Jorge Moll

YNICL Journal 2023 Journal Article

Self-blame-selective hyper-connectivity between anterior temporal and subgenual cortices predicts prognosis in major depressive disorder

• Diede Fennema
• Gareth J. Barker
• Owen O'Daly
• Suqian Duan
• Ewan Carr
• Kimberley Goldsmith
• Allan H. Young
• Jorge Moll

BACKGROUND: Self-blame-related fMRI measures were shown to predict subsequent recurrence in remitted major depressive disorder (MDD). Their role in current MDD, however, is unknown. We hypothesised that these neural signatures reflect a highly recurrent but remitting course of MDD and therefore predict favourable outcomes over a four-month follow-up period in current MDD. METHODS: Forty-five participants with current MDD and non-responders to at least two serotonergic antidepressants, were encouraged to optimise their medication and followed up after receiving four months of primary care treatment-as-usual. Prior to their medication review, participants completed an fMRI paradigm in which they viewed self- and other-blame emotion-evoking statements. Thirty-nine participants met pre-defined fMRI data minimum quality thresholds. Psychophysiological interaction analysis was used to determine baseline connectivity of the right superior anterior temporal lobe (RSATL), with an a priori BA25 region-of-interest for self-blaming vs other-blaming emotions, using Quick Inventory of Depressive Symptomatology (16-item) percentage change as a covariate. RESULTS: (39) = -0.32, p =.05). CONCLUSIONS: This study shows that neural signatures of overgeneralised self-blame are relevant for prognostic stratification of current treatment-resistant MDD. Future studies need to confirm whether this neural signature indeed represents a trait-like feature of a fully remitting subtype of MDD, or whether it is also modulated by depressive state and related to treatment effects.

YNICL Journal 2021 Journal Article

Internal reliability of blame-related functional MRI measures in major depressive disorder

• Diede Fennema
• Owen O'Daly
• Gareth J. Barker
• Jorge Moll
• Roland Zahn

BACKGROUND: In major depressive disorder (MDD), self-blame-related fMRI measures have shown the potential to be used as prognostic markers for recurrence risk. Like most potential fMRI markers, however, their reliability is unclear. Here, we probed the internal reliability of self-blame-related fMRI measures, as well as the impact of different modelling approaches on reliability metrics and validity. METHODS: Internal consistency (i.e. split-half reliability) was calculated for blood oxygen level-dependent (BOLD) responses and psychophysiological interactions (PPI) related to self-blame-related biases in medication-free remitted MDD participants (n = 81) and healthy controls (n = 41). Trial-length was modelled using three durations (0, 2 and 5 s), which was convolved with the haemodynamic response function (HRF) with and without time and dispersion derivatives. Intraclass correlation coefficients (ICCs) were calculated for simple contrasts examining activation to self-blaming emotions and other-blaming emotions and the more complex contrast of the subtraction-based difference between self- and other-blaming emotions within the following a priori ROIs: right superior anterior temporal lobe seed region, anterior subgenual cingulate cortex, posterior subgenual cortex and right striatum / pallidum. RESULTS: Across ROIs, we obtained fair reliability (ICC ≥ 0.40) for simple, but poor reliability (ICC < 0.40) for more complex fMRI measures related to self-blame. Despite this low internal consistency of complex measures at the individual level, we observed robust activation at the group-level, reproducing previously published results. CONCLUSIONS: While simple BOLD contrasts had fair reliability, previously employed PPI models had poor reliability and simple connectivity measures lacked predictive validity. This calls for the development of functional connectivity measures that strike a better balance between reliability and validity for future clinical applications, which require robust measures at the individual rather than group-level.

YNIMG Journal 2021 Journal Article

Multi‐band FMRI compromises detection of mesolimbic reward responses

• Tara Srirangarajan
• Leili Mortazavi
• Tiago Bortolini
• Jorge Moll
• Brian Knutson

Recent innovations in Functional Magnetic Resonance Imaging (FMRI) have sped data collection by enabling simultaneous scans of neural activity in multiple brain locations, but have these innovations come at a cost? In a meta-analysis and preregistered direct comparison of original data, we examined whether acquiring FMRI data with multi-band versus single-band scanning protocols might compromise detection of mesolimbic activity during reward processing. Meta-analytic results (n = 44 studies; cumulative n = 5005 subjects) indicated that relative to single-band scans, multi-band scans showed significantly decreased effect sizes for reward anticipation in the Nucleus Accumbens (NAcc) by more than half. Direct within-subject comparison of single-band versus multi-band scanning data (multi-band factors = 4 and 8; n = 12 subjects) acquired during repeated administration of the Monetary Incentive Delay task indicated that reductions in temporal signal-to-noise ratio could account for compromised detection of task-related responses in mesolimbic regions (i.e., the NAcc). Together, these findings imply that researchers should opt for single-band over multi-band scanning protocols when probing mesolimbic responses with FMRI. The findings also have implications for inferring mesolimbic activity during related tasks and rest, for summarizing historical results, and for using neuroimaging data to track individual differences in reward-related brain activity.

YNIMG Journal 2021 Journal Article

Striatal and septo-hypothalamic responses to anticipation and outcome of affiliative rewards

• Tiago Bortolini
• Bruno Melo
• Rodrigo Basilio
• Ronald Fischer
• Roland Zahn
• Ricardo de Oliveira-Souza
• Brian Knutson
• Jorge Moll

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.

YNICL Journal 2019 Journal Article

Blame-rebalance fMRI neurofeedback in major depressive disorder: A randomised proof-of-concept trial

• Roland Zahn
• Julie H. Weingartner
• Rodrigo Basilio
• Patricia Bado
• Paulo Mattos
• João R. Sato
• Ricardo de Oliveira-Souza
• Leo F. Fontenelle

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.

YNICL Journal 2019 Journal Article

Cortical lateralization of cheirosensory processing in callosal dysgenesis

• Myriam Monteiro
• Ricardo de Oliveira-Souza
• Juliana Andrade
• Theo Marins
• Erika de Carvalho Rodrigues
• Ivanei Bramati
• Roberto Lent
• Jorge Moll

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.

YNICL Journal 2018 Journal Article

Decoding moral emotions in obsessive-compulsive disorder

• Leonardo F. Fontenelle
• Ilana Frydman
• Sebastian Hoefle
• Ricardo Oliveira-Souza
• Paula Vigne
• Tiago S. Bortolini
• Chao Suo
• Murat Yücel

Background: Patients with obsessive-compulsive disorder (OCD) exhibit abnormal neural responses when they experience particular emotions or when they evaluate stimuli with emotional value. Whether these brain responses are sufficiently distinctive to discriminate between OCD patients and healthy controls is unknown. The present study is the first to investigate the discriminative power of multivariate pattern analysis of regional fMRI responses to moral and non-moral emotions. Method: analysis). Results: We found that different frontostriatal regions discriminated OCD patients from controls based on individual emotional experiences. Most notably, the left nucleus accumbens (NAcc) discriminated OCD patients from controls during both disgust and the multiemotion analysis. Among other regions, the angular gyrus responses to anger and the lingual and the middle temporal gyri in the multi-emotion analysis were highly discriminant between samples. Additional BOLD analyses supported the directionality of these findings. Conclusions: In line with previous studies, differential activity in regions beyond the frontostriatal circuitry differentiates OCD from healthy volunteers. The finding that the response of the left NAcc to different basic and moral emotions is highly discriminative for a diagnosis of OCD confirms current pathophysiological models and points to new venues of research.

YNICL Journal 2014 Journal Article

Enhanced subgenual cingulate response to altruistic decisions in remitted major depressive disorder

• Erdem Pulcu
• Roland Zahn
• Jorge Moll
• Paula D. Trotter
• Emma J. Thomas
• Gabriella Juhasz
• J.F.William Deakin
• Ian M. Anderson

BACKGROUND: Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. METHODS: Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. RESULTS: Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. CONCLUSIONS: We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called "warm glow" of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.

YNIMG Journal 2011 Journal Article

Impairment of prosocial sentiments is associated with frontopolar and septal damage in frontotemporal dementia

• Jorge Moll
• Roland Zahn
• Ricardo de Oliveira-Souza
• Ivanei E. Bramati
• Frank Krueger
• Bernardo Tura
• Alyson L. Cavanagh
• Jordan Grafman

Poets and philosophers have long acknowledged moral sentiments as key motivators of human social behavior. Prosocial sentiments, which include guilt, pity and embarrassment, enable us to care about others and to be concerned about our mistakes. Functional imaging studies have implicated frontopolar, ventromedial frontal and basal forebrain regions in the experience of prosocial sentiments. Patients with lesions of the frontopolar and ventromedial frontal areas were observed to behave inappropriately and less prosocially, which could be attributed to a generalized emotional blunting. Direct experimental evidence for brain regions distinctively associated with moral sentiment impairments is lacking, however. We investigated this issue in patients with the behavioral variant of frontotemporal dementia, a disorder in which early and selective impairments of social conduct are consistently observed. Using a novel moral sentiment task, we show that the degree of impairment of prosocial sentiments is associated with the degree of damage to frontopolar cortex and septal area, as assessed with 18-Fluoro-Deoxy-Glucose-Positron Emission Tomography, an established measure of neurodegenerative damage. This effect was dissociable from impairment of other-critical feelings (anger and disgust), which was in turn associated with dorsomedial prefrontal and amygdala dysfunction. Our findings suggest a critical role of the frontopolar cortex and septal region in enabling prosocial sentiments, a fundamental component of moral conscience.

YNIMG Journal 2010 Journal Article

Selective functional integration between anterior temporal and distinct fronto-mesolimbic regions during guilt and indignation

• Sophie Green
• Matthew A. Lambon Ralph
• Jorge Moll
• Emmanuel A. Stamatakis
• Jordan Grafman
• Roland Zahn

It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e. g. “critical” and “faultfinding”). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals.

YNIMG Journal 2008 Journal Article

Psychopathy as a disorder of the moral brain: Fronto-temporo-limbic grey matter reductions demonstrated by voxel-based morphometry

• Ricardo de Oliveira-Souza
• Robert D. Hare
• Ivanei E. Bramati
• Griselda J. Garrido
• Fátima Azevedo Ignácio
• Fernanda Tovar-Moll
• Jorge Moll

Major advances have been made in the understanding of the neurobiology of psychopathy in the past years, yet the distribution and extent of neuroanatomical abnormalities underlying the disorder are still poorly known. It is also unclear if different dimensions of the construct of psychopathy (e. g. , emotional callousness, antisocial behavior) correspond to structural abnormalities in distinct regions of the brain. We tested the following hypotheses: (1) psychopathy is related to grey matter reductions in regions of the brain that underlie moral conduct and (2) the severity of psychopathy is related to the degree of structural abnormalities. Optimized voxel-based morphometry and the screening version of the Psychopathy Checklist (PCL: SV) were employed to investigate a matched sample of 15 community psychiatric patients with high PCL: SV scores, and 15 healthy normal volunteers. The analyses controlled for total grey matter, white matter and cerebrospinal fluid volumes. Grey matter reductions were observed in the frontopolar, orbitofrontal and anterior temporal cortices, superior temporal sulcus region, and insula of the patients. The degree of structural abnormalities was significantly related to the interpersonal/affective dimension of psychopathy. The pattern of grey matter reductions in patients with high psychopathy scores comprised a distributed fronto-temporal network which plays a critical role in moral sensibility and behavior.

YNIMG Journal 2002 Journal Article

Functional Networks in Emotional Moral and Nonmoral Social Judgments

• Jorge Moll
• Ricardo de Oliveira-Souza
• Ivanei E. Bramati
• Jordan Grafman

Reading daily newspaper articles often evokes opinions and social judgments about the characters and stories. Social and moral judgments rely on the proper functioning of neural circuits concerned with complex cognitive and emotional processes. To examine whether dissociable neural systems mediate emotionally charged moral and nonmoral social judgments, we used a visual sentence verification task in conjunction with functional magnetic resonance imaging (fMRI). We found that a network comprising the medial orbitofrontal cortex, the temporal pole and the superior temporal sulcus of the left hemisphere was specifically activated by moral judgments. In contrast, judgment of emotionally evocative, but non-moral statements activated the left amygdala, lingual gyri, and the lateral orbital gyrus. These findings provide new evidence that the orbitofrontal cortex has dedicated subregions specialized in processing specific forms of social behavior.

YNIMG Journal 2001 Journal Article

Dissociable brain networks subserving social apperception and emotion

• Jorge Moll
• Ricardo Oliveira-Souza
• Janaína Mouräo-Miranda
• Ivanei Bramati
• Fernanda Tovar Moll
• Alexandre Roque Henrique
• Luiz Pessoa
• Pedro Angelo Andreiuolo

YNIMG Journal 2000 Journal Article

Functional MRI of cognitive set-shifting using an oral version of the trail making test

• Jorge Moll
• Ricardo de Oliveira-Souza
• Ivanei Edson Bramati
• Flávia Paes
• Fernando Cimini Cunha
• Marcus Vinicius Adriano