Mnemonic Training Reshapes Brain Networks to Support Superior Memory

Dresler M, Shirer WR, Konrad BN, Müller NC, Wagner IC, Fernández G, Czisch M, Greicius MD
Neuron. 2017 Mar 8;93(5):1227-1235.e6. doi: 10.1016/j.neuron.2017.02.003.

Memory skills strongly differ across the general population; however, little is known about the brain characteristics supporting superior memory performance. Here we assess functional brain network organization of 23 of the world's most successful memory athletes and matched controls with fMRI during both task-free resting state baseline and active memory encoding. We demonstrate that, in a group of naive controls, functional connectivity changes induced by 6 weeks of mnemonic training were correlated with the network organization that distinguishes athletes from controls. During rest, this effect was mainly driven by connections between rather than within the visual, medial temporal lobe and default mode networks, whereas during task it was driven by connectivity within these networks. Similarity with memory athlete connectivity patterns predicted memory improvements up to 4 months after training. In conclusion, mnemonic training drives distributed rather than regional changes, reorganizing the brain's functional network organization to enable superior memory performance.


Effects of Medial Orbitofrontal Cortex Lesions on Self-Control in Intertemporal Choice

Peters J, D'Esposito M
Curr Biol. 2016 Oct 10;26(19):2625-2628. doi: 10.1016/j.cub.2016.07.035.

Many decisions involve a trade-off between the temporal proximity of a reward and its magnitude. A range of clinical conditions are associated with poor self-control during such intertemporal choices, such that smaller rewards that are received sooner are preferred over larger rewards that are received later to a greater extent [1, 2]. According to a prominent neural model of self-control [3-6], subjective reward values are represented in the medial orbitofrontal cortex (mOFC) at the time of choice [7-9]. Successful self-control in this model is then thought to depend on a modulation of these mOFC value representations via the lateral prefrontal cortex (lPFC) [3, 6]. Here we directly tested three key predictions of this model in patients with lesions to the mOFC (n = 9) and matched controls (n = 19). First, we show that mOFC lesions disrupt choice-free valuation ratings. This finding provides causal evidence for a role of the mOFC in reward valuation and contrasts with the effects of lPFC disruption [6]. Second, we show that mOFC damage indeed decreases self-control during intertemporal choice, replicating previous findings [10]. Third, extending these previous observations, we show that the effect of mOFC damage on intertemporal choice depends on the actual self-control demands of the task. Our findings thus provide causal evidence for a role of mOFC in reward valuation and are compatible with the idea that mOFC damage affects self-control specifically under conditions that might normally require a modulation of mOFC value representations, e.g., by the lPFC.


Reversed Procrastination by Focal Disruption of Medial Frontal Cortex

Jha A, Diehl B, Scott C, McEvoy AW, Nachev P.
Curr Biol. 2016 Nov 7;26(21):2893-2898. doi: 10.1016/j.cub.2016.08.016.

An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain.


Dynamical Representation of Dominance Relationships in the Human Rostromedial Prefrontal Cortex

Ligneul R, Obeso I, Ruff CC, Dreher JC
Curr Biol. 2016 Dec 5;26(23):3107-3115. doi: 10.1016/j.cub.2016.09.015.

Humans and other primates have evolved the ability to represent their status in the group's social hierarchy, which is essential for avoiding harm and accessing resources. Yet it remains unclear how the human brain learns dominance status and adjusts behavior accordingly during dynamic social interactions. Here we address this issue with a combination of fMRI and transcranial direct current stimulation (tDCS). In a first fMRI experiment, participants learned an implicit dominance hierarchy while playing a competitive game against three opponents of different skills. Neural activity in the rostromedial PFC (rmPFC) dynamically tracked and updated the dominance status of the opponents, whereas the ventromedial PFC and ventral striatum reacted specifically to competitive victories and defeats. In a second experiment, we applied anodal tDCS over the rmPFC to enhance neural excitability while subjects performed a similar competitive task. The stimulation enhanced the relative weight of victories over defeats in learning social dominance relationships and exacerbated the influence of one's own dominance over competitive strategies. Importantly, these tDCS effects were specific to trials in which subjects learned about dominance relationships, as they were not present for control choices associated with monetary incentives but no competitive feedback. Taken together, our findings elucidate the role of rmPFC computations in dominance learning and unravel a fundamental mechanism that governs the emergence and maintenance of social dominance relationships in humans.


Imbalanced Activity in the Orbitofrontal Cortex and Nucleus Accumbens Impairs Behavioral Inhibition

Meyer HC, Bucci DJ.
Curr Biol. 2016 Oct 24;26(20):2834-2839. doi: 10.1016/j.cub.2016.08.034.

Contemporary models of behavioral regulation maintain that balanced activity between cognitive control areas (prefrontal cortex, PFC) and subcortical reward-related regions (nucleus accumbens, NAC) mediates the selection of appropriate behavioral responses, whereas imbalanced activity (PFC < NAC) results in maladaptive behavior [1-6]. Imbalance can arise from reduced engagement of PFC (via fatigue or stress [7]) or from excessive activity in NAC [8]. Additionally, a concept far less researched is that an imbalance can result from simultaneously low PFC activity and high NAC activity. This occurs during adolescence, when the maturation of PFC lags behind that of NAC and NAC is more functionally active compared to adulthood or pre-adolescence [2, 5, 9, 10]. Accordingly, activity is disproportionately higher in NAC than in PFC, which may contribute to impulsivity and risk-taking exhibited by adolescents [5, 6, 10-12]. Despite having explanatory value, support for this notion has been solely correlational. Here, we causally tested this using chemogenetics to simultaneously decrease neural activity in the orbitofrontal cortex (OFC) and increase activity in NAC in adult rats, mimicking the imbalance during adolescence. We tested the effects on negative occasion setting, an important yet understudied form of inhibitory learning that may be particularly relevant during adolescence. Rats with combined manipulation of OFC and NAC were impaired in learning to use environmental cues to withhold a response, an effect that was greater than that of either manipulation alone. These findings provide direct evidence that simultaneous underactivity in OFC and overactivity in NAC can negatively impact behavioral control and provide insight into the neural systems that underlie inhibitory learning.


Dissociation of Choice Formation and Choice-Correlated Activity in Macaque Visual Cortex

Robbe L.T. Goris, Corey M. Ziemba, Gabriel M. Stine, Eero P. Simoncelli and J. Anthony Movshon
Journal of Neuroscience 21 April 2017, 37 (20) 5195-5203;
DOI: https://doi.org/10.1523/JNEUROSCI.3331-16.2017

Responses of individual task-relevant sensory neurons can predict monkeys' trial-by-trial choices in perceptual decision-making tasks. Choice-correlated activity has been interpreted as evidence that the responses of these neurons are causally linked to perceptual judgments. To further test this hypothesis, we studied responses of orientation-selective neurons in V1 and V2 while two macaque monkeys performed a fine orientation discrimination task. Although both animals exhibited a high level of neuronal and behavioral sensitivity, only one exhibited choice-correlated activity. Surprisingly, this correlation was negative: when a neuron fired more vigorously, the animal was less likely to choose the orientation preferred by that neuron. Moreover, choice-correlated activity emerged late in the trial, earlier in V2 than in V1, and was correlated with anticipatory signals. Together, these results suggest that choice-correlated activity in task-relevant sensory neurons can reflect postdecision modulatory signals.


Interaction of Instrumental and Goal-Directed Learning Modulates Prediction Error Representations in the Ventral Striatum

Guo R, Böhmer W, Hebart M, Chien S, Sommer T, Obermayer K, Gläscher J.
J Neurosci. 2016 Dec 14;36(50):12650-12660.

Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior.