Nicolas A. McNair

Impaired sensorimotor integration in focal hand dystonia patients in the absence of symptoms

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.

Induction of orientation-specific LTP-like changes in human visual evoked potentials by rapid sensory stimulation.

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.

Disentangling the contributions of grasp and action representations in the recognition of manipulable objects.

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.

Long-term potentiation (LTP) of human sensory-evoked potentials

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

The contextual action relationship between a tool and its action recipient modulates their joint perception

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.

Modeling causal conditional reasoning data using SDT: caveats and new insights

In deductive reasoning, people are asked to infer the truth of an arguments conclusion given a set of premises. Research into the processes underlying deduction has focused on examining how well people discriminate between logically valid and invalid arguments, and how irrelevant factors such as ones prior beliefs interfere with the ability to reason logically (Evans et al., 1983). This normative approach to validity has traditionally informed both practice and theory in the literature. However, its critics argue that “normativism” often leads investigators to biased or misleading interpretations of phenomena (Elqayam and Evans, 2011). Formal modeling of deductive reasoning has often been successful by taking the traditional, normative approach. A case in point is the application of signal detection theory (SDT; Macmillan and Creelman, 2005) to the investigation of belief bias in syllogistic reasoning (Dube et al., 2010). In the SDT model, deductive judgments are based on strength of evidence; an argument is judged to be valid if its strength exceeds a criterion value. Because the choice of criterion is independent of the ability to discriminate between classes of arguments, the SDT model makes it possible to isolate response bias from accuracy. Dube et al. examined these two factors using ROC curves, which plot hits against false alarms at several levels of confidence. Hits and false alarms were defined in normative fashion as responding “valid” to logically valid and logically invalid conclusions, respectively. Their analysis of ROCs led them to argue two significant points. First, contrary to prevailing theories of belief bias, conclusion believability can affect response bias without affecting the quality of reasoning. Second, the curvilinear shape of the ROCs is consistent with the distributional assumptions of SDT. The latter is a key test because finding linear rather than curvilinear ROCs would be problematic for the model. The curvilinear ROCs obtained in syllogistic (see also Dube et al., 2011; Trippas et al., 2013; but see Klauer and Kellen, 2010) and other forms of reasoning (Heit and Rotello, 2010, 2014) are similar to those widely observed in memory and perception (Pazzaglia et al., 2013). This consistency across domains strengthens the case for the usefulness of the SDT approach. It also leads to an expectation of similar findings in other areas of reasoning. Below, we describe findings from conditional reasoning that violate this expectation in a surprising yet enlightening way. Causal conditionals are a form of deduction prevalent in everyday life. Consider the proposition: “If healthy foods are cheaper, then more people will eat healthy foods.” Four types of conditional inferences are possible: modus ponens (MP; “Healthy foods are cheaper, therefore more people will eat healthy foods”), modus tollens (MT; “Fewer people eat healthy foods, therefore healthy foods are not cheaper”), affirmation of the consequent (AC; “More people eat healthy foods, therefore healthy foods are cheaper”), and denial of the antecedent (DA; “Healthy foods are not cheaper, therefore less people eat healthy foods”). From a normative point of view, MP and MT are valid and AC and DA are invalid inferences. Theories differ as to how people determine validity in these problems. According to mental model theory (Johnson-Laird and Byrne, 2002), people construct an initial mental model of the conditional (e.g., p q) which may then be fleshed out by considering additional models (not-p q; not-p not-q). According to the suppositional account of the conditional (Evans et al., 2003, 2002; Evans and Over, 2004, 2012), people evaluate the subjective probability of a conditional by hypothetically supposing p and then assessing the conditional probability of q given p, P(q|p). This relation between the natural language conditional and the conditional probability, P(if p then q) = P(q|p), can be used in a Bayesian/probabilistic model of conditional inference (Oaksford et al., 2000; Oaksford and Chater, 2009, 2013). What these theories have in common is that there is no fundamental difference in how people process affirmation (MP + AC) and denial (MT + DA) inferences. This makes an SDT analysis straightforward and no different to that taken with the study of belief bias in syllogistic reasoning. For our case study, we analyzed aspects of a data set collected as part of a larger project under the direction of the fourth author of this paper1. This study examined the influence of belief in causal conditional problems (e.g., believable: “If oil prices continue to rise, then UK petrol prices will rise”; unbelievable: “If global temperatures rise, then less arctic ice will melt”). Hits were defined as “valid” responses to MP and MT and false alarms were defined as “valid” responses to AC and DA. This produced the ROCs seen in the top panel of Figure ​Figure1.1. The results are similar in some respects to those reported by Dube et al. (2010) for syllogisms: believability had no effect on accuracy (ROCs for believable and unbelievable items fall on the same curve) but seemed to affect response bias (confidence criteria for believable items are shifted to the right)2. However, there is a surprising difference: in contrast to the curvilinear ROCs observed with syllogisms, conditionals produced linear ROCs. A linear regression of the ROC (collapsing over believability) provided a good fit, R2 = 99.9%. Adding a quadratic component did not improve the fit, p = 0.78. Taken at face value, this result suggests that conditional reasoning requires a profoundly different model than the one that has seemed so successful when applied to other forms of reasoning, not to mention other cognitive tasks. Figure 1 ROC curves of causal conditionals. Top panel: Valid (MP + MT) vs. invalid (AC + DA). Bottom left: affirmation conditionals (MP vs. AC). Bottom right: denial conditionals (MT vs. DA). Points on the ROC imply a more liberal response criterion (lower confidence ... A different picture emerges when we depart from the strictly normative approach and consider separately how people respond to affirmation and denial conditionals. In the bottom left panel of Figure ​Figure1,1, plotting MP (hits) against AC (false alarms) yields typically curvilinear ROCs. Linear regression (collapsing over believability) provided a fit, R2 = 96%, that was significantly improved by the addition of a quadratic component, R2 = 99.99%, p < 0.004. Accuracy is defined by the distance of the ROCs from the chance diagonal. Contrary to the poor accuracy on display in the aggregate results in the top panel, people are quite sensitive to argument structure when affirmation is involved. In the bottom right panel of Figure ​Figure1,1, plotting MT (hits) against DA (false alarms) again yields typically curvilinear ROCs. Linear regression (collapsing over believability) provided a fit, R2 = 98%, that was significantly improved by the additional of a quadratic component, R2 = 99.99%, p < 0.002. People were sensitive to argument structure, but the position of the ROCs below the diagonal indicates that their treatment of denial arguments departed from the normative; MT are treated as less valid than AC. Applying the SDT model in a normative fashion, as would seem reasonable given extant theories of conditional reasoning, produced results that contrast sharply with previous findings. The clearly linear ROC in the top panel of Figure ​Figure11 is not only unlike the curvilinear ROCs observed with syllogisms but if taken at face value is problematic for the SDT model. It could be that there is something fundamentally different in the way that people reason about causal conditionals as compared to other types of problems. It seems to us more likely that the difference lies with affirmation and denial inferences; the latter do not seem to be treated in the normatively prescribed fashion. Once this is assumed, the ROC results become more sensible and fall in line with previous results (in a reanalysis of published and unpublished data sets, Heit and Rotello, 2014, have also reported curvilinear ROCs from MP plotted in the manner of Figure ​Figure1,1, lower left). This interpretation converges with Singmann and Klauers (2011) finding, based on state-trace analysis, that affirmation and denial problems may depend on different processes. Why use ROC analysis rather than simply examine the raw validity judgments? Interpreting the latter often relies on assumptions that may not be justified (Klauer et al., 2000; Dube et al., 2010). The main advantage of a formal model like SDT lies in its specification of assumptions. However, models can also produce insights that are not obvious at first glance. A qualitative difference between affirmation and denial inferences is not necessarily predicted by extant theories. Moreover, various manipulations seem to exert a similar effect on both types of inferences (e.g., Cummins, 1995). Finally, it is interesting to note that the production of linear ROCs when performance is driven by multiple underlying processes has been predicted in theory (DeCarlo, 2002). These results may offer a case study of how this can occur in practice.

Summary statistics in the attentional blink

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.

Investigating reasoning with multiple integrated neuroscientific methods

This work was supported by the Economic and Social Research Council Grant RES- 062-23-3285. Dual processes in reasoning: A neuropsychological study of the role of working memory

Dexamphetamine normalises electrophysiological activity in attention deficit-hyperactivity disorder during the Stroop task.

A case study was conducted to investigate whether dexamphetamine enhances interference control in an adult with attention deficit/hyperactivity disorder. Continuous electroencephalography was recorded both on and off dexamphetamine during performance on a Stroop task. An age-, gender- and IQ-matched control also completed the same task. Event related potentials for the control participant revealed a positive potential to incongruent stimuli between 270 and 440 ms, whereas for the participant with attention deficit/hyperactivity disorder off medication, the reverse polarity was observed in a later time window. Following administration of dexamphetamine, however, the event-related potentials for the incongruent condition closely resembled those in the control, suggesting that dexamphetamine successfully normalises electroencephalographic activity.

Human sensory Long-Term Potentiation (LTP) predicts visual memory performance and is modulated by the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism

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, and to gain additional insight into variations in memory function and memory decline. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to BDNF Val66Met; a single nucleotide polymorphism implicated in memory function. Methods 28 participants (15 female) 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 minutes 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.