Biology subjects

Violante, I. R.

Publications and source records attributed to Violante, I. R..

16 recordsLinked to original sources

bioRxiv2026

Hippocampal stimulation timed to memory reactivation shapes human sleep oscillatory dynamics and consolidation

Memory consolidation during sleep depends on the precisely timed coordination of hippocampal reactivation with cortical slow oscillations and spindles. In humans this coupling has been characterised correlationally, while causal investigations have required intracranial stimulation in restricted patient cohorts or used non-invasive approaches targeting cortical regions, often obscuring the underlying sleep rhythms. Here we stimulated the human hippocampus during sleep for the first time, applying temporal interference stimulation to the left hippocampal head either concurrently with or prior to induced memory reactivation. Stimulation concurrent with reactivation reduced associative memory forgetting relative to mistimed stimulation and enhanced fast spindle amplitude, preserving the association between slow oscillation-spindle coupling and memory. This behavioural benefit was mediated by a distributed, left-lateralised set of spindle and coupling features. Non-invasively engaging deep hippocampal circuits during sleep offers both a means to probe human memory and a scalable basis for intervention where consolidation fails.

neuroscience↗

bioRxiv2026

Resonance-driven enhancement of sleep spindles using thalamic temporal interference stimulation

Sleep spindles are hallmarks of non-rapid eye movement sleep and support memory consolidation yet remain difficult to modulate non-invasively. Combining computational modeling and human sleep recordings, we show that thalamus-targeted temporal interference stimulation (TIS) with a 5Hz envelope increases spindle density via subthreshold resonance in thalamocortical relay neurons. Our results demonstrate a mechanistic framework for the rational design of interventions to selectively augment sleep spindles.

neuroscience↗

bioRxiv2026

Tonic REM sleep EEG components predict better mood, cognition and reduce cortical excitability overnight

Rapid Eye Movement (REM) sleep makes up approximately 20% of sleep in the adult human and is altered in psychiatric and neurodegenerative conditions. REM sleep comprises two substates, during which eye movements do (phasic REM) and do not (tonic REM) occur. Tonic REM makes up 70-90% of REM sleep but its role in regulating brain function, mood and cognition remain underexplored. We investigated how seven nights of insufficient sleep (6 h time in bed), compared to sufficient sleep, alter periodic and aperiodic components of the phasic and tonic REM sleep electroencephalography (EEG), in 542 sleep recordings of 36 young adults. Associations between phasic and tonic REM sleep EEG and mood, cognitive performance, and overnight changes in cortical excitability as indexed by 1/f spectral slopes were assessed. Insufficient sleep predominantly affected tonic REM EEG components, specifically the density of theta, the amplitude, density, and frequency of alpha oscillations and the 1/f slope in the 30 to 45 Hz range. These changes associated with mood and cognitive performances, and with overnight reductions in cortical excitability. These results provide evidence for a role of tonic REM sleep in regulating mood and counteracting cognitive deterioration and excitability changes associated with insufficient sleep.

neuroscience↗

bioRxiv2025

Temporal Interference Stimulation Can Enhance or Disrupt Human Memory Encoding as a Function of Brain Location and Frequency

Visual memory relies on synchronized interactions and rhythms between the medial temporal lobes and neocortical brain regions. Non-invasive manipulation of memory-related brain regions, specifically deeper temporal lobe regions, has been limited by the lack of precision of non-invasive neuromodulation - when targeting deeper structures, the cortex is always stimulated, never deeper structures in isolation. Temporal Interference (TI) stimulation, a novel non-invasive technique, uses high-frequency carrier fields to deliver targeted, physiologically relevant neuromodulation via amplitude-modulated envelopes at specific brain regions. Here, we investigate TIs impact on figure memory encoding in 70 healthy participants using the Rey-Osterrieth and Taylor Complex Figure tasks, with TI applied in several brain regions independently and simultaneously - allowing investigation of combinations of medial temporal lobe and neocortical brain regions. Interestingly, higher frequency TI envelopes (130 Hz offset) targeting bilateral hippocampi and temporal cortices significantly impair recall (p = 6.54e-04), while lower frequency TI envelopes (5 Hz offset) targeting only the bilateral hippocampi significantly enhance recall (p = 0.0447). Stimulation using other combinations of medial temporal lobe and neocortical regions showed no effect, underscoring the critical role of frequency and focality of non-invasive brain stimulation and correct target selection. Finally, functional MRI reveals strong differences between the effects of 130 Hz and 5 Hz envelopes, specifically in hippocampal BOLD signals, brain connectivity, default mode, and attentional networks. These findings demonstrate TIs ability to bidirectionally modulate memory encoding through precise frequency and target tuning, offering a powerful tool for cognitive neuroscience and potential therapeutic applications for memory disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/677714v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@8e9db3org.highwire.dtl.DTLVardef@1135a3corg.highwire.dtl.DTLVardef@189345dorg.highwire.dtl.DTLVardef@ccca8f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Temporal Interference stimulation for bidirectional memory modulation assessed via behavioral testing and MRI scanning. C_FIG

neuroscience↗

bioRxiv2025

A universal dynamic routing architecture governs the flow of human cortical activity

Behaviour requires distributed neural processing to be flexibly integrated and segregated, which in turn demands that information be dynamically routed across the brain. However, whether a unifying principle governs the routing of neural activity remains unknown. Here, we report that the flow of cortical activity is directed through canonical routing modes that are conserved across individuals, robust to variations in age, frequency band, brain state, and even the presence of neurodegeneration. These modes are constructed from the divergence and vorticity of the time-varying unit-phase vector field derived from electroencephalogram (EEG) recordings. We show that the canonical routing modes are flexibly combined to generate distinct, state- and function-dependent flow architectures that remain consistent across individuals. Disruption to the routing mode dynamics mechanistically links structural abnormalities and cognitive impairment in Alzheimers disease. Together, these canonical routing modes provide a unified framework for describing, modelling, and predicting the dynamic integration and segregation of macroscopic brain activity underpinning behaviour.

neuroscience↗

bioRxiv2025

Lateralised modulation of posterior alpha oscillations by closed loop auditory stimulation during memory retention

Alpha oscillations have been implicated in the maintenance of working memory representations. Notably, when memorised content is spatially lateralised, the power of posterior alpha activity exhibits corresponding lateralisation during the retention interval, consistent with the retinotopic organisation of the visual cortex. Beyond power, alpha frequency has also been linked to memory performance, with faster alpha rhythms associated with enhanced retention. These findings position alpha oscillations as a promising target for neuromodulation. In this study, we demonstrate that although alpha frequency is not typically lateralised in a retinotopic manner during working memory retention, such lateralisation can be externally induced. Using alpha closed-loop auditory stimulation (CLAS), and leveraging the phase-dependent responsiveness of alpha oscillations to sound, we successfully modulated alpha frequency asymmetrically between the visual cortices. The extent of induced frequency lateralisation was associated with the behavioural asymmetry in task performance.

neuroscience↗

bioRxiv2024

Closed-loop auditory stimulation targeting alpha and theta oscillations during REM sleep induces phase-dependent power and frequency changes

BackgroundAlpha and theta oscillations characterize the waking human electroencephalogram (EEG) and can be modulated by closed-loop auditory stimulation (CLAS). These oscillations also occur during rapid eye movement (REM) sleep, but whether they can be modulated by CLAS is not known. ObjectiveInvestigate whether CLAS can modulate alpha and theta oscillations during REM sleep in a targeted phase-dependent manner. MethodsWe recorded high-density EEG during an extended overnight sleep period in 18 healthy young adults. Auditory stimulation was delivered during both phasic and tonic REM sleep in alternating 6 s ON and 6 s OFF windows. During the ON windows, stimuli were phase-locked to four orthogonal phases of ongoing alpha or theta oscillations detected in a frontal electrode (Fz). ResultsDuring ON windows, the four orthogonal phases of ongoing alpha and theta oscillations were targeted with high accuracy. Alpha and theta CLAS induced phase-dependent changes in power and frequency at the target location. Frequency-specific effects were observed for alpha trough (speeding up) and rising (slowing down) and theta trough (speeding up) conditions. These phase-dependent changes of CLAS were observed during both REM sleep substages, even though the amplitude evoked by auditory stimuli which were not phase-locked was very much reduced in phasic compared to tonic REM sleep. ConclusionsThis study provides evidence that faster REM sleep rhythms can be modulated by CLAS in a phase-dependent manner. This offers a new approach to investigate how modulation of REM sleep oscillations affects the contribution of this vigilance state to brain function. Highlights- REM sleep alpha and theta oscillations can be modulated using phase-locked CLAS - Phase-dependent changes in power and frequency are observed in the target area - Phase-dependent modulation occurs in phasic and tonic REM sleep Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/582907v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@771baborg.highwire.dtl.DTLVardef@1b9b13corg.highwire.dtl.DTLVardef@22e85corg.highwire.dtl.DTLVardef@1c50edc_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Effects of hippocampal noninvasive theta-burst stimulation on consolidation of associative memory in healthy older adults

Stimulation of deep brain areas can offer benefits against cognitive impairments associated with aging. So far, this was only possible via invasive methods accompanied by risks. Grossman et al. proposed a new noninvasive stimulation technique, transcranial temporal interference electric stimulation (tTIS), which can be steered to target and modulate activity of deep brain structures. Memory capacity depends on subcortical structures such as the hippocampus, hence, modulation of hippocampal activity could benefit declining cognitive functions. The current study investigates whether theta-burst patterned tTIS targeting the hippocampus influences performance of associative memory in older adults. We found that theta-burst patterned tTIS, but not the control stimulation, improved recollection time in a follow-up 24h after the stimulation, suggesting that theta-burst patterned tTIS can influence the efficiency of longer-term encoding. This outcome indicates that tTIS may provide a new noninvasive deep brain stimulation method to modulate senescent memory processes.

neuroscience↗

bioRxiv2022

Perfect Timing: Effects of Auditory Stimulation on Alpha Oscillations During Wakefulness and the Transition to Sleep are Phase-dependent in Humans

Alpha oscillations play a vital role in managing the brains resources, inhibiting neural activity as a function of their phase and amplitude, and are changed in many brain disorders. Developing minimally invasive tools to modulate alpha activity and identifying the parameters that determine its response to exogenous modulators, is essential for the implementation of focussed interventions. We introduce Alpha Closed-Loop Auditory Stimulation (CLAS) as an EEG-based method to augment and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across three independent studies, we demonstrate that CLAS alters alpha power, frequency, and connectivity in a phase, amplitude and topography-dependent manner. Using a single-pulse-CLAS evoked potentials approach we show that the effects of auditory stimuli on alpha oscillations and resulting evoked potentials can be explained within the theoretical framework of oscillator theory and a phase-reset mechanism. Finally, we demonstrate the functional relevance of our approach by showing that CLAS modulates sleep onset dynamics in an alpha phase-dependent manner.

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bioRxiv2022

LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here, we show for the first time successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, fMRI studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional roles. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

neuroscience↗

bioRxiv2022

Non-invasive temporal interference electrical stimulation of the human hippocampus

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders however its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modelling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging (fMRI) and behaviour experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.

neuroscience↗

bioRxiv2020

Mapping the common and distinct neural correlates of visual, rule and motor conflict

Flexible behaviour requires cognitive-control mechanisms to efficiently resolve conflict between competing information and alternative actions. Whether a global neural resource mediates all forms of conflict or this is achieved within domainspecific systems remains debated. We use a novel fMRI paradigm to orthogonally manipulate rule, response and stimulus-based conflict within a full-factorial design. Whole-brain voxelwise analyses show that activation patterns associated with these conflict types are distinct but partially overlapping within Multiple Demand Cortex (MDC), the brain regions that are most commonly active during cognitive tasks. Region of interest analysis shows that most MDC sub-regions are activated for all conflict types, but to significantly varying levels. We propose that conflict resolution is an emergent property of distributed brain networks, the functional-anatomical components of which place on a continuous, not categorical, scale from domain-specialised to domain general. MDC brain regions place towards one end of that scale but display considerable functional heterogeneity.

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bioRxiv2020

Investigating the interaction between white matter and brain state on tDCS-induced changes in brain network activity

BackgroundTranscranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure. ObjectivesIn this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. MethodsWe applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n=22) and TBI participants (n=34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure. ResultsWe find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region. ConclusionsOur results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation.

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bioRxiv2020

Preferential activation of the posterior Default-Mode Network with sequentially predictable task switches.

The default-mode network (DMN) has been primarily associated with internally-directed and self-relevant cognition. This perspective is expanding to recognise its importance in executive behaviours like switching. We investigated the effect different task-switching manipulations have on DMN activation in two studies with novel fMRI paradigms. In the first study, the paradigm manipulated visual discriminability, visuo-perceptual distance and sequential predictability during switching. Increased posterior cingulate/precuneus (PCC/PrCC) activity was evident during switching; critically, this was strongest when the occurrence of the switch was predictable. In the second study, we sought to replicate and further investigate this switch-related effect with a fully factorial design manipulating sequential, spatial and visual-feature predictability. Whole-brain analysis again identified a PCC/PrCC-centred cluster that was more active for sequentially predictable versus unpredictable switches, but not for the other predictability dimensions. We propose PCC/PrCC DMN subregions may play a prominent executive role in mapping the sequential structure of complex tasks.

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bioRxiv2017

Assessing tACS-induced phosphene perception using closed-loop Bayesian optimization

Transcranial alternating current stimulation (tACS) can evoke illusory flash-like visual percepts known as phosphenes. The perception of phosphenes represents a major experimental challenge when studying tACS-induced effects on cognitive performance. Besides growing concerns that retinal phosphenes themselves could potentially have neuromodulatory effects, the perception of phosphenes may also modify the alertness of participants. Past research has shown that stimulation intensity, frequency and electrode montage affect phosphene perception. However, to date, the effect of an additional tACS parameter on phosphene perception has been completely overlooked: the relative phase difference between stimulation electrodes. This is a crucial and timely topic given the confounding nature of phosphene perception and the increasing number of studies reporting changes in cognitive function following tACS phase manipulations. However, studying phosphene perception for different frequencies and phases simultaneously is not tractable using standard approaches, as the physiologically plausible range of parameters results in a combinatorial explosion of experimental conditions, yielding impracticable experiment durations. To overcome this limitation, here we applied a Bayesian optimization approach to efficiently sample an exhaustive tACS parameter space. Moreover, unlike conventional methodology, which involves subjects judging the perceived phosphene intensity on a rating scale, our study leveraged the strength of human perception by having the optimization driven based on a subjects relative judgement. Applying Bayesian optimization for two different montages, we found that phosphene perception was affected by differences in the relative phase between cortical electrodes. The results were replicated in a second study involving new participants and validated using computational modelling. In summary, our results have important implications for the experimental design and conclusions drawn from future tACS studies investigating the effects of phase on cognition.

neuroscience↗

bioRxiv2017

Dissociating frontoparietal brain networks with neuroadaptive Bayesian optimization

Understanding the unique contributions of frontoparietal networks (FPN) in cognition is challenging because different FPNs spatially overlap and are co-activated for diverse tasks. In order to characterize these networks involves studying how they activate across many different cognitive tasks, which previously has only been possible with meta-analyses. Here, building upon meta-analyses as a starting point, we use neuroadaptive Bayesian optimization, an approach combining real-time analysis of functional neuroimaging data with machine-learning, to discover cognitive tasks that dissociate ventral and dorsal FPN activity from a large pool of tasks. We identify and subsequently refine two cognitive tasks (Deductive Reasoning and Tower of London) that are optimal for dissociating the FPNs. The identified cognitive tasks are not those predicted by meta-analysis, highlighting a different mapping between cognitive tasks and FPNs than expected. The optimization approach converged on a similar neural dissociation independently for the two different tasks, suggesting a possible common underlying functional mechanism and the need for neurally-derived cognitive taxonomies.

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