A behavioral task sets an upper bound on the time required to access object memories before object segregation.

Traditional theories of vision assume that object segregation occurs before access to object memories. Yet, behavioral evidence shows that familiar configuration is a prior for segregation, and electrophysiological experiments demonstrate these memories are accessed rapidly. A behavioral index of the speed of access is lacking, however. Here we asked how quickly behavior is influenced by object memories that are accessed in the course of object segregation. We investigated whether access to object memories on the groundside of a border can slow behavior during a rapid categorization task. Participants viewed two silhouettes that depicted a real-world and a novel object. Their task was to saccade toward the real-world object as quickly as possible. Half of the nontarget novel objects were ambiguous in that a portion of a real-world object was suggested, but not consciously perceived, on the groundside of their borders. The rest of the nontargets were unambiguous. We tested whether saccadic reaction times were perturbed by the real-world objects suggested on the groundside of ambiguous novel silhouettes. In Experiments 1 and 2, saccadic reaction times were slowed when nontargets were ambiguous rather than unambiguous. Experiment 2 set an upper limit of 190 ms on the time required for object memories in grounds to influence behavior. Experiment 3 ruled out factors that could have produced longer latencies other than access to object memories. These results provide the first behavioral index of how quickly memories of objects suggested in grounds can influence behavior, placing the upper limit at 190 ms.

The subthalamic nucleus contributes to post-error slowing.

pFC is proposed to implement cognitive control via directed "top-down" influence over behavior. But how is this feat achieved? The virtue of such a descriptive model is contingent on a mechanistic understanding of how motor execution is altered in specific circumstances. In this report, we provide evidence that the well-known phenomenon of slowed RTs following mistakes (post-error slowing) is directly influenced by the degree of subthalamic nucleus (STN) activity. The STN is proposed to act as a brake on motor execution following conflict or errors, buying time so a more cautious response can be made on the next trial. STN local field potentials from nine Parkinson disease patients undergoing deep brain stimulation surgery were recorded while they performed a response conflict task. In a 2.5- to 5-Hz frequency range previously associated with conflict and error processing, the degree phase consistency preceding the response was associated with increasingly slower RTs specifically following errors. These findings provide compelling evidence that post-error slowing is in part mediated by a corticosubthalamic "hyperdirect" pathway for increased response caution.

The ground side of an object: perceived as shapeless yet processed for semantics.

Traditional theories of perception posit that only objects access semantics; abutting, patently shapeless grounds do not. Surprisingly, this assumption has been untested until now. In two experiments, participants classified silhouettes as depicting meaningful real-world or meaningless novel objects while event-related potentials (ERPs) were recorded. The borders of half of the novel objects suggested portions of meaningful objects on the ground side. Participants were unaware of these meaningful objects because grounds are perceived as shapeless. In Experiment 1, in which silhouettes were presented twice, N400 ERP repetition effects indicated that semantics were accessed for novel silhouettes that suggested meaningful objects in the ground and for silhouettes that depicted real-world objects, but not for novel silhouettes that did not suggest meaningful objects in the ground. In Experiment 2, repetition was manipulated via matching prime words. This experiment replicated the effect observed in Experiment 1. These experiments provide the first neurophysiological evidence that semantic access can occur for the apparently shapeless ground side of a border.

Transcranial focused ultrasound to the posterior cingulate cortex modulates default mode network and subjective experience: an fMRI pilot study.

Background: Transcranial focused ultrasound (TFUS) is an emerging neuromodulation tool for temporarily altering brain activity and probing network functioning. The effects of TFUS on the default mode network (DMN) are unknown. Objective: The study examined the effects of transcranial focused ultrasound (TFUS) on the functional connectivity of the default mode network (DMN), specifically by targeting the posterior cingulate cortex (PCC). Additionally, we investigated the subjective effects of TFUS on mood, mindfulness, and self-related processing. Methods: The study employed a randomized, single-blind design involving 30 healthy subjects. Participants were randomly assigned to either the active TFUS group or the sham TFUS group. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted before and after the TFUS application. To measure subjective effects, the Toronto Mindfulness Scale, the Visual Analog Mood Scale, and the Amsterdam Resting State Questionnaire were administered at baseline and 30 min after sonication. The Self Scale and an unstructured interview were also administered 30 min after sonication. Results: The active TFUS group exhibited significant reductions in functional connectivity along the midline of the DMN, while the sham TFUS group showed no changes. The active TFUS group demonstrated increased state mindfulness, reduced Global Vigor, and temporary alterations in the sense of ego, sense of time, and recollection of memories. The sham TFUS group showed an increase in state mindfulness, too, with no other subjective effects. Conclusions: TFUS targeted at the PCC can alter DMN connectivity and cause changes in subjective experience. These findings support the potential of TFUS to serve both as a research tool and as a potential therapeutic intervention.

Transcranial focused ultrasound modulates the emergence of learned helplessness via midline theta modification.

BACKGROUND: Helplessness and hopelessness are states closely related to depressive disorders. They ensue following the anticipated absence of valid behavioral options to alleviate an aversive state. One neural structure involved in the detection of such options, is the cingulate cortex (CC), which conveys the evaluation of behavior against the value of its outcome. Accordingly, CC-related EEG measures are thought to correlate to feedback evaluation but also to anxious and conflict-related states, signaling the need for further adaptation to current requirements. Against this background, this study investigated the role of CC functioning in the emergence and prevention of helpless/hopeless states by applying low-intensity transcranial focused ultrasound (litFUS) neuromodulation prior to a learned helplessness task. METHOD: In a randomized controlled double blind experimental setup with 55 participants, litFUS was used to inhibit the right lateral prefrontal cortex (lPFC), a region closely connected to CC modulation. Participants were instructed to play 8 games of chess against a computer that was unbeatable to them, while an EEG was recorded. Theta oscillation in midline electrodes, playing performance and self-rate measures on cognitive, affective and physiological parameters were assessed. RESULTS: The results show a considerable influence of litFUS neuromodulation of the lPFC on midline theta activity (Fz and Pz electrode position) which in turn correlated to several psychological variables including self-report data on emotion, cognition, and arousal as well as behavioral measures (playing performance). LIMITATIONS: Due to the small sample size and sample characteristics, results cannot be generalized to the field of clinical application. A replication of results in larger samples and in context of other sonication parameters is needed to increase the robustness of results and to maximize the efficacy of litFUS application. CONCLUSIONS: We conclude that the development of learned helplessness/hopelessness could be positively influenced in its course by litFUS neuromodulation of the right lPFC. In line with previous results, especially the posterior midline electrode Pz seems to be an interesting target for further research in this field as theta activity at this electrode is correlated to control perception and motivated behavior. To our knowledge, this is the first study to use neuromodulation to monitor and manipulate the development of helplessness in the laboratory.

Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans.

Recent reviews highlighted low-intensity transcranial focused ultrasound (TUS) as a promising new tool for non-invasive neuromodulation in basic and applied sciences. Our preregistered double-blind within-subjects study (N = 152) utilized TUS targeting the right prefrontal cortex, which, in earlier work, was found to positively enhance self-reported global mood, decrease negative states of self-reported emotional conflict (anxiety/worrying), and modulate related midfrontal functional magnetic resonance imaging activity in affect regulation brain networks. To further explore TUS effects on objective physiological and behavioral variables, we used a virtual T-maze task that has been established in prior studies to measure motivational conflicts regarding whether participants execute approach versus withdrawal behavior (with free-choice responses via continuous joystick movements) while allowing to record related electroencephalographic data such as midfrontal theta activity (MFT). MFT, a reliable marker of conflict representation on a neuronal level, was of particular interest to us since it has repeatedly been shown to explain related behavior, with relatively low MFT typically preceding approach-like risky behavior and relatively high MFT typically preceding withdrawal-like risk aversion. Our central hypothesis is that TUS decreases MFT in T-maze conflict situations and thereby increases approach and reduces withdrawal. Results indicate that TUS led to significant MFT decreases, which significantly explained increases in approach behavior and decreases in withdrawal behavior. This study expands TUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct TUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Ultimately, this can serve as a foundation for future clinical work to establish TUS interventions for emotional and motivational mental health.

Investigating the role of the right inferior frontal gyrus in control perception: A double-blind cross-over study using ultrasonic neuromodulation.

Being able to control inner and environmental states is a basic need of living creatures. The perception of such control is based on the perceived ratio of outcome probabilities given the presence and the absence of agentic behavior. If an organism believes that options exist to change the probability of a given outcome, control perception (CP) may emerge. Nonetheless, regarding this model, not much is known about how the brain processes CP from this information. This study uses low-intensity transcranial focused ultrasound neuromodulation in a randomized-controlled double blind cross-over design to investigate the impact of the right inferior frontal gyrus of the lateral prefrontal cortex (lPFC) on this process. 39 healthy participants visited the laboratory twice (once in a sham, once in a neuromodulation condition) and rated their control perception regarding a classical control illusion task. EEG alpha and theta power density were analyzed in a hierarchical single trial-based mixed modeling approach. Results indicate that the litFUS neuromodulation changed the processing of stimulus probability without changing CP. Furthermore, neuromodulation of the right lPFC was found to modulate mid-frontal theta by altering its relationship with self-reported effort and worrying. While these data indicate lateral prefrontal sensitivity to stimulus probability, no evidence emerged for the dependency of CP on this processing.

Focusing in on the Future of Focused Ultrasound as a Translational Tool.

This article summarizes the field of focused ultrasound for use in neuromodulation and discusses different ways of targeting, delivering, and validating focused ultrasound. A discussion is focused on parameter space and different ongoing theories of ultrasonic neuromodulation. Current and future applications of the technique are discussed.

Current State of Potential Mechanisms Supporting Low Intensity Focused Ultrasound for Neuromodulation.

Low intensity focused ultrasound (LIFU) has been gaining traction as a non-invasive neuromodulation technology due to its superior spatial specificity relative to transcranial electrical/magnetic stimulation. Despite a growing literature of LIFU-induced behavioral modifications, the mechanisms of action supporting LIFU's parameter-dependent excitatory and suppressive effects are not fully understood. This review provides a comprehensive introduction to the underlying mechanics of both acoustic energy and neuronal membranes, defining the primary variables for a subsequent review of the field's proposed mechanisms supporting LIFU's neuromodulatory effects. An exhaustive review of the empirical literature was also conducted and studies were grouped based on the sonication parameters used and behavioral effects observed, with the goal of linking empirical findings to the proposed theoretical mechanisms and evaluating which model best fits the existing data. A neuronal intramembrane cavitation excitation model, which accounts for differential effects as a function of cell-type, emerged as a possible explanation for the range of excitatory effects found in the literature. The suppressive and other findings need additional theoretical mechanisms and these theoretical mechanisms need to have established relationships to sonication parameters.

Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans.

Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.

Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation.

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS is currently unknown. Objective: We aimed to examine the effects of a commercial diagnostic tUS device using an imaging protocol on cortical excitability. We hypothesized that imaging tUS applied to motor cortex could induce changes in cortical excitability as measured using a transcranial magnetic stimulation (TMS) motor evoked potential (MEP) paradigm. Methods: Forty-three subjects were assigned to receive either verum (n = 21) or sham (n = 22) diagnostic tUS in a single-blind design. Baseline motor cortex excitability was measured using MEPs elicited by TMS. Diagnostic tUS was subsequently administered to the same cortical area for 2 min, immediately followed by repeated post-stimulation MEPs recorded up to 16 min post-stimulation. Results: Verum tUS increased excitability in the motor cortex (from baseline) by 33.7% immediately following tUS (p = 0.009), and 32.4% (p = 0.047) 6 min later, with excitability no longer significantly different from baseline by 11 min post-stimulation. By contrast, subjects receiving sham tUS showed no significant changes in MEP amplitude. Conclusion: These findings demonstrate that tUS delivered via a commercially available diagnostic imaging ultrasound system transiently increases excitability in the motor cortex as measured by MEPs. Diagnostic tUS devices are currently used for internal imaging in many health care settings, and the present results suggest that these same devices may also offer a promising tool for noninvasively modulating activity in the central nervous system. Further studies exploring the use of diagnostic imaging devices for neuromodulation are warranted.

The Benefits of Closed-Loop Transcranial Alternating Current Stimulation on Subjective Sleep Quality.

BACKGROUND: Poor sleep quality is a common complaint, affecting over one third of people in the United States. While sleep quality is thought to be related to slow-wave sleep (SWS), there has been little investigation to address whether modulating slow-wave oscillations (SWOs) that characterize SWS could impact sleep quality. Here we examined whether closed-loop transcranial alternating current stimulation (CL-tACS) applied during sleep impacts sleep quality and efficiency. METHODS: CL-tACS was used in 21 participants delivered at the same frequency and in phase with endogenous SWOs during sleep. Sleep quality was assessed in the morning following either verum or sham control stimulation during sleep, with order counterbalanced within participants. RESULTS: Higher sleep quality and efficiency were found after verum stimulation nights compared to control. The largest effects on sleep quality were found immediately following an adaptation night in the laboratory for which sleep quality was reduced. CONCLUSIONS: Applying CL-tACS at the same frequency and phase as endogenous SWOs may offer a novel method to improve subjective sleep quality after a night with poor quality sleep. CL-tACS might be helpful for increasing sleep quality and efficiency in otherwise healthy people, and in patients with clinical disorders that involve sleep deficits.

Increased alpha band activity indexes inhibitory competition across a border during figure assignment.

Figure-ground assignment is thought to entail inhibitory competition between potential objects on opposite sides of a shared border; the winner is perceived as the figure, and the loser as the shapeless ground. Computational models and response time measures support this understanding but to date no online measure of inhibitory competition during figure-ground assignment has been reported. The current study assays electroencephalogram (EEG) alpha power as a measure of inhibitory competition during figure-ground assignment. Activity in the EEG alpha band has been linked to functional inhibition in the brain, and it has been proposed that increased alpha power reflects increased inhibition. In 2 experiments participants viewed silhouettes designed so that the insides would be perceived as figures. Real-world silhouettes depicted namable objects. Novel silhouettes depicted novel objects on the insides of their borders, but varied in the amount of hypothesized cross-border competition for figural status: In "Low-Competition" silhouettes, the borders suggested novel objects on the outside as well as on the inside. In "High-Competition" silhouettes the borders suggested portions of real-world objects on the outside; these compete with the figural properties favoring the inside as figure. Participants accurately categorized both types of novel silhouettes as "novel" objects and were unaware of the real world objects suggested on the outside of the High-Competition silhouettes. In both experiments, we observed more alpha power while participants viewed High- rather than Low-Competition novel silhouettes. These are the first results to show via an online index of neural activity that figure assignment entails inhibitory competition.

Topographic deficits in alpha-range resting EEG activity and steady state visual evoked responses in schizophrenia.

Deficits in both resting alpha-range (8-12Hz) electroencephalogram (EEG) activity and steady state evoked potential (SSVEP) responses have been reported in schizophrenia. However, the topographic specificity of these effects, the relationship between resting EEG and SSVEP, as well as the impact of antipsychotic medication on these effects, have not been clearly delineated. The present study sought to address these questions with 256 channel high-density EEG recordings in a group of 13 schizophrenia patients, 13 healthy controls, and 10 non-schizophrenia patients with psychiatric diagnoses currently taking antipsychotic medication. At rest, the schizophrenia group demonstrated decreased alpha EEG power in frontal and occipital areas relative to healthy controls. With SSVEP stimulation centered in the alpha band (10Hz), but not with stimulation above (15Hz) or below (7Hz) this range, the occipital deficit in alpha power was partially reverted. However, the frontal deficit persisted and contributed to a significantly reduced topographic relationship between occipital and frontal alpha activity for resting EEG and 10Hz SSVEP alpha power in schizophrenia patients. No significant differences were observed between healthy and medicated controls or between medicated controls and schizophrenia. These findings suggest a potential intrinsic deficit in frontal eyes-closed EEG alpha oscillations in schizophrenia, whereby potent visual stimulation centered in that frequency range results in an increase in the occipital alpha power of these patients, which however does not extend to frontal regions. Future research to evaluate the cortical and subcortical mechanisms of these effects is warranted.

Semantic access occurs outside of awareness for the ground side of a figure.

Traditional theories of vision assume that figures and grounds are assigned early in processing, with semantics being accessed later and only by figures, not by grounds. We tested this assumption by showing observers novel silhouettes with borders that suggested familiar objects on their ground side. The ground appeared shapeless near the figure's borders; the familiar objects suggested there were not consciously perceived. Participants' task was to categorize words shown immediately after the silhouettes as naming natural versus artificial objects. The words named objects from the same or from a different superordinate category as the familiar objects suggested in the silhouette ground. In Experiment 1, participants categorized words faster when they followed silhouettes suggesting upright familiar objects from the same rather than a different category on their ground sides, whereas no category differences were observed for inverted silhouettes. This is the first study to show unequivocally that, contrary to traditional assumptions, semantics are accessed for objects that might be perceived on the side of a border that will ultimately be perceived as a shapeless ground. Moreover, although the competition for figural status results in suppression of the shape of the losing contender, its semantics are not suppressed. In Experiment 2, we used longer silhouette-to-word stimulus onset asynchronies to test whether semantics would be suppressed later in time, as might occur if semantics were accessed later than shape memories. No evidence of semantic suppression was observed; indeed, semantic activation of the objects suggested on the ground side of a border appeared to be short-lived. Implications for feedforward versus dynamical interactive theories of object perception are discussed.