A guide for concurrent TMS-fMRI to investigate functional brain networks.

Transcranial Magnetic Stimulation (TMS) allows for the direct activation of neurons in the human neocortex and has proven to be fundamental for causal hypothesis testing in cognitive neuroscience. By administering TMS concurrently with functional Magnetic Resonance Imaging (fMRI), the effect of cortical TMS on activity in distant cortical and subcortical structures can be quantified by varying the levels of TMS output intensity. However, TMS generates significant fluctuations in the fMRI time series, and their complex interaction warrants caution before interpreting findings. We present the methodological challenges of concurrent TMS-fMRI and a guide to minimize induced artifacts in experimental design and post-processing. Our study targeted two frontal-striatal circuits: primary motor cortex (M1) projections to the putamen and lateral prefrontal cortex (PFC) projections to the caudate in healthy human participants. We found that TMS parametrically increased the BOLD signal in the targeted region and subcortical projections as a function of stimulation intensity. Together, this work provides practical steps to overcome common challenges with concurrent TMS-fMRI and demonstrates how TMS-fMRI can be used to investigate functional brain networks.

Dissociable Neural Systems Support the Learning and Transfer of Hierarchical Control Structure.

Humans can draw insight from previous experiences to quickly adapt to novel environments that share a common underlying structure. Here we combine functional imaging and computational modeling to identify the neural systems that support the discovery and transfer of hierarchical task structure. Human subjects (male and female) completed multiple blocks of a reinforcement learning task that contained a global hierarchical structure governing stimulus-response action mapping. First, behavioral and computational evidence showed that humans successfully discover and transfer the hierarchical rule structure embedded within the task. Next, analysis of fMRI BOLD data revealed activity across a frontoparietal network that was specifically associated with the discovery of this embedded structure. Finally, activity throughout a cingulo-opercular network supported the transfer and implementation of this discovered structure. Together, these results reveal a division of labor in which dissociable neural systems support the learning and transfer of abstract control structures.SIGNIFICANCE STATEMENT A fundamental and defining feature of human behavior is the ability to generalize knowledge from the past to support future action. Although the neural circuits underlying more direct forms of learning have been well established over the last century, we still lack a solid framework from which to investigate more abstract, higher-order human learning and knowledge generalization. We designed a novel behavioral paradigm to specifically isolate a learning process in which previous knowledge, rather than directly indicating the correct action, instead guides the search for the correct action. Moreover, we identify that this learning process is achieved via the coordinated and temporally specific activity of two prominent cognitive control brain networks.

Causal Evidence for a Role of Theta and Alpha Oscillations in the Control of Working Memory.

Working memory (WM) relies on the prioritization of relevant information and suppression of irrelevant information [1, 2]. Prioritizing relevant information has been linked to theta frequency neural oscillations in lateral prefrontal cortex and suppressing irrelevant information has been linked to alpha oscillations in occipito-parietal cortex [3,11]. Here, we used a retrospective-cue WM paradigm to manipulate prioritization and suppression task demands designed to drive theta oscillations in prefrontal cortex and alpha oscillations in parietal cortex, respectively. To causally test the role of these neural oscillations, we applied rhythmic transcranial magnetic stimulation (TMS) in either theta or alpha frequency to prefrontal and parietal regions identified using functional MRI. The effect of rhythmic TMS on WM performance was dependent on whether the TMS frequency matched or mismatched the expected underlying task-driven oscillations of the targeted region. Functional MRI in the targeted regions predicted subsequent TMS effects across subjects supporting a model by which theta oscillations are excitatory to neural activity, and alpha oscillations are inhibitory. Together, these results causally establish dissociable roles for prefrontal theta oscillations and parietal alpha oscillations in the control of internally maintained WM representations.

Practical Considerations for Navigating Registered Reports.

Recent open science efforts to improve rigor and reliability have sparked great enthusiasm. Among these, the Registered Report publication format integrates best practices in hypothesis-driven research with peer review that occurs before the research is conducted. Here, we detail practical recommendations to help researchers negotiate the mechanics of this developing format.

Serial Dependence across Perception, Attention, and Memory.

Information that has been recently perceived or remembered can bias current processing. This has been viewed as both a corrupting (e.g., proactive interference in short-term memory) and stabilizing (e.g., serial dependence in perception) phenomenon. We hypothesize that this bias is a generally adaptive aspect of brain function that leads to occasionally maladaptive outcomes.

Striatal prediction errors support dynamic control of declarative memory decisions.

Adaptive memory requires context-dependent control over how information is retrieved, evaluated and used to guide action, yet the signals that drive adjustments to memory decisions remain unknown. Here we show that prediction errors (PEs) coded by the striatum support control over memory decisions. Human participants completed a recognition memory test that incorporated biased feedback to influence participants' recognition criterion. Using model-based fMRI, we find that PEs-the deviation between the outcome and expected value of a memory decision-correlate with striatal activity and predict individuals' final criterion. Importantly, the striatal PEs are scaled relative to memory strength rather than the expected trial outcome. Follow-up experiments show that the learned recognition criterion transfers to free recall, and targeting biased feedback to experimentally manipulate the magnitude of PEs influences criterion consistent with PEs scaled relative to memory strength. This provides convergent evidence that declarative memory decisions can be regulated via striatally mediated reinforcement learning signals.

Overlapping neural response to the pain or harm of people, animals, and nature.

Interpersonal pain perception is a fundamental and evolutionarily beneficial social process. While critical for navigating the social world, whether or not people rely on similar processes to perceive and respond to the harm of the non-human biological world remains largely unknown. Here we investigate whether neural reactivity toward the suffering of other people is distinct from or overlapping with the neural response to pain and harm inflicted upon non-human entities, specifically animals and nature. We used fMRI to measure neural activity while participants (n=15) perceived and reported how badly they felt for the pain or harm of humans, animals, and nature, relative to neutral situations. Neural regions associated with perceiving the pain of other people (e.g. dorsal anterior cingulate cortex, bilateral anterior insula) were similarly recruited when perceiving and responding to painful scenes across people, animals, and nature. These results suggest that similar brain responses are relied upon when perceiving the harm of social and non-social biological entities, broadly construed, and that activity within the dorsal anterior cingulate cortex and bilateral anterior insula in response to pain-relevant stimuli is not uniquely specific to humans.

Selecting and tracking multiple objects.

When interacting with the world, people can dynamically split attention across multiple objects in the environment, both when the objects are stationary and when the objects are moving. This type of visual processing is commonly studied in lab settings using either static selection tasks or moving tracking tasks. We describe performance limits that are common to both tasks, including limits on capacity, crowding, visual hemifield arrangement, and speed. Because these shared limits on performance suggest common underlying mechanisms, we examine a set of models that might account for limits across both. We also review cognitive neuroscience data relevant to these limits, which can provide constraints on the set of models. Finally, we examine performance limits that are unique to tracking tasks, such as trajectory encoding, and identity encoding. We argue that a complete model of multiple object tracking must account for both those limits shared between static selection and dynamic tracking, as well as limits unique to tracking. It must also provide neurally plausible mechanisms for the underlying processing resources.

Ventral striatum and the evaluation of memory retrieval strategies.

Adaptive memory retrieval requires mechanisms of cognitive control that facilitate the recovery of goal-relevant information. Frontoparietal systems are known to support control of memory retrieval. However, the mechanisms by which the brain acquires, evaluates, and adapts retrieval strategies remain unknown. Here, we provide evidence that ventral striatal activation tracks the success of a retrieval strategy and correlates with subsequent reliance on that strategy. Human participants were scanned with fMRI while performing a lexical decision task. A rule was provided that indicated the likely semantic category of a target word given the category of a preceding prime. Reliance on the rule improved decision-making, as estimated within a drift diffusion framework. Ventral striatal activation tracked the benefit that relying on the rule had on decision-making. Moreover, activation in ventral striatum correlated with a participant's subsequent reliance on the rule. Taken together, these results support a role for ventral striatum in learning and evaluating declarative retrieval strategies.

Cultural modulation of the neural correlates of emotional pain perception: the role of other-focusedness.

Cultures vary in the extent to which they emphasize group members to habitually attend to the needs, perspectives, and internal experiences of others compared to the self. Here we examined the influence that collectivistic and individualistic cultural environments may play on the engagement of the neurobiological processes that underlie the perception and processing of emotional pain. Using cross-cultural fMRI, Korean and Caucasian-American participants passively viewed scenes of others in situations of emotional pain and distress. Regression analyses revealed that the value of other-focusedness was associated with heightened neural response within the affective pain matrix (i.e. anterior cingulate cortex and insula) to a greater extent for Korean relative to Caucasian-American participants. These findings suggest that mindsets promoting attunement to the subjective experience of others may be especially critical for pain-related and potentially empathic processing within collectivistic relative to individualistic cultural environments.

Striatal contributions to declarative memory retrieval.

Declarative memory is known to depend on the medial temporal lobe memory system. Recently, there has been renewed focus on the relationship between the basal ganglia and declarative memory, including the involvement of striatum. However, the contribution of striatum to declarative memory retrieval remains unknown. Here, we review neuroimaging and neuropsychological evidence for the involvement of the striatum in declarative memory retrieval. From this review, we propose that, along with the prefrontal cortex (PFC), the striatum primarily supports cognitive control of memory retrieval. We conclude by proposing three hypotheses for the specific role of striatum in retrieval: (1) striatum modulates the re-encoding of retrieved items in accord with their expected utility (adaptive encoding), (2) striatum selectively admits information into working memory that is expected to increase the likelihood of successful retrieval (adaptive gating), and (3) striatum enacts adjustments in cognitive control based on the outcome of retrieval (reinforcement learning).

Flexible visual processing of spatial relationships.

Visual processing breaks the world into parts and objects, allowing us not only to examine the pieces individually, but also to perceive the relationships among them. There is work exploring how we perceive spatial relationships within structures with existing representations, such as faces, common objects, or prototypical scenes. But strikingly, there is little work on the perceptual mechanisms that allow us to flexibly represent arbitrary spatial relationships, e.g., between objects in a novel room, or the elements within a map, graph or diagram. We describe two classes of mechanism that might allow such judgments. In the simultaneous class, both objects are selected concurrently. In contrast, we propose a sequential class, where objects are selected individually over time. We argue that this latter mechanism is more plausible even though it violates our intuitions. We demonstrate that shifts of selection do occur during spatial relationship judgments that feel simultaneous, by tracking selection with an electrophysiological correlate. We speculate that static structure across space may be encoded as a dynamic sequence across time. Flexible visual spatial relationship processing may serve as a case study of more general visual relation processing beyond space, to other dimensions such as size or numerosity.

Cultural influences on neural basis of intergroup empathy.

Cultures vary in the extent to which people prefer social hierarchical or egalitarian relations between individuals and groups. Here we examined the effect of cultural variation in preference for social hierarchy on the neural basis of intergroup empathy. Using cross-cultural neuroimaging, we measured neural responses while Korean and American participants observed scenes of racial ingroup and outgroup members in emotional pain. Compared to Caucasian-American participants, Korean participants reported experiencing greater empathy and elicited stronger activity in the left temporo-parietal junction (L-TPJ), a region previously associated with mental state inference, for ingroup compared to outgroup members. Furthermore, preferential reactivity within this region to the pain of ingroup relative to outgroup members was associated with greater preference for social hierarchy and ingroup biases in empathy. Together, these results suggest that cultural variation in preference for social hierarchy leads to cultural variation in ingroup-preferences in empathy, due to increased engagement of brain regions associated with representing and inferring the mental states of others.