Word recall process and physiological activation in the tip-of-the-tongue state: Comparison of young and middle-aged groups.

To clarify the feeling of knowing a name but not being able to recall it, known as having a "tip-of-the-tongue" (TOT) experience, we proposed a TOT model consisting of three stages combining a face recognition model and autonomic sympathetic nerve activity. Since TOT increases with age, we compared two age groups: young (N = 27, M = 20.4 ± 1.5 years) and middle-aged (N = 29, M = 58.5 ± 8.0 years). Experiment 1 showed that successfully naming low-frequency common names increased the skin conductance response (SCR) value, and the time to reach the maximum SCR value was longer. Experiment 2 was a naming task for face photographs. The younger group showed higher SCR values during successfully naming, while the middle-aged group showed similar SCR values for successfully naming and experiencing TOT. Both groups had the longest time to reach maximum SCR in TOT. In this study, physiological arousal of TOT was not affected by aging.

Paradoxical somatic information processing for interoception and anxiety in alexithymia.

The concept of alexithymia has garnered much attention in an attempt to understand the psychological mechanisms underlying the experience of feeling an emotion. In this study, we aimed to understand how the interoceptive processing in an emotional context relates to problems of alexithymia in recognizing self-emotions. Therefore, we prepared experimental conditions to induce emotional awareness based on interoceptive information. As such, we asked participants to be aware of interoception under an anxiety-generating situation anticipating pain, having them evaluate their subjective anxiety levels in this context. High alexithymia participants showed attenuated functional connectivity within their 'interoception network', particularly between the insula and the somatosensory areas when they focused on interoception. In contrast, they had enhanced functional connectivity between these regions when they focused on their anxiety about pain. Although access to somatic information is supposed to be more strongly activated while attending to interoception in the context of primary sensory processing, high alexithymia individuals were biased as this process was activated when they felt emotions, suggesting they recognize primitive and unprocessed bodily sensations as emotions. The paradoxical somatic information processing may reflect their brain function pathology for feeling emotions and their difficulty with context-dependent emotional control.

Comparison of emotional processing assessed with fear conditioning by interpersonal conflicts in patients with depression and schizophrenia.

AIM: While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli. METHODS: We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors' faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants. RESULTS: Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition. CONCLUSION: Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

Strictly Conserved Residues in Euphorbia tirucalli ß-Amyrin Cyclase: Trp612 Stabilizes Transient Cation through Cation-π Interaction and CH-π Interaction of Tyr736 with Leu734 Confers Robust Local Protein Architecture.

The functions of Trp612, Leu734, and Tyr736 of Euphorbia tirucalli ß-amyrin synthase were examined. The aliphatic variants (Ala, Val, Met) of Trp612 showed almost no activity, but the aromatic variants exhibited high activities: 12.5 % of the wild-type activity for the W612H variant, 43 % for W612F, and 63 % for W612Y. That is, the enzymatic activities of the variants increased in proportion to the increase in π-electron density. Thus, the major function of Trp612 is to stabilize transient cations through a cation-π interaction. The Phe and Tyr variants caused a distorted folding conformation, especially at the E-ring site, which generated the aberrantly cyclized products germanicol and lupeol. The L734G and L734A variants exhibited significantly decreased activities but yielded taraxerol in a high production ratio. The Val, Ile, and Met variants showed markedly high activities (56-78 % of wild-type activity); therefore, appropriate steric bulk is required at this position. The aliphatic variants of Tyr736 showed markedly decreased activities, but the Phe mutant exhibited high activity (67 %), which indicates that the π electrons are critical for catalysis. Homology modeling indicated that Tyr736 and Leu734 are perpendicular to the substrate and are situated face to face, which suggests that a CH-π interaction occurs between Tyr736 and Leu734, reinforcing the protein architecture, and that Tyr736 cannot stabilize cationic intermediates through a cation-π interaction.

Squalene-Hopene Cyclase: Mechanistic Insights into the Polycyclization Cascades of Squalene Analogs Bearing Ethyl and Hydroxymethyl Groups at the C-2 and C-23 Positions.

Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene 1 into 6,6,6,6,5-fused pentacyclic hopene 2 and hopanol 3. To elucidate the binding sites for the terminal positions of 1, four analogs, having the larger ethyl (Et) and the hydrophilic CH2 OH groups at the 23E or 23Z positions of 1, were incubated with SHC. The analog with the Et group at the 23E position (23E-Et-1) yielded two tetra- and three pentacyclic products; however, the analog possessing the Et group at the 23Z position (23Z-Et-1) gave two hopene homologs and the neohopane skeleton, but no hopanol homologs. Hopene homolog (C31 ) was generated from 23E-Et-1 by deprotonation from 23Z-Me (normal cyclization cascade). Intriguingly, the same homolog was also generated from the geometrical isomer 23Z-Et-1, indicating C-C bond rotation about the C-21-C-22 axis of the hopanyl cation and the more compact nature of the binding domain at 23Z compared with 23E. On the other hand, analogs with the CH2 OH group gave novel hopane skeletons having 1-formylethyl and 1-hydroxyprop-2-en-2-yl residues at C-21. Products bearing an aldehyde group were generated in higher yield from 23Z-CH2 OH-1 (89 %), than from 23E-CH2 OH-1 (26 %). The significant yield (26 %) of the aldehyde products from 23E-CH2 OH-1 indicated that C-C bond rotation had occurred owing to the absence of hydrophobic interactions between the hydrophilic 23E-CH2 OH and its binding site. The polycyclization mechanisms of the four different analogs are discussed.

Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal signals of fear.

BACKGROUND: Emotional information is frequently processed below the level of consciousness, where subcortical regions of the brain are thought to play an important role. In the absence of conscious visual experience, patients with visual cortex damage discriminate the valence of emotional expression. Even in healthy individuals, a subliminal mechanism can be utilized to compensate for a functional decline in visual cognition of various causes such as strong sleepiness. In this study, sleep deprivation was simulated in healthy individuals to investigate functional alterations in the subliminal processing of emotional information caused by reduced conscious visual cognition and attention due to an increase in subjective sleepiness. Fourteen healthy adult men participated in a within-subject crossover study consisting of a 5-day session of sleep debt (SD, 4-h sleep) and a 5-day session of sleep control (SC, 8-h sleep). On the last day of each session, participants performed an emotional face-viewing task that included backward masking of nonconscious presentations during magnetic resonance scanning. RESULTS: Finally, data from eleven participants who were unaware of nonconscious face presentations were analyzed. In fear contrasts, subjective sleepiness was significantly positively correlated with activity in the amygdala, ventromedial prefrontal cortex, hippocampus, and insular cortex, and was significantly negatively correlated with the secondary and tertiary visual areas and the fusiform face area. In fear-neutral contrasts, subjective sleepiness was significantly positively correlated with activity of the bilateral amygdala. Further, changes in subjective sleepiness (the difference between the SC and SD sessions) were correlated with both changes in amygdala activity and functional connectivity between the amygdala and superior colliculus in response to subliminal fearful faces. CONCLUSION: Sleepiness induced functional decline in the brain areas involved in conscious visual cognition of facial expressions, but also enhanced subliminal emotional processing via superior colliculus as represented by activity in the amygdala. These findings suggest that an evolutionally old and auxiliary subliminal hazard perception system is activated as a compensatory mechanism when conscious visual cognition is impaired. In addition, enhancement of subliminal emotional processing might cause involuntary emotional instability during sleep debt through changes in emotional response to or emotional evaluation of external stimuli.

Altered brain activity for phonological manipulation in dyslexic Japanese children.

Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.

Interoceptive sensitivity predicts sensitivity to the emotions of others.

Some theories of emotion emphasise a close relationship between interoception and subjective experiences of emotion. In this study, we used facial expressions to examine whether interoceptive sensibility modulated emotional experience in a social context. Interoceptive sensibility was measured using the heartbeat detection task. To estimate individual emotional sensitivity, we made morphed photos that ranged between a neutral and an emotional facial expression (i.e., anger, sadness, disgust and happy). Recognition rates of particular emotions from these photos were calculated and considered as emotional sensitivity thresholds. Our results indicate that participants with accurate interoceptive awareness are sensitive to the emotions of others, especially for expressions of sadness and happy. We also found that false responses to sad faces were closely related with an individual's degree of social anxiety. These results suggest that interoceptive awareness modulates the intensity of the subjective experience of emotion and affects individual traits related to emotion processing.

Interoceptive training impacts the neural circuit of the anterior insula cortex.

Interoception is the perception of afferent information that arises from anywhere and everywhere within the body. Recently, interoceptive accuracy could be enhanced by cognitive training. Given that the anterior insula cortex (AIC) is a key node of interoception, we hypothesized that resting functional connectivity (RSFC) from AIC was involved in an effect of interoceptive training. To address this issue, we conducted a longitudinal intervention study using interoceptive training and obtained RSFC using fMRI before and after the intervention. A heartbeat perception task evaluated interoceptive accuracy. Twenty-two healthy volunteers (15 females, age 19.9 ± 2.0 years) participated. After the intervention, interoceptive accuracy was enhanced, and anxiety levels and somatic symptoms were reduced. Also, RSFC from AIC to the dorsolateral prefrontal cortex (DLPFC), superior marginal gyrus (SMG), anterior cingulate cortex (ACC), and brain stem, including nucleus tractus solitarius (NTS) were enhanced, and those from AIC to the visual cortex (VC) were decreased according to enhanced interoceptive accuracy. The neural circuit of AIC, ACC, and NTS is involved in the bottom-up process of interoception. The neural circuit of AIC, DLPFC, and SMG is involved in the top-down process of interoception, which was thought to represent the cognitive control of emotion. The findings provided a better understanding of neural underpinnings of the effect of interoceptive training on somatic symptoms and anxiety levels by enhancing both bottom-up and top-down processes of interoception, which has a potential contribution to the structure of psychotherapies based on the neural mechanism of psychosomatics.

How does interoceptive awareness interact with the subjective experience of emotion? An fMRI study.

Recent studies in cognitive neuroscience have suggested that the integration of information about the internal bodily state and the external environment is crucial for the experience of emotion. Extensive overlap between the neural mechanisms underlying the subjective emotion and those involved in interoception (perception of that which is arising from inside the body) has been identified. However, the mechanisms of interaction between the neural substrates of interoception and emotional experience remain unclear. We examined the common and distinct features of the neural activity underlying evaluation of emotional and bodily state using functional magnetic resonance imaging (fMRI). The right anterior insular cortex and ventromedial prefrontal cortex (VMPFC) were identified as commonly activated areas. As both of these areas are considered critical for interoceptive awareness, these results suggest that attending to the bodily state underlies awareness of one's emotional state. Uniquely activated areas involved in the evaluation of emotional state included the temporal pole, posterior and anterior cingulate cortex, medial frontal gyrus, and inferior frontal gyrus. Also the precuneus was functionally associated with activity of the right anterior insular cortex and VMPFC when evaluating emotional state. Our findings indicate that activation in these areas and the precuneus are functionally associated for accessing interoceptive information and underpinning subjective experience of the emotional state. Thus, awareness of one's own emotional state appears to involve the integration of interoceptive information with an interpretation of the current situation.

[Perspective on Emotion from Allostasis Mediated by Interoception].

Feeling emotional responses, such as heartbeat and respiration, influence subjective feeling of emotion. The role of interoception as a link in this relationship has been the focus of much attention. The predictive coding model is suggested for understanding the mechanism of interoception, and the model is also closely related to allostasis. This paper introduces a perspective on emotion from the allostasis mediated by interoception.

[Mental Disorders from the Perspective of Interoception and Allostasis].

The classical concept of allostasis is proposed as a dynamic adaptive capacity to stressors. The overload of allostasis results in adaptive disorders, and then lead to various psychiatric disorders. The recent concept of allostasis explains not only physiological adaptation but also behavioural changes. Furthermore, the relationship between interoception and the sense of self as well as emotion has attracted attention in recent years. These conceptual extensions and their abnormalities could help in understanding the symptoms of schizophrenia.

Modulation of heartbeat-evoked potential and cardiac cycle effect by auditory stimuli.

Interoception has been proposed as a factor that influences various psychological processes (Khalsa et al., 2018). Afferent signals from the cardiovascular system vary across cardiac cycle phases. Heartbeat-evoked potentials (HEP) and event-related potentials (ERP) were measured to examine whether interoceptive signals differed between cardiac cycle phases. Simultaneously, participants performed an auditory oddball task in which the timing of the presenting stimulus was synchronized with the heartbeat. Pure tones were presented at 10 ms (late diastole condition), 200 ms (systole condition), or 500 ms after the R wave (diastole condition). Greater HEP amplitudes were observed when the tone was presented during diastole than during systole or late diastole. ERP showed the same tendency: a greater amplitude was observed during diastole than systole or late diastole. These results suggest that the processing of interoception reflected by HEP and exteroception reflected by ERP share attentional resources when both stimuli coincide. When the tone was presented during systole, attention to the internal state decreased compared with when the tone was presented during diastole, and attention was distributed to both exteroception and interoception. Our study suggests that HEP may be considered an indication of a relative amount of resources to process the interoception.

Effect of subconscious changes in bodily response on thought shifting in people with accurate interoception.

Our thought states shift from one state to another from moment to moment. The relationship between the thought shifting and bodily responses is yet to be directly examined. This exploratory study examined the influence of cardiovascular reactivity and interoception-sensing an internal bodily state-on the shifting of thought states. Participants (N = 100, 70 women) completed two tasks: the heartbeat counting task (HCT) and the vigilance task (VT). We assessed their interoceptive accuracy through their performance on the HCT. The VT was a simple sustained attention task in which participants pressed a key when the target stimulus appeared and were asked to report their thoughts. We presented subliminal vibration stimuli to induce alterations in heart rate (i.e., vibration block). Results showed that participants with higher interoceptive accuracy reported more continuation of self-referential thought (about past episodes and future plans regarding themselves) during the vibration block than did those with lower interoceptive accuracy. These results suggest that individuals with higher interoceptive accuracy are more likely to be influenced by their subliminal bodily response, resulting in divergent attention from the task and intermittent self-referential thought.

The effect of cognitive behavioral therapy on future thinking in patients with major depressive disorder: A randomized controlled trial.

Background: Pessimistic thinking about the future is one of the cardinal symptoms of major depression. Few studies have assessed changes in pessimistic thinking after undergoing cognitive behavioral therapy (CBT). A randomized clinical trial (RCT) was conducted with patients diagnosed with major depressive disorder (MDD) to determine whether receiving a course of CBT affects pessimistic future thinking using a future thinking task. Methods: Thirty-one patients with MDD were randomly assigned to either CBT (n = 16) or a talking control (TC) (n = 15) for a 16-week intervention. The main outcomes were the change in response time (RT) and the ratio of the responses for positive valence, measured by the future thinking task. Secondary outcomes included the GRID-Hamilton Depression Rating Scale, the Beck Depression Inventory-Second Edition (BDI-II), the Dysfunctional Attitude Scale (DAS), and the word fluency test (WFT). Results: Regarding the main outcomes, the CBT group showed reduced RT for the positive valence (within-group Cohen's d = 0.7, p = 0.012) and negative valence (within-group Cohen's d = 0.6, p = 0.03) in the distant future condition. The ratio of positive valence responses in both groups for all temporal conditions except for the distant past condition increased within group (distant future: CBT: Cohen's d = 0.5, p = 0.04; TC: Cohen's d = 0.8, p = 0.008; near future: CBT: Cohen's d = 1.0, p < 0.001; TC: Cohen's d = 1.1, p = 0.001; near past: CBT: Cohen's d = 0.8, p = 0.005; TC: Cohen's d = 1.0, p = 0.002). As for secondary outcomes, the CBT group showed greater improvement than the TC group regarding the need for social approval as measured by the DAS (p = 0.012). Conclusion: Patients with MDD who received CBT showed a reduced RT for the positive and negative valence in the distant future condition. RT in the future thinking task for depressed patients may be a potential objective measure for the CBT treatment process. Because the present RCT is positioned as a pilot RCT, a confirmatory trial with a larger number of patients is warranted to elucidate the CBT treatment process that influences future thinking. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021028, identifier UMIN000018155.

Functional connectivity changes between frontopolar cortex and nucleus accumbens following cognitive behavioral therapy in major depression: A randomized clinical trial.

Cognitive behavioral therapy (CBT) is a psychotherapy that challenges distorted cognitions; however, the neural mechanisms that underpin CBT remain unclear. Hence, we aimed to assess the treatment-related resting-state functional connectivity (rsFC) changes in the brain regions associated with future thinking and the associations between rsFC changes and clinical improvements. Thirty-eight adult patients with MDD were randomly assigned with equal likelihood to receive 16-week individual CBT or talking control with a 12-month follow-up period. We evaluated the rsFC changes in the frontal regions, nucleus accumbens, amygdala, and limbic structures key to the depression pathophysiology and future thinking with 2 ×  2 mixed ANOVA interaction analysis. Pearson's correlation analysis with Bonferroni's correction was also performed to examine the associations with clinical symptoms, such as depression severity and automatic thoughts in follow-up evaluations. Treatment-specific changes include enhancement in frontopolar connectivity with the nucleus accumbens. An increased rsFC was associated with lower negative automatic thoughts postoperatively, together with lower depressive symptoms and higher positive automatic thoughts at follow-up. Conclusively, rsFC changes in the fronto-limbic neural control circuit after CBT, particularly between the frontal pole and nucleus accumbens, may be clinically meaningful functional changes related to the depression recovery process.

Cognitive behavioral therapy effects on frontopolar cortex function during future thinking in major depressive disorder: A randomized clinical trial.

BACKGROUND: Despite the importance of Beck's theoretical cognitive model of psychopathology, the neural mechanisms underlying future thinking in cognitive behavioral therapy (CBT) remain elusive. Recent neuroimaging studies have shown that the function of the frontopolar cortex (Brodmann area 10 [BA10]) is associated with future thinking. We hypothesized that, compared with unstructured psychotherapy (talking control: TC), CBT may involve different neural responses in BA10 associated with future thinking. METHODS: This randomized clinical trial included 38 adult patients with moderate-to-severe major depressive disorder who underwent up to 16 weeks of CBT or TC with a 6-month follow-up period. We evaluated changes in BA10 activation during distant future thinking using functional magnetic resonance imaging with a future-thinking task. We assessed frontal neurocognitive function and clinical symptoms at baseline and post-treatment. Depression severity and automatic thoughts were assessed at the 6-month follow-up. RESULTS: We found decreased activation in the frontopolar cortex during distant future thinking after CBT (t = 3.00, df=15, p = 0.009) and no changes after TC. Further, the reduction in BA10 activity significantly correlated with changes in frontal cognitive function after the treatment (r = 0.48, p = 0.007), and in positive automatic thought after 6 months of treatments (r = 0.39; p = 0.03). LIMITATIONS: Relatively small sample size and homogenous clinical profile could limit the generalizability. Patients received pharmacotherapy including antidepressant. CONCLUSIONS: CBT appears to improve frontopolar cortex function during future thinking in a manner distinct from TC. Larger clinical trials are necessary to provide firm evidence whether BA10 activity may serve as a neuro-marker for monitoring successful depression treatment with CBT.

Passive Way of Measuring QOL/Well-Being Levels Using Smartphone Log.

Research on mental health states involves paying increasing attention to changes in daily life. Researchers have attempted to understand such daily changes by relying on self-reporting through frequent assessment using devices (smartphones); however, they are mostly focused on a single aspect of mental health. Assessing the mental health of a person from various perspectives may help in the primary prevention of mental illness and the comprehensive measurement of mental health. In this study, we used users' smartphone logs to build a model to estimate whether the scores on three types of questionnaires related to quality of life and well-being would increase compared to the previous week (fluctuation model) and whether they would be higher compared to the average for that user (interval model). Sixteen participants completed three questionnaires once per week, and their smartphone logs were recorded over the same period. Based on the results, estimation models were built, and the F-score ranged from 0.739 to 0.818. We also analyzed the features that the estimation model emphasized. Information related to "physical activity," such as acceleration and tilt of the smartphone, and "environment," such as atmospheric pressure and illumination, were given more weight in the estimation than information related to "cyber activity," such as usage of smartphone applications. In particular, in the Positive and Negative Affect Schedule (PANAS), 9 out of 10 top features in the fluctuation model and 7 out of 10 top features in the interval model were related to activities in the physical world, suggesting that short-term mood may be particularly heavily influenced by subjective activities in the human physical world.

[Dynamic Functional Connectivity in Resting-State fMRI and Its Clinical Applications].

The conventional analysis assumes a constant mental state during scanning and assesses the strength of functional connectivity as the average of the entire fMRI data. However, it is suggested that even at rest, functional connectivity may change with time, and the conventional analysis has not been able to fully evaluate its properties. To overcome this limitation, many studies propose an index called dynamic functional connectivity (dFC) or time-varying functional connectivity (TVFC) or the chronnectome. This article reviews the significance and methods of dFC, examples of its application in clinical studies, and its limitations. Finally, we discuss its potential for clinical application.

Products With High Purchase Frequency Require Greater Inhibitory Control: An Event-Related Potential Study.

One's past behavior influences their present behavior. The effects of such response history have often been tested using response inhibition tasks. Since previous studies have highlighted the effect of immediate action history formed directly before the subsequent response in a laboratory environment, we aimed to elucidate the longer-term effects of response history, using repetitive and habitual consumer behavior in daily life as the response history. We used event-related potentials recorded in a Go/No-go task to investigate brain activity related to inhibitory control, hypothesizing that stimuli with a high frequency of choice in everyday life would elicit stronger inhibition-related activity, that is, the No-go-N2 component. Participants were asked to evaluate the frequency of purchase and use of some products, such as food and drink or social networking services (SNS) in everyday situations. Images of each product were assigned as stimuli in the Go and No-go trials according to the frequency of choice. The results showed that frequently purchased No-go stimuli yielded a larger amplitude of the No-go-N2 component and a negative shift between 200 and 300ms after the presentation of No-go stimuli. The results suggest that frequently chosen products evoke stronger inhibition conflicts and require greater cognitive control to withhold a response. Our findings showed that repeated purchase behavior in daily life forms a response history and has a long-term influence on the inhibition of even simple approaching behaviors, such as button pressing.