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Witnessing another's pain can heighten pain in the observer. However, research has focused on the observer's intrapersonal experience. Here, a social transmission-chain explored the spread of socially-acquired nocebo hyperalgesia. Dyads of genuine participants were randomised to 'Generations' (G1-G3). G1-Demonstrators, observed by G2-Observers, experienced high/low thermal pain contingent on supposed activity/inactivity of a sham-treatment. G2 became Demonstrators, witnessed by G3-Observers. They experienced fixed low-temperature stimuli irrespective of sham-treatment 'activity'. G3 then Demonstrated for G4-Observers (a confederate), also experiencing low-temperature stimuli only. Pain ratings, electrodermal activity, and facial action units were measured. G1's treatment-related pain propagated throughout the chain. G2 and G3 participants showed heightened subjective and physiological response to sham-treatment, despite equivalent stimulus temperatures, and G3 never witnessing the initial pain-event. Dyadic interpersonal physiological synchrony (electrodermal activity) and psychological synchrony (Observer's ability to predict the Demonstrator's pain), predicted subsequent socially-acquired pain. Implications relate to the interpersonal spread of maladaptive pain experiences.

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Actions are rarely devoid of emotional content. Thus, a more complete picture of the neural mechanisms underlying the mental simulation of observed actions requires more research using emotion information. The present study used high-density electroencephalography to investigate mental simulation associated with facial emotion categorisation. Alpha-mu rhythm modulation was measured at each frequency, from 8 Hz to 13 Hz, to infer the degree of sensorimotor simulation. Results suggest the sensitivity of the sensorimotor activity to emotional information, because (1) categorising static images of neutral faces as happy or sad was associated with stronger suppression in the central region than categorising clearly happy faces, (2) there was preliminary evidence indicating that the strongest suppression in the central region was in response to neutral faces, followed by sad and then happy faces and (3) in the control task, which required categorising images with the head oriented right, left, or forward as right or left, differences between conditions showed a pattern more indicative of task difficulty rather than sensorimotor engagement. Dissociable processing of emotional information in facial expressions and directionality information in head orientations was further captured in beta band activity (14-20 Hz). Stronger mu suppression to neutral faces indicates that sensorimotor simulation extends beyond crude motor mimicry. We propose that mu rhythm responses to facial expressions may serve as a biomarker for empathy circuit activation. Future research should investigate whether atypical or inconsistent mu rhythm responses to facial expressions indicate difficulties in understanding or sharing emotions.

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Children with conduct problems and high callous-unemotional (CP+CU) traits are characterized by dampened emotional responding, limiting their ability for affective empathy and impacting the development of prosocial behaviors. However, research documenting this dampening in young children is sparse and findings vary, with attachment-related stimuli hypothesized to ameliorate deficits in emotional responding. Here we test emotional responsiveness across various emotion-eliciting stimuli using multiple measures of emotional responsiveness (behavioral, physiological, self-reported) and attention, in young children aged 2-8 years (M age = 5.37), with CP+CU traits (CP+CU; n = 36), CPs and low CU traits (CP-CU; n = 82) and a community control sample (CC; n = 27). We found no evidence that attachment-related stimulus ameliorated deficits in emotional responding. Rather, at a group level we found a consistent pattern of reduced responding across all independent measures of responsiveness for children with CP+CU compared to the CC group. Few differences were found between CP+CU and CP-CU groups. When independent measures were standardized and included in a regression model predicting to CU trait score, higher CU traits were associated with reduced emotional responding, demonstrating the importance of multimodal measurement of emotional responsiveness when investigating the impact of CU traits in young children.

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ABSTRACT: Pain is a ubiquitous experience encompassing perceptual, autonomic, and motor responses. Expectancy is known to amplify the perceived and autonomic components of pain, but its effects on motor responses are poorly understood. Understanding expectancy modulation of corticospinal excitability has important implications regarding deployment of adaptive and maladaptive protective behaviours in anticipation of pain. We developed a protocol to compare corticospinal excitability to expected high pain, expected low pain, and critically low pain when high pain was expected. Expecting high pain suppressed corticospinal excitability and heightened perceptual and autonomic responses to the low-pain stimulus, as with increased noxious stimulation (ie, expected high pain). Multilevel modelling revealed that perceived pain mediated the effect of both noxious stimulation and this expectancy-modulated pain on autonomic responses, but corticospinal excitability did not. These results demonstrate that merely expecting pain influenced all pain components. Findings shed new light on the aetiology of expectancy-modulated pain, whereby expecting pain mobilises the motor system to protect the body from harm by a protective withdrawal reflex, associated with reduced corticospinal excitability, and activates similar processes as increased nociceptive stimulation. This has significant practical implications for the treatment of pain, particularly in scenarios where avoidance of pain-related movement contributes to its maintenance.

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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.

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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.

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Background: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor (BDNF) Val66Met; a single-nucleotide polymorphism (SNP) implicated in memory function. Methods: Participants were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-like enhancements of the visually-evoked response, and a test of visual memory. Results: The magnitude of LTP 40 min after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance. Conclusions: The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.

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Previous behavioral and neuroimaging studies have suggested that the motor properties associated with graspable objects may be automatically accessed when people passively view these objects. We directly tested this by measuring the excitability of the motor pathway when participants viewed pictures of graspable objects that were presented during the attentional blink (AB), when items frequently go undetected. Participants had to identify two briefly presented objects separated by either a short or long SOA. Motor-evoked potentials were measured from the right hand in response to a single TMS pulse delivered over the left primary motor cortex 250 msec after the onset of the second target. Behavioral results showed poorer identification of objects at short SOA compared with long SOA, consistent with an AB, which did not differ between graspable and nongraspable objects. However, motor-evoked potentials measured during the AB were significantly higher for graspable objects than for nongraspable objects, irrespective of whether the object was successfully identified or undetected. This provides direct evidence that the motor system is automatically activated during visual processing of objects that afford a motor action.

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We used the attentional blink (AB) paradigm to investigate the processing stage at which extraction of summary statistics from visual stimuli ("ensemble coding") occurs. Experiment 1 examined whether ensemble coding requires attentional engagement with the items in the ensemble. Participants performed two sequential tasks on each trial: gender discrimination of a single face (T1) and estimating the average emotional expression of an ensemble of four faces (or of a single face, as a control condition) as T2. Ensemble coding was affected by the AB when the tasks were separated by a short temporal lag. In Experiment 2, the order of the tasks was reversed to test whether ensemble coding requires more working-memory resources, and therefore induces a larger AB, than estimating the expression of a single face. Each condition produced a similar magnitude AB in the subsequent gender-discrimination T2 task. Experiment 3 additionally investigated whether the previous results were due to participants adopting a subsampling strategy during the ensemble-coding task. Contrary to this explanation, we found different patterns of performance in the ensemble-coding condition and a condition in which participants were instructed to focus on only a single face within an ensemble. Taken together, these findings suggest that ensemble coding emerges automatically as a result of the deployment of attentional resources across the ensemble of stimuli, prior to information being consolidated in working memory.

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BACKGROUND: To date, transcranial magnetic stimulation (TMS) studies manipulating stimulation parameters have largely used blocked paradigms. However, altering these parameters on a trial-by-trial basis in Magstim stimulators is complicated by the need to send regular (1Hz) commands to the stimulator. Additionally, effecting such control interferes with the ability to send TMS pulses or simultaneously present stimuli with high-temporal precision. NEW METHOD: This manuscript presents the MagPy toolbox, a Python software package that provides full control over Magstim stimulators via the serial port. It is able to maintain this control with no impact on concurrent processing, such as stimulus delivery. In addition, a specially-designed "QuickFire" serial cable is specified that allows MagPy to trigger TMS pulses with very low-latency. RESULTS: In a series of experimental simulations, MagPy was able to maintain uninterrupted remote control over the connected Magstim stimulator across all testing sessions. In addition, having MagPy enabled had no effect on stimulus timing - all stimuli were presented for precisely the duration specified. Finally, using the QuickFire cable, MagPy was able to elicit TMS pulses with sub-millisecond latencies. COMPARISON WITH EXISTING METHODS: The MagPy toolbox allows for experiments that require manipulating stimulation parameters from trial to trial. Furthermore, it can achieve this in contexts that require tight control over timing, such as those seeking to combine TMS with fMRI or EEG. CONCLUSIONS: Together, the MagPy toolbox and QuickFire serial cable provide an effective means for controlling Magstim stimulators during experiments while ensuring high-precision timing.

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Previous studies have demonstrated that functionally related objects are perceptually grouped during visual identification if they are depicted as if interacting with each other (Green and Hummel in J Exp Psychol Hum Percept Perform 32(5):1107-1119, 2006). However, it is unclear whether this integration requires attention or occurs pre-attentively. Here, we used a divided-attention task with variable attentional load to address this question. Participants matched a word label to a target object that was immediately preceded by a briefly presented, task-irrelevant tool that was either functionally related or unrelated to the word label (e.g., axe | "log" or hammer | "log"). The tool was either positioned to interact with the target object or faced away from it. The amount of attention available to process the tool was manipulated by asking participants to make a concurrent perceptual discrimination of varying difficulty on a surrounding frame stimulus. The previously demonstrated advantage for the related-and-interacting condition was replicated under conditions of no or low attentional load. This benefit disappeared under high competing attentional load, indicating that attention is required to integrate functionally related objects together into a single perceptual unit.

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RATIONALE: A novel group of designer drugs containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been available worldwide for more than a decade; however, their effects on human brain function have not been extensively described. OBJECTIVES: In a double-blind, placebo-controlled crossover study, the acute effects of BZP and TFMPP (alone and in combination) on the neural networks involved in executive function were investigated using an event-related Stroop functional magnetic resonance imaging (fMRI) paradigm. METHODS: Thirteen healthy participants aged 18-40 years undertook the Stroop task 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. A change in activity in neural regions reflects an increase in local demand for oxygen, due to an increase in neuronal activity. RESULTS: Relative to placebo, an increase in neural activation was observed in the dorsal striatum following BZP, and in the thalamus following TFMPP, when performing the Stroop task. CONCLUSION: These data suggest that additional compensatory resources were recruited to maintain performance during the Stroop task. When BZP and TFMPP were administered together, both the dorsal striatum and thalamus were activated. However, the combination of BZP/TFMPP attenuated activation in the caudate, possibly due to TFMPP's indirect effects on dopamine release via 5HT2C receptors.

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Facilitatory effects have been noted between tools and the objects that they act upon (their "action recipients") across several paradigms. However, it has not been convincingly established that the motor system is directly involved in the joint visual processing of these object pairings. Here, we used the attentional blink (AB) paradigm to demonstrate privileged access to perceptual awareness for tool-action recipient object pairs and to investigate how motor affordances modulate their joint processing. We demonstrated a reduction in the size of the AB that was greater for congruent tool-action recipient pairings (e.g., hammer-nail) than for incongruent pairings (e.g., scissors-nail). Moreover, the AB was reduced only when action recipients followed their associated tool in the temporal sequence, but not when this order was reversed. Importantly, we also found that the effect was sensitive to manipulations of the motor congruence between the tool and the action recipient. First, we observed a greater reduction in the AB when the tool and action recipient were correctly aligned for action than when the tool was rotated to face away from the action recipient. Second, presenting a different tool as a distractor between the tool and action recipient target objects removed any benefit seen for congruent pairings. This was likely due to interference from the motor properties of the distractor tool that disrupted the motor synergy between the congruent tool and action recipient targets. Overall, these findings demonstrate that the contextual motoric relationship between tools and their action recipients facilitates their visual encoding and access to perceptual awareness.

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There is an increasing evidence that the action properties of manipulable objects can play a role in object recognition, as objects with similar action properties can facilitate each other's recognition [Helbig et al. Exp Brain Res 174:221-228, 2006]. However, it is unclear whether this modulation is driven by the actions involved in using the object or the grasps afforded by the objects, because these factors have been confounded in previous studies. Here, we attempted to disentangle the relative contributions of the action and grasp properties by using a priming paradigm in which action and grasp similarity between two objects were varied orthogonally. We found that target tools with similar grasp properties to the prime tool were named more accurately than those with dissimilar grasps. However, naming accuracy was not affected by the similarity of action properties between the prime and target tools. This suggests that knowledge about how an object is used is not automatically accessed when identifying a manipulable object. What are automatically accessed are the transformations necessary to interact directly with the object--i.e., the manner in which one grasps the object.

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BACKGROUND: Functional imaging studies of people with focal hand dystonia (FHD) have indicated abnormal activity in sensorimotor brain regions. Few studies however, have examined FHD during movements that do not provoke symptoms of the disorder. It is possible, therefore, that any differences between FHD and controls are confounded by activity due to the occurrence of symptoms. Thus, in order to characterise impairments in patients with FHD during movements that do not induce dystonic symptoms, we investigated the neural correlates of externally paced finger tapping movements. METHODS: Functional MRI (fMRI) was used to compare patients with FHD to controls with respect to activation in networks modulated by task complexity and hand used to perform simple and complex tapping movements. RESULTS: In the 'complexity network,' patients with FHD showed significantly less activity relative to controls in posterior parietal cortex, medial supplementary motor area (SMA), anterior putamen and cerebellum. In the 'hand network,' patients with FHD showed less activation than controls in primary motor (M1) and somatosensory (S1) cortices, SMA and cerebellum. Conjunction analysis revealed that patients with FHD demonstrated reduced activation in the majority of combined network regions (M1, S1 and cerebellum). CONCLUSION: Dysfunction in FHD is widespread in both complexity and hand networks, and impairments are demonstrated even when performing tasks that do not evoke dystonic symptoms. These results suggest that such impairments are inherent to, rather than symptomatic of, the disorder.

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Long-term potentiation (LTP) is the principal candidate synaptic mechanism underlying learning and memory, and has been studied extensively at the cellular and molecular level in laboratory animals. Inquiry into the functional significance of LTP has been hindered by the absence of a human model as, until recently, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non-human preparations. In this brief review, we describe the results of paradigms recently developed in our laboratory for inducing LTP-like changes in visual-, and auditory-evoked potentials. We describe how rapid, repetitive presentation of sensory stimuli leads to a persistent enhancement of components of sensory-evoked potential in normal humans. Experiments to date, investigating the locus, stimulus specificity, and NMDA receptor dependence of these LTP-like changes suggest that they have the essential characteristics of LTP seen in experimental animals. The ability to elicit LTP from non-surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

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Recent research suggests that rapid visual stimulation can induce long-term potentiation-like effects non-invasively in humans. However, to date, this research has provided only limited evidence for input-specificity, a fundamental property of cellular long-term potentiation. In the present study we extend the evidence for input-specificity by investigating the effect of stimulus orientation. We use sine wave gratings of two different orientations to show that rapid visual stimulation can induce orientation-specific potentiation, as indexed by changes in the amplitude of a late phase of the N1 complex of the visual-evoked potential. This result suggests that discrete populations of orientation-tuned neurons can be selectively potentiated by rapid visual stimulation. Furthermore, our results support earlier studies that have suggested that the locus of potentiation induced by rapid visual stimulation is visual cortex.

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