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The Global ECT MRI Research Collaboration (GEMRIC) has collected clinical and neuroimaging data of patients treated with electroconvulsive therapy (ECT) from around the world. Results to date have focused on neuroimaging correlates of antidepressant response. GEMRIC sites have also collected longitudinal cognitive data. Here, we summarize the existing GEMRIC cognitive data and provide recommendations for prospective data collection for future ECT-imaging investigations. We describe the criteria for selection of cognitive measures for mega-analyses: Trail Making Test Parts A (TMT-A) and B (TMT-B), verbal fluency category (VFC), verbal fluency letter (VFL), and percent retention from verbal learning and memory tests. We performed longitudinal data analysis focused on the pre-/post-ECT assessments with healthy comparison (HC) subjects at similar timepoints and assessed associations between demographic and ECT parameters with cognitive changes. The study found an interaction between electrode placement and treatment number for VFC (F(1,107) = 4.14, p = 0.04). Higher treatment was associated with decreased VFC performance with right unilateral electrode placement. Percent retention showed a main effect for group, with post-hoc analysis indicating decreased cognitive performance among the HC group. However, there were no significant effects of group or group interactions observed for TMT-A, TMT-B, or VFL. We assessed the current GEMRIC cognitive data and acknowledge the limitations associated with this data set including the limited number of neuropsychological domains assessed. Aside from the VFC and treatment number relationship, we did not observe ECT-mediated neurocognitive effects in this investigation. We provide prospective cognitive recommendations for future ECT-imaging investigations focused on strong psychometrics and minimal burden to subjects., Competing Interests: Declaration of competing interest HBM part in educational events sponsored by Livanova and Rovi. RH has received consulting and speaker fees from Boehringer Ingelheim International GmbH, Janssen-Cilag GmbH and ROVI GmbH in the last three years. All other authors report no biomedical financial interests or potential conflicts of interest with this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This review addresses key findings on loneliness from the social, neurobiological and clinical fields. From a translational perspective, results from studies in humans and animals are included, with a focus on social interaction, mental and physical illness and the role of oxytocin in loneliness. In terms of social interactions, lonely individuals tend to exhibit a range of abnormal behaviors based on dysfunctional social cognitions that make it difficult for them to form meaningful relationships. Neurobiologically, a link has been established between loneliness and the hypothalamic peptide hormone oxytocin. Since social interactions and especially social touch regulate oxytocin signaling, lonely individuals may have an oxytocin imbalance, which in turn affects their health and well-being. Clinically, loneliness is a predictor of physical and mental illness and leads to increased morbidity and mortality. There is evidence that psychopathology is both a cause and a consequence of loneliness. The final section of this review summarizes the findings from social, neurobiological and clinical perspectives to present a new model of the complex construct of loneliness., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Humans hold social motives that are expressed in social preferences and influence how they evaluate and share payoffs. Established models in psychology and economics quantify social preferences such as general social value orientation, which captures people's tendency to be prosocial or individualistic. Prosocials further differ by how much they maximize joint gains or minimize inequality. Functional neuroimaging studies have linked increased amygdala activity in prosocials to payoff inequality between self and other. However, it is unclear whether amygdala lesions alter social motives. We used two tasks to test a patient with selective bilateral amygdala lesions and three healthy samples (a priori matched control sample N = 20, online sample N = 603, student sample N = 40), which allowed us to assess and model social motives across a relatively large number of participants. In a social value orientation task, the patient was categorized as prosocial and her social value orientation score did not differ from healthy participants. Importantly, the patient differed in prosocial motivation by maximizing joint gains rather than minimizing payoff inequality. In a joint payoff evaluation task, Bayesian model comparisons revealed that participants' evaluations were best described by models, which link participants' evaluations to the payoff magnitude and to inequality. Overall, amygdala lesions did not seem to alter general social value orientation but shifted prosocial motivation toward maximizing joint gains., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Generosity is an important behavior enriching human society and can be observed across cultures. However, generosity has been shown to be modulated as a function of social distance, also referred to as social discounting. Oxytocin and empathy are other factors that have been shown to play an important role in generous behavior. However, how exactly oxytocin and empathy impact social discounting is yet unknown. Here, we administered oxytocin or placebo in a double-blind design, and measured social discounting behavior. Additionally, individual differences in empathy were assessed. Our results show that the effect of oxytocin on generous behavior is modulated by trait empathy; only for those subjects who received oxytocin there was a positive correlation between individual trait empathy and their generous behavior towards close others., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

People with autism spectrum disorders (ASD) have pervasive impairments in social interactions, a diagnostic component that may have its roots in atypical social motivation and attention. One of the brain structures implicated in the social abnormalities seen in ASD is the amygdala. To further characterize the impairment of people with ASD in social attention, and to explore the possible role of the amygdala, we employed a series of visual search tasks with both social (faces and people with different postures, emotions, ages, and genders) and non-social stimuli (e.g., electronics, food, and utensils). We first conducted trial-wise analyses of fixation properties and elucidated visual search mechanisms. We found that an attentional mechanism of initial orientation could explain the detection advantage of non-social targets. We then zoomed into fixation-wise analyses. We defined target-relevant effects as the difference in the percentage of fixations that fell on target-congruent vs. target-incongruent items in the array. In Experiment 1, we tested 8 high-functioning adults with ASD, 3 adults with focal bilateral amygdala lesions, and 19 controls. Controls rapidly oriented to target-congruent items and showed a strong and sustained preference for fixating them. Strikingly, people with ASD oriented significantly less and more slowly to target-congruent items, an attentional deficit especially with social targets. By contrast, patients with amygdala lesions performed indistinguishably from controls. In Experiment 2, we recruited a different sample of 13 people with ASD and 8 healthy controls, and tested them on the same search arrays but with all array items equalized for low-level saliency. The results replicated those of Experiment 1. In Experiment 3, we recruited 13 people with ASD, 8 healthy controls, 3 amygdala lesion patients and another group of 11 controls and tested them on a simpler array. Here our group effect for ASD strongly diminished and all four subject groups showed similar target-relevant effects. These findings argue for an attentional deficit in ASD that is disproportionate for social stimuli, cannot be explained by low-level visual properties of the stimuli, and is more severe with high-load top-down task demands. Furthermore, this deficit appears to be independent of the amygdala, and not evident from general social bias independent of the target-directed search., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Evidence from animal studies suggests that the social attraction and bonding effects of the neuropeptide oxytocin (OXT) are mediated by its modulation of dopamine (DA) release in brain reward centers, but this has not yet been demonstrated in humans. DA release can be measured by positron emission tomography (PET) using the radioligand [11C]raclopride. Its binding to DA D2 receptors (D2R) is sensitive and reciprocally related to endogenous DA, especially in the striatum. In a randomized double-blind placebo-controlled within-subjects trial on 18 adult male volunteers we combined [11C]raclopride PET and a facial attractiveness rating task to establish whether intranasal OXT (24 IU) increased both the perceived attractiveness of unfamiliar female faces and striatal DA release compared with placebo administration. While our behavioral data confirmed that subjects rated unfamiliar female faces as more attractive following OXT treatment, and this correlated with an increased perfusion rate in the striatum, there was no evidence for altered [11C]raclopride binding in the striatum or pallidum. Instead under OXT we rather observed an increased [11C]raclopride binding and reduced perfusion rate in subregions of the right dorsomedial prefrontal gyrus and superior parietal gyrus. The absence of OXT effects on dopamine release and D2 receptors in brain reward centers, despite increased striatal activity, implies that the peptide may facilitate perceived attraction via non-dopaminergic actions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Prosody (i.e. speech melody) is an important cue to infer an interlocutor's emotional state, complementing information from face expression and body posture. Inferring fear from face expression is reported as impaired after amygdala lesions. It remains unclear whether this deficit is specific to face expression, or is a more global fear recognition deficit. Here, we report data from two twins with bilateral amygdala lesions due to Urbach-Wiethe syndrome and show they are unimpaired in a multinomial emotional prosody classification task. In a two-alternative forced choice task, they demonstrate increased ability to discriminate fearful and neutral prosody, the opposite of what would be expected under an hypothesis of a global role for the amygdala in fear recognition. Hence, we provide evidence that the amygdala is not required for recognition of fearful prosody., (© 2013 The Author. Published by Elsevier Ltd. All rights reserved.)

More than 5 million deaths a year are attributable to tobacco smoking, making it the largest single cause of preventable death worldwide. The primary addictive component in tobacco is nicotine. Its addictive power is exemplified by the fact that by far most attempts to quit smoking fail. It is therefore mandatory to understand the biological mechanisms by which nicotine leads to continued smoking despite its harmful consequences. While current research perspectives on nicotine addiction emphasize the contribution of reward-related mesocorticolimbic dopamine (DA) systems, the role of the amygdala remains less well characterized, although it is crucially engaged in the emotional and motivational modulation of cognition and behavior. Consequently, we here review brain imaging studies reporting altered neural responses of the amygdala in nicotine addiction. A major focus is placed upon resting-state and cue-induction studies documenting that nicotine addiction is associated with aberrant amygdala activity. Importantly, unprovoked abstinence-induced nicotine cravings have been shown to interfere with the amygdala's ability to detect and adequately respond to harm signals. In light of this empirical evidence, we propose that impaired amygdala-guided harm avoidance and executive functions may be instrumental in maintaining nicotine addiction despite serious health consequences., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The idea that the amygdala is crucially involved in automatically prioritising relevant events rests on evidence from a single lesion study where a patient with bilateral temporal lobe lesions, acquired in adulthood, was impaired in recall facilitation during the attentional blink. Here, in a comparable task, we show that two individuals with selective bilateral amygdala lesions retain facilitated recall of aversive words during the attentional blink. Recall facilitation was statistically significant for both patients and akin to that seen in young students and age- and education-matched controls. This challenges the amygdala's role as a crucial hub in prioritising attention and at a minimum implies that this role can be compensated for when lesions are acquired early in life. Previous findings might be explained by the described fact that lesions were acquired later in life and encompassed areas beyond the amygdala, including visual pathways. We propose that in the absence of a functioning amygdala, prioritised visual processing may rely on alternative structures such as pulvinar and cortical visual areas., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The use of functional MRI (fMRI) in combination with pharmacological challenges has increased exponentially in recent years, motivated by the idea not only to elucidate the neurochemical foundations of human emotional and cognitive faculties, but also to optimize human brain function in healthy individuals and identify novel drug targets, with the ultimate goal to design more specific pharmacological therapies for the various disorders of human emotion and cognition. In particular, emotional responding of the amygdala has become a central interest, and pharmacological fMRI has been used to specifically probe, and modulate, amygdala activation in response to facial expressions of emotion and emotionally laden scenes. This article reviews recent fMRI experiments manipulating the amygdala's physiological response to such stimuli by pharmacological means and lays a particular focus on monoaminergic, glutamatergic, GABAergic, and hormonal/peptidergic challenges., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Adaptive behavior in dynamic environments critically depends on the ability to learn rapidly and flexibly from the outcomes of prior choices. In social environments, facial expressions of emotion often serve as performance feedback and thereby guide declarative learning. Abundant evidence implicates beta-noradrenergic signaling in the modulatory influence of emotion on declarative learning. It is currently unclear whether a similar mechanism also mediates a guidance of declarative learning by social-emotional feedback administered in the form of facial expressions. We therefore conducted a double-blind randomized placebo-controlled trial to test the effects of a 40-mg single oral dose of the nonspecific beta-noradrenergic antagonist propranolol in a behavioral task that required gradual declarative learning of item-category associations from either social-emotional (happy vs. angry faces) or nonsocial (green vs. red color signals) trial-by-trial feedback. As predicted on the basis of our previous experiments, learning from social-emotional feedback was more effective than learning from nonsocial feedback in placebo-treated subjects. This advantage of social-emotional over nonsocial feedback was abolished by propranolol treatment. Propranolol had no effect on learning during the nonsocial feedback condition. Our findings suggest that a facilitation of declarative learning by social-emotional feedback critically involves signaling via beta-noradrenergic receptors., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

A paradigmatic example of an emotional bias in decision making is the framing effect, where the manner in which a choice is posed--as a potential loss or a potential gain--systematically biases an ensuing decision. Two fMRI studies have shown that the activation in the amygdala is modulated by the framing effect. Here, contrary to an expectation based on these studies, we show that two patients with Urbach-Wiethe (UW) disease, a rare condition associated with congenital, complete bilateral amygdala degeneration, exhibit an intact framing effect. However, choice preference in these patients did show a qualitatively distinct pattern compared to controls evident in an increased propensity to gamble, indicating that loss of amygdala function does exert an overall influence on risk-taking. These findings suggest either that amygdala does contribute to decision making but does not play a causal role in framing, or that UW is not a pure lesion model of amygdala function., (2010 Elsevier Ltd. All rights reserved.)

When presented in a neutral context, emotional items interfere with episodic encoding of temporally contiguous non-emotional items, resulting in dissociable valence-dependent retrograde and arousal-dependent anterograde modulatory effects. By studying two rare patients with congenital lipoid proteinosis (Urbach-Wiethe) and a focal disease emphasis on the basolateral amygdala (BLA), we demonstrate that this bidirectional modification of episodic encoding by emotion depends on the integrity of the amygdala, as both retrograde and anterograde modulatory effects are absent. Our findings implicate the amygdala in a neural circuitry that orchestrates rapid retrograde and anterograde regulation of episodic memory access upon criteria of behavioral significance.