Sequence Of Stimuli Research Articles

Stereodivergent Macrocyclization in Dynamic Chiral Confinement

The absolute and relative configurations of a macrocyclic natural product bearing multiple chirality have a crucial influence on its physical and biological properties. Nevertheless, their preparation with full stereocontrol remains largely unexplored in synthetic community. Here, we show a stereodivergent macrocyclization under dynamic chiral confinement in which the stepwise chirality switching of a chiral space directs complete stereocontrol. To confine a substrate in a dynamic chiral space, we used a chiral capsule enclosing a substrate which is collectively switchable in the chirality in response to external stimuli, but their conformations are firmly fixed by subsequent self‐assembly. The consecutive chirality switching enables the confined reactions of an enclosed achiral substrate to sequentially install diverse chirality on a macrocycle product with full stereocontrol in a single pot operation, thus changing only a sequence of physical stimuli enables access to a remarkable stereodivergence in a macrocyclization process.

Trans-retinal predictive signals of visual features are precise, saccade-specific and operate over a wide range of spatial frequencies.

Saccadic eye movements successively project the saccade target on two retinal locations: a peripheral one before the saccade, and the fovea after the saccade. Typically, performance in discriminating stimulus features changes between these two projections is very poor. However, a short (~ 200 ms) blanking of the target upon saccade onset drastically improves performance, demonstrating that a precise signal of the peripheral projection is retained during the saccade. While little is known about the nature of that transsaccadic signal, previous reports conjectured that it relies on information processed by the magnocellular system. Across two experiments, we investigated the feature blanking effect for a wide range of spatial frequencies (0.5 to 8 cycles per degree of visual angle, dva), stimulus sizes (1 to 4 dva) and eccentricities (6 to 10 dva). In each trial, participants executed a saccade to a high-contrast grating presented either left or right of fixation. During the saccade, the grating changed orientation (clockwise or counter-clockwise) either instantaneously or after a 200 ms blank, and participants reported the change's direction. We contrasted this saccade condition with a trans-retinal fixation condition mimicking the peripheral-then-foveal sequence of the target stimulus occurring across a saccade. Remarkably, blanking improved performance reliably for each spatial frequency, stimulus size, and eccentricity, but only in the saccade condition. Performance with blanking in saccade trials systematically exceeded performance in the fixation condition. Our results demonstrate a robust feature blanking effect across saccades, suggesting that transsaccadic processes involve low-level visual features beyond those processed in the magnocellular system.

Perturbation context in paced finger tapping tunes the error-correction mechanism

Sensorimotor synchronization (SMS) is the mainly specifically human ability to move in sync with a periodic external stimulus, as in keeping pace with music. The most common experimental paradigm to study its largely unknown underlying mechanism is the paced finger-tapping task, where a participant taps to a periodic sequence of brief stimuli. Contrary to reaction time, this task involves temporal prediction because the participant needs to trigger the motor action in advance for the tap and the stimulus to occur simultaneously, then an error-correction mechanism takes past performance as input to adjust the following prediction. In a different, simpler task, it has been shown that exposure to a distribution of individual temporal intervals creates a “temporal context” that can bias the estimation/production of a single target interval. As temporal estimation and production are also involved in SMS, we asked whether a paced finger-tapping task with period perturbations would show any time-related context effect. In this work we show that a perturbation context can indeed be generated by exposure to period perturbations during paced finger tapping, affecting the shape and size of the resynchronization curve. Response asymmetry is also affected, thus evidencing an interplay between context and intrinsic nonlinearities of the correction mechanism. We conclude that perturbation context calibrates the underlying error-correction mechanism in SMS.

Do smaller P300 amplitudes in schizophrenia result from larger variability in temporal processing?

The P3b is a prominent event-related potential (ERP) with maximal amplitude between 250 ms and 500 ms after the onset of a rare target stimulus within a sequence of standard non-target stimuli (oddball paradigm). Several studies found reduced P3b amplitudes in patients with schizophrenia compared to neurotypicals. Our work and the literature suggest that temporal imprecision may play a large pathophysiological role in schizophrenia. Here, we investigated whether reduced P3b amplitudes result from reduced neural activity (power) or temporal imprecision (inter-trial phase coherence; ITC) in delta and theta bands, using two EEG datasets from different studies with different oddball paradigms (Study 1: 19 patients with schizophrenia and 17 matched controls, Study 2: 26 patients and 26 controls). Both studies revealed typical P3b ERP components with smaller amplitudes in patients. Reduced ITC in patients was found in the delta band, which correlated with P3b peak amplitudes for all participant groups (ρ = 0.58–0.89). In Study 1, we also found significant differences between patients and controls in ITC in the theta band, which also correlated with P3b peak amplitudes (patients’ ρ = 0.64, controls’ ρ = 0.54). This was not found in Study 2. The results indicate that P3b amplitude reduction in patients with schizophrenia is linked to a reduction in temporal precision of neural activity. These results expand the notion of imprecision in temporal processing at phenomenological, psychological, and neurological levels that have been related to disturbances of the sense of self. They confirm that temporal imprecision may be more important than the reduction of neural activity itself.

Long sequence Hopfield memory*

Abstract Sequence memory is an essential attribute of natural and artificial intelligence that enables agents to encode, store, and retrieve complex sequences of stimuli and actions. Computational models of sequence memory have been proposed where recurrent Hopfield-like neural networks are trained with temporally asymmetric Hebbian rules. However, these networks suffer from limited sequence capacity (maximal length of the stored sequence) due to interference between the memories. Inspired by recent work on Dense Associative Memories, we expand the sequence capacity of these models by introducing a nonlinear interaction term, enhancing separation between the patterns. We derive novel scaling laws for sequence capacity with respect to network size, significantly outperforming existing scaling laws for models based on traditional Hopfield networks, and verify these theoretical results with numerical simulation. Moreover, we introduce a generalized pseudoinverse rule to recall sequences of highly correlated patterns. Finally, we extend this model to store sequences with variable timing between states’ transitions and describe a biologically-plausible implementation, with connections to motor neuroscience.

Comparing Static and Dynamic Vibration Cues in Wristband Haptic Feedback for Enhanced Driver Response in Automated Vehicles

Higher levels of driving automation make effective takeover requests critical. The wrist’s sensitivity to vibration makes wristband devices a potential carrier for sending these requests. However, the impacts of conveying takeover requests through directional vibrotactile patterns such as dynamic patterns (sequential stimuli occurring at different locations on the wrist) and static patterns (fixed stimuli at the same locations on the wrist) are unclear. Therefore, this study examined the effects of directional vibrotactile patterns on takeover performance among younger and older adults. Participants responded to four patterns (two dynamic, one static, and one baseline) in a simulated SAE Level 3 automated vehicle. Takeover performance was evaluated using reaction time and takeover time. The results show that the static and baseline patterns had shorter reaction and takeover times compared to the dynamic patterns. In addition, younger adults react faster to takeover requests compared to older adults. Findings provide important insights for the future design of human-machine interfaces via wristband devices for automated vehicles.

Computation with Sequences of Assemblies in a Model of the Brain.

Even as machine learning exceeds human-level performance on many applications, the generality, robustness, and rapidity of the brain's learning capabilities remain unmatched. How cognition arises from neural activity is the central open question in neuroscience, inextricable from the study of intelligence itself. A simple formal model of neural activity was proposed in Papadimitriou etal. (2020) and has been subsequently shown, through both mathematical proofs and simulations, to be capable of implementing certain simple cognitive operations via the creation and manipulation of assemblies of neurons. However, many intelligent behaviors rely on the ability to recognize, store, and manipulate temporal sequences of stimuli (planning, language, navigation, to list a few). Here we show that in the same model, sequential precedence can be captured naturally through synaptic weights and plasticity, and, as a result, a range of computations on sequences of assemblies can be carried out. In particular, repeated presentation of a sequence of stimuli leads to the memorization of the sequence through corresponding neural assemblies: upon future presentation of any stimulus in the sequence, the corresponding assembly and its subsequent ones will be activated, one after the other, until the end of the sequence. If the stimulus sequence is presented to two brain areas simultaneously, a scaffolded representation is created, resulting in more efficient memorization and recall, in agreement with cognitive experiments. Finally, we show that any finite state machine can be learned in a similar way, through the presentation of appropriate patterns of sequences. Through an extension of this mechanism, the model can be shown to be capable of universal computation. Taken together, these results provide a concrete hypothesis for the basis of the brain's remarkable abilities to compute and learn, with sequences playing a vital role.

Distraction by unexpected sounds: comparing response repetition and response switching.

Numerous studies using oddball tasks have shown that unexpected sounds presented in a predictable or repeated sequence (deviant vs. standard sounds) capture attention and negatively impact ongoing behavioral performance. Here, we examine an aspect of this effect that has gone relatively unnoticed: the impact of deviant sounds is stronger for response repetitions than for response switches. Our approach was two-fold. First, we carried out a simulation to estimate the likelihood that stimuli sequences used in past work may not have used balanced proportions of response repetition and switch trials. More specifically, we sought to determine whether the larger distraction effect for response repetitions may have reflected a rarer, and thereby more surprising, occurrence of such trials. To do so, we simulated 10,000 stimuli sets for a 2-AFC task with a proportion of deviant trial of 0.1 or 0.16. Second, we carried out a 2-AFC oddball task in which participants judged the duration of a tone (short vs. long). We carefully controlled the sequence of stimuli to ensure to balance the proportions of response repetitions and response switches across the standard and deviant conditions. The results of the stimuli simulation showed that, contrary to our concerns, response switches were more likely than response repetitions when left uncontrolled for. This suggests that the larger distraction found for response repetition in past work may in fact have been underestimated. In the tone duration judgment task, the results showed a large impact of the response type on distraction as measured by response times: Deviants sounds significantly delayed response repetitions but notably accelerated switches. These findings suggest that deviant sound hinder response repetition and encourage or bias the cognitive system towards a change of responses. We discuss these findings in relation to the adaptive nature of the involuntary detection of unexpected stimuli and in relation to the notion of partial repetition costs. We argue that results are in line with the binding account as well as with the signaling theory.

Using the Cocktail Party Effect to Add the Coding Dimension of Auditory Event Related Potential Brain-Computer Interface.

The auditory event-related potential based brain-computer interface (aERP-BCI) is a classical paradigm of brain-computer communication. To improve the coding efficiency of aERP-BCI, this study proposes a method using two parallel voice channels to add the coding dimension based on the cocktail party effect. The novel paradigm used male and female voices to establish two parallel oddball sound stimulus sequences. In comparison, the baseline paradigm only presented male or female stimulus sequences. Both the double voice condition (DVC) and the single voice condition (SVC) paradigms carried out offline experiments and the DVC also carried out online experiment. Subsequently, the EEG signal and BCI operation results were compared and analyzed. The cocktail party effect caused a significant difference in the EEG responses of non-target stimulus between the focused vocal channel and the ignored vocal channel under the DVC paradigm, and the focused and ignored channels achieved a recognition accuracy of 97.2%. The target recognition rate of DVC was 82.3%, with no significant difference compared with 85% of SVC while the information transfer rate (ITR) of DVC reaching 15.3 bits/min was significantly higher than that of SVC. The cocktail party effect improves the coding efficiency by adding parallel channels without reducing the target/non-target stimulus recognition in the focused vocal channel. This provides a novel direction for the performance improvement of aERP-BCI.

Changes in high-frequency neural inputs to muscles during movement cancellation

Objective.Cortical beta (13-30 Hz) and gamma (30-60 Hz) oscillations are prominent in the motor cortex and are known to be transmitted to the muscles despite their limited direct impact on force modulation. However, we currently lack fundamental knowledge about the saliency of these oscillations at spinal level. Here, we developed an experimental approach to examine the modulations in high-frequency inputs to motoneurons under different motor states while maintaining a stable force, thus constraining behaviour.Approach.Specifically, we acquired brain and muscle activity during a 'GO'/'NO-GO' task. In this experiment, the effector muscle for the task (tibialis anterior) was kept tonically active during the trials, while participants (N= 12) reacted to sequences of auditory stimuli by either keeping the contraction unaltered ('NO-GO' trials), or by quickly performing a ballistic contraction ('GO' trials). Motor unit (MU) firing activity was extracted from high-density surface and intramuscular electromyographic signals, and the changes in its spectral contents in the 'NO-GO' trials were analysed.Main results.We observed an increase in beta and low-gamma (30-45 Hz) activity after the 'NO-GO' cue in the MU population activity. These results were in line with the brain activity changes measured with electroencephalography. These increases in power occur without relevant alterations in force, as behaviour was restricted to a stable force contraction.Significance.We show that modulations in motor cortical beta and gamma rhythms are also present in muscles when subjects cancel a prepared ballistic action while holding a stable contraction in a 'GO'/'NO-GO' task. This occurs while force levels produced by the task effector muscle remain largely unaltered. Our results suggest that muscle recordings are informative also about motor states that are not force-control signals. This opens up new potential use cases of peripheral neural interfaces.

A Coupled Hidden Markov Model framework for measuring the dynamics of categorization

We introduce a new framework for measuring the dynamics of category learning using Coupled Hidden Markov Models (CHMMs). The key assumptions of the framework are that people maintain a latent assignment of every stimulus to a category, and that they can update the assignments for all stimuli whenever they encounter any stimulus. These assumptions contrast with many existing accounts of category learning, which either do not allow for what is learned about one stimulus to influence the category association of others, or allow only for indirect influence. The CHMM framework allows tailored models to be developed for specific category learning tasks, taking as input the stimulus sequence and category responses people make, and producing as output inferences about the underlying dynamics of category assignments and the mechanics of the response processes. We demonstrate the framework by applying it to a categorization task considered by Lee and Navarro (2002), showing how the model measures the change in participants’ latent category assignments as they learn the category structure. We conclude by discussing potential applications of the CHMM framework to category learning situations involving prior knowledge, changing category structures, and category learning tasks that involve the consideration of multiple stimuli at one time.

Combinatorial responsiveness of single chemosensory neurons to external stimulation of mouse explants revealed by DynamicNeuronTracker.

Calcium fluorescence imaging enables us to investigate how individual neurons of live animals encode sensory input or drive specific behaviors. Extracting and interpreting large-scale neuronal activity from imaging data are crucial steps in harnessing this information. A significant challenge arises from uncorrectable tissue deformation, which disrupts the effectiveness of existing neuron segmentation methods. Here, we propose an open-source software, DynamicNeuronTracker (DyNT), which generates dynamic neuron masks for deforming and/or incompletely registered 3D calcium imaging data using patch-matching iterations. We demonstrate that DyNT accurately tracks densely populated neurons, whereas a widely used static segmentation method often produces erroneous masks. DyNT also includes automated statistical analyses for interpreting neuronal responses to multiple sequential stimuli. We applied DyNT to analyze the responses of pheromone-sensing neurons in mice to controlled stimulation. We found that four bile acids and four sulfated steroids activated 15 subpopulations of sensory neurons with distinct combinatorial response profiles, revealing a strong bias toward detecting sulfated estrogen and pregnanolone.

Dynamic, multi-color, multi-level stimulus-responsive luminescence in a co-crystallized coordination polymer: Modulation of energy transfer by acid-induced ligand protonation and photo-induced radical generation

Stimulus-responsive luminescent materials (SLMs), which can respond to external stimuli by switching their luminescence properties, hold great promise for a variety of applications. Particularly, multi-level SLMs with a logical stimulus sequence and a dynamic, multi-color transition are highly desirable for anti-counterfeiting and information encryption, but an effective design strategy is lacking. Herein, a co-crystallized coordination polymer multi-level SLM [Cd(9-AC)4]·(HAD)2·(9-HAC)2 (9-HAC for anthracene-9-carboxylic acid and AD for acridine) with dual emission centers of coordination unit ([Cd(9-AC)4]2-) and exciplex ([9-HAC/HAD]+) has been successfully constructed by a stepwise solvent process. This SLM possesses a variety of stimulus-responsive properties, including mechanochromic (MC), mechanochromic luminescence (MCL), reversible acidochromic luminescence (ACL), and reversible photochromic luminescence (PCL). Notably, both ACL and PCL properties are achieved by modulating the energy transfer process between the coordination unit and the exciplex, while there is a logical sequence between these two stimulus actions. The acid-induced activation and radical-regulated PCL performance has been exploited in the development of anti-counterfeiting and information encryption applications. This work provides an effective strategy to realize dynamic, multi-color, multi-level stimuli-responsive luminescence by modulating the energy transfer through acid-induced ligand protonation and photo-induced radical generation.

Mind the gap—What is the appropriate time interval between sequential dentine stimuli to elicit a dentine hypersensitivity pain response in clinical studies?

ObjectivesTo determine the time interval required for a tooth diagnosed with DH to recover from a stimulus (cold air-blast/tactile) and respond with a similar elicited pain response to a repeat stimulus. MethodsA single-centre, non-randomised, clinical study in healthy adult volunteers. Eligible participants with ≥1 tooth with either a qualifying Schiff score ≥2 following cold air-blast or tactile Yeaple score of ≤20 g were allocated to tactile or air-blast group. Following primary stimulation, the designated tooth was restimulated 10, 5, 2 min and immediately after initial pain cessation. Pain was recorded with participant VAS and investigator Schiff for air-blast. Results40 participants completed the study per group. There was a significant difference in VAS scores for tactile 4 delay intervals (p < 0.001) but not air-blast stimulus, and a significant difference in mean change in VAS score from immediate to two-minute delay between stimuli (8.0 tactile vs 0.8 air-blast, p = 0.011). VAS scores in response to either stimulus showed very wide variation between participants, but changes over delay intervals within participants were relatively slight. There was a significant progressive decrease in mean Schiff score with shortening delay intervals from 10 min (2.38) to stimulation immediately after pain cessation (2.15), p = 0.018. ConclusionsThe findings suggest healthy teeth recover after DH stimulation more quickly following an air-blast than tactile stimulus, with around 2 min allowing recovery from both. Many factors including habituation and pain measurement subjectivity need to be considered. It would be prudent for future studies to use of ≥3 min delays. Clinical significanceNo clinical study has attempted to determine the appropriate interval between successive stimuli in DH patients. The results will impact directly on the conduct of DH trials. These findings suggest the interval could be reduced to around 2-min, but the current standard of 5-min is sufficiently long to give valid results.

Feature binding is slow: Temporal integration explains apparent ultrafast binding.

Visual perception involves binding of distinct features into a unified percept. Although traditional theories link feature binding to time-consuming recurrent processes, Holcombe and Cavanagh (2001) demonstrated ultrafast, early binding of features that belong to the same object. The task required binding of orientation and luminance within an exceptionally short presentation time. However, because visual stimuli were presented over multiple presentation cycles, their findings can alternatively be explained by temporal integration over the extended stimulus sequence. Here, we conducted three experiments manipulating the number of presentation cycles. If early binding occurs, one extremely short cycle should be sufficient for feature integration. Conversely, late binding theories predict that successful binding requires substantial time and improves with additional presentation cycles. Our findings indicate that task-relevant binding of features from the same object occurs slowly, supporting late binding theories.

Relationships between the expectations based on the regularity of preceding sound sequences and the medial olivocochlear reflex.

Rhythms are the most natural cue for temporal anticipation because many sounds in our living environment have rhythmic structures. Humans have cortical mechanisms that can predict the arrival of the next sound based on rhythm and periodicity. Herein, we showed that temporal anticipation, based on the regularity of sound sequences, modulates peripheral auditory responses via efferent innervation. The medial olivocochlear reflex (MOCR), a sound-activated efferent feedback mechanism that controls outer hair cell motility, was inferred noninvasively by measuring the suppression of otoacoustic emissions (OAE). First, OAE suppression was compared between conditions in which sound sequences preceding the MOCR elicitor were presented at regular (predictable condition) or irregular (unpredictable condition) intervals. We found that OAE suppression in the predictable condition was stronger than that in the unpredictable condition. This implies that the MOCR is strengthened by the regularity of preceding sound sequences. In addition, to examine how many regularly presented preceding sounds are required to enhance the MOCR, we compared OAE suppression within stimulus sequences with 0-3 preceding tones. The OAE suppression was strengthened only when there were at least three regular preceding tones. This suggests that the MOCR was not automatically enhanced by a single stimulus presented immediately before the MOCR elicitor, but rather that it was enhanced by the regularity of the preceding sound sequences.

Extent of magnitude representation deficit and relationship with arithmetic skills in children with 22q11.2DS

BackgroundPrevious studies have produced conflicting results concerning the extent of magnitude representation deficit and its relationship with arithmetic achievement in children with 22q11.2 deletion syndrome. More specifically, it remains unclear whether deficits are restricted to visuospatial content or are more general and whether they could explain arithmetical impairment.MethodsFifteen 5- to 12-year-old children with 22q11.2 deletion syndrome and 23 age-matched healthy controls performed a non-symbolic magnitude comparison task. Depending on the trial, participants had to compare stimuli with high or low visuospatial load (visuospatial stimuli or temporal sequence of visual stimuli). The participants also completed a battery of arithmetic skills (ZAREKI-R) and a battery of global cognitive functioning (WISC-V or WPPSI-IV), from which working memory and visuospatial indices were derived.ResultsChildren with 22q11.2DS responded as fast as healthy controls did but received fewer correct responses, irrespective of visuospatial load. In addition, their performance in the non-symbolic magnitude comparison task did not correlate with the ZAREKI total score, while the working memory index did.ConclusionChildren with 22q11.2DS might suffer from a global magnitude representation deficit rather than a specific deficit due to visuospatial load. However, this deficit alone does not seem to be related to arithmetic achievement. Working memory might be a better concern of interest in favoring arithmetic skills in patients with 22q11.2 deletion syndrome.Trial registrationClinicaltrials, NCT04373226. Registered 16 September 2020.

Perirhinal cortex learns a predictive map of the task environment

Goal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that can progressively be decoded earlier in the trial as training advances and that generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and systemic pharmacological perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.

Measuring attentional selection of object categories using hierarchical frequency tagging.

In the present study, we used Hierarchical Frequency Tagging (Gordon etal., 2017) to investigate in electroencephalography how different levels of the neural processing hierarchy interact with category-selective attention during visual object recognition. We constructed stimulus sequences of cyclic wavelet scrambled face and house stimuli at two different frequencies (f1 = 0.8Hz and f2 = 1Hz). For each trial, two stimulus sequences of different frequencies were superimposed and additionally augmented by a sinusoidal contrast modulation with f3 = 12.5Hz. This allowed us to simultaneously assess higher level processing using semantic wavelet-induced frequency-tagging (SWIFT) and processing in earlier visual levels using steady-state visually evoked potentials (SSVEPs), along with their intermodulation (IM) components. To investigate the category specificity of the SWIFT signal, we manipulated the category congruence between target and distractor by superimposing two sequences containing stimuli from the same or different object categories. Participants attended to one stimulus (target) and ignored the other (distractor). Our results showed successful tagging of different levels of the cortical hierarchy. Using linear mixed-effects modeling, we detected different attentional modulation effects on lower versus higher processing levels. SWIFT and IM components were substantially increased for target versus distractor stimuli, reflecting attentional selection of the target stimuli. In addition, distractor stimuli from the same category as targets elicited stronger SWIFT signals than distractor stimuli from a different category indicating category-selective attention. In contrast, for IM components, this category-selective attention effect was largely absent, indicating that IM components probably reflect more stimulus-specific processing.

A Molecular Communication Perspective on Synchronization of Coupled Microfluidic-Spectroscopy.

A challenge for real-time monitoring of biochemical processes, such as cells, is detection of biologically relevant molecules. This is due to the fact that spectroscopy methods for detection may perturb the cellular environment. One approach to overcome this problem is coupled microfluidic-spectroscopy, where a microfluidic output channel is introduced in order to observe biologically relevant molecules. This approach allows for non-passive spectroscopy methods, such as mass spectrometry, to identify the structure of molecules released by the cell. Due to the non-negligible length of the microfluidic channel, when a sequence of stimuli are applied to a cell it is not straightforward to determine which spectroscopy samples correspond to a given stimulus. In this paper, we propose a solution to this problem by taking a molecular communication (MC) perspective on the coupled microfluidic-spectroscopy system. In particular, assignment of samples to a stimulus is viewed as a synchronization problem. We develop two new algorithms for synchronization in this context and carry out a detailed theoretical and numerical study of their performance. Our results show improvements over maximum-likelihood synchronization algorithms in terms of detection performance when there are uncertainties in the composition of the microfluidic channel.