral negativity), before and after the stimulation such that electrical stimulation could not help any further, which also accurately accounts for our behavioral observations. Together, these results suggest that there is indeed a fixed upper limit in VSTM, but the low performers can benefit from neurostimulation to reach that maximum via enhanced comparison processes, and such behavioral improvement can be directly quantified and visualized by the magnitude of its associated electrophysiological waveforms.

Right temporoparietal junction and attentional reorienting.

The interaction between goal-directed and stimulus-driven attentional control allows humans to rapidly reorient to relevant objects outside the focus of attention--a phenomenon termed contingent reorienting. Neuroimaging studies have observed activation of the ventral and dorsal attentional networks, but specific involvement of each network remains unclear. The present study aimed to determine whether both networks are critical to the processes of top-down contingent reorienting. To this end, we combined the contingent attentional capture paradigm with the use of transcranial magnetic stimulation (TMS) to interfere with temporoparietal junction (TPJ; ventral network) and frontal eye field (dorsal network) activity. The results showed that only right TPJ (rTPJ) TMS modulated contingent orienting. Furthermore, this modulation was highly dependent on visual fields: rTPJ TMS increased contingent capture in the left visual field and decreased the effect in the right visual field. These results demonstrate a critical involvement of the ventral network in attentional reorienting and reveal the spatial selectivity within such network.

Resting State Dynamics in People with Varying Degrees of Anxiety and Mindfulness: A Nonlinear and Nonstationary Perspective.

Anxiety and mindfulness are two inversely linked traits shown to be involved in various physiological domains. The current study used resting state electroencephalography (EEG) to explore differences between people with low mindfulness-high anxiety (LMHA) (n = 29) and high mindfulness-low anxiety (HMLA) (n = 27). The resting EEG was collected for a total of 6 min, with a randomized sequence of eyes closed and eyes opened conditions. Two advanced EEG analysis methods, Holo-Hilbert Spectral Analysis and Holo-Hilbert cross-frequency phase clustering (HHCFPC) were employed to estimate the power-based amplitude modulation of carrier frequencies, and cross-frequency coupling between low and high frequencies, respectively. The presence of higher oscillation power across the delta and theta frequencies in the LMHA group than the HMLA group might have been due to the similarity between the resting state and situations of uncertainty, which reportedly triggers motivational and emotional arousal. Although these two groups were formed based on their trait anxiety and trait mindfulness scores, it was anxiety that was found to be significant predictor of the EEG power, not mindfulness. It led us to conclude that it might be anxiety, not mindfulness, which might have contributed to higher electrophysiological arousal. Additionally, a higher δ-ß and δ-γ CFC in LMHA suggested greater local-global neural integration, consequently a greater functional association between cortex and limbic system than in the HMLA group. The present cross-sectional study may guide future longitudinal studies on anxiety aiming with interventions such as mindfulness to characterize the individuals based on their resting state physiology.

The association between working memory precision and the nonlinear dynamics of frontal and parieto-occipital EEG activity.

Electrophysiological working memory (WM) research shows brain areas communicate via macroscopic oscillations across frequency bands, generating nonlinear amplitude modulation (AM) in the signal. Traditionally, AM is expressed as the coupling strength between the signal and a prespecified modulator at a lower frequency. Therefore, the idea of AM and coupling cannot be studied separately. In this study, 33 participants completed a color recall task while their brain activity was recorded through EEG. The AM of the EEG data was extracted using the Holo-Hilbert spectral analysis (HHSA), an adaptive method based on the Hilbert-Huang transforms. The results showed that WM load modulated parieto-occipital alpha/beta power suppression. Furthermore, individuals with higher frontal theta power and lower parieto-occipital alpha/beta power exhibited superior WM precision. In addition, the AM of parieto-occipital alpha/beta power predicted WM precision after presenting a target-defining probe array. The phase-amplitude coupling (PAC) between the frontal theta phase and parieto-occipital alpha/beta AM increased with WM load while processing incoming stimuli, but the PAC itself did not predict the subsequent recall performance. These results suggest frontal and parieto-occipital regions communicate through theta-alpha/beta PAC. However, the overall recall precision depends on the alpha/beta AM following the onset of the retro cue.

A holo-spectral EEG analysis provides an early detection of cognitive decline and predicts the progression to Alzheimer's disease.

Aims: Our aim was to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from cognitively normal (CN) individuals and predict the progression from MCI to AD within a 3-year longitudinal follow-up. A newly developed Holo-Hilbert Spectral Analysis (HHSA) was applied to resting state EEG (rsEEG), and features were extracted and subjected to machine learning algorithms. Methods: A total of 205 participants were recruited from three hospitals, with CN (n = 51, MMSE > 26), MCI (n = 42, CDR = 0.5, MMSE ≥ 25), AD1 (n = 61, CDR = 1, MMSE < 25), AD2 (n = 35, CDR = 2, MMSE < 16), and AD3 (n = 16, CDR = 3, MMSE < 16). rsEEG was also acquired from all subjects. Seventy-two MCI patients (CDR = 0.5) were longitudinally followed up with two rsEEG recordings within 3 years and further subdivided into an MCI-stable group (MCI-S, n = 36) and an MCI-converted group (MCI-C, n = 36). The HHSA was then applied to the rsEEG data, and features were extracted and subjected to machine-learning algorithms. Results: (a) At the group level analysis, the HHSA contrast of MCI and different stages of AD showed augmented amplitude modulation (AM) power of lower-frequency oscillations (LFO; delta and theta bands) with attenuated AM power of higher-frequency oscillations (HFO; beta and gamma bands) compared with cognitively normal elderly controls. The alpha frequency oscillation showed augmented AM power across MCI to AD1 with a reverse trend at AD2. (b) At the individual level of cross-sectional analysis, implementation of machine learning algorithms discriminated between groups with good sensitivity (Sen) and specificity (Spec) as follows: CN elderly vs. MCI: 0.82 (Sen)/0.80 (Spec), CN vs. AD1: 0.94 (Sen)/0.80 (Spec), CN vs. AD2: 0.93 (Sen)/0.90 (Spec), and CN vs. AD3: 0.75 (Sen)/1.00 (Spec). (c) In the longitudinal MCI follow-up, the initial contrasted HHSA between MCI-S and MCI-C groups showed significantly attenuated AM power of alpha and beta band oscillations. (d) At the individual level analysis of longitudinal MCI groups, deploying machine learning algorithms with the best seven features resulted in a sensitivity of 0.9 by the support vector machine (SVM) classifier, with a specificity of 0.8 yielded by the decision tree classifier. Conclusion: Integrating HHSA into EEG signals and machine learning algorithms can differentiate between CN and MCI as well as also predict AD progression at the MCI stage.

Modulation of motor control in saccadic behaviors by TMS over the posterior parietal cortex.

The right posterior parietal cortex (rPPC) has been found to be critical in shaping visual selection and distractor-induced saccade curvature in the context of predictive as well as nonpredictive visual cues by means of transcranial magnetic stimulation (TMS) interference. However, the dynamic details of how distractor-induced saccade curvatures are affected by rPPC TMS have not yet been investigated. This study aimed to elucidate the key dynamic properties that cause saccades to curve away from distractors with different degrees of curvature in various TMS and target predictability conditions. Stochastic optimal feedback control theory was used to model the dynamics of the TMS saccade data. This allowed estimation of torques, which was used to identify the critical dynamic mechanisms producing saccade curvature. The critical mechanisms of distractor-induced saccade curvatures were found to be the motor commands and torques in the transverse direction. When an unpredictable saccade target occurred with rPPC TMS, there was an initial period of greater distractor-induced torque toward the side opposite the distractor in the transverse direction, immediately followed by a relatively long period of recovery torque that brought the deviated trace back toward the target. The results imply that the mechanisms of distractor-induced saccade curvature may be comprised of two mechanisms: the first causing the initial deviation and the second bringing the deviated trace back toward the target. The pattern of the initial torque in the transverse direction revealed the former mechanism. Conversely, the later mechanism could be well explained as a consequence of the control policy in this model. To summarize, rPPC TMS increased the initial torque away from the distractor as well as the recovery torque toward the target.

The location probability effects of saccade reaction times are modulated in the frontal eye fields but not in the supplementary eye field.

The visual system constantly utilizes regularities that are embedded in the environment and by doing so reduces the computational burden of processing visual information. Recent findings have demonstrated that probabilistic information can override attentional effects, such as the cost of making an eye movement away from a visual target (antisaccade cost). The neural substrates of such probability effects have been associated with activity in the superior colliculus (SC). Given the immense reciprocal connections to SC, it is plausible that this modulation originates from higher oculomotor regions, such as the frontal eye field (FEF) and the supplementary eye field (SEF). To test this possibility, the present study employed theta burst transcranial magnetic stimulation (TMS) to selectively interfere with FEF and SEF activity. We found that TMS disrupted the effect of location probability when TMS was applied over FEF. This was not observed in the SEF TMS condition. Together, these 2 experiments suggest that the FEF plays a critical role not only in initiating saccades but also in modulating the effects of location probability on saccade production.

Time-frequency analysis of pupil size modulated by global luminance, arousal, and saccade preparation signals using Hilbert-Huang transform.

Pupil size changes constantly and is mainly determined by global luminance signals. In addition, the pupil responds to various cognitive and arousal processes, with larger pupil dilation observed in higher levels of cognitive or arousal processing. Although these task-evoked pupillary responses are extensively used in the pupil research, pupil analysis focusing on the frequency domain, particularly in the context of arousal and cognitive modulations, is less established. Fourier Transform method (FFT) has been used to understand the modulation of task difficulty on pupil oscillations. However, physiological signals are often characterized as non-linear and non-stationary waves, and the conventional spectral analytical method with linearity presumption is less appropriate to reveal modulation dynamics between time and frequency. Here, we used Hilbert-Huang Transform (HHT) to examine the time-frequency modulations on pupil size regulated by arousal, cognitive, and global luminance signals. Consistent with previous research, using FFT, higher spectral densities were obtained with lower luminance background. Moreover, higher spectral densities were found in the high emotional arousal condition. With HHT, we further demonstrated temporal changes on amplitude spectrum and inter-trial phase coherence (ITPC) in each intrinsic mode function (IMF), with stronger amplitudes in higher IMFs (i.e., low frequencies). Moreover, although global luminance, arousal and saccade preparation modulated pupil oscillatory responses, the modulation pattern in different IMFs was different. Together, our results demonstrated dynamics between the time and frequency domain on pupil oscillatory responses, highlighting the importance of examining the time-frequency interactions in the context of various pupil modulations.