Multimodal imaging investigation of structural rich club alterations in Alzheimer's disease and mild cognitive impairment: Amyloid deposition, structural atrophy, and functional activation differences.

Alzheimer's disease (AD) is characterized by significant cerebral dysfunction, including increased amyloid deposition, gray matter atrophy, and changes in brain function. The involvement of highly connected network hubs, known as the "rich club," in the pathology of the disease remains inconclusive despite previous research efforts. In this study, we aimed to systematically assess the link between the rich club and AD using a multimodal neuroimaging approach. We employed network analyses of diffusion magnetic resonance imaging (MRI), longitudinal assessments of gray matter atrophy, amyloid deposition measurements using positron emission tomography (PET) imaging, and meta-analytic data on functional activation differences. Our study focused on evaluating the role of both the structural brain network's core and extended rich club regions in individuals with mild cognitive impairment (MCI) and those diagnosed with AD. Our findings revealed that structural rich club regions exhibited accelerated gray matter atrophy and increased amyloid deposition in both MCI and AD. Importantly, these regions remained unaffected by altered functional activation patterns observed outside the core rich club regions. These results shed light on the connection between two major AD biomarkers and the rich club, providing valuable insights into AD as a potential disconnection syndrome.

Error-Related Brain Activity in Patients With Obsessive-Compulsive Disorder and Unaffected First-Degree Relatives: Evidence for Protective Patterns.

Background: Indicators of increased error monitoring are associated with obsessive-compulsive disorder (OCD), as shown in electroencephalography and functional magnetic resonance imaging studies. As most studies used strictly controlled samples (excluding comorbidity and medication), it remains open whether these findings extend to naturalistic settings. Thus, we assessed error-related brain activity in a large, naturalistic OCD sample. We also explored which activity patterns might qualify as vulnerability endophenotypes or protective factors for the disorder. To this aim, a sample of unaffected first-degree relatives of patients with OCD was also included. Methods: Participants (84 patients with OCD, 99 healthy control participants, and 37 unaffected first-degree relatives of patients with OCD) completed a flanker task while blood oxygen level-dependent responses were measured with functional magnetic resonance imaging. Aberrant error-related brain activity in patients and relatives was identified. Results: Patients with OCD showed increased error-related activity in the supplementary motor area and within the default mode network, specifically in the precuneus and postcentral gyrus. Unaffected first-degree relatives showed increased error-related activity in the bilateral inferior frontal gyrus. Conclusions: Increased supplementary motor area and default mode network activity in patients with OCD replicates previous studies and might indicate excessive error signals and increased self-referential error processing. Increased activity of the inferior frontal gyrus in relatives may reflect increased inhibition. Impaired response inhibition in OCD has been demonstrated in several studies and might contribute to impairments in suppressing compulsive actions. Thus, increased inferior frontal gyrus activity in the unaffected relatives of patients with OCD may have contributed to protection from symptom development.

Robots facilitate human language production.

Despite recent developments in integrating autonomous and human-like robots into many aspects of everyday life, social interactions with robots are still a challenge. Here, we focus on a central tool for social interaction: verbal communication. We assess the extent to which humans co-represent (simulate and predict) a robot's verbal actions. During a joint picture naming task, participants took turns in naming objects together with a social robot (Pepper, Softbank Robotics). Previous findings using this task with human partners revealed internal simulations on behalf of the partner down to the level of selecting words from the mental lexicon, reflected in partner-elicited inhibitory effects on subsequent naming. Here, with the robot, the partner-elicited inhibitory effects were not observed. Instead, naming was facilitated, as revealed by faster naming of word categories co-named with the robot. This facilitation suggests that robots, unlike humans, are not simulated down to the level of lexical selection. Instead, a robot's speaking appears to be simulated at the initial level of language production where the meaning of the verbal message is generated, resulting in facilitated language production due to conceptual priming. We conclude that robots facilitate core conceptualization processes when humans transform thoughts to language during speaking.

Bringing Together Robotics, Neuroscience, and Psychology: Lessons Learned From an Interdisciplinary Project.

The diversified methodology and expertise of interdisciplinary research teams provide the opportunity to overcome the limited perspectives of individual disciplines. This is particularly true at the interface of Robotics, Neuroscience, and Psychology as the three fields have quite different perspectives and approaches to offer. Nonetheless, aligning backgrounds and interdisciplinary expectations can present challenges due to varied research cultures and practices. Overcoming these challenges stands at the beginning of each productive collaboration and thus is a mandatory step in cognitive neurorobotics. In this article, we share eight lessons that we learned from our ongoing interdisciplinary project on human-robot and robot-robot interaction in social settings. These lessons provide practical advice for scientists initiating interdisciplinary research endeavors. Our advice can help to avoid early problems and deal with differences between research fields, prepare for and anticipate challenges, align project expectations, and speed up research progress, thus promoting effective interdisciplinary research across Robotics, Neuroscience, and Psychology.

Effect of odor pleasantness on heat-induced pain: An fMRI study.

Odor modulates the experience of pain, but the neural basis of how the two sensory modalities, olfaction and pain, are linked in the central nervous system is far from clear. In this study, we investigated the mechanisms by which the brain modulates the pain experience under concurrent odorant stimulation. We conducted an fMRI study using a 2 × 3 factorial design, in which one of two temperatures (warm, hot) and one of three types of odors (pleasant, unpleasant, no odor) were presented simultaneously. "Hot" temperatures were individually determined as those perceived as painful (mean temperature = 46.9 °C). The non-painful "warm" temperature was set to 40 °C. Participants rated hot compared to warm stimuli as more intense and unpleasant, especially in the presence of an unpleasant odor. Parametric modeling on the intensity ratings activated the pain network, covering brain regions activated by the hot stimuli. The presence of an odor, irrespective of its valence, activated the amygdalae. In addition, the amygdalae showed stimulus-dependent functional couplings with the right supramarginal gyrus and with the left superior frontal gyrus. The coupling between the right amygdala and the left superior frontal gyrus was related to the intensity and unpleasantness ratings of the pain experience. Our results suggest that these functional connections may reflect the integrating process of the two sensory modalities, enabling olfactory influence on the pain experience.

Meta-analytic evidence for a joint neural mechanism underlying response inhibition and state anger.

Although anger may weaken response inhibition (RI) by allowing outbursts to bypass deliberate processing, it is equally likely that RI deficits precipitate a state of anger (SA). In adolescents, for instance, anger occurs more frequently and often leads to escalating aggressive behaviors. Even though RI is considered a key component in explaining individual differences in SA expression, the neural overlap between SA and RI remains elusive. Here, we aimed to meta-analytically revisit and update the neural correlates of motor RI, to determine a consistent neural architecture of SA, and to identify their joint neural network. Considering that inhibitory abilities follow a protracted maturation until early adulthood, we additionally computed RI meta-analyses in youths and adults. Using activation likelihood estimation, we calculated twelve meta-analyses across 157 RI and 39 SA experiments on healthy individuals. Consistent with previous findings, RI was associated with a broad frontoparietal network including the anterior insula/inferior frontal gyrus (aI/IFG), premotor and midcingulate cortices, extending into right temporoparietal areas. Youths showed convergent activity in right midcingulate and medial prefrontal areas, left aI/IFG, and the temporal poles. SA, on the other hand, reliably recruited the right aI/IFG and anterior cingulate cortex. Conjunction analyses between RI and SA yielded a single convergence cluster in the right aI/IFG. While frontoparietal networks and bilateral aI are ubiquitously recruited during RI, the right aI/IFG cluster likely represents a node in a dynamically-adjusting monitoring network that integrates salient information thereby facilitating the execution of goal-directed behaviors under highly unpredictable scenarios.

Neural correlates of depression in women across the reproductive lifespan - An fMRI review.

INTRODUCTION: Depressive disorders in women emerge largely during transitions in their reproductive aging cycle, which can be attributed to internal endocrine possesses that affect emotion-associated brain circuits. A review was performed to outline the neural basis in depression during female puberty, premenstrual dysphoric disorder (PMDD), postpartum depression disorder (PPD) and perimenopausal depression disorder. METHODS: For this review, Web of science, Pubmed and PsychInfo databases were searched for functional brain imaging studies addressing reproductive cycle-related mood disorder. The results are summarized and discussed within a broader theoretical framework of major depression disorder (MDD) to determine how reproductive-sensitive phases contribute to affective symptoms and how they relate to the neurobiology of MDD. RESULTS: Neural activation patterns of all depressive disorders related to female reproductive cycle, except for puberty depression, differ from these observed in MDD. While the PMDD results are widely divergent, the activation patterns in PPD show general hypoactivation in all respects. LIMITATIONS: Systematic comparisons between the diverse depression disorders are impeded by the heterogeneous experimental protocols used on different samples, reproductive aging stages and depression types. CONCLUSION: Given that hormonal fluctuations strongly influence the development of a reproductive cycle-related depression, it is possible that the hormonal and neural patterns are indicative of distinct mood disorder with phase specific biotypes, that only show behavioral similarities to MDD. Understanding the similarities and differences in the neural functioning of female cycle-related mood disorders evaluated against MDD might help elucidate the role of neuroendocrine involvement in development of depression in women, and potentially facilitate the search for prevention and treatment approaches for women' reproductive-related depressions.

Peripheral Oxytocin Predicts Higher-Level Social Cognition in Men Regardless of Empathy Quotient.

INTRODUCTION: Pharmaceutical oxytocin (OT) administration is being tested as a novel treatment for social deficits in various psychiatric populations. However, little is known about how naturally occurring variation in peripheral OT relates to differences in social cognition. This study investigates whether healthy individuals with very high or very low levels of empathy differ in endogenous OT and whether OT plasma levels can predict performance in a mentalizing task. METHODS: 40 healthy men were included based upon their score above the 85th or below the 15th percentile of the empathy quotient inventory 1. Participants' abilities to interpret social information was assessed via the Social Detection Task 2. Plasma OT levels were analyzed using enzyme immunoassay. RESULTS: OT plasma levels predicted mentalizing performance for more ambiguous social scenes (i. e., difficult items) for all participants. We found no group differences in OT plasma levels between subjects with high and low empathy. DISCUSSION: These findings confirm a link between peripheral OT and the ability to read subtle nonverbal social cues in healthy individuals, which is independent of self-reported empathy.

Risk factors of suicidal ideation in Huntington's disease: literature review and data from Enroll-HD.

Suicide is a leading cause of death in Huntington's disease (HD), following pneumonia. Up to one-fifth of individuals with HD report suicidal ideation. Identifying the risk factors of suicidal ideation in this clinical population is thus pivotal. Here, we review the literature on prevalence rates and risk factors of suicidal ideation in premanifest and manifest patients and re-evaluate them using the largest currently existing clinical dataset from the ongoing observational study "Enroll-HD" (N = 5709). Large scale studies yielded important insights regarding suicidal ideation in HD. However, estimated prevalence rates vary among studies and risk factors are still poorly understood. According to the Enroll-HD data, pre- and manifest disease stages are associated with current (5.8-10%) and a history of suicidal ideation (18.6-30.9%). Throughout the course of HD, a history of suicidal ideation and the presence of depressive symptoms were strongly associated with current suicidal ideation. However, while for premanifest individuals, socio-demographics and activities of daily living appear to be important, in manifest patients, suicidal ideation is more closely linked to anxiety, irritability, psychosis, and apathy. These results highlight the importance of treating depressive symptoms in patients with HD and addressing potential suicidal ideation during clinical monitoring. The relevance of risk factors may differ among premanifest and manifest patients.

Impulsive aggression and response inhibition in attention-deficit/hyperactivity disorder and disruptive behavioral disorders: Findings from a systematic review.

BACKGROUND: Although impulsive aggression (IA) and dysfunctional response inhibition (RI) are hallmarks of attention-deficit/hyperactivity disorder (ADHD) and disrupted behavioral disorders (DBDs), little is known about their shared and distinct deviant neural mechanisms. AIMS AND METHODS: Here, we selectively reviewed s/fMRI ADHD and DBD studies to identify disorder-specific and shared IA and RI aberrant neural mechanisms. RESULTS: In ADHD, deviant prefrontal and cingulate functional activity was associated with increased IA. Structural alterations were most pronounced in the cingulate cortex. Subjects with DBDs showed marked cortico-subcortical dysfunctions. ADHD and DBDs share similar cortico-limbic structural and functional alterations. RI deficits in ADHD highlighted hypoactivity in the dorso/ventro-lateral PFC, insula, and striatum, while the paralimbic system was primarily dysfunctional in DBDs. Across disorders, extensively altered cortico-limbic dysfunctions underlie IA, while RI was mostly associated with aberrant prefrontal activity. CONCLUSION: Control network deficits were evidenced across clinical phenotypes in IA and RI. Dysfunctions at any level within these cortico-subcortical projections lead to deficient cognitive-affective control by ascribing emotional salience to otherwise irrelevant stimuli. The clinical implications of these findings are discussed.

Addicted to love: What is love addiction and when should it be treated?

Recent research suggests that romantic love can be literally addictive. Although the exact nature of the relationship between love and addiction has been described in inconsistent terms throughout the literature, we offer a framework that distinguishes between a narrow view and a broad view of love addiction. The narrow view counts only the most extreme, harmful forms of love or love-related behaviors as being potentially addictive in nature. The broad view, by contrast, counts even basic social attachment as being on a spectrum of addictive motivations, underwritten by similar neurochemical processes as more conventional addictions. We argue that on either understanding of love-as-addiction, treatment decisions should hinge on considerations of harm and well-being rather than on definitions of disease. Implications for the ethical use of anti-love biotechnology are considered.

Chemosensory anxiety cues enhance the perception of fearful faces - An fMRI study.

Recent evidence suggests that humans can communicate emotion via chemosensory signals. Olfactory cues signaling anxiety can bias the perception of ambiguous stimuli, but the underlying neurobiological mechanisms of this effect are currently unknown. Here, we investigated the brain responses to subtle changes in facial expressions in response to anxiety chemosensory cues. Ten healthy individuals donated their sweat in two situations: while anticipating an important oral examination (anxiety condition) and during physical exercise (control condition). Subsequently, 24 participants completed a parametrically morphed (neutral to fearful) emotion recognition task under exposure to the olfactory cues of anxiety and sports, in the fMRI scanner. Behaviorally, the participants rated more discernible fearful faces as more fearful and neutral faces as more neutral under exposure to the anxiety cues. For brain response, under exposure to the anxiety cues, increased fearfulness of the face corresponded to increased activity in the left insula and the left middle occipital gyrus extending into fusiform gyrus. Moreover, with higher subjective ratings of facial fearfulness, participants additionally showed increased activity in the left hippocampus. These results suggest that chemosensory anxiety cues facilitate processing of socially relevant fearful stimuli and boost memory retrieval due to enhanced emotional context.

Follow your nose: Implicit spatial processing within the chemosensory systems.

Although most studies agree that humans cannot smell in stereo, it was recently suggested that olfactory localization is possible when assessed implicitly. In a spatial cueing paradigm, lateralized olfactory cues impaired the detection of congruently presented visual targets, an effect contrary to the typical facilitation observed in other sensory domains. Here, we examined the specificity and the robustness of this finding by studying implicit localization abilities in another chemosensory system and by accounting for possible confounds in a modified paradigm. Sixty participants completed a spatial cueing task along with an explicit localization task, using trigeminal (Experiment 1) and olfactory (Experiment 2) stimuli. A control task was implemented to control for residual somatosensory stimulation (Experiment 3). In the trigeminal experiment, stimuli were localized with high accuracy on the explicit level, while the cueing effect in form of facilitation was limited to response accuracy. In the olfactory experiment, responses were slowed by congruent cues on the implicit level, while no explicit localization was observed. Our results point to the robustness of the olfactory interference effect, corroborating the implicit-explicit dissociation of olfactory localization, and challenging the view that humans lost the ability to extract spatial information from smell. The absence of a similar interference for trigeminal cues suggests distinct implicit spatial processing mechanisms within the chemosensory systems. Moreover, the lack of a typical facilitation effect in the trigeminal domain points to important differences from spatial information processing in other, nonchemosensory domains. The possible mechanisms driving the effects are discussed. (PsycINFO Database Record

Chemosensory anxiety cues moderate the experience of social exclusion - an fMRI investigation with Cyberball.

Recent evidence suggests that the experience of stress can be communicated between individuals via chemosensory cues. Little is known, however, about the impact of these cues on neurophysiological responses during a socially threatening situation. In the current investigation we implemented a widely used paradigm to study social exclusion-Cyberball-to examine whether chemosensory cues signaling anxiety modulate the neuronal effects of ostracism. In a double-blind, within-subjects design, 24 healthy, normosmic participants were presented with chemosensory cues of anxiety (or control samples) and completed the Cyberball task while in a 3T fMRI scanner. Axillary sweat collected from male students awaiting an oral examination served as the anxiety cues while the chemosensory control stimuli consisted of sweat collected from the same individuals participating in an ergometer training session. The neuroimaging data revealed that under the control chemosensory condition, exclusion from Cyberball was associated with significantly higher orbitofrontal cortex and anterior cingulate cortex activity, which is consistent with previous studies in the field. However, when participants were primed with the anxiety sweat, the activity in these regions was not observed. Further, under exposure to anxiety cues during ostracism the participants showed deactivations in brain regions involved in memory (hippocampus), social cognition (middle temporal gyrus, superior temporal gyrus) and processing of salience (inferior frontal gyrus). These results suggest that successful communication of anxiety via the chemosensory domain may moderate the experience of social exclusion. It is possible that the anxiety signals make it easier for the individuals to detach from the group, pointing to the communicative role of chemosensory anxiety cues in enhancing adjustment mechanisms in light of a distressing situation.

If I could just stop loving you: anti-love biotechnology and the ethics of a chemical breakup.

"Love hurts"-as the saying goes-and a certain amount of pain and difficulty in intimate relationships is unavoidable. Sometimes it may even be beneficial, since adversity can lead to personal growth, self-discovery, and a range of other components of a life well-lived. But other times, love can be downright dangerous. It may bind a spouse to her domestic abuser, draw an unscrupulous adult toward sexual involvement with a child, put someone under the insidious spell of a cult leader, and even inspire jealousy-fueled homicide. How might these perilous devotions be diminished? The ancients thought that treatments such as phlebotomy, exercise, or bloodletting could "cure" an individual of love. But modern neuroscience and emerging developments in psychopharmacology open up a range of possible interventions that might actually work. These developments raise profound moral questions about the potential uses-and misuses-of such anti-love biotechnology. In this article, we describe a number of prospective love-diminishing interventions, and offer a preliminary ethical framework for dealing with them responsibly should they arise.

Enhanced dimension-specific visual working memory in grapheme-color synesthesia.

There is emerging evidence that the encoding of visual information and the maintenance of this information in a temporarily accessible state in working memory rely on the same neural mechanisms. A consequence of this overlap is that atypical forms of perception should influence working memory. We examined this by investigating whether having grapheme-color synesthesia, a condition characterized by the involuntary experience of color photisms when reading or representing graphemes, would confer benefits on working memory. Two competing hypotheses propose that superior memory in synesthesia results from information being coded in two information channels (dual-coding) or from superior dimension-specific visual processing (enhanced processing). We discriminated between these hypotheses in three n-back experiments in which controls and synesthetes viewed inducer and non-inducer graphemes and maintained color or grapheme information in working memory. Synesthetes displayed superior color working memory than controls for both grapheme types, whereas the two groups did not differ in grapheme working memory. Further analyses excluded the possibilities of enhanced working memory among synesthetes being due to greater color discrimination, stimulus color familiarity, or bidirectionality. These results reveal enhanced dimension-specific visual working memory in this population and supply further evidence for a close relationship between sensory processing and the maintenance of sensory information in working memory.

Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations.

PURPOSE OF REVIEW: Well-functioning romantic relationships are important for long-term health and well being, but they are often difficult to sustain. This difficulty arises (in part) because of an underlying tension between our psychobiological natures, culture/environment, and modern love and relationship goals. One possible solution to this predicament is to intervene at the level of psychobiology, enhancing partners' interpersonal connection through neurochemical modulation. This article focuses on a single, promising biobehavioral sub-system for such intervention: the attachment system, based largely upon the expression of the neuropeptide oxytocin. Could the exogenous administration of oxytocin - under the right conditions - be used to facilitate relational or marital well being? RECENT FINDINGS: If so, it would require considerable forethought. Recent research complicates the popular image of oxytocin as a universal social enhancer or 'love hormone' and shows that it may exert a variety of different effects, at different dosages, on different people, under different circumstances. Accordingly, we discuss what is known about oxytocin, including its 'good' and 'bad' effects on human behavior and on higher-order functional processes. SUMMARY: Building upon animal-model, human preclinical, and clinical findings, we outline a proposal for the use of oxytocin in the therapeutic neuroenhancement of contemporary romantic relationships. Highlighting key targets for future research along the way, we then conclude by discussing some of the clinical and ethical considerations that would pertain to the implementation of this knowledge in applied settings.