Stimulus Direction Research Articles

Perception of postural verticality in roll and pitch while sitting and standing in healthy subjects

Assessment of verticality perception is increasingly used in patients with disorders of upright body orientation, e.g. in pusher behavior after hemispheric stroke or in retropulsion in neurovascular or degenerative diseases. The subjective postural vertical (SPV) assesses the individual’s perceived upright body orientation in space and can be determined in a sitting or a standing position. As somatosensory input differs between sitting and standing, we suppose a different representation of verticality. Thus, the aim of this study was to compare the SPV while sitting and while standing, and to determine the influence of proprioceptive and visual stimulations on the SPV in both positions.Twenty healthy subjects (18–40 years, 9 female) participated in two experiments. In experiment 1 the SPV was assessed in the pitch and roll planes while sitting and standing. In experiment 2 we additionally applied somatosensory Achilles tendon vibration and visual optokinetic stimulation.Results of experiment 1 revealed no difference of the SPV error between sitting and standing. Though, we found an increased SPV variability while sitting. Experiment 2 showed no effect of sensory manipulation in the pitch plane, but an effect of optokinetic stimulation in the roll plane. The tilt in direction of the visual stimuli was more pronounced while sitting. Optokinetic stimulation also resulted in a larger SPV variability in roll, indicating larger insecurity in verticality estimation during stimulation.In conclusion, even though the SPV assessment while sitting and standing resulted in similar mean values, the larger variability and the higher sensitivity to visual stimuli while sitting suggest different strategies for verticality estimation while sitting and while standing.

Pop-out for illusory rather than veridical trajectories with double-drift stimuli.

If a patch of texture drifts in one direction while its internal texture drifts in the orthogonal direction, the perceived direction of this double-drift stimulus (also known as the infinite regress and curveball illusions) deviates strongly from its physical direction. Here, we use double-drift stimuli to construct two types of search arrays: The first had an oddball target in terms of the physical trajectories, but no oddball for the perceived trajectory, whereas the second had a perceptual oddball, but no physical oddball. We used these two arrays to determine whether pop-out operates over physical or perceived trajectories. Participants reported the location of the odd double-drift stimulus that had either a unique physical or perceived trajectory in a set of four or eight items. When the distractors all shared one perceived trajectory, but the target had an odd perceived trajectory, it popped out even though the physical trajectories of the stimuli were mixed: Accuracy rates were at ceiling, and response times decreased with increasing set size. In contrast, participants were significantly less accurate and slower at finding the physical oddball when all the paths had a common perceived trajectory. Moreover, responses became less accurate and slower with increasing set size. Our findings suggest that, at least for this type of stimulus, perceptual features can be processed rapidly, whereas the search for physical features is very inefficient.

Evidence for macromolecular crowding as a direct apoptotic stimulus.

Potassium loss and persistent shrinkage have both been implicated in apoptosis but their relationship and respective roles remain controversial. We approached this problem by clamping intracellular sodium and potassium in HeLa or MDCK cells using a combination of ionophores. Although ionophore treatment caused significant cell swelling, the initial volume could be restored and further reduced by application of sucrose. The swollen cells treated with ionophores remained viable for at least 8 h without any signs of apoptosis. Application of sucrose and the resulting shrinkage caused volume-dependent intrinsic apoptosis with all its classical features: inversion of phosphatidylserine, caspase activation and Bcl-2-dependent release of cytochrome c from mitochondria. In other experiments, apoptosis was induced by addition of the protein kinase inhibitor staurosporine at various degrees of swelling. Our results show that: (1) persistent shrinkage can cause apoptosis regardless of intracellular sodium or potassium composition or of the state of actin cytoskeleton; (2) strong potassium dependence of caspase activation is only observed in swollen cells with a reduced density of cytosolic proteins. We conclude that macromolecular crowding can be an important factor in determining the transition of cells to apoptosis.

Training With Direct Versus Indirect Spatial Stimulus–Response Compatibility in Combat Sports

The study examined effects of spatial stimulus-response compatibility on response time and response accuracy in 20 novice combat sport athletes. Two equivalent groups, based on initial reaction time measures, were required to perceive and move quickly and accurately in response to an unspecific visual stimulus presented on a large screen during the two types of perceptual training in eight laboratory sessions. One group reacted by moving the fist toward the stimulus location on the target (direct compatibility condition). Another group was required to move the fist away from target in the opposite direction (indirect compatibility condition). Specifically, the indirect compatibility group achieved faster reaction times than the direct compatibility group during the two posttests containing video-projected attacks of the opponents, and in one of the two posttests containing real opponents' attacks. Results seem to reveal higher combat performance against real opponents when athletes trained with an indirect stimulus-response compatibility condition.

Emotion-behavior decoupling in individuals with schizophrenia, bipolar disorder, and major depressive disorder.

Failure in translating emotional salience into effortful behavior is thought to be a core feature of anhedonia and avolition in individuals with schizophrenia (SCZ), but little is known about emotion-behavior coupling in individuals with bipolar disorder (BD) and major depressive disorder (MDD). In this study, we compared emotion-behavior correspondence in participants with SCZ, BD, and MDD. Forty-two participants with SCZ, 44 participants with MDD, 43 participants with BD, and 43 healthy controls were recruited. A computerized anticipatory and consummatory pleasure task was used to evaluate emotion-behavior correspondence. Clinical ratings of negative symptoms and self-report anhedonia questionnaires were also administered. We found that participants with SCZ, MDD, and BD exhibited different levels of negative symptoms and self-reported anhedonia, as well as emotion-behavior decoupling. In SCZ participants, both desirable and undesirable images elicited lower correspondence between self-reported liking and behavior. In MDD and BD participants, undesirable images elicited lower emotion-behavior correspondence under both direct stimulus presentation and representation conditions, whereas deficits in emotion-behavior coupling under desirable conditions were only observed when stimuli were present. Taken together, emotion-behavior decoupling showed both common and unique patterns in participants with SCZ, MDD, and BD, and showed some associations with negative symptoms and anhedonia across the combined clinical sample. This finding may be helpful for early identification and the development of novel interventions for different psychiatric diagnoses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Is There a Link between Stress and Cognition, and Capacity to Execute Motor Skill?

This study aimed to examine the link between stress (measured via salivary cortisol and testosterone), cognition (measured via pupillometry, with greater pupil constriction and reduced pupil constriction latency associated with increased attention and improved information processing), and motor skill capacity (measured via somatosensory processing). Twenty-five professional rugby players participated in this study. Saliva samples were collected upon waking, before pupillometry and somatosensory processing testing, and after testing. Testing times varied for participants; however, it was always in the morning, and the order of testing was randomized. Very small differences in hormone concentrations were seen across the morning (effect size = 0.01). Moderate to large differences in left eye pupil constriction for direct (left eye) versus consensual (right eye) stimulus were also seen (P < 0.01; effect size = 0.51 to 1.04). No differences for pupil constriction latency were seen for direct versus consensual stimulus. Some positive weak to moderate relationships were seen for testosterone and pupil constriction latency (r = 0.37 to 0.39, P < 0.05). Moderate to strong inverse relationships were seen for hormones with left eye pupil constriction difference between direct and consensual stimulus, and for pre- to posttest testosterone-to-cortisol ratio decline with left eye pupil constriction for direct and consensual stimulus (r = 0.41 to 0.52, P < 0.05). Weak to moderate inverse relationships for testosterone-to-cortisol ratio decline and somatosensory processing were seen (r = 0.36 to 0.47, P < 0.05). Stress may affect ability to receive information and ability to execute motor tasks. Thus, stress may compromise ability to make appropriate objective decisions and consequently execute skill/task behavior. Strategies to help mitigate negative stress responses are noted.

Relative posture between head and finger determines perceived tactile direction of motion

The hand explores the environment for obtaining tactile information that can be fruitfully integrated with other functions, such as vision, audition, and movement. In theory, somatosensory signals gathered by the hand are accurately mapped in the world-centered (allocentric) reference frame such that the multi-modal information signals, whether visual-tactile or motor-tactile, are perfectly aligned. However, an accumulating body of evidence indicates that the perceived tactile orientation or direction is inaccurate; yielding a surprisingly large perceptual bias. To investigate such perceptual bias, this study presented tactile motion stimuli to healthy adult participants in a variety of finger and head postures, and requested the participants to report the perceived direction of motion mapped on a video screen placed on the frontoparallel plane in front of the eyes. Experimental results showed that the perceptual bias could be divided into systematic and nonsystematic biases. Systematic bias, defined as the mean difference between the perceived and veridical directions, correlated linearly with the relative posture between the finger and the head. By contrast, nonsystematic bias, defined as minor difference in bias for different stimulus directions, was highly individualized, phase-locked to stimulus orientation presented on the skin. Overall, the present findings on systematic bias indicate that the transformation bias among the reference frames is dominated by the finger-to-head posture. Moreover, the highly individualized nature of nonsystematic bias reflects how information is obtained by the orientation-selective units in the S1 cortex.

Common causation and offset effects in human visual-inertial heading direction integration.

Movement direction can be determined from a combination of visual and inertial cues. Visual motion (optic flow) can represent self-motion through a fixed environment or environmental motion relative to an observer. Simultaneous visual and inertial heading cues present the question of whether the cues have a common cause (i.e., should be integrated) or whether they should be considered independent. This was studied in eight healthy human subjects who experienced 12 visual and inertial headings in the horizontal plane divided in 30° increments. The headings were estimated in two unisensory and six multisensory trial blocks. Each unisensory block included 72 stimulus presentations, while each multisensory block included 144 stimulus presentations, including every possible combination of visual and inertial headings in random order. After each multisensory stimulus, subjects reported their perception of visual and inertial headings as congruous (i.e., having common causation) or not. In the multisensory trial blocks, subjects also reported visual or inertial heading direction (3 trial blocks for each). For aligned visual-inertial headings, the rate of common causation was higher during alignment in cardinal than noncardinal directions. When visual and inertial stimuli were separated by 30°, the rate of reported common causation remained >50%, but it decreased to 15% or less for separation of ≥90°. The inertial heading was biased toward the visual heading by 11-20° for separations of 30-120°. Thus there was sensory integration even in conditions without reported common causation. The visual heading was minimally influenced by inertial direction. When trials with common causation perception were compared with those without, inertial heading perception had a stronger bias toward visual stimulus direction.NEW & NOTEWORTHY Optic flow ambiguously represents self-motion or environmental motion. When these are in different directions, it is uncertain whether these are integrated into a common perception or not. This study looks at that issue by determining whether the two modalities are consistent and by measuring their perceived directions to get a degree of influence. The visual stimulus can have significant influence on the inertial stimulus even when they are perceived as inconsistent.

The Effect of Optical Flow Motion Direction on Vection Strength.

In some phenomena of visual perception, the motion direction of visual stimuli can affect perception. In particular, asymmetries between oblique directions and cardinal (horizontal and vertical) directions have been reported and are known as oblique effects (e.g., contrast sensitivity and motion threshold). In this study, we investigated how vection strength depends on motion direction. Participants observed random-dot optical flow in a circular field and rated the perceived vection strength. Dot movement was systematically controlled using the following angles: 0° (up), 30°, 45°, 60°, 90°, 120°, 135°, 150°, and 180° (down). We found that vection strength depended on motion direction and was weaker in the oblique directions than cardinal directions. Thus, the effect of motion direction on vection strength was variable, as seen in the shape of the oblique effect.

Technological innovation management: Case study with enterprises in the peanut-processing sector

Technological innovations are the basis of the development of new products, production processes, and business formats, contributing decisively to the success of contemporary business strategies. Recognition of the importance of this issue to the development of enterprises and regions has been reflected in an array of studies and theoretical models seeking to improve technological innovation management in organizations. The present study is part of this context. Based on a broad literature review, it uses knowledge about technological innovation management to propose and test a theoretical analytical framework to evaluate and contribute to the improvement of the innovation management process in manufacturing enterprises. The various theoretical constructs used to create the proposed analytical framework address aspects specific to the success of the technological innovation process. Although it is important to deepen the focal point prioritized by the constructs in their analysis, by focusing on specific factors, they can bias the manager’s perspective or hinder a more holistic and complete view of the problem. The proposed framework was tested using three case studies in the peanut agrifood business in the State of São Paulo, Brazil. Main results show that it was capable of capturing the differences in how the studied enterprises carried out technological management. The three companies were classified into one of two groups. The first prioritized process innovation, which responds to direct stimuli from the companies that purchase their product. These companies do not sell directly to end consumers but to other processing companies. The second group privileged product innovation guided by the demands of the final consumer market. The analyses carried out provide data to establish technological management processes adapted to the competitive strategies of the investigated organizations.

SPARC Regulation of PMN Clearance Protects from Pristane Induced Lupus and Rheumatoid Arthritis

One step along the pathogenesis of Systemic lupus erythematosus (SLE) is associated with polymorphonuclear leukocyte (PMN) death and their ineffective removal by M2-macrophages. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in M2-macrophages and myeloid cells. To investigate the role of SPARC in autoimmunity, we adopted a pristane–induced model of lupus in mice, which recapitulates clinical manifestations of human SLE. Sparc-/- mice developed earlier and more severe renal disease, lung and liver parenchymal damage than the WT counterpart. Most prominently, Sparc-/- mice had anticipated and severe occurrence of arthritis. An intermediate phenotype was obtained in Sparc-/- hemizygous mice, a result that suggests Sparc gene-dosage as relevant in autoimmune-related events. Mechanistically, a defective Sparc expression in PMN blocks their clearance by macrophages, through a defective delivery of eat-me and don’t eat-me signals. Sparc-/- PMN that escape macrophage scavenging becomes a source of autoantigens for dendritic cell (DC) presentation and a direct stimulus for IL-17 expression in γδ-T-cells. Gene profile analysis of synovial biopsies of knees affected by SLE-associated arthritis showed an inverse correlation between SPARC and key autoimmune genes. These results point to SPARC down-regulation as a key event characterizing SLE and associated rheumatoid arthritis pathogenesis.

HOPS/TMUB1 retains p53 in the cytoplasm and sustains p53-dependent mitochondrial apoptosis.

Apoptotic signalling by p53 occurs at both transcriptional and non-transcriptional levels, as p53 may act as a direct apoptogenic stimulus via activation of the intrinsic mitochondrial pathway. HOPS is a highly conserved, ubiquitously expressed shuttling protein with an ubiquitin-like domain. We generated Hops-/- mice and observed that they are viable with no apparent phenotypic defects. However, when treated with chemotherapeutic agents, Hops-/- mice display a significant reduction in apoptosis, suggesting an impaired ability to respond to genotoxic stressors. We show that HOPS acts as a regulator of cytoplasmic p53 levels and function. By binding p53, HOPS inhibits p53 proteasomal degradation and favours p53 recruitment to mitochondria and apoptosis induction. By interfering with importin α, HOPS further increases p53 cytoplasmic levels. Thus, HOPS promotes the p53-dependent mitochondrial apoptosis pathway by preserving cytoplasmic p53 from both degradation and nuclear uptake.

Motor Behavior Selectively Inhibits Hair Cells Activated by Forward Motion in the Lateral Line of Zebrafish

SummaryHow do sensory systems disambiguate events in the external world from signals generated by the animal’s own motor actions? One strategy is to use an “efference copy” of the motor command to inhibit the sensory input caused by active behavior [1]. But does inhibition of self-generated inputs also block transmission of external stimuli? We investigated this question in the lateral line, a sensory system that allows fish and amphibians to detect water currents and that contributes to behaviors such as rheotaxis [2] and predator avoidance [3, 4]. This mechanical sense begins in hair cells grouped into neuromasts dotted along the animal’s body [5]. Each neuromast contains two populations of hair cells, activated by deflection in either the anterior or posterior direction [6], as well as efferent fibers that are active during motor behavior to suppress afferents projecting to the brain [7, 8, 9, 10, 11, 12]. To test how far the efference copy signal modulates responses to external stimuli, we imaged neural and synaptic activity in larval zebrafish during fictive swimming. We find that efferents transmit a precise copy of the motor signal and a single spike in the motor nerve can be associated with ∼50% inhibition of glutamate release. The efference copy signal acted with high selectivity on hair cells polarized to be activated by posterior deflections, as would occur during forward motion. During swimming, therefore, “push-pull” encoding of stimulus direction by afferents of opposite polarity is disrupted while still allowing a subset of hair cells to detect stimuli originating in the external world.

Asymmetric Unilateral Vestibular Perception in Adolescents With Idiopathic Scoliosis.

The cause of Adolescent Idiopathic Scoliosis (AIS) remains unclear, but one proposed cause of AIS is asymmetric vestibular function and the related descending drive to the spine musculature. The objective of this study was to determine if asymmetric vestibular function is present in individuals with AIS. Ten individuals with AIS (8F, 2M) and 10 healthy age- and sex-matched controls were exposed to 10s-long virtual rotations induced by monaural or binaural electrical vestibular stimulation (EVS), and 10s-long real rotations delivered by a rotating chair. Using a forced-choice paradigm, participants indicated their perceived rotation direction (right or left) to stimuli of varying intensity. A Bayesian adaptive algorithm adjusted the stimulus intensity and direction to identify a stimulus level, which we called the direction recognition threshold, at which participants correctly identified the rotation direction 69% of the time. For unilateral vestibular stimuli (monaural EVS), the direction recognition thresholds were more asymmetric in all participants with AIS compared to control participants [(0.22–1.00 mA) vs. (0.01–0.21 mA); p < 0.001]. For bilateral vestibular stimuli, however, the direction recognition thresholds did not differ between groups for either the real or virtual rotations (multiple p > 0.05). Previous reports of semicircular canal orientation asymmetry in individuals with AIS could not explain the magnitude of the vestibular function asymmetry we observed, suggesting a functional cause to the observed vestibular asymmetry. Thus, the present results suggest that a unilateral vestibular dysfunction is linked to AIS, potentially revealing a new path for the screening and monitoring of scoliosis in adolescents.

The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons

BackgroundAlthough neuronal extracellular sensing is emerging as crucial for brain wiring and therefore plasticity, little is known about these processes in neurodevelopmental disorders. Ubiquitin protein ligase E3A (UBE3A) plays a key role in neurodevelopment. Lack of UBE3A leads to Angelman syndrome (AS), while its increase is among the most prevalent genetic causes of autism (e.g., Dup15q syndrome). By using microstructured substrates that can induce specific directional stimuli in cells, we previously found deficient topographical contact guidance in AS neurons, which was linked to a dysregulated activation of the focal adhesion pathway.MethodsHere, we study axon and dendrite contact guidance and neuronal morphological features of wild-type, AS, and UBE3A-overexpressing neurons (Dup15q autism model) on micrograting substrates, with the aim to clarify the role of UBE3A in neuronal guidance.ResultsWe found that loss of axonal contact guidance is specific for AS neurons while UBE3A overexpression does not affect neuronal directional polarization along microgratings. Deficits at the level of axonal branching, growth cone orientation and actin fiber content, focal adhesion (FA) effectors, and actin fiber–binding proteins were observed in AS neurons. We tested different rescue strategies for restoring correct topographical guidance in AS neurons on microgratings, by either UBE3A protein re-expression or by pharmacological treatments acting on cytoskeleton contractility. Nocodazole, a drug that depolymerizes microtubules and increases cell contractility, rescued AS axonal alignment to the gratings by partially restoring focal adhesion pathway activation. Surprisingly, UBE3A re-expression only resulted in partial rescue of the phenotype.ConclusionsWe identified a specific in vitro deficit in axonal topographical guidance due selectively to the loss of UBE3A, and we further demonstrate that this defective guidance can be rescued to a certain extent by pharmacological or genetic treatment strategies. Overall, cytoskeleton dynamics emerge as important partners in UBE3A-mediated contact guidance responses. These results support the view that UBE3A-related deficits in early neuronal morphogenesis may lead to defective neuronal connectivity and plasticity.

Modeling functional resting-state brain networks through neural message passing on the human connectome

In this work, we propose a natural model for information flow in the brain through a neural message-passing dynamics on a structural network of macroscopic regions, such as the human connectome (HC). In our model, each brain region is assumed to have a binary behavior (active or not), the strengths of interactions among them are encoded in the anatomical connectivity matrix defined by the HC, and the dynamics of the system is defined by the Belief Propagation (BP) algorithm, working near the critical point of the network. We show that in the absence of direct external stimuli the BP algorithm converges to a spatial map of activations that is similar to the Default Mode Network (DMN) of the brain, which has been defined from the analysis of functional MRI data. Moreover, we use Susceptibility Propagation (SP) to compute the matrix of long-range correlations between the different regions and show that the modules defined by a clustering of this matrix resemble several Resting State Networks (RSN) determined experimentally. Both results suggest that the functional DMN and RSNs can be seen as simple consequences of the anatomical structure of the brain and a neural message-passing dynamics between macroscopic regions. With the new model, we explore predictions on how functional maps change when the anatomical brain network suffers structural alterations, like in Alzheimer’s disease and in lesions of the Corpus Callosum. The implications and novel interpretations suggested by the model, as well as the role of criticality, are discussed.

Dissociating Sensory and Cognitive Biases in Human Perceptual Decision-Making: A Re-evaluation of Evidence From Reference Repulsion.

Our perception of the world is governed by a combination of bottom-up sensory and top-down cognitive processes. This often begs the question whether a perceptual phenomenon originates from sensory or cognitive processes in the brain. For instance, reference repulsion, a compelling visual illusion in which the subjective estimates about the direction of a motion stimulus are biased away from a reference boundary, is previously thought to be originated at the sensory level. Recent studies, however, suggest that the misperception is not sensory in nature but rather reflects post-perceptual cognitive biases. Here I challenge the post-perceptual interpretations on both empirical and conceptual grounds. I argue that these new findings are not incompatible with the sensory account and can be more parsimoniously explained as reflecting the consequences of motion representations in different reference frames. Finally, I will propose one concrete experiment with testable predictions to shed more insights on the sensory vs. cognitive nature of this visual illusion.

Delayed mite hatching in response to mechanical stimuli simulating egg predation attempts

Delayed or induced hatching in response to predation risk has been reported mainly in aquatic systems, where waterborne cues from predators and injured neighbouring eggs are available. Newly emerged larvae of the terrestrial predatory mite Neoseiulus womersleyi are vulnerable to predation by con- and heterospecific predatory mites, whereas their eggs are not. We examined whether N. womersleyi embryos delay hatching in response to artificial mechanical stimuli that simulates egg predation attempts. When embryos near the hatching stage were artificially stimulated every 5 min for 60 min, most stopped hatching for the duration of the 60-min period, whereas unstimulated embryos did not. Stimulated embryos resumed hatching when the treatment was stopped, and the proportion of hatched stimulated embryos caught up with that of unstimulated embryos within 120 min after stimuli stopped. Since hatching did not stop in response to changes in gravity direction, the effect of direct mechanical stimuli on the eggs was considered a proximate factor in delayed hatching. These results suggest that N. womersleyi embryos recognise immediate predation risk via mechanical stimuli, and delay hatching until the predation risk is reduced.

Quantifying Cochlear Implant Users' Ability for Speaker Identification using CI Auditory Stimuli.

Speaker recognition is a biometric modality that uses underlying speech information to determine the identity of the speaker. Speaker Identification (SID) under noisy conditions is one of the challenging topics in the field of speech processing, specifically when it comes to individuals with cochlear implants (CI). This study analyzes and quantifies the ability of CI-users to perform speaker identification based on direct electric auditory stimuli. CI users employ a limited number of frequency bands (8 ∼ 22) and use electrodes to directly stimulate the Basilar Membrane/Cochlear in order to recognize the speech signal. The sparsity of electric stimulation within the CI frequency range is a prime reason for loss in human speech recognition, as well as SID performance. Therefore, it is assumed that CI-users might be unable to recognize and distinguish a speaker given dependent information such as formant frequencies, pitch etc. which are lost to un-simulated electrodes. To quantify this assumption, the input speech signal is processed using a CI Advanced Combined Encoder (ACE) signal processing strategy to construct the CI auditory electrodogram. The proposed study uses 50 speakers from each of three different databases for training the system using two different classifiers under quiet, and tested under both quiet and noisy conditions. The objective result shows that, the CI users can effectively identify a limited number of speakers. However, their performance decreases when more speakers are added in the system, as well as when noisy conditions are introduced. This information could therefore be used for improving CI-user signal processing techniques to improve human SID.

Nanostructured Materials for Intracellular Cargo Delivery.

Intracellular cargo delivery is an essential step in many biomedical applications including gene editing and biologics therapy. Examples of cargo include nucleic acids (RNA and DNA), proteins, small biomolecules, and drugs, which can vary substantially in terms of their sizes, charges, solubility, and stability. Viruses have been used traditionally to deliver nucleic acids into cells, but the method suffers from limitations such as small cargo size, safety concerns, and viral genome integration into host cells, all of which complicate therapeutic applications. Commercially available techniques using biochemicals and bulk electroporation are, in general, poorly compatible with primary cells such as human induced pluripotent stem cells and immune cells, which are increasingly important candidates for adoptive cell therapy. Nanostructures, with dimensions ranging from tens of nanometers to a few micrometers, may play a critical role in overcoming cellular manipulation and delivery challenges and provide a powerful alternative to conventional techniques. A critical feature that differentiates nanostructures from viral, biochemical, and bulk electroporation techniques is that they interface with cells at a scale measuring ten to hundreds of nanometers in size. This highly local interaction enables application of stronger and more direct stimuli such as mechanical force, heat, or electric fields than would be possible in a bulk treatment. Compared to popular viral, biochemical, and bulk electroporation methods, nanostructures were found to minimally perturb cells with cells remaining in good health during postdelivery culture. These advantages have enabled nanostructures such as nanowires and nanotubes to successfully interface with a wide variety of cells, including primary immune cells and cardiomyocytes, for in vitro and in vivo applications. This Account is focused on using nanostructures for cargo delivery into biological cells. In this Account, we will first outline the historical developments using nanostructures for interfacing with cells. We will highlight how mechanistic understanding of nano-bio interactions has evolved over the last decade and how this improved knowledge has motivated coupling of electric and magnetic fields to nanostructures to improve delivery outcomes. There will also be an in-depth discussion on the merits of nanostructures in comparison to conventional methods using viruses, biochemicals, and bulk electroporation. Finally, motivated by our observations on the lack of consistency in reporting key metrics such as efficiency in literature, we suggest a set of metrics for documenting experimental results with the aim to promote standardization in reporting and ease in comparing. We suggest the use of more sophisticated tools such as RNA transcriptomics for thorough assessment of cell perturbation attributed to intracellular delivery. We hope that this Account can effectively capture the progress of nanostructure-mediated cargo delivery and encourage new innovations.