The Neural Representation of Prospective Choice during Spatial Planning and Decisions

We are remarkably adept at inferring the consequences of our actions, yet the neuronal mechanisms that allow us to plan a sequence of novel choices remain unclear. We used functional magnetic resonance imaging (fMRI) to investigate how the human brain plans the shortest path to a goal in novel mazes with one (shallow maze) or two (deep maze) choice points. We observed two distinct anterior prefrontal responses to demanding choices at the second choice point: one in rostrodorsal medial prefrontal cortex (rd-mPFC)/superior frontal gyrus (SFG) that was also sensitive to (deactivated by) demanding initial choices and another in lateral frontopolar cortex (lFPC), which was only engaged by demanding choices at the second choice point. Furthermore, we identified hippocampal responses during planning that correlated with subsequent choice accuracy and response time, particularly in mazes affording sequential choices. Psychophysiological interaction (PPI) analyses showed that coupling between the hippocampus and rd-mPFC increases during sequential (deep versus shallow) planning and is higher before correct versus incorrect choices. In short, using a naturalistic spatial planning paradigm, we reveal how the human brain represents sequential choices during planning without extensive training. Our data highlight a network centred on the cortical midline and hippocampus that allows us to make prospective choices while maintaining initial choices during planning in novel environments

Conscious perception of errors and its relation to the anterior insula

To detect erroneous action outcomes is necessary for flexible adjustments and therefore a prerequisite of adaptive, goal-directed behavior. While performance monitoring has been studied intensively over two decades and a vast amount of knowledge on its functional neuroanatomy has been gathered, much less is known about conscious error perception, often referred to as error awareness. Here, we review and discuss the conditions under which error awareness occurs, its neural correlates and underlying functional neuroanatomy. We focus specifically on the anterior insula, which has been shown to be (a) reliably activated during performance monitoring and (b) modulated by error awareness. Anterior insular activity appears to be closely related to autonomic responses associated with consciously perceived errors, although the causality and directions of these relationships still needs to be unraveled. We discuss the role of the anterior insula in generating versus perceiving autonomic responses and as a key player in balancing effortful task-related and resting-state activity. We suggest that errors elicit reactions highly reminiscent of an orienting response and may thus induce the autonomic arousal needed to recruit the required mental and physical resources. We discuss the role of norepinephrine activity in eliciting sufficiently strong central and autonomic nervous responses enabling the necessary adaptation as well as conscious error perception

Developing Single-Molecule TPM Experiments for Direct Observation of Successful RecA-Mediated Strand Exchange Reaction

RecA recombinases play a central role in homologous recombination. Once assembled on single-stranded (ss) DNA, RecA nucleoprotein filaments mediate the pairing of homologous DNA sequences and strand exchange processes. We have designed two experiments based on tethered particle motion (TPM) to investigate the fates of the invading and the outgoing strands during E. coli RecA-mediated pairing and strand exchange at the single-molecule level in the absence of force. TPM experiments measure the tethered bead Brownian motion indicative of the DNA tether length change resulting from RecA binding and dissociation. Experiments with beads labeled on either the invading strand or the outgoing strand showed that DNA pairing and strand exchange occurs successfully in the presence of either ATP or its non-hydrolyzable analog, ATPγS. The strand exchange rates and efficiencies are similar under both ATP and ATPγS conditions. In addition, the Brownian motion time-courses suggest that the strand exchange process progresses uni-directionally in the 5′-to-3′ fashion, using a synapse segment with a wide and continuous size distribution

Reduction of Pavlovian bias in schizophrenia: Enhanced effects in clozapine-administered patients

The negative symptoms of schizophrenia (SZ) are associated with a pattern of reinforcement learning (RL) deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action ("Go" or "NoGo") and the valence of the optimal outcome (reward or punishment-avoidance), such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer "Go-learning" in schizophrenia where "Go" responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value

Cascade of Neural Events Leading from Error Commission to Subsequent Awareness Revealed Using EEG Source Imaging

The goal of the present study was to shed light on the respective contributions of three important action monitoring brain regions (i.e. cingulate cortex, insula, and orbitofrontal cortex) during the conscious detection of response errors. To this end, fourteen healthy adults performed a speeded Go/Nogo task comprising Nogo trials of varying levels of difficulty, designed to elicit aware and unaware errors. Error awareness was indicated by participants with a second key press after the target key press. Meanwhile, electromyogram (EMG) from the response hand was recorded in addition to high-density scalp electroencephalogram (EEG). In the EMG-locked grand averages, aware errors clearly elicited an error-related negativity (ERN) reflecting error detection, and a later error positivity (Pe) reflecting conscious error awareness. However, no Pe was recorded after unaware errors or hits. These results are in line with previous studies suggesting that error awareness is associated with generation of the Pe. Source localisation results confirmed that the posterior cingulate motor area was the main generator of the ERN. However, inverse solution results also point to the involvement of the left posterior insula during the time interval of the Pe, and hence error awareness. Moreover, consecutive to this insular activity, the right orbitofrontal cortex (OFC) was activated in response to aware and unaware errors but not in response to hits, consistent with the implication of this area in the evaluation of the value of an error. These results reveal a precise sequence of activations in these three non-overlapping brain regions following error commission, enabling a progressive differentiation between aware and unaware errors as a function of time elapsed, thanks to the involvement first of interoceptive or proprioceptive processes (left insula), later leading to the detection of a breach in the prepotent response mode (right OFC)

Examining the role of genetic risk and longitudinal transmission processes underlying maternal parenting and psychopathology and children’s ADHD symptoms and aggression: utilizing the advantages of a prospective adoption design

Although genetic factors may contribute to initial liability for ADHD onset, there is growing evidence of the potential importance of the rearing environment on the developmental course of ADHD symptomatology. However, associations between family-level variables (maternal hostility, maternal depressive symptoms) and child behaviors (developmental course of ADHD and aggression) may be explained by genes that are shared by biologically related parents and children. Furthermore, ADHD symptoms and aggression commonly co-occur: it is important to consider both simultaneously to have a better understanding of processes underlying the developmental course of ADHD and aggression. To addresses these issues, we employed a longitudinal genetically sensitive parent–offspring adoption design. Analyses were conducted using Cohort I (n = 340) of the Early Growth and Development Study with cross-validation analyses conducted with Cohort II (n = 178). Adoptive mother hostility, but not depression, was associated with later child ADHD symptoms and aggression. Mothers and their adopted children were genetically unrelated, removing passive rGE as a possible explanation. Early child impulsivity/activation was associated with later ADHD symptoms and aggression. Child impulsivity/activation was also associated with maternal hostility, with some evidence for evocative gene-environment correlation processes on adoptive mother depressive symptoms. This study provides novel insights into family-based environmental influences on child ADHD and aggression symptoms, independent of shared parental genetic factors, implications of which are further explicated in the discussion

Dorsal anterior cingulate cortex shows fMRI response to internal and external error signals.

In our event-related functional magnetic resonance imaging (fMRI) experiment, participants learned to select between two response options by trial-and-error, using feedback stimuli that indicated monetary gains and losses. The results of the experiment indicate that error responses and error feedback activate the same region of dorsal anterior cingulate cortex, suggesting that this region is sensitive to both internal and external sources of error information

The effects of context in item-based directed forgetting: Evidence for “one-shot” context storage

The effects of context on item-based directed forgetting were assessed. Study words were presented against different background pictures and were followed by a cue to remember (R) or forget (F) the target item. The effects of incidental and intentional encoding of context on recognition of the study words were examined in Experiments 1 and 2. Recognition memory for the picture contexts was assessed in Experiments 3a and 3b. Recognition was greater for R-cued compared to F-cued targets, demonstrating an effect of directed forgetting. In contrast, no directed forgetting effect was seen for the background pictures. An effect of context-dependent recognition was seen in Experiments 1 and 2, such that the hit rate and the false-alarm rate were greater for items tested in an old compared to a novel context. An effect of context-dependent discrimination was also observed in Experiment 2 as the hit rate was greater for targets shown in their same old study context compared to a different old context. The effects of context and directed forgetting did not interact. The results are consistent with Malmberg and Shiffrin’s (Journal of Experimental Psychology: Learning, Memory, and Cognition, 31, 322–336, 2005) “one-shot” context storage hypothesis that assumes that a fixed amount of context is stored in the first 1 to 2 s of the presentation of the study item. The effects of context are independent of item-based directed forgetting because context is encoded prior to the R or F cue, and the differential processing of target information that gives rise to the directed forgetting effect occurs after the cue