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Arthritogenic alphaviruses pose a significant public health concern due to their ability to cause joint inflammation, with emerging evidence of potential neurological consequences. In this review, we examine the immunopathology and immune evasion strategies employed by these viruses, highlighting their complex mechanisms of pathogenesis and neurological implications. We delve into how these viruses manipulate host immune responses, modulate inflammatory pathways, and potentially establish persistent infections. Further, we explore their ability to breach the blood-brain barrier, triggering neurological complications, and how co-infections exacerbate neurological outcomes. This review synthesizes current research to provide a comprehensive overview of the immunopathological mechanisms driving arthritogenic alphavirus infections and their impact on neurological health. By highlighting knowledge gaps, it underscores the need for research to unravel the complexities of virus-host interactions. This deeper understanding is crucial for developing targeted therapies to address both joint and neurological manifestations of these infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Oliveira Souza, Duarte Júnior, Della Casa, Santoro Rosa, Renia and Claser.)

The long-term outcome of acquired sociopathy with preservation of cognition is still unknown. Here, we present the long-term outcome of a severe antisocial change in personality that followed a traumatic left frontopolar injury in a previously gentle, loving, and introverted adolescent. Nine years after the accident, antisocial behaviors gradually became sporadic, while, at the same time, the patient's sense of responsibility and care for his family increased. He became more extroverted and assertive, yet flexible enough to deal with the hardships of his poor socioeconomic background. His "new personality" was, in fact, more adjusted than ever. We argue that his late recovery reflected a conjunction of factors, especially (i) his early age, (ii) the static nature of the injury, (iii) the preservation of the ventromedial frontal cortices and related basal forebrain regions, and (iv) an unusual asymmetric representation of social cognition in the cerebral hemispheres. Our case and the case of Franz Binz indicate that social recovery is possible after gross prefrontal injuries, even when they are no longer expected to occur. It also emphasizes the importance of reporting on the long-term follow-up of brain-injured patients., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Loxosceles genus represents one of the main arachnid genera of medical importance in Brazil. Despite the gravity of Loxosceles-related accidents, just a handful of species are deemed medically important and only a few have undergone comprehensive venom characterization. Loxosceles amazonica is a notable example of a potentially dangerous yet understudied Loxosceles species. While there have been limited reports of accidents involving L. amazonica to date, accidents related to Loxosceles are increasing in the North and Northeast regions of Brazil, where L. amazonica has been reported. In this work, we provide a complementary biochemical and immunological characterization of L. amazonica venom, considering its most relevant enzymatic activities and its immunorecognition and neutralization by current therapeutic antivenoms. Additionally, a cDNA library enriched with phospholipase D (PLD) sequences from L. amazonica venom glands was built and subsequently sequenced. The results showed that L. amazonica venom is well immunorecognised by all the tested antibodies. Its venom also displayed proteolytic, hyaluronidase, and sphingomyelinase activities. These activities were at least partially inhibited by available antivenoms. With cDNA sequencing of PLDs, seven new putative isoforms were identified in the venom of L. amazonica. These results contribute to a better knowledge of the venom content and activities of a synanthropic, yet understudied, Loxosceles species. In vivo assays are essential to confirm the medical relevance of L. amazonica, as well as to assess its true toxic potential and elucidate its related pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Functional imaging studies and clinical evidence indicate that cortical areas relevant to social cognition are closely integrated with evolutionarily conserved basal forebrain structures and neighboring regions, enabling human attachment and affiliative emotions. The neural circuitry of human affiliation is continually being unraveled as functional magnetic resonance imaging (fMRI) becomes increasingly prevalent, with studies examining human brain responses to various attachment figures. However, previous fMRI meta-analyses on affiliative stimuli have encountered challenges, such as low statistical power and the absence of robustness measures. To address these issues, we conducted an exhaustive coordinate-based meta-analysis of 79 fMRI studies, focusing on personalized affiliative stimuli, including one's infants, family, romantic partners, and friends. We employed complementary coordinate-based analyses (Activation Likelihood Estimation and Signed Differential Mapping) and conducted a robustness analysis of the results. Findings revealed cluster convergence in cortical and subcortical structures related to reward and motivation, salience detection, social bonding, and cognition. Our study thoroughly explores the neural correlates underpinning affiliative responses, effectively overcoming the limitations noted in previous meta-analyses. It provides an extensive view of the neural substrates associated with affiliative stimuli, illuminating the intricate interaction between cortical and subcortical regions. Our findings significantly contribute to understanding the neurobiology of human affiliation, expanding the known human attachment circuitry beyond the traditional basal forebrain regions observed in other mammals to include uniquely human isocortical structures., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.

A 19-year-old student developed hypoventilation and cyanosis at the end of a cosmetic liposuction procedure. She was awake, but severely abulic, disoriented, and unable to stand and walk due to severe locomotor ataxia. Neuropsychological evaluation showed psychomotor slowness, and deficits in memory encoding and retrieval, and on executive, and visuospatial and visuoperceptual tests; oral comprehension and constructional praxis were spared. ¹H-MRS showed a reduction of NAA. A year later, her cognitive and neurological exam, and NAA returned to normal, and she resumed her normal life. The severity of the acute manifestations of hypoxic encephalopathy not always entail a poor prognosis.

Objectives: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups., Methods: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation., Results: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho =  - 0.816; p < 0.001); REI and MELD score (rho =  - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity)., Conclusions: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast., Key Points: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The ventromedial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) circuit has been implicated in impulsive reward-seeking. This disinhibition has been implicated in obesity and often manifests as binge eating, which is associated with worse treatment outcomes and comorbidities. It remains unclear whether the vmPFC-NAc circuit is perturbed in impulsive eaters with obesity. Initially, we analyzed publicly available, high-resolution, normative imaging data to localize where vmPFC structural connections converged within the NAc. These structural connections were found to converge ventromedially in the presumed NAc shell subregion. We then analyzed multimodal clinical and imaging data to test the a priori hypothesis that the vmPFC-NAc shell circuit is linked to obesity in a sample of female participants that regularly engaged in impulsive eating (i.e., binge eating). Functionally, vmPFC-NAc shell resting-state connectivity was inversely related to body mass index (BMI) and decreased in the obese state. Structurally, vmPFC-NAc shell structural connectivity and vmPFC thickness were inversely correlated with BMI; obese binge-prone participants exhibited decreased vmPFC-NAc structural connectivity and vmPFC thickness. Finally, to examine a causal link to binge eating, we directly probed this circuit in one binge-prone obese female using NAc deep brain stimulation in a first-in-human trial. Direct stimulation of the NAc shell subregion guided by local behaviorally relevant electrophysiology was associated with a decrease in number of weekly episodes of uncontrolled eating and decreased BMI. This study unraveled vmPFC-NAc shell circuit aberrations in obesity that can be modulated to restore control over eating behavior in obesity., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Tuberculosis (TB) remains one of the world's leading infectious cause of morbidity and mortality. Positron emission tomography (PET) associated with computed tomography (CT) allows a structural and metabolic evaluation of TB lesions, being an excellent noninvasive alternative for understanding its pathogenesis. DOTATOC labeled with gallium-68 (68Ga-DOTATOC) can bind to somatostatin receptors present in activated macrophages and lymphocytes, cells with a fundamental role in TB pathogenesis. We describe 68Ga-DOTATOC uptake distribution and patterns in thoracic lymph nodes (LN) and pulmonary lesions (PL) in immunocompetent patients with active postprimary TB, analyze the relative LN/PL uptake, and compare this two tracer's uptake. High uptake of both radiotracers in PL and LN was demonstrated, with higher LN/PL ratio on 68Ga-DOTATOC (P < 0.05). Considering that LN in immunocompetent patients are poorly studied, 68Ga-DOTATOC can contribute to the understanding of the complex immunopathogenesis of TB.

Background: Substance addiction encompasses the incapacity to discontinue urgent drug use; many severely disabled patients might be considered appropriate candidates for surgery due to the high rates of relapse despite conservative treatment. A crucial finding in the brain of these patients is increased extracellular concentrations of dopamine in the nucleus accumbens (NAcc)., Objectives: To determine the efficacy and safety of NAcc surgery for the treatment of substance dependence., Materials and Methods: Adhering to PRISMA guidelines, we performed a systematic review to identify all original studies in which NAcc surgery was performed to treat relapsing drug addiction with a minimum follow-up of six months. From database inception to April 10, 2020, we searched PubMed, Scopus, and LILACS. Two reviewers independently selected studies and extracted data. The main outcome was the relapse rate. The GRADE methods were applied to evaluate the quality of evidence. This study was registered with PROSPERO CRD42020177054., Results: Fifteen studies involving 359 participants met inclusion criteria; eight (56%) included NAcc deep brain stimulation (DBS) in 13 patients with addiction for alcohol (N = 6, 46.1%), opioid (N = 4, 30.7%), and nicotine (N = 3, 15.3%); seven studies (N = 346, 44%) performed NAcc radiofrequency (RF) ablation for opioid (N = 334) and alcohol (N = 12) dependence. Relapse rates were 38.4% for DBS and 39% for RF ablation., Conclusions: Despite available studies reporting a benefit in the treatment of drug addictions with NAcc surgery, this systematic review stresses the need for carefully planned prospective studies in order to further address the efficacy and indications., (Copyright © 2021. Published by Elsevier Inc.)

Background: The relatively isolated atrophy of the temporal lobes leads to a clinical radiological pattern, referred to as the temporal variant of frontotemporal dementia. While semantic dementia and behavioral variant frontotemporal dementia are classically related to this syndrome, the logopenic variant of primary progressive aphasia has been less commonly reported. This case report aims to give a pictorial description of a case in which a patient with asymmetric temporal lobe atrophy presented with the logopenic variant of primary progressive aphasia and complex rituals of cleanliness., Case Presentation: We report on the case of a 68-year-old, right-handed White woman with complex rituals and progressive speech impairment. The obsessive-compulsive rituals represented an exacerbation of lifelong preoccupations with cleanliness and orderliness that were praised by her relatives. Neuropsychological assessment revealed a striking impairment of language and memory, with relative sparing of tool-use praxis and visuospatial skills. Magnetic resonance imaging and 18 fluorodeoxyglucose-positron emission tomography scans showed bilateral asymmetrical temporal lobe atrophy and hypometabolism. A year later, she was still able to entertain conversation for a short while, but her vocabulary and fluency had further declined. Praxis and visuospatial skills remained intact. She did not experience pathological elation, delusions, or hallucinations. The disease followed a relentless progression into a partial Klüver-Bucy syndrome, abulia, and terminal dementia. She died from acute myocardial infarction 8 years after the onset of aphasia. The symptoms and their temporal course supported a diagnosis of logopenic variant of primary progressive aphasia due to asymmetric temporal variant frontotemporal lobar degeneration., Conclusions: This report gives a pictorial description of a temporal variant of frontotemporal dementia in a patient who presented with worsening of a lifelong obsessive-compulsive disorder and logopenic variant of primary progressive aphasia., (© 2022. The Author(s).)

Psychosurgery refers to an ensemble of more or less invasive techniques designed to reduce the burden caused by psychiatric diseases in patients who have failed to respond to conventional therapy. While most surgeries are designed to correct apparent anatomical abnormalities, no discrete cerebral anatomical lesion is evident in most psychiatric diseases amenable to invasive interventions. Finding the optimal surgical targets in mental illness is troublesome. In general, contemporary psychosurgical procedures can be classified into one of two primary modalities: lesioning and stimulation procedures. The first group is divided into (a) thermocoagulation and (b) stereotactic radiosurgery or recently introduced transcranial magnetic resonance-guided focused ultrasound, whereas stimulation techniques mainly include deep brain stimulation (DBS), cortical stimulation, and the vagus nerve stimulation. The most studied psychiatric diseases amenable to psychosurgical interventions are severe treatment-resistant major depressive disorder, obsessive-compulsive disorder, Tourette syndrome, anorexia nervosa, schizophrenia, and substance use disorder. Furthermore, modern neuroimaging techniques spurred the interest of clinicians to identify cerebral regions amenable to be manipulated to control psychiatric symptoms. On this way, the concept of a multi-nodal network need to be embraced, enticing the collaboration of psychiatrists, psychologists, neurologists and neurosurgeons participating in multidisciplinary groups, conducting well-designed clinical trials., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Humans are intrinsically motivated to bond with others. The ability to experience affiliative emotions (such as affection/tenderness, sexual attraction, and admiration/awe) may incentivize and promote these affiliative bonds. Here, we interrogate the role of the critical reward circuitry, especially the Nucleus Accumbens (NAcc) and the septo-hypothalamic region, in the anticipation of and response to affiliative rewards using a novel incentive delay task. During Functional Magnetic Resonance Imaging (FMRI), participants (n = 23 healthy humans; 14 female) anticipated and watched videos involving affiliative (tenderness, erotic desire, and awe) and nonaffiliative (i.e., food) rewards, as well as neutral scenes. On the one hand, anticipation of both affiliative and nonaffiliative rewards increased activity in the NAcc, anterior insula, and supplementary motor cortex, but activity in the amygdala and the ventromedial prefrontal cortex (vmPFC) increased in response to reward outcomes. On the other hand, affiliative rewards more specifically increased activity in the septo-hypothalamic area. Moreover, NAcc activity during anticipation correlated with positive arousal for all rewards, whereas septo-hypothalamic activity during the outcome correlated with positive arousal and motivation for subsequent re-exposure only for affiliative rewards. Together, these findings implicate a general appetitive response in the NAcc to different types of rewards but suggests a more specific response in the septo-hypothalamic region in response to affiliative rewards outcomes. This work also presents a new task for distinguishing between neural responses to affiliative and non-affiliative rewards., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Social feelings have conceptual and empirical connections with affect and emotion. In this review, we discuss how they relate to cognition, emotion, behavior and well-being. We examine the functional neuroanatomy and neurobiology of social feelings and their role in adaptive social functioning. Existing neuroscience literature is reviewed to identify concepts, methods and challenges that might be addressed by social feelings research. Specific topic areas highlight the influence and modulation of social feelings on interpersonal affiliation, parent-child attachments, moral sentiments, interpersonal stressors, and emotional communication. Brain regions involved in social feelings were confirmed by meta-analysis using the Neurosynth platform for large-scale, automated synthesis of functional magnetic resonance imaging data. Words that relate specifically to social feelings were identfied as potential research variables. Topical inquiries into social media behaviors, loneliness, trauma, and social sensitivity, especially with recent physical distancing for guarding public and personal health, underscored the increasing importance of social feelings for affective and second person neuroscience research with implications for brain development, physical and mental health, and lifelong adaptive functioning., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 65-year-old right-handed man gradually became socially indifferent and less active. Four years later, he was indicted for molesting children on multiple occasions. Psychomotor slowness and executive impairment contrasted with sparing of language, semantic memory, visuospatial perception, construction praxis, and right-left orientation. Neuroimaging showed asymmetric atrophy of dorsomedial frontal and anterior temporal lobes, and hypoperfusion of medial prefrontal cortex consistent with a diagnosis of behavioral variant of frontotemporal dementia. Further information revealed that the patient exhibited pedophilic behavior several years prior to symptom onset. We conclude that preexisting developmental pedophilia was "unmasked" by the underlying progressive frontotemporal degeneration.

Behavioral evidence of impaired response inhibition (RI) and hyperactive error monitoring (EM) in obsessive-compulsive disorder (OCD) is inconsistent. Recent neuroimaging work suggests that EM plays a role in RI impairments in OCD, but this has rarely been investigated using behavioral measures. The aims of this study were to (1) compare RI and EM performance between adults with OCD and non-psychiatric controls (NPC) while investigating possible moderators, and (2) assess whether excessive EM influences RI in OCD. We compared RI and EM performance on the Stop-Signal Task (SST) between 92 adults with OCD and 65 NPC from two Brazilian sites. We used linear regression to investigate which variables (group, age, medication use, clinical symptomatology) influenced performance, as well as to examine possible associations between RI and EM. OCD and NPC did not differ in RI and EM. However, age moderated RI performance in OCD with a medium effect size, reflecting differential effects of age on RI between groups: age was positively associated with RI in OCD but not NPC. Further, OCD severity predicted EM with a medium to large effect size, suggesting that more symptomatic patients showed greater monitoring of their mistakes. Finally, group moderated the relationship between RI and EM with a small effect size. Our findings suggest that demographic factors may influence RI, whereas clinical factors may influence EM. Further, we found preliminary behavioral evidence to indicate that impaired RI and excessive EM are related in OCD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The clinicoanatomic cases of acquired pedophilia that have been published in the medical and forensic literature up to 2019 are reviewed. Twenty-two cases fit our inclusion criteria. All but one were men, and in only one case the injury was localized to the left hemisphere. Hypersexuality was present in 18 cases. The damaged areas fell within the frontotemporoinsular cortices and related subcortical nuclei; however, the anterior hypothalamus was spared. Damage to parts of the right frontotemporoinsular lobes with sparing of the anterior hypothalamus seems to be critical for the emergence of acquired pedophilia.

Background: Although a behavioural addiction model of obsessive-compulsive disorder (OCD) has been proposed, it is still unclear if and how self-report and neurocognitive measures of impulsivity (such as risk-taking-, reflection- and motor-impulsivities) are impaired and/or inter-related in this particular clinical population., Methods: Seventeen OCD patients and 17 age-, gender-, education- and IQ-matched controls completed the Barratt Impulsivity Scale, the Obsessive-Compulsive Inventory-Revised, and the Beck Depression Inventory and were evaluated with the Yale-Brown Obsessive-Compulsive Scale and three computerized paradigms including reward (the Cambridge Gambling Task), reflection (the Information Sampling Task) and motor impulsivity (Stop Signal Task)., Results: Despite not differing from healthy controls in any neurocognitive impulsivity domain, OCD patients demonstrated increased impulsivity in a self-report measure (particularly attentional impulsivity). Further, attentional impulsivity was predicted by severity of obsessive-compulsive symptoms., Conclusions: Our findings suggest that OCD is characterized by a subjective (rather than objective) impulsivity; in addition, self-reported impulsivity was largely determined by severity of OCD symptoms., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Moral motivations drive humans to sacrifice selfish needs to serve the needs of others and internalized sociocultural norms. Over the past two decades, several brain regions have been associated with different aspects of moral cognition and behaviour. Only more recently, however, investigations have highlighted the importance of the basal forebrain for moral motivation. This includes the septo-hypothalamic region, implicated in kinship bonding across mammal species, and the closely connected subgenual frontal cortex. Understanding the neuroanatomy of moral motivation and its impairments will be fundamental for future research aiming to promote prosocial behaviour and mental health., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Narrative discourse (ND) refers to one's ability to verbally reproduce a sequence of temporally and logically-linked events. Impairments in ND may occur in subjects with Amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD), but correlates across this function, neuroimaging and cerebrospinal fluid (CSF) AD biomarkers remain understudied., Objectives: We sought to measure correlates among ND, Diffusion Tensor Imaging (DTI) indexes and AD CSF biomarkers in patients within the AD spectrum., Results: Groups differed in narrative production (NProd) and comprehension. aMCI and AD presented poorer inference abilities than controls. AD subjects were more impaired than controls and aMCI regarding WB (p<0.01). ROIs DTI assessment distinguished the three groups. Mean Diffusivity (MD) in the uncinate, bilateral parahippocampal cingulate and left inferior occipitofrontal fasciculi negatively correlated with NProd. Changes in specific tracts correlated with T-tau/Aβ1-42 ratio in CSF., Conclusions: AD and aMCI patients presented more ND impairments than controls. Those findings were associated with changes in ventral language-associated and in the inferior parahippocampal pathways. The latest were correlated with biomarkers' levels in the CSF., Methods: AD (N=14), aMCI (N=31) and Control (N=39) groups were compared for whole brain (WB) and regions of interest (ROI) DTI parameters, ND and AD CSF biomarkers.

Previously, using fMRI, we demonstrated lower connectivity between right anterior superior temporal (ATL) and anterior subgenual cingulate (SCC) regions while patients with major depressive disorder (MDD) experience guilt. This neural signature was detected despite symptomatic remission which suggested a putative role in vulnerability. This randomised controlled double-blind parallel group clinical trial investigated whether patients with MDD are able to voluntarily modulate this neural signature. To this end, we developed a fMRI neurofeedback software (FRIEND), which measures ATL-SCC coupling and displays its levels in real time. Twenty-eight patients with remitted MDD were randomised to two groups, each receiving one session of fMRI neurofeedback whilst retrieving guilt and indignation/anger-related autobiographical memories. They were instructed to feel the emotion whilst trying to increase the level of a thermometer-like display on a screen. Active intervention group: The thermometer levels increased with increasing levels of ATL-SCC correlations in the guilt condition. Control intervention group: The thermometer levels decreased when correlation levels deviated from the previous baseline level in the guilt condition, thus reinforcing stable correlations. Both groups also received feedback during the indignation condition reinforcing stable correlations. We confirmed our predictions that patients in the active intervention group were indeed able to increase levels of ATL-SCC correlations for guilt vs. indignation and their self-esteem after training compared to before training and that this differed significantly from the control intervention group. These data provide proof-of-concept for a novel treatment target for MDD patients and are in keeping with the hypothesis that ATL-SCC connectivity plays a key role in self-worth. https://clinicaltrials.gov/ct2/show/results/NCT01920490., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Over the past 150 years, the frontal lobes (FLs) have been implicated in the neural mediation of both normal and abnormal moral conduct and social behavior (MCSB). Despite the remarkable advances that have permeated this period up to the present, a comprehensive account of the neural underpinnings of MCSB has stubbornly defied the best minds of psychology, psychiatry, and neurology. The goal of this chapter is to review a few practical and conceptual achievements that have proved heuristically valuable as an impetus for further advance of knowledge. In virtually all cases in which MCSB was compromised by brain damage, the injuries were located (i) in the prefrontal cortices, (ii) in their connections with the temporal poles and anterior insula, or (iii) in related subcortical structures and pathways, such as the thalamic dorsomedial nucleus or the anterior thalamic radiation. The clinicoanatomic associations among these structures originated the "frontal network systems" concept, which satisfactorily explains the occurrence of classical FL syndromes in patients with lesions outside the prefrontal cortices. Overall, clinicoanatomic observational studies and experimental evidence from patients with acquired sociopathy/psychopathy indicate that abnormalities of MCSB are the final common pathway of single or mixed impairments of subordinate psychologic and neural domains that support MCSB. Independent studies on normal volunteers concur with this view, indicating that MCSB is shaped by the dynamic interplay of subordinate psychologic domains, such as moral sensitivity and judgment, and their neural correlates., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The paradoxical absence of a split-brain syndrome in most cases of callosal dysgenesis has originated three main hypotheses, namely, (i) bilateral cortical representation of language, (ii) bilateral thalamocortical projections of somatosensory pathways conveyed by the spinothalamic-medial lemniscus system, and (iii) a variable combination of (i) and (ii). We used functional neuroimaging to investigate the cortical representation and lateralization of somatosensory information from the palm of each hand in six cases of callosal dysgenesis (hypothesis [ii]). Cortical regions of interest were contralateral and ipsilateral S1 (areas 3a and 3b, 1 and 2 in the central sulcus and postcentral gyrus) and S2 (parts of areas 40 and 43 in the parietal operculum). The degree of cortical asymmetry was expressed by a laterality index (LI), which may assume values from -1 (fully left-lateralized) to +1 (fully right-lateralized). In callosal dysgenesis, LI values for the right and the left hands were, respectively, -1 and + 1 for both S1 and S2, indicating absence of engagement of ipsilateral S1 and S2. In controls, LI values were - 0.70 (S1) and - 0.51 (S2) for right hand stimulation, and 0.82 (S1) and 0.36 (S2) for left hand stimulation, reflecting bilateral asymmetric activations, which were significantly higher in the hemisphere contralateral to the stimulated hand. Therefore, none of the main hypotheses so far entertained to account for the callosal dysgenesis-split-brain paradox have succeeded. We conclude that the preserved interhemispheric transfer of somatosensory tactile information in callosal dysgenesis must be mediated by a fourth alternative, such as aberrant interhemispheric bundles, reorganization of subcortical commissures, or both., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The cerebral correlates of altruistic decisions have increasingly attracted the interest of neuroscientists. To date, investigations on the neural underpinnings of altruistic decisions have primarily been conducted in healthy adults undergoing functional neuroimaging as they engaged in decisions to punish third parties. The chief purpose of the present study was to investigate altruistic decisions following focal brain damage with a novel altruistic decision task. In contrast to studies that have focused either on altruistic punishment or donation, the Altruistic Decision Task allows players to anonymously punish or donate to 30 charitable organizations involved with salient societal issues such as abortion, nuclear energy and civil rights. Ninety-four Vietnam War veterans with variable patterns of penetrating traumatic brain injury and 28 healthy veterans who also served in combat participated in the study as normal controls. Participants were asked to invest $1 to punish or reward real societal organizations, or keep the money for themselves. Associations between lesion distribution and performance on the task were analysed with multivariate support vector regression, which enables the assessment of the joint contribution of multiple regions in the determination of a given behaviour of interest. Our main findings were: (i) bilateral dorsomedial prefrontal lesions increased altruistic punishment, whereas lesions of the right perisylvian region and left temporo-insular cortex decreased punishment; (ii) altruistic donations were increased by bilateral lesions of the dorsomedial parietal cortex, whereas lesions of the right posterior superior temporal sulcus and middle temporal gyri decreased donations; (iii) altruistic punishment and donation were only weakly correlated, emphasizing their dissociable neuroanatomical associations; and (iv) altruistic decisions were not related to post-traumatic personality changes. These findings indicate that altruistic punishment and donation are determined by largely non-overlapping cerebral regions, which have previously been implicated in social cognition and moral experience such as evaluations of intentionality and intuitions of justice and morality.10.1093/brain/awy064&#95;video1awy064media15758316955001.

In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer's disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.

Humans have a strong need to belong to social groups and a natural inclination to benefit ingroup members. Although the psychological mechanisms behind human prosociality have extensively been studied, the specific neural systems bridging group belongingness and altruistic motivation remain to be identified. Here, we used soccer fandom as an ecological framing of group membership to investigate the neural mechanisms underlying ingroup altruistic behaviour in male fans using event-related functional magnetic resonance. We designed an effort measure based on handgrip strength to assess the motivation to earn money (i) for oneself, (ii) for anonymous ingroup fans, or (iii) for a neutral group of anonymous non-fans. While overlapping valuation signals in the medial orbitofrontal cortex (mOFC) were observed for the three conditions, the subgenual cingulate cortex (SCC) exhibited increased functional connectivity with the mOFC as well as stronger hemodynamic responses for ingroup versus outgroup decisions. These findings indicate a key role for the SCC, a region previously implicated in altruistic decisions and group affiliation, in dovetailing altruistic motivations with neural valuation systems in real-life ingroup behaviour.

The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.

The concept of left hemispheric dominance for praxis, speech, and language has been one of the pillars of neurology since the mid-19th century. In 1906, Hermann Oppenheim reported a patient with bilateral stereoagnosia (astereognosis) caused by a left parietal lobe tumor and proposed that the left hemisphere was also dominant for stereognosis. Surprisingly, few cases of bilateral stereoagnosia caused by a unilateral cerebral lesion have been documented in the literature since then. Here we report a 75-year-old right-handed man who developed bilateral stereoagnosia after suffering a small infarct in the crown of the left postcentral gyrus. He could not recognize objects with either hand, but retained the ability to localize stimuli applied to the palm of his left (ipsilesional) hand. He was severely disabled in ordinary activities requiring the use of his hands. The lesion corresponded to Brodmann area 1, where probabilistic anatomic, functional, and electrophysiologic studies have located one of the multiple somatosensory representations of the hand. The lesion was in a strategic position to interrupt both the processing of afferent tactile information issuing from the primary somatosensory cortex (areas 3a and 3b) and the forward higher-order processing in area 2, the secondary sensory cortex, and the contralateral area 1. The lesion also deprived the motor hand area of its afferent regulation from the sensory hand area (grasping), while leaving intact the visuomotor projections from the occipital cortex (reaching). Our patient supports Oppenheim's proposal that the left postcentral gyrus of some individuals is dominant for stereognosis.

A 45-year-old married woman with fits of episodic dyscontrol since an early age suffered a bilateral injury of the dorsolateral temporal lobe after which such episodes vanished for good. The remission of her lifelong proneness to aggression was so remarkable that her relatives and friends unanimously welcomed her "new personality". The post-traumatic taming in this case was an unanticipated collateral effect of brain damage with a salutary change of personality. This change possibly resulted from the release, due to the bitemporal injury, of inclinations that had not hitherto been fully expressed in the patient's mind and behavior due to the overriding influence of episodic dyscontrol on her ordinary conduct.

A large left hemisphere porencephalic cyst was incidentally found in a 48-year-old woman (MS) with a Diagnostic and Statistical Manual (DSM)-5 diagnosis of schizophrenia. The encephaloclastic characteristics of the cyst indicated that it was acquired between the 22nd and 24th gestational weeks, after the major waves of neuronal migration had tapered off. The cyst destroyed the left temporal and occipital lobes, and the inferior parietal lobule. Surprisingly, MS had no evidence of aphasia, alexia, agraphia, or ideational apraxia; in contrast, cognitive functions dependent on the integrity of the right hemisphere were severely impaired. To test the hypothesis that the development of language in MS took place at the expense of functions that are normally carried out by the right hemisphere, we investigated MS's correlates of oral comprehension with fMRI as a proxy for auditory comprehension and other cognitive functions strongly lateralized to the posterior left hemisphere, such as ideational praxis and reading. Comprehension of spoken language engaged the homologous of Wernicke's area in the right planum temporale. Porencephaly may represent a natural model of neuroplasticity supervening at predictable epochs of prenatal development.

Control over spinal and brainstem somatomotor neurons is exerted by two sets of descending fibers, corticospinal/pyramidal and extrapyramidal. Although in nonhuman primates the effect of bilateral pyramidal lesions is mostly limited to an impairment of the independent use of digits in skilled manual actions, similar injuries in humans result in the locked-in syndrome, a state of mutism and quadriplegia in which communication can be established only by residual vertical eye movements. This behavioral contrast makes humans appear to be outliers compared with other primates because of our almost total dependence on the corticospinal/pyramidal system for the effectuation of movement. Here we propose, instead, that an increasing preponderance of the corticospinal/pyramidal system over motor control is an expected consequence of increasing brain size in primates because of the faster scaling of the number of neurons in the primary motor cortex over the brainstem and spinal cord motor neuron pools, explaining the apparent uniqueness of the corticalization of motor control in humans., (© 2015 Wiley Periodicals, Inc.)

Broca coined the neologism "aphemia" to describe a syndrome consisting of a loss of the ability to speak without impairment of language and paralysis of the faciolingual territories in actions unrelated to speech, such as protruding the tongue or pursing the lips. Upon examining the brains of patients with aphemia, Broca concluded that the minimum possible lesion responsible for aphemia localized to the posterior left inferior frontal gyrus and lower portion of the middle frontal gyrus. A review of Broca's writings led us to conclude that (a) Broca localized speech, not language, to the left hemisphere, (b) Broca's aphemia is a form of apraxia, (c) Broca's aphemia is not, therefore, a terminological forerunner of aphasia, and (d) Broca was an outspoken equipotentialist concerning the cerebral localization of language. Broca's claim about the role of the left hemisphere in the organization of speech places him as the legitimate forebear of the two most outstanding achievements of Liepmann's work, namely, the concepts of apraxia and of a left hemisphere specialization for action.

Clinical psychopathology has largely ignored the developments in the field of social neuroscience. The so-called moral emotions are a group of affective experiences thought to promote cooperation, group cohesion, and reorganization. In this review, we: (i) briefly describe a provisional taxonomy of a limited set of moral emotions and their neural underpinnings; and (ii) discuss how disgust, guilt, anger/indignation, and shame/embarrassment can be conceptualized as key affective experiences in different neuropsychiatric disorders. Based on a concise review of the literature linking moral emotions, psychopathology, and neuropsychiatry, we have devised a simple and preliminary scheme where we conjecture how specific moral emotions can be implicated in some categories of DSM-5 diagnoses, potentially helping to bridge psychopathology and neurobiologically plausible variables, in line with the Research Domain Criteria initiative. We hope this stimulates new empirical work exploring how moral emotional changes and their underlying neurobiology can help elucidating the neural underpinnings of mental disorders.