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Sack, A. T.

Publications and source records attributed to Sack, A. T..

17 recordsLinked to original sources

Predictable Timing Enhances the Use of Predictable Content

As events unfold, they carry structure in both their timing and content, with these dimensions often interrelated. Most research has treated these dimensions separately, although processing them jointly may provide important computational benefits. It is an open question whether the brain processes a sequence's timing and predictable content structure independently, or integrates these two sources of information to guide prediction. We hypothesised that predictable timing would allow listeners to better exploit structure in the content, with this effect increasing as content structure becomes stronger. To test this, we presented tone sequences with pitch trajectories following a 1/f^{beta} structure, where {beta} determines how strongly the content of each tone persists, while independently varying the temporal periodicity of the sequence. Performance was quantified using response errors relative to outcome predictions of a Gaussian Process Regression model and a model-free measure of how strongly preceding tones influenced responses. Response error decreased and reliance on preceding tones increased with higher {beta} and periodic timing. Moreover, the influence of preceding tones showed an interaction between timing and content, such that the effect of periodicity grew with increasing {beta}. The response error showed no such interaction, although the effect of periodic timing was reliable only for the most structured sequences. Our findings suggest an interdependency between content and timing, where predictable timing helps listeners make greater use of predictable content.

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tACS induces state-dependent shifts in inhibitory phase preference consistent with phase precession

Phase-dependent modulation of motor inhibition suggests that oscillatory timing plays a key role in inhibitory control. Here we show that rhythmic brain stimulation can selectively alter this timing in a manner consistent with phase precession. Participants performed an anticipatory stop-signal task while receiving 20 Hz transcranial alternating current stimulation (tACS) over the pre-supplementary motor area, with stop signals presented at defined phases of the stimulation waveform. An additional control experiment with no tACS was conducted, in which the stop signal phase was derived post-hoc from the ongoing EEG. In both tACS and control sessions, stopping efficacy varied sinusoidally with beta phase, confirming that inhibitory control is intrinsically phase-dependent. During tACS, however, the phase associated with the strongest inhibition advanced progressively across the session by about 180{degrees}, and this effect was specific to failed-stop trials. No comparable shift occurred without stimulation. These findings indicate that rhythmic drive can bias the temporal phase at which inhibition is most effective when the brain is in an error-prone state, revealing a state-dependent, precession-like reorganization of inhibitory timing. We propose that tACS interacts with error-related plasticity to promote gradual phase advancement, placing the system within spike-timing-dependent learning windows, whereas intrinsic fluctuations alone appear insufficient to facilitate cumulative precession. More broadly, these results suggest that phase precession may represent a general coding principle extending beyond hippocampal circuits, enabling the motor system to adaptively adjust inhibitory control through oscillatory timing mechanisms. HighlightsO_LIBeta tACS over preSMA induces shifts in phase preference during motor inhibition C_LIO_LIPrecession-like phase shifts emerge selectively during failed but not successful stops C_LIO_LIPhase precession was absent in a control experiment without tACS C_LIO_LItACS might provide a method to probe phase precession mechanisms in cognition C_LI

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Closed-loop anti-phase tACS over preSMA reduced oscillatory beta synchronization and modulated motor inhibition performance

Neural oscillations dynamically coordinate communication across distributed brain networks, and their pathological synchronization is a common feature of neurological and psychiatric disease. In Parkinsons disease, excessive beta-band synchronization within cortico-basal ganglia-thalamo-cortical loops is closely linked to motor impairment, highlighting the need for neuromodulation strategies that can selectively and adaptively reshape this brain synchrony online. Transcranial alternating current stimulation (tACS) offers a non-invasive approach to modify endogenous oscillatory activity, yet it is typically delivered in an open-loop manner, limiting control over the timing, direction, and functional network consequences of oscillatory modulation. Here, we developed an online adaptive EEG-guided closed-loop system that continuously tracked the instantaneous phase of ongoing cortical oscillations and delivered stimulation either aligned (in-phase) or 180 degrees opposed (anti-phase) to the endogenous beta rhythm. Thirty-eight right-handed healthy participants performed a stop-signal task while receiving adaptive closed-loop 4 x 1 HD-tACS over pre-supplementary motor cortex (preSMA) targeting beta-band activity (15-30 Hz) implicated in motor inhibition, under in-phase, anti-phase, or sham stimulation. Anti-phase tACS produced a robust suppression of beta synchrony relative to both in-phase and sham stimulation, consistent with destructive interference of the endogenous rhythm. Behaviorally, anti-phase tACS reduced inhibition performance by impairing the stopping process, whereas in-phase stimulation reduced peak force rate during go trials and decreased variability of the go response, consistent with increased inhibitory tone and stabilization of ongoing motor states. These results provide converging behavioral and neurophysiological evidence for destructive interference of anti-phase tACS and establish a mechanistic framework for phase-specific closed-loop neuromodulation, paving the way to implement a non-invasive therapeutic strategy aimed at desynchronizing pathological beta in neurological conditions such as Parkinsons disease.

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In-phase and anti-phase dual-site beta tACS differentially influence functional connectivity and motor inhibition

Inhibitory control relies on coordinated beta-band activity within a fronto-basal ganglia network, which implements inhibition via downstream effects on (pre)motor areas. In this study, we employed dual-site transcranial alternating current stimulation (tACS) targeting the right inferior frontal gyrus (rIFG) and primary motor cortex (M1) to directly manipulate phase relationships in the beta band and assess their effects on both functional connectivity and motor inhibition. Fifty-two healthy participants received in-phase, anti-phase and sham stimulation while performing a stop-signal task. The results revealed that connectivity between rIFG and lM1 increased following in-phase but decreased after anti-phase stimulation. Although no direct modulation of task performance was observed, the greater connectivity increase between the targets during in-phase stimulation was predictive of faster inhibitory performance. In contrast, greater connectivity decreases during anti-phase stimulation were related to faster go responses, suggesting a shift towards less inhibition on the motor system. These findings provide evidence that dual-site beta-tACS can both enhance and impair inhibitory control depending on phase alignment, highlighting its potential as a non-invasive intervention for disorders marked by impaired inhibition.

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The cardiac, respiratory and gastric rhythms independently modulate corticospinal excitability

Interoception refers to the brains sensing of internal body state and encompasses various bodily systems, notably the cardiac, respiratory and gastric rhythms. Beyond their roles in physiological regulation and emotional states, each of these visceral rhythms has been shown to influence brain activity and cognition, prompting for the development of various interpretative functional frameworks. However, both experimental data and functional hypothesis leave it unclear whether and how each visceral rhythm acts simultaneously and independently on brain activity. Here we address this question by measuring in human participants how the corticospinal excitability of the motor system varies with the phase of each of the three visceral rhythms. We applied single pulse Transcranial Magnetic Stimulation (TMS) over the hand region in primary motor cortex to elicit Motor Evoked Potentials (MEP), whose amplitude reflects corticospinal excitability, and tested whether MEP amplitude depends on the phase of the simultaneously measured cardiac, respiratory and gastric rhythms. All three visceral rhythms were coupled to motor excitability with similar effect sizes at the group level. However, we found no relation between coupling strengths: participants displaying high coupling with one organ did not necessarily display high coupling to the other organs. These results indicate that independent mechanisms could underly the coupling between the cardiac, respiratory and gastric rhythm and motor excitability. We further introduce the concept of individual interoceptive profiles, and show that such interoceptive profiles obtained from objective coupling strength measures were not explained by self-reported awareness of the organ. Altogether our results call for refined specifications of the frameworks offering a functional or clinical interpretation of viscera-brain coupling taking into account both independent mechanisms and individual interoceptive profiles.

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Using TMS-EEG to study the intricate interplay between GABAergic inhibition and glutamatergic excitation during reactive and proactive motor inhibition

Transcranial magnetic stimulation (TMS) studies have provided insight into the neurotransmission underlying motor inhibition but are limited to the primary motor cortex (M1). To investigate {gamma}-aminobutyric acid (GABA) and glutamatergic neurotransmission across the broader motor inhibition network, we combined TMS with electroencephalography (EEG). The N45 and N100 components of the TMS-evoked potentials (TEPs) have been liked to GABAa and GABAb signaling, respectively, whereas the N15, P30 and P60 TEPs are believed to reflect glutamatergic neurotransmission. This study investigates how these components are modulated during reactive and proactive motor inhibition. Twenty-four healthy participants completed two TMS-EEG sessions targeting either the left M1 or the pre-supplementary motor area (preSMA) at rest and during a stop-signal task. We compared TEP amplitudes across TMS conditions (active/sham) and trial types and assessed their relationship with task performance. Participants with a higher N45 amplitude over M1 at rest demonstrated a faster stop-signal reaction time. Active TMS during successful motor inhibition evoked higher N15 amplitudes over preSMA than during uncertain go trials, suggesting that an early excitatory signal from preSMA is crucial for reactive inhibition. In contrast, proactive inhibition was linked to lower P30 amplitudes in M1, possibly reflecting reduced motor facilitation. These findings provide novel empirical insights into the neurophysiological mechanisms underpinning motor inhibition, emphasizing the importance of a coordinated balance between inhibitory processes in M1 and early glutamatergic excitatory signals from preSMA for effective inhibition.

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The phase of tACS-entrained pre-SMA beta oscillations modulates motor inhibition

Inhibitory control has been linked to beta oscillations in the fronto-basal ganglia network. Here we aim to investigate the functional role of the phase of this oscillatory beta rhythm for successful motor inhibition. We applied 20 Hz transcranial alternating current stimulation (tACS) to the pre-supplementary motor area (pre-SMA) while presenting stop signals at 4 (Experiment 1) and 8 (Experiment 2) equidistant phases of the tACS entrained beta oscillations. Participants showed better inhibitory performance when stop signals were presented at the trough of the beta oscillation whereas their inhibitory control performance decreased with stop signals being presented at the oscillatory beta peak. These results are consistent with the communication through coherence theory, in which postsynaptic effects are thought to be greater when an input arrives at an optimal phase within the oscillatory cycle of the target neuronal population. The current study provides mechanistic insights into the neural communication principles underlying successful motor inhibition and may have implications for phase-specific interventions aimed at treating inhibitory control disorders such as PD or OCD.

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Assessing TMS-evoked cognitive network responses depending on neurocognitive and oscillatory brain state: A simultaneous TMS-EEG-fMRI project

Human cognition arises from information exchange within and between functionally connected brain networks. Alterations in such signal propagation across networks are linked to numerous disorders. Brain-wide signal propagation can be experimentally studied with simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI), where TMS pulses introduce a signal at a certain network node and fMRI charts its propagation through the network. Yet, this approach ignores the fact that the (network) impact of a TMS pulse depends on brain state, where brain state fluctuates spontaneously from moment to moment (e.g. oscillatory state) as well as depending on what a participant does (neurocognitive state). Here, we assessed TMS-evoked fMRI activations as a function of neurocognitive state (eyes open versus eyes closed in complete darkness) and oscillatory state (low versus high pre-TMS alpha power, as measured with simultaneous electroencephalography (EEG)). We applied supra-versus sub-threshold triple-pulse TMS to the right posterior parietal cortex in eight participants, while simultaneously recording EEG and fMRI during two different ocular states. In this first application of the multimodal TMS-EEG-fMRI paradigm to a cognitive network hub, we did not find evidence for a brain state modulation of TMS-induced signal propagation. Instead, we found state-independent TMS-evoked fMRI responses mostly in sensory areas such as the insula, superior temporal gyrus, anterior cingulate cortex, and thalamus, but also in the frontal eye fields. Interestingly, neurocognitive state did seem to modulate the fMRI response to indirect TMS effects such as sensory stimulation. These results lead to several important insights for future cognitive multimodal TMS experiments.

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Alpha oscillatory activity causally linked to working memory retention: insights from online phase-locking closed-loop transcranial alternating current stimulation (tACS)

Although previous studies have reported correlations between alpha oscillations and the "retention" sub-process of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain. Conventional tACS is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention sub-process). Here, we developed an online phase-corrected closed-loop transcranial alternating current stimulation (tACS) system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits both up- and down-regulation of brain oscillations at the target stimulation frequency within a short stimulation period, and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to 39 participants during the retention sub-processes of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. Moreover, the in-phase tACS-induced changes in WM performance were positively correlated with alpha oscillatory activity. These findings strongly support a causal link between alpha oscillations and WM retention, and illustrate the broad application prospects of phase-corrected tACS.

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Transcranial alternating current stimulation at theta frequency to the parietal cortex impairs associative, but not perceptual, memory encoding

Neural oscillations in the theta range (4-6 Hz) are thought to underlie associative memory function in the hippocampal-cortical network. While there is ample evidence supporting a role of theta oscillations in animal and human memory, most evidence is correlational. Non-invasive brain stimulation (NIBS) can be employed to modulate cortical oscillatory activity to influence brain activity, and possibly modulate deeper brain regions, such as hippocampus, through strong and reliable cortico-hippocampal functional connections. We applied high-definition transcranial alternating current stimulation (HD-tACS) at 6 Hz over left parietal cortex to modulate brain activity in the putative cortico-hippocampal network to influence associative memory encoding. After encoding and brain stimulation, participants completed an associative memory and a perceptual recognition task. Results showed that theta tACS significantly decreased associative memory performance but did not affect perceptual memory performance. These results show that parietal theta tACS modulates associative processing separately from perceptual processing, and further substantiate the hypothesis that theta oscillations are implicated in the cortico-hippocampal network and associative encoding.

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Reduced risk-taking behavior during frontal oscillatory theta band neurostimulation

BackgroundMost of our decisions involve a certain degree of risk regarding the outcomes of our choices. People vary in the way they make decisions, resulting in different levels of risk-taking behavior. These differences have been linked to prefrontal theta band activity. However, a direct functional relationship between prefrontal theta band activity and risk-taking has not yet been demonstrated. ObjectiveWe used noninvasive brain stimulation to test the functional relevance of prefrontal oscillatory theta activity for the regulatory control of risk-taking behavior. MethodsIn a within-subject experiment, 32 healthy participants received theta [4-8 Hertz (Hz)], gamma (30-50 Hz), and sham transcranial alternating current stimulation (tACS) over the left prefrontal cortex (lPFC). During stimulation, participants completed a task assessing their risk-taking behavior as well as response times and sensitivity to value and outcome probabilities. Electroencephalography (EEG) was recorded before and immediately after stimulation. ResultsTheta-band, but not gamma-band or sham, tACS led to a significant reduction in risk-taking behavior, indicating a frequency-specific effect of prefrontal brain stimulation on the modulation of risk-taking behavior. Moreover, theta-band stimulation led to increased response times and decreased sensitivity to reward values. EEG data analyses did not show an increase in power in the stimulated frequencies. ConclusionThese findings provide direct empirical evidence for the effects of prefrontal theta-band stimulation on behavioral risk-taking regulation.

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Transcranial Magnetic stimulation (TMS) modulates functional activity of SH-SY5Y cells: An in vitro model provides support for assumed excitability changes

Repetitive Transcranial Magnetic Stimulation (rTMS) is an established neuromodulation technique, using electromagnetic pulses that, depending on the precise parameters, are assumed to lead to lasting neural excitability changes. rTMS has widespread applications in both research and therapy, where it has been FDA approved and is considered a first-line treatment for depression, according to recent North American and European guidelines. However, these assumed excitability effects are often difficult to replicate, and highly unreliable on the single subject/patient level. Given the increasing application of rTMS, especially in clinical practice, the absence of a method to unequivocally determine effects of rTMS on human neuronal excitability is problematic. We have taken a first step in addressing this bottleneck, by administering excitatory and inhibitory rTMS protocols, iTBS and cTBS, to a human in vitro neuron model; differentiated SH-SY5Y cells. We use live calcium imaging to assess changes in neural activity following stimulation, through quantifying fluorescence response to chemical depolarization. We found that iTBS and cTBS have opposite effects on fluorescence response; with iTBS increasing and cTBS decreasing response to chemical depolarization. Our results are promising, as they provide a clear demonstration of rTMS after-effects in a living human neuron model. We here present an in-vitro live calcium imaging setup that can be further applied to more complex human neuron models, for developing and evaluating subject/patient-specific brain stimulation protocols.

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Frequency-specific transcranial neuromodulation of oscillatory alpha power alters and predicts human visuospatial attention performance

Unilateral transcranial alternating current stimulation (tACS) at alpha frequency modulates the locus of spatial attention. However, the neural mechanisms by which tACS influences spatial attention remain poorly understood. Here, we applied high-definition tACS at the individual alpha frequency (IAF), two control frequencies (IAF+/-2Hz) and sham to the left posterior parietal cortex and measured its effects on visuospatial attention performance as well as alpha power (using electroencephalography, EEG). Our results revealed a leftward lateralization of alpha power relative to sham. At a high value of leftward alpha lateralization, we also observed a leftward attention bias, which differed from sham. Moreover, the magnitude of the alpha lateralization effect predicted the attention bias. These effects occurred for tACS at IAF but not for the control frequencies. This suggests that tACS operates through oscillatory interactions with ongoing brain rhythms in line with the synchronization theory. Our results also highlight the importance of personalized stimulation protocols, especially in potential clinical settings.

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Does alpha phase modulate visual target detection? Three experiments with tACS phase-based stimulus presentation.

In recent years the influence of alpha (7-13 Hz) phase on visual processing has received a lot of attention. Magneto-/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. If occipital alpha phase is functionally relevant, the phase of occipital alpha-frequency transcranial alternating current stimulation (tACS) could modulate visual processing. Visual stimuli presented at different pre-determined, experimentally controlled, phases of the entraining tACS signal should then result in an oscillatory pattern of visual performance. We studied this in a series of experiments. In experiment one, we applied 10 Hz tACS to right occipital cortex (O2) and used independent psychophysical staircases to obtain contrast thresholds for detection of visual gratings in left or right hemifield, in six equidistant tACS phase conditions. In experiments two and three, tACS was at EEG-based individual peak alpha frequency. In experiment two, we measured detection rates for gratings with (pseudo-)fixed contrast levels. In experiment three, participants detected brief luminance changes in a custom-built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one-cycle sinusoid as predicted. However, post-hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT in both experiments 1 and 2 (not measured in experiment 3). This observation is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.

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Can processing of face trustworthiness bypass early visual cortex? A transcranial magnetic stimulation masking study

As a highly social species, we constantly evaluate human faces to decide whether we can trust someone. Previous studies suggest that face trustworthiness can be processed unconsciously, but the underlying neural pathways remain unclear. Specifically, the question remains whether processing of face trustworthiness relies on early visual cortex (EVC), required for conscious perception. If processing of trustworthiness can bypass EVC, then disrupting EVC should impair conscious trustworthiness perception while leaving forced-choice trustworthiness judgment intact. We applied double-pulse transcranial magnetic stimulation (TMS) to right EVC, at different stimulus onset asynchronies (SOAs) from presentation of a face in either the left or right hemifield. Faces were slightly rotated clockwise or counterclockwise, and were either trustworthy or untrustworthy. On each trial, participants discriminated 1) trustworthiness, 2) stimulus rotation, and 3) subjective visibility of trustworthiness. At early SOAs and specifically in the left hemifield, orientation processing (captured by the rotation task) was impaired by TMS. Crucially, though TMS also impaired subjective visibility of trustworthiness, no effects on trustworthiness discrimination were obtained. Conscious perception of face trustworthiness (captured by visibility ratings) relies on intact EVC, while forced-choice trustworthiness judgments may not. These results are consistent with the hypothesis that trustworthiness processing can bypass EVC. For basic visual features, extrastriate pathways are well-established; but face trustworthiness depends on a complex configuration of features. Its processing without EVC and outside of awareness is therefore of particular interest, further highlighting its ecological relevance.

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Left parietal tACS at alpha frequency induces a shift of visuospatial attention

BackgroundVoluntary shifts of visuospatial attention are associated with a lateralization of occipitoparietal alpha power (7-13Hz), i.e. higher power in the hemisphere ipsilateral and lower power contralateral to the locus of attention. Recent noninvasive neuromodulation studies demonstrated that alpha power can be experimentally increased using transcranial alternating current stimulation (tACS).\n\nObjective/HypothesisWe hypothesized that tACS at alpha frequency over the left parietal cortex induces shifts of attention to the left hemifield. However, spatial attention shifts not only occur voluntarily (endogenous), but also stimulus-driven (exogenous). In order to study the task-specificity of the potential effects of tACS on attentional processes, we administered three conceptually different spatial attention tasks.\n\nMethods36 healthy volunteers were recruited from an academic environment. In two seperate sessions, we applied either high-density tACS at 10Hz, or sham tACS, for 35-40 minutes to their left parietal cortex. We systematically compared performance on endogenous attention, exogenous attention, and stimulus detection tasks.\n\nResultsIn the Endogenous attention task, we found a greater leftward bias in reaction times during left parietal 10Hz tACS as compared to sham. There were no stimulation effects in the exogenous attention or stimulus detection task.\n\nConclusionThe study shows that high-density tACS at 10Hz can be used to modulate visuospatial attention performance. The tACS effect is task-specific, indicating that not all forms of attention are equally susceptible to the stimulation.

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Faded visual afterimages reappear after TMS over early visual cortex

In the complete absence of small transients in visual inputs (e.g. by experimentally stabilizing an image on the retina, or in everyday life during intent staring), information perceived by the eyes will fade from the perceptual experience. While the mechanisms of visual fading remain poorly understood, one possibility is that higher-level brain regions actively suppress the stable visual signals via targeted inhibitory feedback onto Early Visual Cortex (EVC). Here, we used positive afterimages and multisensory conflict to induce gestaltlike fading of participants own hands. In two separate experiments, participants rated the perceived quality of their hands both before and after Transcranial Magnetic Stimulation (TMS) was applied over EVC. In a first experiment, triple pulse TMS was able to make a faded hand appear less faded after the pulses were applied, compared to placebo pulses. A second experiment demonstrated that this was because triple pulse TMS inoculated the removed hand from fading over time. Interestingly, TMS similarly affected the left and right hand, despite being applied only over right EVC. Together, our results suggest that TMS can lift inhibitory processes in EVC and reverse the effects of visual fading. And it might do so by crossing transcollosal connections, or via multimodal integration sites in which both hands are represented.

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