You eye what you eat: BMI, consumption patterns, and dieting status predict temporal attentional bias to food-associated images.

People know that overconsumption of high-fat high-sugar (HFHS) foods have negative consequences for physical and cognitive wellbeing but continue to consume these foods in excess, leading to recent proposals to model obesity as an addiction disorder. The current experiment tested, in a large undergraduate sample (N = 306), the hypothesis that obesity and overconsumption is linked with an oversensitivity to rewards that drives attentional biases towards foods and food-associated cues. Using a modified emotion-induced blindness task with food-related distractors, we examined the extent to which attentional biases to images of HFHS foods were accounted for by BMI, HFHS food intake, self-reported hunger, time since last meal, diet status, food preferences, and attentional control. We also examined whether the same individual differences predicted attentional priority to cues that have a learned association with HFHS foods (i.e., images of food logos). Contrary to our predictions, higher BMI predicted less attentional priority for images of food and food logos. At the same time, increased consumption of HFHS foods predicted increased attentional priority for food images, whereas dieting predicted increased attentional priority for food logo images. Our results suggest that different people may preferentially attend to food versus food logo imagery based on their relationships with food. More broadly, our results support the theoretical perspective that attentional biases to food-associated stimuli can be affected by various competing, state-related factors.

The effect of staircase stopping accuracy and testing environment on stop-signal reaction time.

The stop-signal task is widely used in experimental psychology and cognitive neuroscience research, as well as neuropsychological and clinical practice for assessing response inhibition. The task requires participants to make speeded responses on a majority of trials, but to inhibit responses when a stop signal appears after the imperative cue. The stop-signal delay after the onset of the imperative cue determines how difficult it is to cancel an initiated action. The delay is typically staircased to maintain a 50% stopping accuracy for an estimation of stopping speed to be calculated. However, the validity of this estimation is compromised when participants engage in strategic slowing, motivated by a desire to avoid stopping failures. We hypothesized that maintaining stopping accuracy at 66.67% reduces this bias, and that slowing may also be impacted by the level of experimenter supervision. We found that compared with 50%, using a 66.67% stopping accuracy staircase produced slower stop-signal reaction time estimations (≈7 ms), but resulted in fewer strategic slowing exclusions. Additionally, both staircase procedures had similar within-experiment test-retest reliability. We also found that while individual and group testing in a laboratory setting produced similar estimations of stopping speed, participants tested online produced slower estimates. Our findings indicate that maintaining stopping accuracy at 66.67% is a reliable method for estimating stopping speed and can have benefits over the standard 50% staircase procedure. Further, our results show that care should be taken when comparing between experiments using different staircases or conducted in different testing environments.

Expected TMS excites the motor system less effectively than unexpected stimulation.

The brain's response to sensory input is modulated by prediction. For example, sounds that are produced by one's own actions, or those that are strongly predicted by environmental cues, elicit an attenuated N1 component in the auditory evoked potential. It has been suggested that this form of sensory attenuation to stimulation produced by one's own actions is the reason we are unable to tickle ourselves. Here we examined whether the neural response to direct stimulation of the brain is attenuated by prediction in a similar manner. Transcranial magnetic stimulation (TMS) applied over primary motor cortex can be used to gauge the excitability of the motor system. Motor-evoked potentials (MEPs), elicited by TMS and measured in peripheral muscles, are larger when actions are being prepared and smaller when actions are voluntarily suppressed. We tested whether the amplitude of MEPs was attenuated under circumstances where the TMS pulse can be reliably predicted, even though control of the relevant motor effector was never required. Self-initiation of the TMS pulse and reliable cuing of the TMS pulse both produced attenuated MEP amplitudes, compared to those generated programmatically in an unpredictable manner. These results suggest that predictive coding may be governed by domain-general mechanisms responsible for all forms predictive learning. The findings also have important methodological implications for designing TMS experiments that control for the predictability of TMS pulses.

Administrative and Related Barriers to Covering the Costs of Preexposure Prophylaxis at a Safety-net Clinic in Seattle, Washington.

One barrier to human immunodeficiency virus preexposure prophylaxis (PrEP) is lack or perceived lack of health insurance or financial assistance. We performed a medical records review at a safety-net PrEP clinic in Seattle, Washington, and found that barriers to obtaining financial assistance were commonly recorded in association with initiation and persistence on PrEP.

Motor Memory: Revealing Conditioned Action Tendencies Using Transcranial Magnetic Stimulation.

Action tendencies can be elicited by motivationally salient stimuli (e.g., appetitive rewards) or objects that support utilization behaviors. These action tendencies can benefit behavioral performance through speeded RTs in response tasks and improve detection accuracy in attentional capture tasks. However, action tendencies can be counterproductive when goals change (e.g., refraining from junk foods or abstaining from alcohol). Maintaining control over cue-elicited action tendencies is therefore critical for successful behavior modification. To better understand this relationship, we used transcranial magnetic stimulation to investigate the neural signatures of action tendencies in the presence of previously trained response cues. Participants were presented with a continuous letter stream and instructed to respond quickly to two target letters using two different response keys. Following this training phase, the target letters were embedded in a new task (test phase), and we applied transcranial magnetic stimulation to the motor cortex and measured motor evoked potentials as an index of corticospinal excitability (CSE). We found that CSE could be potentiated by a former response cue trained within a single experimental session, even when participants were instructed to withhold responses during the test phase. Critically, attention to the previously trained response cue was required to elicit the primed modulation in CSE, and successful control of this activity was accompanied by CSE suppression. These findings suggest that well-trained response cues can come to prime a conditioned action tendency and provide a model for understanding how the implementation of cognitive control can override action automaticity.

A high-fat high-sugar diet-induced impairment in place-recognition memory is reversible and training-dependent.

A high-fat high-sugar (HFHS) diet is associated with cognitive deficits in people and produces spatial learning and memory deficits in rodents. Notable, such diets rapidly impair place-, but not object-recognition memory in rats within one week of exposure. Three experiments examined whether this impairment was reversed by removal of the diet, or prevented by pre-diet training. Experiment 1 showed that rats switched from HFHS to chow recovered from the place-recognition impairment that they displayed while on HFHS. Experiment 2 showed that control rats ("Untrained") who were exposed to an empty testing arena while on chow, were impaired in place-recognition when switched to HFHS and tested for the first time. However, rats tested ("Trained") on the place and object task while on chow, were protected from the diet-induce deficit and maintained good place-recognition when switched to HFHS. Experiment 3 examined the conditions of this protection effect by training rats in a square arena while on chow, and testing them in a rectangular arena while on HFHS. We have previously demonstrated that chow rats, but not HFHS rats, show geometry-based reorientation on a rectangular arena place-recognition task (Tran & Westbrook, 2015). Experiment 3 assessed whether rats switched to the HFHS diet after training on the place and object tasks in a square area, would show geometry-based reorientation in a rectangular arena. The protective benefit of training was replicated in the square arena, but both Untrained and Trained HFHS failed to show geometry-based reorientation in the rectangular arena. These findings are discussed in relation to the specificity of the training effect, the role of the hippocampus in diet-induced deficits, and their implications for dietary effects on cognition in people.

Rats Fed a Diet Rich in Fats and Sugars Are Impaired in the Use of Spatial Geometry.

A diet rich in fats and sugars is associated with cognitive deficits in people, and rodent models have shown that such a diet produces deficits on tasks assessing spatial learning and memory. Spatial navigation is guided by two distinct types of information: geometrical, such as distance and direction, and featural, such as luminance and pattern. To clarify the nature of diet-induced spatial impairments, we provided rats with standard chow supplemented with sugar water and a range of energy-rich foods eaten by people, and then we assessed their place- and object-recognition memory. Rats exposed to this diet performed comparably with control rats fed only chow on object recognition but worse on place recognition. This impairment on the place-recognition task was present after only a few days on the diet and persisted across tests. Critically, this spatial impairment was specific to the processing of distance and direction.

Planning on Autopilot? Associative Contributions to Proactive Control.

Proactive cognitive control is thought to rely on the active maintenance of goals or contextual information in working memory. It is often measured using the AX-CPT, in which antecedent cues (A/B) are used to proactively prepare a response to a subsequently-presented probe (X/Y). Although control in this task purportedly requires active maintenance of information in working memory, it also provides conditions in which learning the contingencies between relevant events could influence performance via associative learning. We tested this hypothesis using a dot-pattern expectancy version of the AX-CPT whereby a set of new rules (test phase) for responding changed the control operations required for some previously trained cues, while keeping the operations the same for others, allowing us to measure associative interference. We also tested the relationship between associative interference and working memory capacity (operation span; Experiments 1-3) and tested the effect of applying working memory load during the initial acquisition period (Experiment 2) and during the test phase (Experiment 3). We found robust evidence of interference after the rule change based on previously learnt contingencies, suggesting that learnt contingencies come to influence proactive planning, even when they are task-irrelevant. This associative effect had no relationship with working memory capacity or load, based on a load manipulation commonly used in executive control tasks. The findings suggest that proactive control does not always require active maintenance of current goals and environmental cues in working memory. Instead, proactive control may run on autopilot if the individual can rely upon stable relationships in the environment to trigger planning and preparation. SIGNIFICANCE: Navigating daily life requires us to anticipate future events and plan our thoughts and actions accordingly to achieve our goals. This forward planning, or proactive control, is thought to be a resource-intensive and metabolically costly process that recruits higher-order cognitive functions, such as working memory, where relevant thoughts and actions have to be maintained online. The current study challenged this notion by finding that proactive control can be incrementally relegated to simpler processes based on one's learning of stable relationships in the environment, thereby reducing the need to actively maintain information online. Individuals can come to rely on underlying contingencies in stimuli associated with proactive control, even when it is detrimental to their goals.

Is cortical inhibition in primary motor cortex related to executive control?

Recent research using paired-pulse transcranial magnetic stimulation (TMS) has shown that the speed with which people can stop an action is linked to GABAergic inhibitory activity in the motor system. Specifically, a significant proportion of the variance in stop signal reaction time (SSRT; a widely used measure of inhibitory control) is accounted for by short-interval cortical inhibition (SICI). It is still unclear whether this relationship reflects a broader link between GABAergic processes and executive functions, or a specific link between GABAergic processes and motor stopping ability. The current study sought to replicate the correlation between SSRT and SICI while investigating whether this association generalises to other measures of inhibitory control and working memory, and to long-interval cortical inhibition (LICI). Participants completed a battery of inhibition (Stop-Signal, Stroop, Flanker) and working memory (n-back, Digit Span, and Operation Span) tasks. We replicated the correlation between SICI and SSRT but found no other correlations between behavioural measures of executive control and the two cortical measures of inhibition. These findings indicate that the relationship between SSRT and SICI is specific to a particular property of response inhibition and likely reflects the function of local inhibitory networks mediated by GABAA.

Are We Teaching Evidence-Based and Inclusive Practices in Gender-Affirming Care? Perspectives From Plastic Surgery In-Service Examinations.

Background Resident physicians take annual in-service examinations (ISEs) as part of continuing medical education, which set educational priorities, allow for formative feedback, and guide preparation for final board examinations. Gender-affirming care is provided in many specialties but has been an underrepresented area in medical education. Plastic surgeons provide a large portion of gender-affirming surgical care. Educational gaps in standardized ISEs may contribute to ongoing health care disparities for transgender and gender diverse people. Objective To evaluate the quality of content pertaining to gender-affirming surgery (GAS) on plastic surgery ISEs. Methods Plastic surgery ISEs from years 2012 to 2020 were accessed online through the American Council of Academic Plastic Surgeons website in June 2022. All 5 gender diverse authors analyzed examinations for the presence of GAS questions; identified questions were analyzed for quantity, organization based on content category, affirming language, and accuracy against current guidelines. Results Of 1959 ISE questions available for review, 11 GAS questions were identified for a total frequency of 0.56%. Most GAS questions (6 of 11, 55%) were miscategorized. Inappropriate language, including misgendering of patients, occurred in 7 of 11 (64%) questions. No questions discussed GAS beyond chest or genital surgery, or common variations of these procedures. Transgender identities were represented as only binary, with no mention of nonbinary or gender-fluid individuals. Conclusions Our study illustrates that there are significant gaps in educational content pertaining to gender-affirming care on plastic surgery ISEs.

TMS reveals distinct patterns of proactive and reactive inhibition in motor system activity.

Response inhibition is our ability to suppress or cancel actions when required. Deficits in response inhibition are linked with a range of psychopathological disorders including addiction and OCD. Studies on response inhibition have largely focused on reactive inhibition-stopping an action when explicitly cued. Less work has examined proactive inhibition-preparation to stop ahead of time. In the current experiment, we studied both reactive and proactive inhibition by adopting a two-step continuous performance task (e.g., "AX"-CPT) often used to study cognitive control. By combining a dot pattern expectancy (DPX) version of this task with transcranial magnetic stimulation (TMS), we mapped changes in reactive and proactive inhibition within the motor system. Measured using motor-evoked potentials, we found modulation of corticospinal excitability at critical timepoints during the DPX when participants were preparing in advance to inhibit a response (at step 1: during the cue) and while inhibiting a response (at step 2: during the probe). Notably, motor system activity during early timepoints was predicted by a behavioural index of proactive capacity and could predict whether participants would later successfully inhibit their response. Our findings demonstrate that combining TMS with a two-step CPT such as the DPX can be useful for studying reactive and proactive inhibition, and reveal that successful inhibition is determined earlier than previously thought.

Ultrasound-mediated gene delivery of factor VIII plasmids for hemophilia A gene therapy in mice.

Gene therapy offers great promises for a cure of hemophilia A resulting from factor VIII (FVIII) gene deficiency. We have developed and optimized a non-viral ultrasound-mediated gene delivery (UMGD) strategy. UMGD of reporter plasmids targeting mice livers achieved high levels of transgene expression predominantly in hepatocytes. Following UMGD of a plasmid encoding human FVIII driven by a hepatocyte-specific promoter/enhancer (pHP-hF8/N6) into the livers of hemophilia A mice, a partial phenotypic correction was achieved in treated mice. In order to achieve persistent and therapeutic FVIII gene expression, we adopted a plasmid (pHP-hF8-X10) encoding an FVIII variant with significantly increased FVIII secretion. By employing an optimized pulse-train ultrasound condition and immunomodulation, the treated hemophilia A mice achieved 25%-150% of FVIII gene expression on days 1-7 with very mild transient liver damage, as indicated by a small increase of transaminase levels that returned to normal within 3 days. Therapeutic levels of FVIII can be maintained persistently without the generation of inhibitors in mice. These results indicate that UMGD can significantly enhance the efficiency of plasmid DNA transfer into the liver. They also demonstrate the potential of this novel technology to safely and effectively treat hemophilia A.

Prediction-based attenuation as a general property of learning in neural circuits.

One of the mechanisms proposed to underpin perceptual learning is the reduction in salience of predicted stimuli. This reduction is held to affect the representation of (conditioned) stimuli before they have been associated with motivationally meaningful consequences but may also affect (unconditioned) stimuli that automatically elicit responding. The purpose of this article is to review past findings and present new evidence of phenomena across a range of domains that are consistent with the idea that responses automatically triggered by stimulating events will be reduced by prediction. We argue that prediction-based attenuation may serve several adaptive functions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Working memory load reduces corticospinal suppression to former go and trained no-go cues.

Environmental cues associated with an action can prime the motor system, decreasing response times and activating motor regions of the brain. However, when task goals change, the same responses to former go-associated cues are no longer required and motor priming needs to be inhibited to avoid unwanted behavioural errors. The present study tested whether the inhibition of motor system activity to presentations of former go cues is reliant on top-down, goal-directed cognitive control processes using a working memory (WM) load manipulation. Applying transcranial magnetic stimulation over the primary motor cortex to measure motor system activity during a Go/No-go task, we found that under low WM, corticospinal excitability was suppressed to former go and trained no-go cues relative to control cues. Under high WM, the cortical suppression to former go cues was reduced, suggesting that the underlying mechanism required executive control. Unexpectedly, we found a similar result for trained no-go cues and showed in a second experiment that the corticospinal suppression and WM effects were unrelated to local inhibitory function as indexed by short-interval intracortical inhibition. Our findings reveal that the interaction between former response cues and WM is complex and we discuss possible explanations of our findings in relation to models of response inhibition.

Linking cortical and behavioural inhibition: Testing the parameter specificity of a transcranial magnetic stimulation protocol.

Across a series of studies, our laboratory has shown that the efficiency of action stopping is associated with the strength of GABAA-mediated short-intracortical inhibition (SICI) as measured using transcranial magnetic stimulation (TMS). However, these studies used fixed TMS parameters, which may not optimally probe GABAA receptor activity for each individual. In the present study, we measured the relationship between stopping efficiency and SICI using a range of TMS parameters. Participants completed a right-hand unimanual stop signal task to obtain a measure of stopping efficiency. Resting-state SICI was measured from the left primary motor cortex using six combinations of interstimulus intervals and conditioning pulse intensities. We also established the parameters which generated the strongest SICI (SICImax) and weakest SICI (SICImin) for each individual. We found that stopping efficiency was significantly predicted by SICI using various TMS parameters, including SICImax. Interestingly, SICImin accounted for a similar proportion of variance in stopping efficiency as SICI measured using other TMS parameters. The findings suggest that the relationship between stopping efficiency and SICI is robust, reliable, and not influenced by the extent to which SICI is optimally probed.

Treatment of Hemophilia A Using Factor VIII Messenger RNA Lipid Nanoparticles.

Hemophilia A (HemA) patients are currently treated with costly and inconvenient replacement therapy of short-lived factor VIII (FVIII) protein. Development of lipid nanoparticle (LNP)-encapsulated mRNA encoding FVIII can change this paradigm. LNP technology constitutes a biocompatible and scalable system to efficiently package and deliver mRNA to the target site. Mice intravenously infused with the luciferase mRNA LNPs showed luminescence signals predominantly in the liver 4 h after injection. Repeated injections of LNPs did not induce elevation of liver transaminases. We next injected LNPs carrying mRNAs encoding different variants of human FVIII (F8 LNPs) into HemA mice. A single injection of B domain-deleted F8 LNPs using different dosing regimens achieved a wide range of therapeutic activities rapidly, which can be beneficial for various usages in hemophilia treatment. The expression slowly declined yet remained above therapeutic levels up to 5-7 days post-injection. Furthermore, routine repeated injections of F8 LNPs in immunodeficient mice produced consistent expression of FVIII over time. In conclusion, F8 LNP treatment produced rapid and prolonged duration of FVIII expression that could be applied to prophylactic treatment and potentially various other treatment options. Our study showed potential for a safe and effective platform of new mRNA therapies for HemA.

The effect of high fat, high sugar, and combined high fat-high sugar diets on spatial learning and memory in rodents: A meta-analysis.

Evidence from human and animal studies suggests that high-energy diets impair cognitive function. However, the conditions for such impairments are unclear as studies have differed in the type and duration of diet exposure as well as in the tasks used to assess deficits in cognition. Here, we focused on hippocampal-dependent tasks. We conducted separate meta-analyses of the results from rodent studies using: 1) different diets (high in fat, high in sugar, or high in both fat and sugar); and 2) different tasks to assess hippocampal-dependent spatial learning and memory (water maze, place recognition, radial arm maze, and spontaneous alternation). We focused on the effects of relatively short-term dietary manipulations and, therefore, restricted our analyses to studies that provided the diet for 2 months or less. The meta-analyses showed that each type of diet and task adversely affected performance, with the largest effect produced by exposure to a combined high fat-high sugar diet and the use of the radial arm maze to assess the effect of such diets on cognition.

Transcutaneous Ultrasound-Mediated Nonviral Gene Delivery to the Liver in a Porcine Model.

Ultrasound (US)-mediated gene delivery (UMGD) of nonviral vectors was demonstrated in this study to be an effective method to transfer genes into the livers of large animals via a minimally invasive approach. We developed a transhepatic venous nonviral gene delivery protocol in combination with transcutaneous, therapeutic US (tUS) to facilitate significant gene transfer in pig livers. A balloon catheter was inserted into the pig hepatic veins of the target liver lobes via jugular vein access under fluoroscopic guidance. tUS exposure was continuously applied to the lobe with simultaneous infusion of pGL4 plasmid (encoding a luciferase reporter gene) and microbubbles. tUS was delivered via an unfocused, two-element disc transducer (H105) or a novel focused, single-element transducer (H114). We found applying transcutaneous US using H114 and H105 with longer pulses and reduced acoustic pressures resulted in an over 100-fold increase in luciferase activity relative to untreated lobes. We also showed effective UMGD by achieving focal regions of >105 relative light units (RLUs)/mg protein with minimal tissue damage, demonstrating the feasibility for clinical translation of this technique to treat patients with genetic diseases.

Dietary effects on object recognition: The impact of high-fat high-sugar diets on recollection and familiarity-based memory.

Exposure to a high-fat high-sugar (HFHS) diet rapidly impairs novel-place- but not novel-object-recognition memory in rats (Tran & Westbrook, 2015, 2017). Three experiments sought to investigate the generality of diet-induced cognitive deficits by examining whether there are conditions under which object-recognition memory is impaired. Experiments 1 and 3 tested the strength of short- and long-term object-memory trace, respectively, by varying the interval of time between object familiarization and subsequent novel object test. Experiment 2 tested the effect of increasing working memory load on object-recognition memory by interleaving additional object exposures between familiarization and test in an n-back style task. Experiments 1-3 failed to detect any differences in object recognition between HFHS and control rats. Experiment 4 controlled for object novelty by separately familiarizing both objects presented at test, which included one remote-familiar and one recent-familiar object. Under these conditions, when test objects differed in their relative recency, HFHS rats showed a weaker memory trace for the remote object compared to chow rats. This result suggests that the diet leaves intact recollection judgments, but impairs familiarity judgments. We speculate that the HFHS diet adversely affects "where" memories as well as the quality of "what" memories, and discuss these effects in relation to recollection and familiarity memory models, hippocampal-dependent functions, and episodic food memories. (PsycINFO Database Record