Deep Brain Stimulation is an invasive device-based neuromodulation technique that allows the therapeutic direct stimulation of subcortical and deep cortical structures following the surgical placement of stimulating electrodes. DBS is approved by the U.S. Federal Drug Administration for the treatment of movement disorders and obsessive-compulsive disorder, while new indications, including Major Depressive Disorder, are in experimental development. We report the case of a patient with MDD who received DBS to the ventral internal capsule and ventral striatum bilaterally and presented (...) with 2 weeks of voltage-dependent Tourette-like symptoms including brief transient episodes of abrupt-onset and progressively louder coprolalia and stuttered speech; tic-like motor behavior in his right arm and leg; rushes of anxiety, angry prosody, angry affect; and moderate amnesia without confusion. We describe the results of the inpatient neuropsychiatric workup leading to the diagnosis of iatrogenic voltage-dependent activation of cortico-subcortical circuits and discuss insights into the pathophysiology of Tourette as well as safety considerations raised by the case. (shrink)

Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in (...) the control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses. (shrink)

Ras homolog enriched in the striatum (Rhes) is a striatal enriched protein that promotes the formation of thin membranous tubes resembling tunneling nanotubes (TNT)—“Rhes tunnels”—that connect neighboring cell and transport cargoes: vesicles and proteins between the neuronal cells. Here the literature on TNT‐like structures is reviewed, and the implications of Rhes‐mediated TNT, the mechanisms of its formation, and its potential in novel cell‐to‐cell communication in regulating striatal biology and disease are emphasized. Thought‐provoking ideas regarding how Rhes‐mediated TNT, if it (...) exists, in vivo, would radically change the way neurons communicate in the brain are discussed. (shrink)

The effect of concurrent movement on incidental versus intentional statistical learning was examined in two experiments. In Experiment 1, participants learned the statistical regularities embedded within familiarization stimuli implicitly, whereas in Experiment 2 they were made aware of the embedded regularities and were instructed explicitly to learn these regularities. Experiment 1 demonstrated that while the control group were able to learn the statistical regularities, the resistance-free cycling group and the exercise group did not demonstrate learning. This is in contrast with (...) the findings of Experiment 2, where all three groups demonstrated significant levels of learning. The results suggest that the movement demands, rather than the physiological stress, interfered with statistical learning. We suggest movement activates the striatum, which is not only responsible for motor control but also plays a role in incidental learning. (shrink)

Foraging‐ and feeding‐related behaviors across eumetazoans share similar molecular mechanisms, suggesting the early evolution of an optimal foraging behavior called area‐restricted search (ARS), involving mechanisms of dopamine and glutamate in the modulation of behavioral focus. Similar mechanisms in the vertebrate basal ganglia control motor behavior and cognition and reveal an evolutionary progression toward increasing internal connections between prefrontal cortex and striatum in moving from amphibian to primate. The basal ganglia in higher vertebrates show the ability to transfer dopaminergic activity (...) from unconditioned stimuli to conditioned stimuli. The evolutionary role of dopamine in the modulation of goal‐directed behavior and cognition is further supported by pathologies of human goal‐directed cognition, which have motor and cognitive dysfunction and organize themselves, with respect to dopaminergic activity, along the gradient described by ARS, from perseverative to unfocused. The evidence strongly supports the evolution of goal‐directed cognition out of mechanisms initially in control of spatial foraging but, through increasing cortical connections, eventually used to forage for information. (shrink)

Although a great deal of research addresses the neural basis of deliberate and intentional emotion-regulation strategies, less attention has been paid to the neural mechanisms involved in implicit forms of emotion regulation. Behavioural research suggests that romantically involved participants implicitly derogate the attractiveness of alternative partners, and the present study sought to examine the neural basis of this effect. Romantically committed participants in the present study were scanned with functional magnetic resonance imaging (fMRI) while indicating whether they would consider each (...) of a series of attractive (or unattractive) opposite-sex others as a hypothetical dating partner both while under cognitive load and no cognitive load. Successful derogation of attractive others during the no cognitive load compared to the cognitive load trials corresponded with increased activation in the ventrolateral prefrontal cortex (VLPFC) and posterior dorsomedial prefrontal cortex (pDMPFC), and decreased activation in the ventral striatum, a pattern similar to those reported in deliberate emotion-regulation studies. Activation in the VLPFC and pDMPFC was not significant in the cognitive load condition, indicating that while the derogation effect may be implicit, it nonetheless requires cognitive resources. Additionally, activation in the right VLPFC correlated with participants' level of relationship investment. These findings suggest that the RVLPFC may play a particularly important role in implicitly regulating the emotions that threaten the stability of a romantic relationship. (shrink)

Hormonal changes across the menstrual cycle have been shown to influence reward-related motivation and impulsive behaviors. Here, to compare neural mechanisms of cognitive impulse control during the mid-luteal phase (LP) versus during the late follicular phase (FP), we employed functional magnetic resonance imaging (fMRI) with an event-related monetary delay discounting (EMDD) behavioral task (study 1) and then employed resting state (RS)-fMRI (study 2). The imaging data were analyzed and related to behavior-associated neural activation. In study 1, women in the late (...) FP showed a preference for sooner rewards while exhibiting enhanced activity in the dorsal striatum (DS), whereas women in the mid-LP showed a preference for delayed, higher-value rewards with enhanced activity in the dorsolateral prefrontal cortex (dlPFC). Discount rate (transformed k) in the EMDD task correlated with functional connectivity (FC) of the DS-dlPFC circuitry, consistent with the possibility that DS-dlPFC circuitry may regulate impulsivity. In study 2, the right dlPFC was significantly more active in mid-LP than in late FP, and this effect was sensitive to estradiol (E2) and relative E2 levels during mid-LP. The magnitude of DS-dlPFC FC correlated negatively with psychometric impulsivity scores during the late FP. These results replicated findings from study 1 and further indicated that relative E2 levels may play an important role in increasing cognitive control during the mid-LP, which provides new insight into the treatment of conditions characterized by hyper-impulsivity, such as obsessive-compulsive disorder, Parkinson disease, and attention deficit hyperactivity disorder. In conclusion, our results suggest that cyclical gonadal hormones affect cognitive control on impulsive behavior periodically, possibility via DS-dlPFC circuitry. (shrink)

Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness/surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding (...) DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects. Subjects reporting PD-Sx were then grouped into symptom-based clusters: N = 20 into Cluster B (reporting Antisocial, Borderline, Histrionic, or Narcissistic PD-Sx) and N = 28 into Cluster C (reporting Obsessive–Compulsive, Avoidant, or Dependent PD-Sx); N = 11 subjects reported PD-Sx from both clusters, and none reported Cluster A (Paranoid, Schizoid, or Schizotypal) PD-Sx. Compared to control, Cluster C PD-Sx was associated with greater striatal surface area localized to the caudate tail, smaller ventral striatum volumes, and greater cortical thickness in right prefrontal cortex. Both Cluster B and C PD-Sx groups also showed trends toward greater posterior caudate volumes and orbitofrontal surface area anomalies, but these findings did not survive correction for multiple comparisons. The results point to morphological abnormalities that could contribute to Cluster C PD-Sx. In addition, the observations parallel those in substance use disorders, pointing to the importance of considering PD-Sx when interpreting findings in often-comorbid psychiatric disorders. (shrink)

People are motivated by shared social values that, when held with moral conviction, can serve as compelling mandates capable of facilitating support for ideological violence. The current study examined this dark side of morality by identifying specific cognitive and neural mechanisms associated with beliefs about the appropriateness of sociopolitical violence, and determining the extent to which the engagement of these mechanisms was predicted by moral convictions. Participants reported their moral convictions about a variety of sociopolitical issues prior to undergoing functional (...) MRI scanning. During scanning, they were asked to evaluate the appropriateness of violent protests that were ostensibly congruent or incongruent with their views about sociopolitical issues. Complementary univariate and multivariate analytical strategies comparing neural responses to congruent and incongruent violence identified neural mechanisms implicated in processing salience and in the encoding of subjective value. As predicted, neuro-hemodynamic response was modulated parametrically by individuals’ beliefs about the appropriateness of congruent relative to incongruent sociopolitical violence in ventromedial prefrontal cortex, and by moral conviction in ventral striatum. Overall moral conviction was predicted by neural response to congruent relative to incongruent violence in amygdala. Together, these findings indicate that moral conviction about sociopolitical issues serves to increase their subjective value, overriding natural aversion to interpersonal harm. (shrink)

How certain neural mechanisms momentarily endow with the subjective awareness percepts and affects represented elsewhere is more likely to be clarified when structures essential to Mc are identified. The loss of C with bilateral thalmic lesions involving the intralaminar nuclei contrasts with retention of C after large cortical ablations depriving C of specific contents. A role of ILN in the perception of primitive sensations is suggested by their afference of directly ascending pathways. A role for ILN in awareness of cortical (...) activity is suggested by their widespread afference from cortex, a property shared with striatum. A role for ILN in volition is suggested by their heavy projection to striatum. Unlike striatum, ILN also project widely to almost all neocortex, enabling an effect on ideation; this last property is in common with other structures but none of them has the same direct cortical afference. And passage through the reticular nucleus of ILN efferents to cortex could impact the attention-selective action of nRt. It is suggested that the quickest route to a better understanding of C involves more intensive study of ILN. No other structure seems, in the light of our current knowledge, a more likely site for Mc. (shrink)

This review considers a number of recent theories on the neural basis of consciousness, with particular attention to the theories of Bogen, Crick, Llinás, Newman, and Changeux. These theories allot different roles to various key brain areas, in particular the reticular and intralaminar nuclei of the thalamus and the cortex. Crick's hypothesis is that awareness is a function of reverberating corticothalamic loops and that the spotlight ofintramodalattention is controlled by the reticular nucleus of the thalamus. He also proposed different mechanisms (...) for attention and intention . The current review presents a new hypothesis, based on elements from these hypotheses, includingintermodalattention and olfaction and pain, which may pose problems for Crick's original theory. This work reviews the possible role in awareness and intermodal attention and intention of the cholinergic system in the basal forebrain and the tegmentum; the reticular, the intralaminar, and the dorsomedial thalamic nuclei; the raphe and locus coeruleus; the reticular formation; the ventral striatum and extended amygdala; insula cortex, and other selected cortical areas. Both clinical and basic research data are covered. The conclusion is reached that the brain may work by largely nonlinear parallel processing and much intramodal shifts of attention may be effected by intracortical, or multiple corticothalamic mechanisms . But this is constrained by the functional anatomy of the circuits concerned and waking “awareness” is modulated by the many “nonspecific” systems . But the principal agents for intermodal attention shifts, the “searchlight,” may be two key nuclei of the cholinergic system in the mesencephalon. Clinical loss of consciousness results from damage to these nuclei but not from damage to the cholinergic nucleus basalis of the basal forebrain. (shrink)

BackgroundPrevious studies on voxel-based morphometry have found that there were gray matter alterations in patients with hepatic encephalopathy. However, the reported results were inconsistent and lack a quantitative review. Therefore, this study aims for a quantitative meta-analysis of VBM analysis on patients with HE.MethodsThe studies in our meta-analysis were collected from Pubmed, Web of Science, and Embase, which were published from January 1947 to October 2021. The seed-based d mapping method was applied to quantitatively estimate the regional gray matter abnormalities (...) in patients with HE. A meta-regression analysis was applied to evaluate the relationship between plasma ammonia and gray matter alteration.ResultsThere were nine studies, with sixteen datasets consisting of 333 participants with HE and 429 healthy controls. The pooled and subgroup meta-analyses showed an increase in gray matter volume in the bilateral thalamus and the calcarine fissure but a decrease in the GMV in the bilateral insula, the basal ganglia, the anterior cingulate gyrus, and the cerebellum. The meta-regression showed that plasma ammonia was positively associated with the GMV in the left thalamus but was negatively associated with the GMV in the cerebellum and the bilateral striatum.ConclusionGray matter volume in patients with HE largely varied and could be affected by plasma ammonia. The findings of this study could help us to better understand the pathophysiology of cognitive dysfunction in patients with HE. (shrink)

Navigating to goal locations in a known environment (wayfinding) can be accomplished by different strategies, notably by taking habitual, well-learned routes (response strategy) or by inferring novel paths, such as shortcuts, from spatial knowledge of the environment's layout (place strategy). Human and animal neuroscience studies reveal that these strategies reflect different brain systems, with response strategies relying more on activation of the striatum and place strategies associated with activation of the hippocampus. In addition to individual differences in strategy, recent (...) behavioral studies show sex differences such that men use place strategies more than women, and age differences such that older adults use more response strategies than younger adults. This paper takes a comprehensive multilevel approach to understanding these differences, characterizing wayfinding as a complex information processing task. This analysis reveals factors that affect navigation strategy, including availability of the relevant type of environmental knowledge, momentary access to this knowledge, trade-offs between physical and mental effort in different navigation contexts, and risk taking. We consider how strategies are influenced by the computational demands of a navigation task and by factors that affect the neural circuits underlying navigation. We also discuss limitations of laboratory studies to date and outline priorities for future research, including relating wayfinding strategies to independent measures of spatial knowledge, and studying wayfinding strategies in naturalistic environments. (shrink)

A complex brain network, centered on the hippocampus, supports episodic memories throughout their lifetimes. Classically, upon memory encoding during active behavior, hippocampal activity is dominated by theta oscillations (6-10Hz). During inactivity, hippocampal neurons burst synchronously, constituting sharp waves, which can propagate to other structures, theoretically supporting memory consolidation. This 'two-stage' model has been updated by new data from high-density electrophysiological recordings in animals that shed light on how information is encoded and exchanged between hippocampus, neocortex and subcortical structures such as (...) the striatum. Cell assemblies (tightly related groups of cells) discharge together and synchronize across brain structures orchestrated by theta, sharp waves and slow oscillations, to encode information. This evolving dynamical schema is key to extending our understanding of memory processes. (shrink)

Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 (...) years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell‐derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP. (shrink)

Using delay differential equations to study mathematical models of Parkinson's disease and Huntington's disease is important to show how important it is for synchronization between basal ganglia loops to work together. We used the delay circuit RLC (resistor, inductor, capacitor) model to show how the direct pathway and the indirect pathway in the basal ganglia excite and inhibit the motor cortex, respectively. A term has been added to the mathematical model without time delay in the case of the hyperdirect pathway. (...) It is proposed to add a non-linear term to adjust the synchronization. We studied Hopf bifurcation conditions for the proposed models. The desynchronization of response times between the direct pathway and the indirect pathway leads to different symptoms of Parkinson's disease. Tremor appears when the response time in the indirect pathway increases at rest. The simulation confirmed that tremor occurs and the motor cortex is in an inhibited state. The direct pathway can increase the time delay in the dopaminergic pathway, which significantly increases the activity of the motor cortex. The hyperdirect pathway regulates the activity of the motor cortex. The simulation showed bradykinesia occurs when we switch from one movement to another that is less exciting for the motor cortex. A decrease of GABA in the striatum or delayed excitation of the substantia nigra from the subthalamus may be a major cause of Parkinson's disease. An increase in the response time delay in one of the pathways results in the chaotic movement characteristic of Huntington's disease. (shrink)

The adaptive BCI known as ‘closed-loop deep brain stimulation’ (clDBS) is a device that stimulates the brain in order to prevent pathological neural activity and automatically adjusts stimulation levels based on computational algorithms that detect or predict those pathological processes. One of the prominent ethical concerns raised by clDBS is that, by inhibiting or modulating the undesirable neural states of a cognitive agent automatically, the device potentially undermines her autonomy. It has been argued that clDBS is not a threat because (...) autonomy is fundamentally relational, i.e., it essentially depends on external (e.g., social or cultural) factors. If the relational approach to autonomy includes human-computer interaction, then the mechanisms of clDBS, even if external to the brain and exerting some degree of control over the individual, may support her autonomy. However, DBS applications are substantially different from one another, each involving a specific neurological or psychiatric condition, neural target, mechanism and symptom(s), and therefore at least some of them may not fit into the relational analysis. I examine different clDBS applications for treatment resistant depression and claim that while internal capsule/ventral striatum (VC/VS) clDBS is a case of relational autonomy, subgenual cingulate gyrus (Cg25) clDBS is not. Autonomy (relational or otherwise) requires some degree of self-regulation of our motivational states, which is supported by VC/VS DBS but is absent in Cg25 DBS. In Cg25 DBS the device itself directly influences motivational states, thus substituting or overriding (instead of supporting) the auto-regulatory cognitive processes required for autonomous action. (shrink)

Increasingly, functional and evolutionary research has highlighted the important contribution emotion processing makes to complex human social cognition. As such, it may be asked whether neural structures involved in emotion processing, commonly referred to as limbic structures, have been impacted in human brain evolution. To address this question, we performed an extensive evolutionary analysis of multiple limbic structures using modern phylogenetic tools. For this analysis, we combined new volumetric data for the hominoid (human and ape) amygdala and 4 amygdaloid nuclei, (...) hippocampus, and striatum, collected using stereological methods in complete histological series, with previously published datasets on the amygdala, orbital and medial frontal cortex, and insula, as well as a non-limbic structure, the dorsal frontal cortex, for contrast. We performed a parallel analysis using large published datasets including many anthropoid species (human, ape, and monkey), but fewer hominoids, for the amygdala and 2 amygdaloid subdivisions, hippocampus, schizocortex, striatum, and septal nuclei. To address evolutionary change, we compared observed human values to values predicted from regressions run through a) nonhuman hominoids and b) nonhuman anthropoids, assessing phylogenetic influence using phylogenetic generalized least squares regression.Compared with other hominoids, the volumes of the hippocampus, the lateral nucleus of the amygdala, and the orbital frontal cortex were, respectively, 50%, 37%, and 11% greater in humans than predicted for an ape of human hemisphere volume, while the medial and dorsal frontal cortex were, respectively, 26% and 29% significantly smaller. Compared with other anthropoids, only human values for the striatum fell significantly below predicted values. Overall, the data present support for the idea that regions involved in emotion processing are not necessarily conserved or regressive, but may even be enhanced in recent human evolution. (shrink)

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called “conflict of paradigms.” Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's (...) disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting “horizontal modulation” of cortico-cortical relation. Furthermore, alteration in “top-down modulation” reflecting “vertical modulation” of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered “bottom-up modulation” between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation – “vertical” and “horizontal” modulation, respectively. Key Words: Bottom-up modulation; catatonia; horizontal modulation; Parkinson's disease; top-down modulation; vertical modulation. (shrink)

This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students ( N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students’ membership to the independent MT, or the peer-and-teacher-dependent (...) MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students’ individual motivation and (2) its potential neurobiological basis. (shrink)

The neural correlates of two hypothesized emotional processing modes, i.e., schematic and propositional modes, were investigated with positron emission tomography. Nineteen subjects performed an emotional mental imagery task while mentally repeating sentences linked to the meaning of the imagery script. In the schematic conditions, participants repeated metaphoric sentences, whereas in the propositional conditions, the sentences were explicit questions about specific emotional appraisals of the imagery scenario. Five types of emotional scripts were proposed to the subjects (happiness, anger, affection, sadness, and (...) a neutral scenario). The results supported the hypothesized distinction between schematic and propositional emotional processing modes. Specifically, schematic mode was associated with increased activity in the ventromedial prefrontal cortex whereas propositional mode was associated with activation of the anterolateral prefrontal cortex. In addition, interaction analyses showed that schematic versus propositional processing of happiness (compared with the neutral scenario) was associated with increased activity in the ventral striatum whereas “schematic anger” was tentatively associated with activation of the ventral pallidum. © 2003 Elsevier Science (USA). All rights reserved. (shrink)

Raine (2019) reviewed previous research on the neural correlates of antisocial, violent, and psychopathic behavior based on previous studies of neuroscience of morality. The author identified neural circuitries associated with the aforementioned types of antisocial behaviors. However, in the review, Raine acknowledged a limitation in his arguments, the lack of evidence supporting the presence of the neural circuitries. In this correspondence, I intend to show that some of his concerns, particularly those about the insula and cingulate cortex, can be addressed (...) with additional evidence from recent neuroimaging research. In addition, I will propose that the additional evidence can also provide some insights about how to design future neuroimaging studies to examine the functionality of the striatum in the circuitries. (shrink)

Objective: The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Method: Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n (...) = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity. (shrink)

When we are fatigued, we feel that our performance is worse than when we are fresh. Yet, for over 100 years, researchers have been unable to identify an objective, behavioral measure that covaries with the subjective experience of fatigue. Previous work suggests that the metrics of signal detection theory —response bias and perceptual certainty —may change as a function of fatigue, but no work has yet been done to examine whether these metrics covary with fatigue. Here, we investigated cognitive fatigue (...) using SDT. We induced fatigue through repetitive performance of the n-back working memory task, while functional magnetic resonance imaging data was acquired. We also assessed cognitive fatigue at intervals throughout. This enabled us to assess not only whether criterion and d’ covary with cognitive fatigue but also whether similar patterns of brain activation underlie cognitive fatigue and SDT measures. Our results show that both criterion and d’ were correlated with changes in cognitive fatigue: as fatigue increased, subjects became more conservative in their response bias and their perceptual certainty declined. Furthermore, activation in the striatum of the basal ganglia was also related to cognitive fatigue, criterion, and d’. These results suggest that SDT measures represent an objective measure of cognitive fatigue. Additionally, the overlap and difference in the fMRI results between cognitive fatigue and SDT measures indicate that these measures are related while also separate. In sum, we show the relevance of SDT measures in the understanding of fatigue, thus providing researchers with a new set of tools with which to better understand the nature and consequences of cognitive fatigue. (shrink)

Revenge is common in our daily lives, and people feel good when engaging in revenge behavior. However, revenge behavior is a complex process and remains somewhat of a puzzle of human behavior. Neuroimaging studies have revealed that revenge behaviors are associated with activation of a neural network containing the anterior cingulate cortex, ventral striatum, inferior frontal gyrus, and dorsolateral prefrontal cortex. Recent brain stimulation research using transcranial direct current stimulation and transcranial magnetic stimulation has shown a causal relationship between (...) brain regions and revenge behaviors, but the findings have been mixed. In the present study, we aimed to study whether stimulation in the DLPFC can change participants’ revenge behavior in conditions where participants’ wealth was taken away in different ways. We adapted the moonlighting game and designed a new paradigm. Our study revealed that revenge behavior increased following activation in the right DLPFC, suggesting that the right DLPFC plays an important role in overriding self-interest and retaliation. In addition, our results revealed that the right DLPFC is crucial in revenge behavior related to the motivation of invasion. (shrink)

Humans can consolidate and carry out habits other animals cannot. This statement is mainly sustained by the fact that humans have a unique cognitive control of their actions: we can let our attention fade away to perform automatic tasks more efficiently, we can detect if there has been an unexpected problem in their implementation, and we can regain conscious control of the action if necessary. We tend to dichotomize this cognitive process into two “systems”, namely goal-directed versus habitual (Dickinson, 1985), (...) conscious versus unconscious (Crick and Koch, 1998), or slow versus fast (Kahneman, 2011). If we just put it in those terms, these two ways of tackling the challenges of a changing environment seem to be present in non-human animals. However, all dichotomies imply a difficulty to deal with: the regulation of the transition between the two systems. Is this carried out by a third element, or regulated by one of the systems? Could it be more convenient to view it as a continuum, rather than a dichotomy? In any case, we believe this transition has a level of complexity in humans that makes it qualitatively different from its analogue in animals. In fact, this ‘cognitive bridge’ might be a major feature to characterize a reliable behavior, since a particular task or problem is more efficiently tackled when the transition between the two systems is more adequate. Moreover, the integrity of this link could be an indicator to detect prodromal psychiatric conditions, as it has been suggested for slips-of-action (Gillan et al., 2011). In order to justify these ideas, we will focus first on Kahneman’s distinction between systems 1 and 2 (Kahneman, 2011). On the one hand, System 1 is responsible for making decisions rapidly. The purpose of this system is to give us an assessment of the environment around us as quickly as possible so that we are able to respond as fast as possible. To perform this task, System 1 follows general rules or guidelines (heuristics). In all, System 1 is intended to help us make decisions more quickly, and is very useful (let’s say ‘just fine’) in most cases. However, one of the characteristics of these decisions is the lack of voluntary control, what is a problem considering this system is responsible of many of the decisions and judgments we make. Given to its “automatic” nature, System 1 also has biases and systematic errors that are likely to happen in some situations.On the other hand, System 2 acts when a problem which System 1 has no solution for arises. System 2, apparently, can take control of the whole process at any time. It is somewhat triggered by some external or internal alarm that draws its attention and makes it take “conscious” control of the situation. One of the problems of this system is that it is lazy and can be easily exhausted. Therefore, it usually accepts the decisions of System 1 without monitoring them. One proof of System 2’s negligence is what Kahneman calls WYSIATI ("What You See Is All There Is"), a general rule that “facilitates the achievement of coherence and of the cognitive ease that causes us to accept a statement as true”. System 1 easily gets that coherence, and System 2 usually allows it to jump to conclusions and act. In different sets of experiments, Kahneman demonstrates that humans are not good at all with statistics or handling mathematics; in his opinion, this is because humans simplify judgments to make them more understandable and deal with them just through heuristics that System 1 can handle. This general view of humans as poor rational decision-makers is also supported by other authors (see, for example, Ariely, 2008).In our opinion, this division of human cognition into two systems fits well with the usual opposition between goal-directed versus habitual systems (Dickinson, 1985). In general, goal-directed actions are viewed as conscious, flexible, and sensitive to outcome devaluation, whereas habits are mainly unconscious, rigid and insensitive to changes in the value of the outcome. The features of goal-directed and habit systems were mainly drawn from studies in animals. The typical experiment about this subject consists on teaching the contingency between an instrumental action (for example, a lever press) and a reward to the animal (Adams and Dickinson, 1981). At the beginning, the animal’s behavior is goal directed, and it performs the action to obtain the reward. However, this behavior becomes “habitual” (in this context, a motor routine) after many repetitions. When that happens, the value of the reward is transferred to the lever press itself: even though the outcome is devalued (gets the animal sick) or the animal is sated, it keeps pressing the lever. This is why habits have been opposed to goal-directed behavior.A quick look suggests that habits and goal-directed actions are intimately related to Systems 1 and 2, respectively. This is also supported by the identification of the goal-directed system with a model-based reinforcement learning scheme, since it can be viewed “in terms of sophisticated, computationally demanding, prospective planning, in which a decision tree of possible future states and actions is built using a learned internal model of the environment” (Dolan and Dayan, 2013). The habitual system, on the other hand, follows a model-free scheme, which “is computationally efficient, since it replaces computation (i.e., the burdensome simulation of future states) with memory (i.e., stored discounted values of expected future reward); however, the forward-looking nature of the prediction error makes it statistically inefficient” (Dolan and Dayan, 2013). Following these analogies between systems, we can assume that some actions that at the beginning fall under the domain of System 2 might be transferred to System 1 through learning, like goal-directed actions become habits through experience.Concerning the neural bases of these systems, the striatum and its cortical afferents and –indirect– target areas in the cortex play a major role. It is widely accepted that the cognitive part of the striatum –caudate nucleus and anterior putamen– are involved in the planning and execution of goal-directed actions, together with the prefrontal cortex (Balleine et al., 2007). On the other hand, the sensorimotor striatal aspects –mainly the posterior putamen– and the supplementary motor area of the cortex are particularly active when the agent is performing a well-learned action (Ashby et al., 2010; Miyachi et al., 2002). Furthermore, the activity of the neurons in these areas follows a “chunked” pattern: they are mainly active at certain stages of the motor routine (for example at the beginning and the end of the sequence, when a particular switch or turn is needed, etc), and this activity is reduced in the rest of the motor sequence (Graybiel, 1998). Although some authors question a sharp neuroanatomical basis of Kahneman’s Systems 1 and 2 (Gold and Shadlen, 2007), our train of thought in this manuscript suggests that the more reflective System 2 should be based in the prefrontal cortex –both dorsal and ventral–, and the cognitive regions of the basal ganglia. Likewise, the more automatic System 1 would lie on motor and premotor cortical regions, as well as on the sensorimotor aspects of those subcortical nuclei.This neuroscientific framework identifies the habit system with automaticity, rigidity and unconsciousness; however, we are intending to challenge this view in past and forthcoming contributions (Bernacer et al., 2014; Bernacer and Gimenez-Amaya, 2013). In a nutshell, we propose to view the phenomenon of action from the point of view of the agent as a whole, and not from an isolated movement. Hence, it could be more convenient to understand System 1 –or habits– as a resource of System 2, rather than as opposed systems in competition. Whereas a motor routine (i.e., what is commonly called “habit” in neuroscience) implies the sequential and unconscious performance of movements, they usually pursue the goal set by the agent. In fact, the more engrained the routine is, the easier for the agent to achieve that goal. Furthermore, the agent can consciously stop or correct the movement at any point, since the habit releases the higher cognitive regions of the brain to improve the performance of the action. A very simple example of this is a tennis service, which should be “goal directed” to place the ball wherever the player wants. It involves a set of movements such as throwing the ball upwards, moving the feet, putting the arm back, etc. Only when these motor routines are learned correctly, the player is able to concentrate on other aspects of the service such as the speed, spin, or exploiting the weaknesses of the receiver. This can be also exemplified with other kinds of habits such as driving, playing an instrument, tackling a mathematical problem, and so on. They all suggest that “automatic” routines are governed by higher cognitive functions to better achieve a particular goal.Kahneman’s Systems 1 and 2 allow as well this release of consciousness from everyday decisions to focus on more complicated situations. As Kahneman himself and other authors defend (Ariely, 2008), the problem arises when System 2 is rarely used or either system is applied to inadequate situations. However, we believe that the most effective agent does not exclusively rely on System 2, but efficiently uses all resources of ‘each system’ in the right situation and, more importantly, carries out an appropriate transition between them. That is, in our opinion, a ‘rational’ agent. This could be also said about goal-directed and habitual systems. Moreover, we believe that this transition between systems is subject to learning, and it can be performed more effectively through experience.If we understand these fragmentations of cognition as independent systems in competition, we encounter an important problem: is there an additional mechanism in charge of the transition between systems, or is this regulated by one of the systems itself? If the first option were true, we would find the difficulty of defining the nature –both conceptually and anatomically– of a “third system” qualitatively different than the other two. This would lead us to an ad infinitum process –the need of a fourth element to regulate the activity of the third, and so on–, and therefore we believe this hypothesis should be rejected. Considering the second option, it seems that only the highly cognitive System 2 could be in charge of leading the transition between systems, which in turn dissolves a rigorous separation in two systems. The role of System 2 in leading the transition is clear when the agent decides to regain conscious control of a task generally performed in an unconscious manner. In this sense, the interaction of the orbitofrontal cortex with either the cognitive or sensorimotor aspects of the striatum plays a central role in shifting between goal-directed actions and motor routines (Gremel and Costa, 2013). In other situations, an external cue such as an error may set the alarm for System 2 to retake control of the action. Regarding this, the anterior cingulate cortex has been reported to be active in highly-conflictive decision making situations (Goñi et al., 2011); for that reason, some authors relate this cortical area with error monitoring (Carter, 1998; Botvinick et al., 2004). A recent report suggests a new model of reinforcement learning and conflict monitoring, which involves a wide network including different areas of the cortex (posterior parietal, precentral, anterior cingulate and prefrontal) and the basal ganglia (Zendehrouh et al., 2013).To sum up, this opinion article suggests viewing Kahneman’s systems as analogous to the goal-directed/habits dichotomy in order to improve the understanding of some aspects of human cognition. Further, we believe a strict separation between systems in competition is problematic, since System 2 is always in charge of governing the interplay between systems: therefore, System 1 –or habits– should be understood as a resource of System 2. This view could shed some light on the understanding of habits as a source of learning, plasticity and freedom for the agent. Finally, an inappropriate cognitive control of habits could be an indicator of certain psychiatric conditions. (shrink)

Obsessive-compulsive disorder (OCD) symptoms arise when a “natural” feeling of certainty is lost. OCD patients typically attempt to regain this feeling of certainty by means of overly conscious thinking, magical rituals, and repetitive behaviors. Ironically, these OCD symptoms might provide some relief in the short term but lead to a further loss of certainty over the long term. The loss of certainty that is clinically observed in OCD patients has been made more tangible by recent neuroscientific research. It has been (...) shown that the feeling of certainty or uncertainty is likely to be encoded by distinct firing patterns of dopaminergic neurons in the brain’s reward system. As OCD is often associated with dopamine alterations in the striatum, this might very well explain the altered subjective feeling of certainty and its phenomenology in OCD. Additionally, treatment with deep brain stimulation in OCD patients, in which specific brain targets are stimulated directly with implanted electrodes, reveals from direct clinical observations that patients experience primarily more “confidence” as a first sign of improvement. Linking the phenomenological study of the subjective experience of certainty and its implicated mechanisms is an important start toward a neurophenomenology of OCD. (shrink)

Bidirectional deep brain stimulation (DBS) platforms have enabled a surge in hours of recordings in naturalistic environments, allowing further insight into neurological and psychiatric disease states. However, high amplitude, high frequency stimulation generates artifacts that contaminate neural signals and hinder our ability to interpret the data. This is especially true in psychiatric disorders, for which high amplitude stimulation is commonly applied to deep brain structures where the native neural activity is miniscule in comparison. Here, we characterized artifact sources in recordings (...) from a bidirectional DBS platform, the Medtronic Summit RC + S, with the goal of optimizing recording configurations to improve signal to noise ratio (SNR). Data were collected from three subjects in a clinical trial of DBS for obsessive-compulsive disorder. Stimulation was provided bilaterally to the ventral capsule/ventral striatum (VC/VS) using two independent implantable neurostimulators. We first manipulated DBS amplitude within safe limits (2–5.3 mA) to characterize the impact of stimulation artifacts on neural recordings. We found that high amplitude stimulation produces slew overflow, defined as exceeding the rate of change that the analog to digital converter can accurately measure. Overflow led to expanded spectral distortion of the stimulation artifact, with a six fold increase in the bandwidth of the 150.6 Hz stimulation artifact from 147–153 to 140–180 Hz. By increasing sense blank values during high amplitude stimulation, we reduced overflow by as much as 30% and improved artifact distortion, reducing the bandwidth from 140–180 Hz artifact to 147–153 Hz. We also identified artifacts that shifted in frequency through modulation of telemetry parameters. We found that telemetry ratio changes led to predictable shifts in the center-frequencies of the associated artifacts, allowing us to proactively shift the artifacts outside of our frequency range of interest. Overall, the artifact characterization methods and results described here enable increased data interpretability and unconstrained biomarker exploration using data collected from bidirectional DBS devices. (shrink)

In Parkinson’s disease, the fronto-striatal network is involved in motor and cognitive symptoms. Working memory updating training engages this network in healthy populations, as observed by improved cognitive performance and increased striatal BOLD signal. This two-part study aimed to assess the feasibility of WM updating training in PD and measure change in cognition, movement and functional brain response in one individual with PD after WM updating training. A feasibility and single-subject study were performed in which patients with PD completed computerized (...) WM updating training. The outcome measures were the pre-post changes in criterion and transfer cognitive tests; cognitive complaints; psychological health; movement kinematics; and task-related BOLD signal. Participants in the feasibility study showed improvements on the criterion tests at post-test. FL displayed the largest improvements on the criterion tests and smaller improvements on transfer tests. Furthermore, FL reported improved cognitive performance in everyday life. A shorter onset latency and smoother upper-limb goal-directed movements were measured at post-test, as well as increased activation within the striatum and decreased activation throughout the fronto-parietal WM network. This two-part study demonstrated that WM updating training is feasible to complete for PD patients and that change occurred in FL at post-test in the domains of cognition, movement and functional brain response. (shrink)

The effects of striatal dopamine (DA) on behavior have been widely investigated over the past decades, with “phasic” burst firings considered as the key expression of a reward prediction error responsible for reinforcement learning. Less well studied is “tonic” DA, where putative functions include the idea that it is a regulator of vigor, incentive salience, disposition to exert an effort and a modulator of approach strategies. We present a model combining tonic and phasic DA to show how different outflows triggered (...) by either intrinsically or extrinsically motivating stimuli dynamically affect the basal ganglia by impacting on a selection process this system performs on its cortical input. The model, which has been tested on the simulated humanoid robot iCub interacting with a mechatronic board, shows the putative functions ascribed to DA emerging from the combination of a standard computational mechanism coupled to a differential sensitivity to the presence of DA across the striatum. (shrink)

A great variety of medical conditions are subject to the placebo effect. Although there is mounting evidence to suggest that the placebo effect is related to the expectation of clinical benefit, little is still known about the biochemical bases underlying placebo responses. Positron emission tomography studies have recently shown that the placebo effect in Parkinson’s disease, pain, and depression is related to the activation of the limbic circuitry. The observation that placebo administration induces the release of dopamine in the ventral (...) striatum of patients with Parkinson’s disease suggests a link between the placebo effect and reward mechanisms. In addition to Parkinson’s disease, the placebo-reward model may also apply to other disorders. However, the relative contribution of the different neurotransmitters and neuropeptides that are known to be involved in modulating the activity of the limbic system may be disease-specific. Thus, while the placebo-induced clinical benefit observed in Parkinson’s disease would mostly reflect the release of dopamine in the dorsal striatum, the activation of opioid and serotonin pathways could be particularly implicated in mediating placebo responses encountered in pain and depression, respectively. (shrink)

ObjectiveLeveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis and to explore potential correlations within the “joint-inflammation-brain” axis during the period of central neural system development.MethodsTwenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model and the ROI-to-voxel functional connectivity to measure the hippocampal shape (...) and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices.ResultsCompared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately.ConclusionAs with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA. (shrink)

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that (...) the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory. (shrink)

BACKGROUND AND PURPOSE: In vivo MR imaging and postmortem neuropathologic studies have demonstrated elevated iron concentration and atrophy within the striatum of patients with Huntington disease, implicating neuronal loss and iron accumulation in the pathogenesis of this neurodegenerative disorder. We used 7T MR imaging to determine whether quantitative phase, a measurement that reflects both iron content and tissue microstructure, is altered in subjects with premanifest Huntington disease. MATERIALS AND METHODS: Local field shift, calculated from 7T MR phase images, was (...) quantified in 13 subjects with premanifest Huntington disease and 13 age- and sex-matched controls. All participants underwent 3T and 7T MR imaging, including volumetric T1 and 7T gradient recalled-echo sequences. Local field shift maps were created from 7T phase data and registered to caudate ROIs automatically parcellated from the 3T T1 images. Huntington disease-specific disease burden and neurocognitive and motor evaluations were also performed and compared with local field shift. RESULTS: Subjects with premanifest Huntington disease had smaller caudate volume and higher local field shift than controls. A significant correlation between these measurements was not detected, and prediction accuracy for disease state improved with inclusion of both variables. A positive correlation between local field shift and genetic disease burden was also found, and there was a trend toward significant correlations between local field shift and neurocognitive tests of working memory and executive function. CONCLUSIONS: Subjects with premanifest Huntington disease exhibit differences in 7T MR imaging phase within the caudate nuclei that correlate with genetic disease burden and trend with neurocognitive assessments. Ultra-high-field MR imaging of quantitative phase may be a useful approach for monitoring neurodegeneration in premanifest Huntington disease. (shrink)

Down syndrome (DS), the most common genetic cause of intellectual disability, results from the partial or complete triplication of chromosome 21. Individuals with DS are impaired at using a high-resolution, allocentric spatial representation to learn and remember discrete locations in a controlled environment. Here, we assessed the capacity of individuals with DS to perform low-resolution spatial learning, depending on two competing memory systems: (1) the place learning system, which depends on the hippocampus and creates flexible relational representations of the environment; (...) and (2) the response learning system, which depends on the striatum and creates fixed stimulus-response representations of behavioral actions. Individuals with DS exhibited a preservation of the low-resolution spatial learning capacities subserved by these two systems. In place learning, although the average performance of individuals with DS was lower than that of typically-developing (TD) mental age-matched children and TD young adults, the number of individuals with DS performing above chance level did not differ from TD children. In response learning, the average performance of individuals with DS was lower than that of TD adults, but it did not differ from that of TD children. Moreover, the number of individuals with DS performing above chance level did not differ from TD adults, and was higher than that of TD children. In sum, whereas low-resolution place learning appears relatively preserved in individuals with DS, response learning appears facilitated. Our findings are consistent with the hypothesis that the neural pathways supporting low-resolution place learning and response learning are relatively preserved in DS. (shrink)

Socioeconomic status -related health disparities persist for numerous chronic diseases, with lower-SES individuals exhibiting greater risk of morbidity and mortality compared to their higher-SES counterparts. One likely contributor is disparities in health messaging efforts, which are currently less effective for motivating health behavior change among those lower in SES. Drawing on communication neuroscience and social neuroscience research, we describe a conceptual framework to improve health messaging effectiveness in lower SES communities. The framework is based on evidence that health-message-induced activity in (...) the ventral striatum and subdivisions of the medial pre-frontal cortex predicts behavior change. Additionally, we draw from social neuroscience work showing that activity in these regions during valuation and the processing of self-related vs. social information, differs as a function of SES. Bringing together these previously disparate lines of work, we argue that health messages emphasizing the benefits to close others of engaging in behavior change will be more effective among lower SES individuals. We also outline a research agenda based on our framework. Ultimately, we hope that this framework utilizing a “brain-as-predictor” approach generates novel insights about the neural underpinnings of message-induced behavior change among lower SES individuals, and helps to close the gap in SES-based health disparities by harnessing the power of neuroimaging. (shrink)