Differential Recruitment of Inhibitory Control Processes by Directed Forgetting and Thought Substitution.

Humans have the ability to intentionally forget information via different strategies, included suppression of encoding (directed forgetting) and mental replacement of the item to encode (thought substitution). These strategies may rely on different neural mechanisms; namely, encoding suppression may induce prefrontally mediated inhibition, whereas thought substitution is potentially accomplished through modulating contextual representations. Yet, few studies have directly related inhibitory processing to encoding suppression, or tested its involvement in thought substitution. Here, we directly tested whether encoding suppression recruits inhibitory mechanisms with a cross-task design, relating the behavioral and neural data from male and female participants in a Stop Signal task (a task specifically testing inhibitory processing) to a directed forgetting task with both encoding suppression (Forget) and thought substitution (Imagine) cues. Behaviorally, Stop Signal task performance (stop signal reaction times) was related to the magnitude of encoding suppression, but not thought substitution. Two complementary neural analyses corroborated the behavioral result. Namely, brain-behavior analysis demonstrated that the magnitude of right-frontal beta activity following stop signals was related to stop signal reaction times and successful encoding suppression, but not thought substitution; and classifiers trained to discriminate successful and unsuccessful stopping in the Stop Signal task could also classify successful and unsuccessful forgetting following Forget cues, but not Imagine cues. Importantly, inhibitory neural mechanisms were engaged following Forget cues at a later time than motor stopping. These findings not only support an inhibitory account of directed forgetting, and that thought substitution engages separate mechanisms, but also potentially identify a specific time in which inhibition occurs when suppressing encoding.SIGNIFICANCE STATEMENT Forgetting often seems like an unintended experience, but forgetting can be intentional, and can be accomplished with multiple strategies. These strategies, including encoding suppression and thought substitution, may rely on different neural mechanisms. Here, we test the hypothesis that encoding suppression engages domain-general prefrontally driven inhibitory control mechanisms, while thought substitution does not. Using cross-task analyses, we provide evidence that encoding suppression engages the same inhibitory mechanisms used for stopping motor actions, but these mechanisms are not engaged by thought substitution. These findings not only support the notion that mnemonic encoding processes can be directly inhibited, but also have broad relevance, as certain populations with disrupted inhibitory processing may be more successful accomplishing intentional forgetting through thought substitution strategies.

The Impact of Linguistic Prediction Violations on Downstream Recognition Memory and Sentence Recall.

Predicting upcoming words during language comprehension not only affects processing in the moment but also has consequences for memory, although the source of these memory effects (e.g., whether driven by lingering pre-activations, re-analysis following prediction violations, or other mechanisms) remains underspecified. Here, we investigated downstream impacts of prediction on memory in two experiments. First, we recorded EEG as participants read strongly and weakly constraining sentences with expected, unexpected but plausible, or semantically anomalous endings ("He made a holster for his gun / father / train") and were tested on their recognition memory for the sentence endings. Participants showed similar rates of false alarms for predicted but never presented sentence endings whether the prediction violation was plausible or anomalous, suggesting that these arise from pre-activation of the expected words during reading. During sentence reading, especially in strongly constraining sentences, plausible prediction violations elicited an anterior positivity; anomalous endings instead elicited a posterior positivity, whose amplitude was predictive of later memory for those anomalous words. ERP patterns at the time of recognition differentiated plausible and anomalous sentence endings: Words that had been plausible prediction violations elicited enhanced late positive complex amplitudes, suggesting greater episodic recollection, whereas anomalous sentence endings elicited greater N1 amplitudes, suggesting attentional tagging. In a follow-up behavioral study, a separate group of participants read the same sentence stimuli and were tested for sentence-level recall. We found that recall of full sentences was impaired when sentences ended with a prediction violation. Taken together, the results suggest that prediction violations draw attention and affect encoding of the violating word, in a manner that depends on plausibility, and that this, in turn, may impair future memory of the gist of the sentence.

Intramuscular Electrical Stimulation for the Treatment of Trigger Points in Patients with Chronic Migraine: A Protocol for a Pilot Study Using a Single-Case Experimental Design.

Background and Objectives: Trigger points (TrPs) are prevalent in patients with migraine headaches. Needling interventions targeting TrPs in migraine patients may reduce the intensity and frequency of headaches, yet systematic reviews reveal a lack of robust evidence. Intramuscular electrical stimulation (IMES) is a modality that delivers electrical current into muscles and TrPs, with recent studies suggesting it may amplify the therapeutic effects of dry needling peripherally and centrally. This could be advantageous for patients with migraine and symptomatic TrPs. Materials and Methods: This study will implement a multiple baseline single-case experimental design (SCED). In a clinical setting, a SCED study lends itself to conducting research with only a few patients that each serve as their own controls. In this SCED study, four participants with chronic migraine will be enrolled in a non-concurrent manner and randomized to one of four baseline measurement periods (4, 5, 6 or 7 weeks), leading to four potentially different start dates for each participant in the intervention phase. During the intervention phase, patients will receive five sessions of dry needling with IMES, one session per week for five weeks. The primary outcome measure will be headache frequency, i.e., the reduction in the number of headache days over a one-month period using electronic headache diary data from the Migraine Buddy smartphone application. Secondary outcome measures will be changes in mean migraine pain intensity using a numeric pain rating scale (NPRS), migraine disability using the Migraine Disability Assessment Test (MIDAS), the Headache Impact Test (HIT-6), and changes in selected cervical musculoskeletal impairments including pressure pain thresholds (PPTs) over TrPs, the craniocervical flexion test (CCFT), and cervical active range of motion (AROM). Primary and secondary outcome measures will be analyzed separately using both visual and statistical analyses. Results: Actively recruiting participants. This project was approved by the Mass General Brigham Institutional Review Board (protocol #2023P000931) and is registered with ClinicalTrials.gov (NCT05893914). Conclusions: This study will seek to determine the effects of a five-week intervention period of IMES to TrPs in the posterior cervical muscles of subjects with chronic migraine.

Representational Pattern Similarity of Electrical Brain Activity Reveals Rapid and Specific Prediction during Language Comprehension.

Predicting upcoming events is a critical function of the brain, and language provides a fertile testing ground for studying prediction, as comprehenders use context to predict features of upcoming words. Many aspects of the mechanisms of prediction remain elusive, partly due to a lack of methodological tools to probe prediction formation in the moment. To elucidate what features are neurally preactivated and when, we used representational similarity analysis on previously collected sentence reading data. We compared EEG activity patterns elicited by expected and unexpected sentence final words to patterns from the preceding words of the sentence, in both strongly and weakly constraining sentences. Pattern similarity with the final word was increased in an early time window following the presentation of the pre-final word, and this increase was modulated by both expectancy and constraint. This was not seen at earlier words, suggesting that predictions were precisely timed. Additionally, pre-final word activity-the predicted representation-had negative similarity with later final word activity, but only for strongly expected words. These findings shed light on the mechanisms of prediction in the brain: rapid preactivation occurs following certain cues, but the predicted features may receive reduced processing upon confirmation.

Why physicians have authority over patients.

In this article, we argue that physicians have normative authority over patients. First we elaborate on the nature of normative authority. We then examine and critique Arthur Isak Applbaum's view that physicians lack authority over patients. Our argument appeals to four cases that demonstrate physicians' authority.

Surrogates and Artificial Intelligence: Why AI Trumps Family.

The increasing accuracy of algorithms to predict values and preferences raises the possibility that artificial intelligence technology will be able to serve as a surrogate decision-maker for incapacitated patients. Following Camillo Lamanna and Lauren Byrne, we call this technology the autonomy algorithm (AA). Such an algorithm would mine medical research, health records, and social media data to predict patient treatment preferences. The possibility of developing the AA raises the ethical question of whether the AA or a relative ought to serve as surrogate decision-maker in cases where the patient has not issued a medical power of attorney. We argue that in such cases, and against the standard practice of vesting familial surrogates with decision making authority, the AA should have sole decision-making authority. This is because the AA will likely be better at predicting what treatment option the patient would have chosen. It would also be better at avoiding bias and, therefore, choosing in a more patient-centered manner. Furthermore, we argue that these considerations override any moral weight of the patient's special relationship with their relatives.

Responding to religious patients: why physicians have no business doing theology.

A survey of the recent literature suggests that physicians should engage religious patients on religious grounds when the patient cites religious considerations for a medical decision. We offer two arguments that physicians ought to avoid engaging patients in this manner. The first is the Public Reason Argument. We explain why physicians are relevantly akin to public officials. This suggests that it is not the physician's proper role to engage in religious deliberation. This is because the public character of a physician's role binds him/her to public reason, which precludes the use of religious considerations. The second argument is the Fiduciary Argument. We show that the patient-physician relationship is a fiduciary relationship, which suggests that the patient has the clinical expectation that physicians limit themselves to medical considerations. Since engaging in religious deliberations lies outside this set of considerations, such engagement undermines trust and therefore damages the patient-physician relationship.

The common rule's 'reasonable person' standard for informed consent.

Laura Odwazny and Benjamin Berkman have raised several challenges regarding the new reasonable person standard in the revised Common Rule, which states that informed consent requires potential research subjects be provided with information a reasonable person would want to know to make an informed decision on whether to participate in a study. Our aim is to offer a response to the challenges Odwazny and Berkman raise, which include the need for a reasonable person standard that can be applied consistently across institutional review boards and that does not stigmatize marginal groups. In response, we argue that the standard ought to be based in an ordinary rather than ideal person conception of reasonable person and that the standard ought to employ what we call a liberal constraint: the reasonability standard must be malleable enough such that a wide variety of individuals with different, unique value systems would endorse it. We conclude by suggesting some of the likely consequences our view would have, if adopted.

The King-Devick test in mixed martial arts: the immediate consequences of knock-outs, technical knock-outs, and chokes on brain functions.

The aim of this prospective cohort study was to determine the effect of an 'event,' defined as a knock-out (KO), technical knock-out (TKO), choke, or submission, on King-Devick (K-D) test times in mixed martial arts (MMA) athletes. MMA athletes (28.3 ± 6.6 years, n = 92) underwent K-D testing prior to and following a workout or match. Comparison of baseline and post-workout/match K-D times to assess any significant change. K-D tests worsened (longer) in a majority of athletes following an 'event' (N = 21) (49.6 ± 7.8 s vs 46.6 ± 7.8 s, p = 0.0156, Wilcoxon signed-rank test). K-D tests improved (shorter) following a standard workout or match in which no 'event' occurred in a majority of cases (n = 69) (44.2 ± 7.2 s vs 49.2 ± 10.9 s, p = <0.0001, Wilcoxon signed-rank test). Longer duration (worsening) of post-match K-D tests occurred in most athletes sustaining an 'event'; K-D tests shortened (improved) in a majority of athletes not sustaining an 'event'. Our study suggests MMA athletes suffering an 'event' may have sustained a brain injury similar to a concussion.

Parental Decision Making: The Best Interest Principle, Child Autonomy, and Reasonableness.

On what basis should we judge whether a parent's medical decision for their child is morally acceptable? In a recent article, Johan Bester attempts to answer this question by defending a version of the Best Interest Standard (BIS) for parental decision making. The purpose of this paper is to identify a number of problems faced by Bester's version of BIS and to suggest ways to redress these problems. Accordingly, we intend to advance the project of formulating a method for guiding parents' medical decision making for their children. We argue that Bester's standard fails to accommodate the autonomy of the child and that his criteria for assessing the reasonableness of the parents' argument for their decision is too weak. We conclude that properly addressing these worries renders his test otiose and that it ought to be replaced with the three commonly held principles of bioethics-the principles of autonomy, beneficence, non-maleficence-and a standard of reasonableness.

2-Dimensional Speckle Tracking Echocardiography predicts severe coronary artery disease in women with normal left ventricular function: a case-control study.

BACKGROUND: Women who have coronary artery disease (CAD) often present with atypical symptoms that may lead to misdiagnosis. We assessed strain, systolic strain rate and left ventricular dyssynchrony with 2- dimensional- speckle tracking echocardiography to evaluate its use as a non-invasive method for detecting CAD in women with normal ejection fraction compared with healthy women controls with a normal angiogram. METHODS: We included 35 women with CAD confirmed by coronary angiography and a positive exercise stress echocardiography and 35 women in a control group with a low pretest probability of CAD, normal angiogram and a normal stress echocardiography with normal EF. RESULTS: Statistically significant 2D-STE findings for the CAD vs control groups were as follows for the mean of: global circumferential strain (CS) (-19.4% vs -22.4%, P = .02); global radial S (49% vs 34%, P = .03); global radial SR (2.4 s-1 vs 1.9 s-1, P = .05); global longitudinal LV S (GLS) (-14.3% vs -17.2%, P < .001). For mechanical dyssynchrony, SD of the GLS time-to-peak (TTP) was computed (99 vs 33 ms, P < .001). The receiver operating characteristic and area under the curve (AUC) were calculated. A cutoff value of 45 ms for 1 SD of the longitudinal S TTP had 97% sensitivity and 89% specificity (AUC, 0.96). GLS cutoff value of -15.87% had 71% sensitivity and 74% specificity; AUC, 0.74 in differentiating CAD and control groups. The combined GLS, CS, and SD of the longitudinal S TTP had an AUC of 0.96 (sensitivity 97%, specificity 86%). Interclass correlations of the GLS segment and GLS TTP measurements were 0.49 (95% CI, 0.227-0.868) and 0.74 (95% CI, 0.277-0.926), respectively. CONCLUSION: In women with a normal echocardiogram and LVEF, CAD can be identified by dyssynchrony and abnormal strain values, as evidenced by 2D-STE.

Trial-level fluctuations in pupil dilation at encoding reflect strength of relational binding.

Eye-tracking methodologies have revealed that eye movements and pupil dilations are influenced by our previous experiences. Dynamic fluctuations in pupil size during learning reflect in part the formation of memories for learned information, while viewing behavior during memory testing is influenced by memory retrieval and drawn to previously learned associations. However, no study to date has linked fluctuations in pupil dilation at encoding to the magnitude of viewing behavior at test. The current investigation involved monitoring eye movements both in single item recognition and relational recognition tasks. In the item task, all faces were presented with the same background scene and memory for faces was subsequently tested, whereas in the relational task each face was presented with its own unique background scene and memory for the face-scene association was subsequently tested. Pupil size changes during encoding predicted the magnitude of preferential viewing during test, as well as future recognition accuracy. These effects emerged only in the relational task, but not in the item task, and were replicated in an additional experiment in which stimulus luminance was more tightly controlled. A follow-up experiment and additional analyses ruled out differences in orienting instructions or number of fixations to the encoding display as explanations of the observed effects. The results shed light on the links between pupil dilation, memory encoding, and eye movement patterns during recognition and suggest that trial-level fluctuations in pupil dilation during encoding reflect relational binding of items to their context rather than general memory formation or strength. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predictability and decomposability separately contribute to compositional processing of idiomatic language.

When reading, comprehenders construct a message-level representation and integrate new information as it becomes available. Such compositional processing may differ for idioms, where the meanings of the individual words do not always relate to the figurative meaning. Here, we examined how predictability and idiom decomposability contribute to compositional processing. Participants' EEG was recorded while they read sentences containing idioms that varied in decomposability and phrase-final word cloze probability, or their literal match (break the ice/slip on the ice) with little context prior to the phrase, along with adjective insertion conditions (break the freezing ice/slip on the freezing ice). Cloze probability modulated N400 amplitudes to critical words for both idiomatic and literal phrases, whereas P600 amplitudes only elicited by idiomatic phrases were also modulated. Phrases with adjective insertions reduced acceptability judgments, particularly for idioms, and led to N400 amplitude differences compared to critical words, but only for idioms. N400 differences were also found between idiomatic and literal contexts at the point of adjective insertion. Additionally, both cloze probability and decomposability modulated gamma band activity, with greater gamma activity for more predictable and less decomposable idioms, but at different times and with different scalp topographies, suggesting dissociable components of processing. These results support a hybrid model of processing in which multiple linguistic factors determine the type of processing engaged by the brain to comprehend non-literal language. When prior context is minimal, compositional processing may still be engaged when reading idioms.

Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation.

Introduction: Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects. Methods: To measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry. Results: Unilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge. Discussion: We propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death.

Should Employment Division v Smith Be Overturned?

Health professionals seeking religious exemption from caring for some patients or providing some interventions receive robust legal protection. Similarly, religiously affiliated organizations have great latitude in deciding which services to offer. These protections could soon become stronger, as the US Supreme Court considers 2 cases that revisit constraints on exemption claims established in Employment Division, Department of Human Resources of Oregon v Smith (1990). This article contends that overturning this case's precedent might result in clinicians claiming more religious exemptions, which, barring acts of US Congress, would erode the rule of law and increase risk of harm to patients.

Separable neural mechanisms support intentional forgetting and thought substitution.

Psychological and neuroscientific experiments have established that people can intentionally forget information via different strategies: direct suppression and thought substitution. However, few studies have directly compared the effectiveness of these strategies in forgetting specific items, and it remains an open question if the neural mechanisms supporting these strategies differ. Here, we developed a novel item-method directed forgetting paradigm with Remember, Forget, and Imagine cues, and recorded EEG to directly compare these strategies. Behaviorally, Forget and Imagine cues produced similar forgetting compared to Remember cues, but through separable neural processes; Forget cues elicited frontal oscillatory power changes that were predictive of future forgetting, whereas item-cue representational similarity was predictive of later accuracy for Imagine cues. These results suggest that both strategies can lead to intentional forgetting, but directed forgetting may rely on frontally-mediated suppression, while thought substitution may lead to contextual shifting, impairing successful retrieval.

Dividing attention influences contextual facilitation and revision during language comprehension.

Although we often seem to successfully comprehend language in the face of distraction, few studies have examined the role of sustained attention in critical components of sentence processing, such as integrating information over a sentence and revising predictions when unexpected information is encountered. The current study investigated the impact of attention on sentence processing using a novel dual-task paradigm. Participants read weakly and strongly constraining sentences with expected or unexpected endings while also tracking the motion of dots in the background, and their EEG was recorded. Under full attention, the amplitude of the N400 component of the ERP, a measure of semantic access, was reduced (facilitated) in a graded fashion by contextual strength and fit. This context-based facilitation was attenuated when attention was divided, suggesting that sustained attention is important for building up message-level representations. In contrast, the post-N400 frontal positivity that has been observed to prediction violations and associated with revision processes was unaffected by dividing attention. However, under divided attention, participants also elicited posteriorly-distributed effects to these violations. Thus, predictive processes seem to be engaged even when attention is divided, but additional resources may then be required to process unexpected information.

Brain connectivity alterations during sleep by closed-loop transcranial neurostimulation predict metamemory sensitivity.

Metamemory involves the ability to correctly judge the accuracy of our memories. The retrieval of memories can be improved using transcranial electrical stimulation (tES) during sleep, but evidence for improvements to metamemory sensitivity is limited. Applying tES can enhance sleep-dependent memory consolidation, which along with metamemory requires the coordination of activity across distributed neural systems, suggesting that examining functional connectivity is important for understanding these processes. Nevertheless, little research has examined how functional connectivity modulations relate to overnight changes in metamemory sensitivity. Here, we developed a closed-loop short-duration tES method, time-locked to up-states of ongoing slow-wave oscillations, to cue specific memory replays in humans. We measured electroencephalographic (EEG) coherence changes following stimulation pulses, and characterized network alterations with graph theoretic metrics. Using machine learning techniques, we show that pulsed tES elicited network changes in multiple frequency bands, including increased connectivity in the theta band and increased efficiency in the spindle band. Additionally, stimulation-induced changes in beta-band path length were predictive of overnight changes in metamemory sensitivity. These findings add new insights into the growing literature investigating increases in memory performance through brain stimulation during sleep, and highlight the importance of examining functional connectivity to explain its effects.