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Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD) 1 . However, achieving stable recovery is unpredictable 2 , typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting 3 . We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment., (© 2023. The Author(s).)

Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9-19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more stability across most networks, unpredictability was associated with stability only in SAL connectivity, and threat was associated with stability in FPN and DMN-SAL connectivity. In youth exposed to higher levels of any adversity, lower initial levels and more stability in connectivity were related to smaller increases in internalizing symptoms. Our findings suggest that whereas deprivation is associated with widespread neurodevelopmental differences in cognitive and emotion processing networks, unpredictability is related selectively to salience detection circuitry. Studies with wider developmental windows should examine whether these neurodevelopmental alterations are adaptive or serve to maintain internalizing symptoms.

The prelimbic and infralimbic cortices of the rodent medial prefrontal cortex mediate the effects of context and goals on instrumental behavior. Recent work from our laboratory has expanded this understanding. Results have shown that the prelimbic cortex is important for the modulation of instrumental behavior by the context in which the behavior is learned (but not other contexts), with context potentially being broadly defined (to include at least previous behaviors). We have also shown that the infralimbic cortex is important in the expression of extensively-trained instrumental behavior, regardless of whether that behavior is expressed as a stimulus-response habit or a goal-directed action. Some of the most recent data suggest that infralimbic cortex may control the currently active behavioral state (e.g., habit vs. action or acquisition vs. extinction) when two states have been learned. We have also begun to examine prelimbic and infralimbic cortex function as key nodes of discrete circuits and have shown that prelimbic cortex projections to an anterior region of the dorsomedial striatum are important for expression of minimally-trained instrumental behavior. Overall, the use of an associative learning perspective on instrumental learning has allowed the research to provide new perspectives on how these two "cognitive" brain regions contribute to instrumental behavior., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Brain-computer interfaces (BCIs) are capable of translating human intentions into signals controlling an external device to assist patients with severe neuromuscular disorders. Prior work has demonstrated that participants with mindfulness meditation experience evince improved BCI performance, but the underlying neural mechanisms remain unclear. Here, we conducted a large-scale longitudinal intervention study by training participants in mindfulness-based stress reduction (MBSR; a standardized mind-body awareness training intervention), and investigated whether and how short-term MBSR affected sensorimotor rhythm (SMR)-based BCI performance. We hypothesize that MBSR training improves BCI performance by reducing mind wandering and enhancing self-awareness during the intentional rest BCI control, which would mainly be reflected by modulations of default-mode network and limbic network activity. We found that MBSR training significantly improved BCI performance compared to controls and these behavioral enhancements were accompanied by increased frontolimbic alpha activity (9-15 Hz) and decreased alpha connectivity among limbic network, frontoparietal network, and default-mode network. Furthermore, the modulations of frontolimbic alpha activity were positively correlated with the duration of meditation experience and the extent of BCI performance improvement. Overall, these data suggest that mindfulness allows participant to reach a state where they can modulate frontolimbic alpha power and improve BCI performance for SMR-based BCI control.

Lesioning or inactivating the infralimbic (IL) subregion of the medial prefrontal cortex before acquisition produces more generalized and extinction-resistant fear memories. However, whether and how it modulates memory specificity and extinction susceptibility while consolidation takes place is still unknown. The present study aims to investigate these questions using muscimol-induced temporary inactivation and anisomycin-induced protein synthesis inhibition in the rat IL following contextual fear conditioning. Results indicate that the IL activity immediately after acquisition, but not six hours later, controls memory generalization over a week, regardless of its strength. Such IL function depends on the context-shock pairing since muscimol induced no changes in animals exposed to immediate shocks or the conditioning context only. Animals in which the IL was inactivated during consolidation extinguished similarly to controls within the session but were unable to recall the extinction memory the following day. Noteworthy, these post-acquisition IL inactivation-induced effects were not associated with changes in anxiety, as assessed in the elevated plus-maze test. Anisomycin results indicate that the IL protein synthesis during consolidation contributes more to producing extinction-sensitive fear memories than memory specificity. Collectively, present results provide evidence for the IL's role in controlling generalization and susceptibility to extinction during fear memory consolidation.

Touch, such as affective caress, can be interpreted as being pleasant. The emotional valence that is assigned to touch is related to certain bottom-up factors, such as the optimal activation of C-tactile (CT) afferents. Tactile processing with a hedonic or emotional component has been defined as affective touch-a component that CT fibers are likely to convey. Tactile deficiencies are frequent in the psychiatric population but also in healthy people with disorganized attachment; accordingly, it is likely that affective difficulties in adults with disorganized attachment are reflected in altered perception of affective touch. To test this hypothesis, we combined methods from clinical psychology, psychophysics, and neuroimaging. We found that people with a history of traumatic parental bonds and a disorganized attachment pattern perceive a "caress-like" stimulus as being unpleasant, whereas participants with organized attachment consider the same tactile stimulation to be pleasant. Further, unlike in organized adults, the responses of disorganized adults to CT and non-CT stimulation activated limbic and paralimbic structures in a fight-or-flight manner, suggesting that early experiences with parental deficiencies shape the physiological responses of peripheral CT fibers and central nervous networks.

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement ('None-Go' task, n = 7, 28 recording sites); second, pressing a button after every tone ('All-Go' task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones ('Go-NoGo' task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation., (Copyright © 2019. Published by Elsevier Inc.)

The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex-nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task. This ability is dependent on an intact dopaminergic tone in the NAc, as local dopamine denervation impaired the performance of the animal in the switching of tasks. In addition, based on a brain-slice preparation obtained from Drd2-EGFP BAC transgenic mice, we demonstrated direct innervation of D2 receptor-expressing medium spiny neurons (D2-MSNs) in the NAc by prelimbic cortical neurons, which is under the regulation by presynaptic dopamine receptors. While presynaptic D1-type receptor activation enhances the glutamatergic transmission from the prelimbic cortex to D2-MSNs, D2-type receptor activation suppresses this synaptic connection. Furthermore, manipulation of this pathway by optogenetic activation or administration of a D1-type agonist or a D2-type antagonist could restore impaired task-switching flexibility in mice with local NAc dopamine depletion; this restoration is consistent with the effects of knocking down the expression of specific dopamine receptors in the pathway. Our results point to a critical role of a specific prelimbic cortex-NAc subpathway in mediating strategy abandoning, allowing the switching from one strategy to another in problem solving., Competing Interests: The authors declare no conflict of interest.

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral responses to emotionally stressful experiences, and chronic disruption of these systems chronically is implicated in the pathogenesis of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA activity, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Moreover, information regarding how endocrine and behavioral responses are integrated has remained obscure. Here we summarize work from our laboratory showing that anteroventral (av) bed nuclei of the stria terminalis (BST) acts as a point of convergence between the limbic forebrain and PVH, receiving and coordinating upstream influences, and restraining HPA axis output in response to inescapable stressors. Recent studies highlight a more expansive modulatory role for avBST as one that coordinates HPA-inhibitory influences while concurrently suppressing passive behavioral responses via divergent pathways. avBST is uniquely positioned to convey endocrine and behavioral alterations resulting from chronic stress exposure, such as HPA axis hyperactivity and increased passive coping strategies, that may result from synaptic reorganization in upstream limbic cortical regions. We discuss how these studies give new insights into understanding the systems-level organization of stress response circuitry, the neurobiology of coping styles, and BST circuit dysfunction in stress-related psychiatric disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Create a software tool to facilitate tractography-based deep brain stimulation (DBS) electrode targeting within the patient-specific stereotactic coordinate system used in the operating room., Approach: StimVision was developed with Visualization Toolkit libraries and integrates four major components: 1) medical image visualization, 2) tractography visualization, 3) DBS electrode positioning, and 4) DBS activation volume calculation with tractography intersection., Results: Initial applications of StimVision are focused on the study of subcallosal cingulate (SCC) DBS for the treatment of depression. Retrospective modeling results on SCC DBS have suggested that direct stimulation of a specific collection of tractographic pathways are necessary for therapeutic benefit; thereby creating a tractography-based DBS surgical targeting hypotheses. StimVision is the tool we created to facilitate prospective clinical evaluation of that hypothesis., Significance: Retrospective tractography-based analyses are common in DBS research; however, intraoperative software tools for interactive selection of a tractography-based DBS target are not readily available. StimVision provides an academic research tool to assist clinical implementation of new DBS targeting strategies and postoperative evaluation of targeting outcome., (© 2017 International Neuromodulation Society.)

Previous studies of trait emotional awareness (EA) have not yet examined whether differences in cortical structure might account for differences in EA. Based on previous research on the relationship between EA and both emotion conceptualization and visceromotor control processes, we tested two hypotheses in a sample of 26 healthy participants: that higher EA would be predicted by greater cortical thickness within (1) regions of the default mode network (DMN; linked with conceptualization processes), and/or (2) regions of the limbic network (linked with affect generation and visceromotor control processes). A non-significant correlation was found between EA and cortical thickness in the DMN. In contrast, a significant positive correlation was observed between EA and cortical thickness within the limbic network. These findings suggest that the structural integrity of cortical regions involved in the generation of affective bodily reactions may play a more important role in explaining differences in EA than previously thought., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The prelimbic (PrL) cortex constitutes one of the highest levels of cortical hierarchy dedicated to the execution of adaptive behaviors. We have identified a specific local field potential (LFP) pattern generated in the PrL cortex and associated with cognition-related behaviors. We used this pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected θ to β-γ (θ/β-γ) transition pattern across training sessions. The selected LFP pattern appeared to coincide with a significant decrease in the firing of PrL pyramidal neurons and did not seem to propagate to other cortical or subcortical areas. An indication of the PrL cortex's cognitive nature is that the experimental disruption of this θ/β-γ transition pattern prevented the proper performance of the acquired task without affecting the generation of other motor responses. The use of this LFP pattern to trigger an operant task evoked only minor changes in its electrophysiological properties. Thus, the PrL cortex has the capability of generating an oscillatory pattern for dealing with environmental constraints. In addition, the selected θ/β-γ transition pattern could be a useful tool to activate the presentation of external cues or to modify the current circumstances. SIGNIFICANCE STATEMENT Brain-machine interfaces represent a solution for physically impaired people to communicate with external devices. We have identified a specific local field potential pattern generated in the prelimbic cortex and associated with goal-directed behaviors. We used the pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected field potential pattern across training. The selected pattern was not modified when used to activate the touch screen. Electrical stimulation of the recording site prevented the proper performance of the task. Our findings show that the prelimbic cortex can generate oscillatory patterns that rats can use to control their environment for achieving specific goals., (Copyright © 2017 the authors 0270-6474/17/375923-13$15.00/0.)

Imitation and observation of actions and facial emotional expressions activates the human fronto-parietal mirror network. There is skepticism regarding the role of this low-level network in more complex high-level social behaviour. We sought to test whether neural activation during an observation/imitation task was related to both lower and higher level social cognition. We employed an established observe/imitate task of emotional faces during functional MRI in 28 healthy adults, with final analyses based on 20 individuals following extensive quality control. Partial least squares (PLS) identified patterns of relationships between spatial activation and a battery of objective out-of-scanner assessments that index lower and higher-level social cognitive performance, including the Penn emotion recognition task, reading the mind in the eyes, the awareness of social inference test (TASIT) parts 1, 2, and 3, and the relationships across domains (RAD) test. Strikingly, activity in limbic, right inferior frontal, and inferior parietal areas during imitation of emotional faces correlated with performance on emotion evaluation (TASIT1), social inference - minimal (TASIT2), social inference - enriched (TASIT3), and the RAD tests. These results show a role for this network in both lower-level and higher-level social cognitive processes which are collectively critical for social functioning in everyday life.

The limbic lobe defined by Broca is a cortical region with highly diverse structure and functions, and comprises the paleo-, archi-, and neocortices as well as their transitional zones. In the limbic lobe, Brodmann designated areas 27, 28, 34, 35, and 36 adjacent to the hippocampus, and areas 23, 24, 25, 26, 29, 30, 31, 32, and 33 around the corpus callosum. In the current literature, areas 27 and 28 correspond to the presubiculum and entorhinal cortex, respectively. Area 34 represents the cortico-medial part of the amygdaloid complex. Areas 35 and 36 roughly cover the perirhinal and parahippocampal cortices. Areas 24, 25, 32, and 33 belong to the anterior cingulate gyrus, while areas 23, 26, 29, 30, and 31 to the posterior cingulate gyrus. Areas 25, 32, and the anteroinferior portion of area 24 are deeply involved in emotional responses, particularly in their autonomic functions, through reciprocal connections with the amygdaloid complex, anterior thalamus and projections to the brainstem and spinal visceral centers. Areas 29 and 30 have dense reciprocal connections with areas 23 and 31, the dorsolateral prefrontal areas, and the regions related to the hippocampus. They play pivotal roles in mediating spatial cognition, working memory processing, and episodic memory formation.

Mind-wandering has a controversial relationship with cognitive control. Existing psychological evidence supports the hypothesis that episodes of mind-wandering reflect a failure to constrain thinking to task-relevant material, as well the apparently alternative view that control can facilitate the expression of self-generated mental content. We assessed whether this apparent contradiction arises because of a failure to consider differences in the types of thoughts that occur during mind-wandering, and in particular, the associated level of intentionality. Using multi-modal magnetic resonance imaging (MRI) analysis, we examined the cortical organisation that underlies inter-individual differences in descriptions of the spontaneous or deliberate nature of mind-wandering. Cortical thickness, as well as functional connectivity analyses, implicated regions relevant to cognitive control and regions of the default-mode network for individuals who reported high rates of deliberate mind-wandering. In contrast, higher reports of spontaneous mind-wandering were associated with cortical thinning in parietal and posterior temporal regions in the left hemisphere (which are important in the control of cognition and attention) as well as heightened connectivity between the intraparietal sulcus and a region that spanned limbic and default-mode regions in the ventral inferior frontal gyrus. Finally, we observed a dissociation in the thickness of the retrosplenial cortex/lingual gyrus, with higher reports of spontaneous mind-wandering being associated with thickening in the left hemisphere, and higher repots of deliberate mind-wandering with thinning in the right hemisphere. These results suggest that the intentionality of the mind-wandering state depends on integration between the control and default-mode networks, with more deliberation being associated with greater integration between these systems. We conclude that one reason why mind-wandering has a controversial relationship with control is because it depends on whether the thoughts emerge in a deliberate or spontaneous fashion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Conflicting evidence exists regarding the role of infralimbic cortex (IL) in the environmental control of appetitive behavior. Inhibition of IL, irrespective of its intrinsic neural activity, attenuates not only the ability of environmental cues predictive of reward availability to promote reward seeking, but also the ability of environmental cues predictive of reward omission to suppress this behavior. Here we report that such bidirectional behavioral modulation in rats is mediated by functionally distinct units of neurons (neural ensembles) that are concurrently localized within the same IL brain area but selectively reactive to different environmental cues. Ensemble-specific neural activity is thought to function as a memory engram representing a learned association between environment and behavior. Our findings establish the causal evidence for the concurrent existence of two distinct engrams within a single brain site, each mediating opposing environmental actions on a learned behavior., Competing Interests: The authors declare that no competing interests exist.

Life history theory suggests that adult reward sensitivity should be best explained by childhood, but not current, socioeconomic conditions. In this functional magnetic resonance imaging (fMRI) study, 83 participants from a larger longitudinal sample completed the monetary incentive delay (MID) task in adulthood (∼25 years old). Parent-reports of neighborhood quality and parental SES were collected when participants were 13 years of age. Current income level was collected concurrently with scanning. Lower adolescent neighborhood quality, but neither lower current income nor parental SES, was associated with heightened sensitivity to the anticipation of monetary gain in putative mesolimbic reward areas. Lower adolescent neighborhood quality was also associated with heightened sensitivity to the anticipation of monetary loss activation in visuo-motor areas. Lower current income was associated with heightened sensitivity to anticipated loss in occipital areas and the operculum. We tested whether externalizing behaviors in childhood or adulthood could better account for neighborhood quality findings, but they did not. Findings suggest that neighborhood ecology in adolescence is associated with greater neural reward sensitivity in adulthood above the influence of parental SES or current income and not mediated through impulsivity and externalizing behaviors., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Procrastination is a prevalent problematic behavior that brings serious consequences to individuals who suffer from it. Although this phenomenon has received increasing attention from researchers, the underpinning neural substrates of it is poorly studied. To examine the neural bases subserving procrastination, the present study employed resting-state fMRI. The main results were as follows: (1) the behavioral procrastination was positively correlated with the regional activity of the ventromedial prefrontal cortex (vmPFC) and the parahippocampal cortex (PHC), while negatively correlated with that of the anterior prefrontal cortex (aPFC). (2) The aPFC-seed connectivity with the anterior medial prefrontal cortex and the posterior cingulate cortex was positively associated with procrastination. (3) The connectivity between vmPFC and several other regions, such as the dorsomedial prefrontal cortex, the bilateral inferior prefrontal cortex showed a negative association with procrastination. These results suggested that procrastination could be attributed to, on the one hand, hyper-activity of the default mode network (DMN) that overrides the prefrontal control signal; while on the other hand, the failure of top-down control exerted by the aPFC on the DMN. Therefore, the present study unravels the biomarkers of procrastination and provides treatment targets for procrastination prevention.

The striatum contains neurochemically defined compartments termed patches and matrix. Previous studies suggest patches preferentially receive limbic inputs and project to dopamine neurons in substantia nigra pars compacta (SNc), whereas matrix neurons receive sensorimotor inputs and do not innervate SNc. Using BAC-Cre transgenic mice with viral tracing techniques, we mapped brain-wide differences in the input-output organization of the patch/matrix. Findings reveal a displaced population of striatal patch neurons termed "exo-patch," which reside in matrix zones but have neurochemistry, connectivity, and electrophysiological characteristics resembling patch neurons. Contrary to previous studies, results show patch/exo-patch and matrix neurons receive both limbic and sensorimotor information. A novel inhibitory projection from bed nucleus of the stria terminalis to patch/exo-patch neurons was revealed. Projections to SNc were found to originate from patch/exo-patch and matrix neurons. These findings redefine patch/matrix beyond traditional neurochemical topography and reveal new principles about their input-output connectivity, providing a foundation for future functional studies., Competing Interests: None of the authors declare any conflict of interest, financial or otherwise., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a substantial projection. Conversely, only one area of the auditory orienting system, the auditory field of the anterior ectosylvian sulcus (fAES), and no area involved in somatosensory orienting, shows significant corticotectal inputs. Although small relative to visual inputs, the projection from the fAES is of particular interest, as it represents the only bilateral cortical input to the SC. This detailed, quantitative study allows for comparison across modalities in an animal that serves as a useful model for both auditory and visual perception. Moreover, the differences in patterns of corticotectal projections between modalities inform the ways in which orienting systems are modulated by cortical feedback. J. Comp. Neurol. 524:2623-2642, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

When we evaluate an option, how is the neural representation of its value linked to information that identifies it, such as its position in space? We hypothesized that value information and identity cues are not bound together at a particular point but are represented together at the single unit level throughout the entirety of the choice process. We examined neuronal responses in two-option gambling tasks with lateralized and asynchronous presentation of offers in five reward regions: orbitofrontal cortex (OFC, area 13), ventromedial prefrontal cortex (vmPFC, area 14), ventral striatum (VS), dorsal anterior cingulate cortex (dACC), and subgenual anterior cingulate cortex (sgACC, area 25). Neuronal responses in all areas are sensitive to the positions of both offers and of choices. This selectivity is strongest in reward-sensitive neurons, indicating that it is not a property of a specialized subpopulation of cells. We did not find consistent contralateral or any other organization to these responses, indicating that they may be difficult to detect with aggregate measures like neuroimaging or studies of lesion effects. These results suggest that value coding is wed to factors that identify the object throughout the reward system and suggest a possible solution to the binding problem raised by abstract value encoding schemes., (Copyright © 2016 the American Physiological Society.)

Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (β=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Paul Broca's concept of the "great limbic lobe" has had a huge impact on neuroscience. In this commentary, which accompanies the first English translation of the original paper, we comment on Broca's contribution and its influence on the understanding of the brain bases of emotion., (© 2015 Wiley Periodicals, Inc.)

Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

"Out of the body" tactile illusion refers to the phenomenon in which one can perceive tactility as if emanating from a location external to the body without any stimulator present there. Taking advantage of such a tactile illusion is one way to provide and realize richer interaction feedback without employing and placing actuators directly at all stimulation target points. However, to further explore its potential, it is important to better understand the underlying physiological and neural mechanism. As such, we measured the brain wave patterns during such tactile illusion and mapped out the corresponding brain activation areas. Participants were given stimulations at different levels with the intention to create veridical (i.e., non-illusory) and phantom sensations at different locations along an external hand-held virtual ruler. The experimental data and analysis indicate that both veridical and illusory sensations involve, among others, the parietal lobe, one of the most important components in the tactile information pathway. In addition, we found that as for the illusory sensation, there is an additional processing resulting in the delay for the ERP (event-related potential) and involvement by the limbic lobe. These point to regarding illusion as a memory and recognition task as a possible explanation. The present study demonstrated some basic understanding; how humans process "virtual" objects and the way associated tactile illusion is generated will be valuable for HCI (Human-Computer Interaction).

New Findings: What is the central question of this study? A brief experience of stress can cause structural remodelling in the infralimbic cortex. In the present study, we addressed the potential role played by opioidergic neurotransmission in the infralimbic cortex in the modulation of stress-evoked autonomic responses. What is the main finding and its importance? Using the restraint stress model, we showed that infralimbic cortex κ-opioid receptors, but not μ- and δ-opioid receptors, modulate stress-evoked cardiovascular responses. The infralimbic cortex (IL) is known to modulate behavioural and physiological responses during aversive situations. We investigated the hypothesis that opioid neurotransmission in the IL modulates the autonomic responses induced in rats subjected to restraint stress (RS). Male Wistar rats (250-280 g) were used. Guide cannulae were implanted bilaterally in the IL for the microinjection of either drugs or vehicle, and a polyethylene catheter was implanted into the femoral artery for recording of mean arterial pressure (MAP) and heart rate (HR) using a computerized acquisition system. Tail temperature was evaluated using a thermal camera. Rats were subjected to RS 10 min after the microinjection of drugs or vehicle into the IL. Exposure to RS evoked hypertension, tachycardia and a reduction in tail temperature. Bilateral microinjections of the non-selective opioid antagonist naloxone into the IL generated an inverted U-shaped dose-inhibition curve on RS-evoked MAP and HR responses. Microinjection of nor-BNI (κ-selective antagonist) reduced the increases in MAP and HR evoked by RS. In contrast, pretreatment of the IL with CTAP (μ-selective antagonist) or naltrindole (δ-selective antagonist) had no effect on the restraint-evoked increases in MAP and HR. None of these treatments altered the reduction in the tail temperature evoked by RS. In conclusion, κ-opioid receptors in the IL modulate pressor and tachycardiac responses caused by RS, suggesting a facilitatory role of this structure in this aversive situation., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

Several lines of evidence indicate that the dorsal hippocampus (dH) and medial prefrontal cortex (mPFC) regulate contextual fear conditioning. The prelimbic (PrL), infralimbic (IL) and the anterior cingulate cortex (ACC) subregions of the mPFC likely play distinct roles in the expression of fear. Moreover, studies have highlighted the role of serotonin (5-hydroxytryptamine, 5-HT)- and γ-aminobutyric acid (GABA)-mediated mechanisms in the modulation of innate fear in the mPFC. The present study characterized dH-mPFC pathways and investigated the role of serotonergic and GABAergic mechanisms of the PrL, IL and ACC-area 1 (Cg1) in the elaboration of contextual fear conditioning using fear-potentiated startle (FPS) and freezing behavior in Rattus norvegicus. The results of neurotracing with microinjections of biotinylated dextran amine into the dH revealed a neural link of the dH with the PrL and ACC. Intra-PrL injections of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and the GABAA receptor-selective agonist muscimol reduced contextual FPS and freezing responses. Intra-Cg1 injections of muscimol but not 8-OH-DPAT decreased FPS and freezing responses. However, neither intra-IL injections of a 5-HT1A agonist nor of a GABAA agonist affected these defensive responses. Labeled neuronal fibers from the dH reached the superficial layers of the PrL cortex and spread to the inner layers of PrL and Cg1 cortices, supporting the pharmacological findings. The present results confirmed the involvement of PrL and Cg1 in the expression of FPS and freezing responses to aversive conditions. In addition, PrL serotoninergic mechanisms play a key role in contextual fear conditioning. This study suggests that PrL, IL and Cg1 distinctively contribute to the modulation of contextual fear conditioning., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

In mammals, the presence of the mother can reduce or "buffer" stress responses of her young in threatening conditions. We compared the effect of the mother, a familiar littermate, and an unfamiliar adult male on three classes of response shown by guinea pig pups in a novel environment: short latency active behaviors, particularly vocalizing; slower developing passive behaviors that appear mediated by inflammatory mechanisms; and hypothalamic-pituitary-adrenal activity. We also examined Fos induction in the prelimbic cortex, a region hypothesized to mediate buffering effects. Only the mother significantly suppressed all classes of behavior. The greatest selectivity was observed for passive behavioral responses. Contrary to expectations, the adult male reduced plasma cortisol levels of pups as effectively as did the mother. The presence of the male also resulted in increased Fos induction in the prelimbic cortex and high levels of social interaction. Maternal buffering was not associated with prelimbic activity. These results confirm the ability of the mother to reduce active behavioral and HPA responses and suggest a specific maternal buffering effect on the later developing passive behavioral responses. The findings also demonstrate an unexpected ability of adult males to reduce HPA responses and raise the possibility that different social partners buffer HPA activity through different underlying processes., (© 2014 Wiley Periodicals, Inc.)

Projection is a spontaneous and complex mental activity responsible for the subjective meaning attribution. The hypotheses of this study were that the neural correlate of projection may involve frontal, parietal, and temporal brain areas, and that alexithymia may be negatively associated with intensities in limbic and paralimbic areas during projection. EEG data were recorded continuously at 250 Hz using NetStation 4.5.1 with 256-channels HydroCel Geodesic Sensor Net in 20 healthy subjects during the presentation of structured and not-structured visual stimuli. The tasks were paying attention to the stimuli and thinking about the possible meaning of each image. Event related potential (ERP) components and low-resolution electromagnetic tomography (sLoreta) were analyzed. Participants were administered the 20-Item Toronto Alexithymia Scale before stimulus presentation. Source analyses (sLORETA) showed a greater activated source in the left primary somatosensory cortex (BA1) compared to all the others BA in both conditions through all the ERP components. An involvement of the frontal (right-BA4, left- and right-BA9, left-BA11) and parietal (left and right-BA2 and left-BA7) areas was found in projective response to not-structured visual stimuli. Alexithymia levels were negatively correlated with the anterior (right-BA32) and posterior (left-BA29) cingulate cortex. Findings show the relevance of fronto-parieto circuits during projection, where the internally generating somatosensory representations could drive an intermodal meaning attribution during the task. Moreover, high alexithymia levels were associated with a reduced activation of the cingulated cortex., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The dynorphin/κ-opioid receptor (KOP-R) system has been shown to play a role in different types of behavior regulation, including reward-related behavior and drug craving. It has been shown that alleles with 3 or 4 repeats (HH genotype) of the variable nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the prodynorphin (PDYN) gene are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype). We used fMRI on N = 71 prescreened healthy participants to investigate the effect of this polymorphism on cerebral activation in the limbic-corticostriatal loop during reward anticipation. Individuals with the HH genotype showed higher activation than those with the LL genotype in the medial orbitofrontal cortex (mOFC) when anticipating a possible monetary reward. In addition, the HH genotype showed stronger functional coupling (as assessed by effective connectivity analyses) of mOFC with VMPFC, subgenual anterior cingulate cortex, and ventral striatum during reward anticipation. This hints at a larger sensitivity for upcoming rewards in individuals with the HH genotype, resulting in a higher motivation to attain these rewards. These findings provide first evidence in humans that the PDYN polymorphism modulates neural processes associated with the anticipation of rewards, which ultimately may help to explain differences between genotypes with respect to addiction and drug abuse.

The hypothetical mechanism of functioning of neural networks that include limbic structures, neocortex and basal ganglia is proposed. A hypothesis is based on known data that the hippocampus, amygdala and prefrontal cortex interreact with each other, that their efferents converge on spiny cells of nucleus accumbens, that these inputs are topically organised and could be modified. Since GABAergic spiny cells of nucleus accumbens innervate neurons in the output basal ganglia nuclei which inhibit excitatory transmission through the thalamic nuclei into limbic structures and neocortex, the degree of activation of neurones in mentioned structures and, hence, a behaviour selection essentially depends on the character of responses of spiny cells. A summation of excitation of spiny cells and amplification of their responses during simultaneous firing of neurons of a limbic structure and neocortex, ultimately will lead to rising in neocortical activity and increase of its influence on a behaviour selection. If two structures are excited with temporary shift, activation of neurons of that structure which has firstly been strongly excited can be additionally increased due to a disinhibition of thalamic nuclei through the basal ganglia, whereas activity of neurons in other structure can be depressed if responses of spiny cells evoked by excitation arriving from this structure are decreased. Such suppression can be a consequence of heterosynaptic depression which is based on potentiation of efficacy of excitatory inputs from the different structures converging on inhibitory interneurons in the nucleus accumbens and basolateral amygdala. As a result, the behaviour choice will be determined by that structure which has been involved in activity firstly. A damage of different inputs into the nucleus accumbens from limbic structures must result in various behaviour disorders owing to the topical organisation of these inputs.