Professional Education

  • PhD, University of Cambridge, Experimental Psychology (2017)
  • MSc, Vita-Salute San Raffaele University, Cognitive Neuroscience (2012)
  • BA, Vita-Salute San Raffaele University, Psychology (2010)

Stanford Advisors

All Publications

  • Compulsivity is linked to reduced adolescent development of goal-directed control and frontostriatal functional connectivity. Proceedings of the National Academy of Sciences of the United States of America Vaghi, M. M., Moutoussis, M. n., Váša, F. n., Kievit, R. A., Hauser, T. U., Vértes, P. E., Shahar, N. n., Romero-Garcia, R. n., Kitzbichler, M. G., Bullmore, E. T., Dolan, R. J. 2020


    A characteristic of adaptive behavior is its goal-directed nature. An ability to act in a goal-directed manner is progressively refined during development, but this refinement can be impacted by the emergence of psychiatric disorders. Disorders of compulsivity have been framed computationally as a deficit in model-based control, and have been linked also to abnormal frontostriatal connectivity. However, the developmental trajectory of model-based control, including an interplay between its maturation and an emergence of compulsivity, has not been characterized. Availing of a large sample of healthy adolescents (n = 569) aged 14 to 24 y, we show behaviorally that over the course of adolescence there is a within-person increase in model-based control, and this is more pronounced in younger participants. Using a bivariate latent change score model, we provide evidence that the presence of higher compulsivity traits is associated with an atypical profile of this developmental maturation in model-based control. Resting-state fMRI data from a subset of the behaviorally assessed subjects (n = 230) revealed that compulsivity is associated with a less pronounced change of within-subject developmental remodeling of functional connectivity, specifically between the striatum and a frontoparietal network. Thus, in an otherwise clinically healthy population sample, in early development, individual differences in compulsivity are linked to the developmental trajectory of model-based control and a remodeling of frontostriatal connectivity.

    View details for DOI 10.1073/pnas.1922273117

    View details for PubMedID 32989168

  • Obsessive-Compulsive Disorder: Puzzles and Prospects NEURON Robbins, T. W., Vaghi, M. M., Banca, P. 2019; 102 (1): 27–47


    Obsessive-compulsive disorder is a severe and disabling psychiatric disorder that presents several challenges for neuroscience. Recent advances in its genetic and developmental causation, as well as its neuropsychological basis, are reviewed. Hypotheses concerning an imbalance between goal-directed and habitual behavior together with neural correlates in cortico-striatal circuitry are evaluated and contrasted with metacognitive theories. Treatments for obsessive-compulsive disorder (OCD) tend to be of mixed efficacy but include psychological, pharmacological, and surgical approaches, the underlying mechanisms of which are still under debate. Overall, the prospects for new animal models and an integrated understanding of the pathophysiology of OCD are considered in the context of dimensional psychiatry.

    View details for DOI 10.1016/j.neuron.2019.01.046

    View details for Web of Science ID 000463337900009

    View details for PubMedID 30946823

  • Action-Outcome Knowledge Dissociates From Behavior in Obsessive-Compulsive Disorder Following Contingency Degradation BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING Vaghi, M. M., Cardinal, R. N., Apergis-Schoute, A. M., Fineberg, N. A., Sule, A., Robbins, T. W. 2019; 4 (2): 200–209


    In obsessive-compulsive disorder (OCD), actions persist despite being inappropriate to the situation and without relationship to the overall goal. Dysfunctional beliefs have traditionally been postulated to underlie this condition. More recently, OCD has been characterized in terms of an imbalance between the goal-directed and the habit systems. To test these competing hypotheses, we used a novel experimental task designed to test subjective action-outcome knowledge of the effectiveness of actions (i.e., instrumental contingency), together with the balance between goal-directed and habitual responding.Twenty-seven patients with OCD and 27 healthy control subjects were tested on a novel task involving the degradation of an action-outcome contingency. Sensitivity to instrumental contingency and the extent to which explicitly reported action-outcome knowledge guided behavior were probed by measuring response rate and subjectively reported judgments.Patients with OCD responded more than healthy control subjects in situations in which an action was less causally related to obtaining an outcome. However, patients showed intact explicit action-outcome knowledge, as assessed by self-report. In patients, the relationship between causality judgment and responding was altered; therefore, their actions were dissociated from explicit action-outcome knowledge.These findings indicate reduced sensitivity to instrumental contingency in OCD, reinforcing the notion of a deficient goal-directed system in this disorder. By showing a dissociation between subjectively reported action-outcome knowledge and behavior, the data provide experimental evidence for the ego-dystonic nature of OCD.

    View details for DOI 10.1016/j.bpsc.2018.09.014

    View details for Web of Science ID 000494386400012

    View details for PubMedID 30545754

    View details for PubMedCentralID PMC6374986

  • Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING Vaghi, M. M., Hampshire, A., Fineberg, N. A., Kaser, M., Bruehl, A. B., Sahakian, B. J., Chamberlain, S. R., Robbins, T. W. 2017; 2 (8): 655–63


    The symptoms of obsessive-compulsive disorder (OCD) have been postulated to result from impaired executive functioning and excessive habit formation at the expense of goal-directed control and have been objectively demonstrated using neuropsychological tests in such patients. This study tested whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in patients with OCD and in their unaffected first-degree relatives.In total, 21 comorbidity-free patients with OCD, 19 clinically asymptomatic first-degree relatives of these patients, and 20 control participants were tested on a functional magnetic resonance optimized version of the Tower of London task. Group differences in brain activation during goal-directed planning were measured together with associated frontostriatal functional connectivity.Patients with OCD and their clinically asymptomatic relatives manifested hypoactivation of the right dorsolateral prefrontal cortex during goal-directed planning coupled with reduced functional connectivity between this cortical region and the basal ganglia (putamen).Hypoactivation of cortical regions associated with goal-directed planning and associated frontostriatal dysconnectivity represent a candidate endophenotype for OCD. These findings accord with abnormalities in neural networks supporting the balance between goal-directed and habitual behavior, with implications for recent neuropsychological theories of OCD and the major neurobiological model for this disorder.

    View details for DOI 10.1016/j.bpsc.2017.05.005

    View details for Web of Science ID 000493955300004

    View details for PubMedID 29167834

    View details for PubMedCentralID PMC5684958

  • Compulsivity Reveals a Novel Dissociation between Action and Confidence NEURON Vaghi, M. M., Luyckx, F., Sule, A., Fineberg, N. A., Robbins, T. W., De Martino, B. 2017; 96 (2): 348-+


    Confidence and actions are normally tightly interwoven-if I am sure that it is going to rain, I will take an umbrella-therefore, it is difficult to understand their interplay. Stimulated by the ego-dystonic nature of obsessive-compulsive disorder (OCD), where compulsive actions are recognized as disproportionate, we hypothesized that action and confidence might be independently updated during learning. Participants completed a predictive-inference task designed to identify how action and confidence evolve in response to surprising changes in the environment. While OCD patients (like controls) correctly updated their confidence according to changes in the environment, their actions (unlike those of controls) mostly disregarded this knowledge. Therefore, OCD patients develop an accurate, internal model of the environment but fail to use it to guide behavior. Results demonstrated a novel dissociation between confidence and action, suggesting a cognitive architecture whereby confidence estimates can accurately track the statistic of the environment independently from performance.

    View details for DOI 10.1016/j.neuron.2017.09.006

    View details for Web of Science ID 000412767600014

    View details for PubMedID 28965997

    View details for PubMedCentralID PMC5643443

  • Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity BIOLOGICAL PSYCHIATRY Vaghi, M. M., Vertes, P. E., Kitzbichler, M. G., Apergis-Schoute, A. M., van der Flier, F. E., Fineberg, N. A., Sule, A., Zaman, R., Voon, V., Kundu, P., Bullmore, E. T., Robbins, T. W. 2017; 81 (8): 708–17


    A recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity.Multiecho resting-state acquisition, combined with micromovement correction by blood oxygen level-dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects. We measured cognitive flexibility (attentional set-shifting) and goal-directed performance (planning of sequential response sequences) by means of well-validated, standardized behavioral cognitive paradigms. Functional connectivity strength of striatal seed regions was related to cognitive flexibility and goal-directed performance. To gain insights into fundamental network alterations, graph theoretical models of brain networks were derived.Reduced functional connectivity between the caudate and the ventrolateral prefrontal cortex was selectively associated with reduced cognitive flexibility. In contrast, goal-directed performance was selectively related to reduced functional connectivity between the putamen and the dorsolateral prefrontal cortex in OCD patients, as well as to symptom severity. Whole-brain data-driven graph theoretical analysis disclosed that striatal regions constitute a cohesive module of the community structure of the functional connectome in OCD patients as nodes within the basal ganglia and cerebellum were more strongly connected to one another than in healthy control subjects.These data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable frontostriatal circuits and those cognitive processes underlying OCD symptoms.

    View details for DOI 10.1016/j.biopsych.2016.08.009

    View details for Web of Science ID 000397300800014

    View details for PubMedID 27769568

    View details for PubMedCentralID PMC6020061

  • Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder. Journal of child psychology and psychiatry, and allied disciplines Marzuki, A. A., Vaghi, M. M., Conway-Morris, A., Kaser, M., Sule, A., Apergis-Schoute, A., Sahakian, B. J., Robbins, T. W. 2022


    BACKGROUND: Computational research had determined that adults with obsessive-compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients' compulsions despite the knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD.METHODS: Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects' actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence-action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication.RESULTS: Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients' confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem.CONCLUSIONS: Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing 'just-right' compulsions, enhanced error-related negativity, and greater decision uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adult OCD research.

    View details for DOI 10.1111/jcpp.13628

    View details for PubMedID 35537441

  • Preference uncertainty accounts for developmental effects on susceptibility to peer influence in adolescence. Nature communications Reiter, A. M., Moutoussis, M., Vanes, L., Kievit, R., Bullmore, E. T., Goodyer, I. M., Fonagy, P., Jones, P. B., NSPN Consortium, Dolan, R. J., Bullmore, E., Bullmore, E., Dolan, R., Goodyer, I., Jones, P., Hauser, T., Neufeld, S., Romero-Garcia, R., Clair, M. S., Vertes, P., Whitaker, K., Inkster, B., Prabhu, G., Ooi, C., Toseeb, U., Widmer, B., Bhatti, J., Villis, L., Alrumaithi, A., Birt, S., Bowler, A., Cleridou, K., Dadabhoy, H., Davies, E., Firkins, A., Granville, S., Harding, E., Hopkins, A., Isaacs, D., King, J., Kokorikou, D., Maurice, C., McIntosh, C., Memarzia, J., Mills, H., O'Donnell, C., Pantaleone, S., Scott, J., Vaghi, M., van Harmelen, A., Reiter, A. 2021; 12 (1): 3823


    Adolescents are prone to social influence from peers, with implications for development, both adaptive and maladaptive. Here, using a computer-based paradigm, we replicate a cross-sectional effect of more susceptibility to peer influence in a large dataset of adolescents 14 to 24 years old. Crucially, we extend this finding by adopting a longitudinal perspective, showing that a within-person susceptibility to social influence decreases over a 1.5 year follow-up time period. Exploiting this longitudinal design, we show that susceptibility to social influences at baseline predicts an improvement in peer relations over the follow-up period. Using a Bayesian computational model, we demonstratethat in younger adolescents a greater tendency to adopt others' preferences arises out of a higher uncertainty about their own preferences in the paradigmatic case of delay discounting (a phenomenon called 'preference uncertainty'). This preference uncertainty decreases over time and, in turn, leads to a reduced susceptibility of one's own behaviour to an influence from others. Neuro-developmentally, we show that a measure of myelination within medial prefrontal cortex, estimated at baseline, predicts a developmental decrease in preference uncertainty at follow-up. Thus, using computational and neural evidence, we reveal adaptive mechanisms underpinning susceptibility to social influence during adolescence.

    View details for DOI 10.1038/s41467-021-23671-2

    View details for PubMedID 34158482

  • Set-shifting-related basal ganglia deformation as a novel familial marker of obsessive-compulsive disorder. The British journal of psychiatry : the journal of mental science Isobe, M., Vaghi, M., Fineberg, N. A., Apergis-Schoute, A. M., Bullmore, E. T., Sahakian, B. J., Robbins, T. W., Chamberlain, S. R. 1800: 1-4


    The symptoms of obsessive-compulsive disorder (OCD) are suggestive of cognitive rigidity, and previous work identified impaired flexible responding on set-shifting tasks in such patients. The basal ganglia are central to habit learning and are thought to be abnormal in OCD, contributing to inflexible, rigid habitual patterns of behaviour. Here, we demonstrate that increased cognitive inflexibility, indexed by poor performance on the set-shifting task, correlated with putamen morphology, and that patients and their asymptomatic relatives had common curvature abnormalities within this same structure. The association between the structure of the putamen and the extradimensional errors was found to be significantly familial in OCD proband-relative pairs. The data implicate changes in basal ganglia structure linked to cognitive inflexibility as a familial marker of OCD. This may reflect a predisposing heightened propensity toward habitual response patterns and deficits in goal-directed planning.

    View details for DOI 10.1192/bjp.2021.45

    View details for PubMedID 35049465

  • Cognitive Inflexibility in OCD and Related Disorders. Current topics in behavioral neurosciences Chamberlain, S. R., Solly, J. E., Hook, R. W., Vaghi, M. M., Robbins, T. W. 2021


    Cognitive inflexibility is suggested by the hallmark symptoms of obsessive-compulsive disorder (OCD), namely the occurrence of repetitive thoughts and/or behaviours that persist despite being functionally impairing and egodystonic to the individual. As well as being implied by the top-level symptoms, cognitive inflexibility in OCD, and some related conditions, has also been objectively quantified in case-control studies using computerised cognitive tasks. This chapter begins by considering the objective measurement of different aspects of cognitive flexibility using neuropsychological paradigms, with a focus on neural and neurochemical substrates. It moves on to conduct a systematic review and meta-analysis of findings from a widely deployed flexibility task: the Intra-Dimensional/Extra-Dimensional Set-Shift Task (IDED). By pooling data from 11 studies (335 OCD patients and 311 controls), we show that Extra-Dimensional (ED) shift deficits are a robust and reproducible finding (effect size medium-large) in OCD across the literature, and that this deficit is not attributable to group differences in age or IQ. The OCD ED deficit is then discussed in terms of dysfunction of fronto-striatal pathways (as exemplified, for example, by functional connectivity data), and the putative role of different neurotransmitters. We consider evidence that impaired ED shifting constitutes a candidate vulnerability marker (or 'endophenotype') for OCD. Theavailable literature is then surveyed as to ED findings in other obsessive-compulsive (OC) related disorders (e.g. hoarding, body-dysmorphic disorder, and trichotillomania), as well as in non-OC disorders (schizophrenia and anxiety symptoms in general). Lastly, we consider more recent, emerging developments in the quantification of compulsivity using cognitive tasks and questionnaires, as well as key directions for future research, including the need to refine compulsivity and its composite cognitive processes.

    View details for DOI 10.1007/7854_2020_198

    View details for PubMedID 33547598

  • Reduced Glutamate Turnover in the Putamen Is Linked With Automatic Habits in Human Cocaine Addiction. Biological psychiatry Ersche, K. D., Lim, T. V., Murley, A. G., Rua, C., Vaghi, M. M., White, T. L., Williams, G. B., Robbins, T. W. 2020


    BACKGROUND: The balance between goal-directed behavior and habits has been hypothesized to be biased toward the latter in individuals with cocaine use disorder (CUD), suggesting possible neurochemical changes in the putamen, which may contribute to their compulsive behavior.METHODS: We assessed habitual behavior in 48 patients with CUD and 42 healthy control participants using a contingency degradation paradigm and the Creature of Habit Scale. In a subgroup of this sample (CUD: n= 21; control participants: n= 22), we also measured glutamate and glutamine concentrations in the left putamen using ultra-high-field (7T) magnetic resonance spectroscopy. We hypothesized that increased habitual tendencies in patients with CUD would be associated with abnormal glutamatergic metabolites in the putamen.RESULTS: Compared with their non-drug-using peers, patients with CUD exhibited greater habitual tendencies during contingency degradation, which correlated with increased levels of self-reported daily habits. We further identified a significant reduction in glutamate concentration and glutamate turnover (glutamate-to-glutamine ratio) in the putamen in patients with CUD, which was significantly related to the level of self-reported daily habits.CONCLUSIONS: Patients with CUD exhibit enhanced habitual behavior, as assessed both by questionnaire and by a laboratory paradigm of contingency degradation. This automatic habitual tendency is related to a reduced glutamate turnover in the putamen, suggesting a dysregulation of habits caused by chronic cocaine use.

    View details for DOI 10.1016/j.biopsych.2020.12.009

    View details for PubMedID 33581835

  • Experimentally induced and real-world anxiety have no demonstrable effect on goal-directed behaviour. Psychological medicine Gillan, C. M., Vaghi, M. M., Hezemans, F. H., van Ghesel Grothe, S., Dafflon, J., Brühl, A. B., Savulich, G., Robbins, T. W. 2020: 1-12


    Goal-directed control guides optimal decision-making and it is an important cognitive faculty that protects against developing habits. Previous studies have found some evidence of goal-directed deficits when healthy individuals are stressed, and in psychiatric conditions characterised by compulsive behaviours and anxiety. Here, we tested if goal-directed control is affected by state anxiety, which might explain the former results.We carried out a causal test of this hypothesis in two experiments (between-subject N = 88; within-subject N = 50) that used the inhalation of hypercapnic gas (7.5% CO2) to induce an acute state of anxiety in healthy volunteers. In a third experiment (N = 1413), we used a correlational design to test if real-life anxiety-provoking events (panic attacks, stressful events) are associated with impaired goal-directed control.In the former two causal experiments, we induced a profoundly anxious state, both physiologically and psychologically, but this did not affect goal-directed performance. In the third, correlational, study, we found no evidence for an association between goal-directed control, panic attacks or stressful life eventsover and above variance accounted for by trait differences in compulsivity.In sum, three complementary experiments found no evidence that anxiety impairs goal-directed control in human subjects.

    View details for DOI 10.1017/S0033291720000203

    View details for PubMedID 32114998

  • Conservative and disruptive modes of adolescent change in human brain functional connectivity PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vasa, F., Romero-Garcia, R., Kitzbichler, M. G., Seidlitz, J., Whitaker, K. J., Vaghi, M. M., Kundu, P., Patel, A. X., Fonagy, P., Dolan, R. J., Jones, P. B., Goodyer, I. M., Vertes, P. E., Bullmore, E. T., NSPN Consortium 2020; 117 (6): 3248–53


    Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: "conservative" and "disruptive." Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman's correlation between edgewise baseline FC (at 14 y, [Formula: see text]) and adolescent change in FC ([Formula: see text]), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas.

    View details for DOI 10.1073/pnas.1906144117

    View details for Web of Science ID 000513898000068

    View details for PubMedID 31992644

    View details for PubMedCentralID PMC7022153

  • Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes. Biological psychiatry Romero-Garcia, R., Seidlitz, J., Whitaker, K. J., Morgan, S. E., Fonagy, P., Dolan, R. J., Jones, P. B., Goodyer, I. M., Suckling, J., NSPN Consortium, Vertes, P. E., Bullmore, E. T., Bullmore, E., Dolan, R., Goodyer, I., Fonagy, P., Jones, P., Vaghi, M., Moutoussis, M., Hauser, T., Neufeld, S., Romero-Garcia, R., St Clair, M., Whitaker, K., Inkster, B., Prabhu, G., Ooi, C., Toseeb, U., Widmer, B., Bhatti, J., Villis, L., Alrumaithi, A., Birt, S., Bowler, A., Cleridou, K., Dadabhoy, H., Davies, E., Firkins, A., Granville, S., Harding, E., Hopkins, A., Isaacs, D., King, J., Kokorikou, D., Maurice, C., McIntosh, C., Memarzia, J., Mills, H., O'Donnell, C., Pantaleone, S., Scott, J., Fearon, P., Suckling, J., Harmelen, A. v., Kievit, R., Vertes, P. 2019


    BACKGROUND: Genetic risk is thought to drive clinical variation on a spectrum of schizophrenia-like traits, but the underlying changes in brain structure that mechanistically link genomic variation to schizotypal experience and behavior are unclear.METHODS: We assessed schizotypy using a self-reported questionnaire and measured magnetization transfer as a putative microstructural magnetic resonance imaging marker of intracortical myelination in 68 brain regions in 248 healthy young people (14-25 years of age). We used normative adult brain gene expression data and partial least squares analysis to find the weighted gene expression pattern that was most colocated with the cortical map of schizotypy-related magnetization.RESULTS: Magnetization was significantly correlated with schizotypy in the bilateral posterior cingulate cortex and precuneus (and for disorganized schizotypy, also in medial prefrontal cortex; all false discovery rate-corrected ps<.05), which are regions of the default mode network specialized for social and memory functions. The genes most positively weighted on the whole-genome expression map colocated with schizotypy-related magnetization were enriched for genes that were significantly downregulated in two prior case-control histological studies of brain gene expression in schizophrenia. Conversely, the most negatively weighted genes were enriched for genes that were transcriptionally upregulated in schizophrenia. Positively weighted (downregulated) genes were enriched for neuronal, specifically interneuronal, affiliations and coded a network of proteins comprising a few highly interactive "hubs" such as parvalbumin and calmodulin.CONCLUSIONS: Microstructural magnetic resonance imaging maps of intracortical magnetization can be linked to both the behavioral traits of schizotypy and prior histological data on dysregulated gene expression in schizophrenia.

    View details for DOI 10.1016/j.biopsych.2019.12.005

    View details for PubMedID 32029217

  • Brain-behaviour modes of covariation in healthy and clinically depressed young people SCIENTIFIC REPORTS Mihalik, A., Ferreira, F. S., Rosa, M. J., Moutoussis, M., Ziegler, G., Monteiro, J. M., Portugal, L., Adams, R. A., Romero-Garcia, R., Vertes, P. E., Kitzbichler, M. G., Vasa, F., Vaghi, M. M., Bullmore, E. T., Fonagy, P., Goodyer, I. M., Jones, P. B., Hauser, T., Neufeld, S., St Clair, M., Whitaker, K., Inkster, B., Prabhu, G., Ooi, C., Toseeb, U., Widmer, B., Bhatti, J., Villis, L., Alrumaithi, A., Birt, S., Bowler, A., Cleridou, K., Dadabhoy, H., Davies, E., Firkins, A., Granville, S., Harding, E., Hopkins, A., Isaacs, D., King, J., Kokorikou, D., Maurice, C., McIntosh, C., Memarzia, J., Mills, H., O'Donnell, C., Pantaleone, S., Scott, J., Fearon, P., Suckling, J., van Harmelen, A., Kievit, R., Dolan, R., Mourao-Miranda, J., NSPN Consortium 2019; 9: 11536


    Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14-24 y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.

    View details for DOI 10.1038/s41598-019-47277-3

    View details for Web of Science ID 000479187800042

    View details for PubMedID 31395894

    View details for PubMedCentralID PMC6687746

  • Impaired awareness of action-outcome contingency and causality during healthy ageing and following ventromedial prefrontal cortex lesions NEUROPSYCHOLOGIA O'Callaghan, C., Vaghi, M. M., Brummerloh, B., Cardinal, R. N., Robbins, T. W. 2019; 128: 282–89


    Detecting causal relationships between actions and their outcomes is fundamental to guiding goal-directed behaviour. The ventromedial prefrontal cortex (vmPFC) has been extensively implicated in computing these environmental contingencies, via animal lesion models and human neuroimaging. However, whether the vmPFC is critical for contingency learning, and whether it can occur without subjective awareness of those contingencies, has not been established. To address this, we measured response adaption to contingency and subjective awareness of action-outcome relationships in individuals with vmPFC lesions and healthy elderly subjects. We showed that in both vmPFC damage and ageing, successful behavioural adaptation to variations in action-outcome contingencies was maintained, but subjective awareness of these contingencies was reduced. These results highlight two contexts where performance and awareness have been dissociated, and show that learning response-outcome contingencies to guide behaviour can occur without subjective awareness. Preserved responding in the vmPFC group suggests that this region is not critical for computing action-outcome contingencies to guide behaviour. In contrast, our findings highlight a critical role for the vmPFC in supporting awareness, or metacognitive ability, during learning. We further advance the hypothesis that responding to changing environmental contingencies, whilst simultaneously maintaining conscious awareness of those statistical regularities, is a form of dual-tasking that is impaired in ageing due to reduced prefrontal function.

    View details for DOI 10.1016/j.neuropsychologia.2018.01.021

    View details for Web of Science ID 000493910900034

    View details for PubMedID 29355648

    View details for PubMedCentralID PMC6562272

  • Sentential negation of abstract and concrete conceptual categories: a brain decoding multivariate pattern analysis study PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Ghio, M., Haeger, K., Vaghi, M. M., Tettamanti, M. 2018; 373 (1752)


    We rarely use abstract and concrete concepts in isolation but rather embedded within a linguistic context. To examine the modulatory impact of the linguistic context on conceptual processing, we isolated the case of sentential negation polarity, in which an interaction occurs between the syntactic operator not and conceptual information in the negation's scope. Previous studies suggested that sentential negation of concrete action-related concepts modulates activation in the fronto-parieto-temporal action representation network. In this functional magnetic resonance imaging study, we examined the influence of negation on a wider spectrum of meanings, by factorially manipulating sentence polarity (affirmative, negative) and fine-grained abstract (mental state, emotion, mathematics) and concrete (related to mouth, hand, leg actions) conceptual categories. We adopted a multivariate pattern analysis approach, and tested the accuracy of a machine learning classifier in discriminating brain activation patterns associated to the factorial manipulation. Searchlight analysis was used to localize the discriminating patterns. Overall, the neural processing of affirmative and negative sentences with either an abstract or concrete content could be accurately predicted by means of multivariate classification. We suggest that sentential negation polarity modulates brain activation in distributed representational semantic networks, through the functional mediation of syntactic and cognitive control systems.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.

    View details for DOI 10.1098/rstb.2017.0124

    View details for Web of Science ID 000435534700003

    View details for PubMedID 29914992

    View details for PubMedCentralID PMC6015826

  • Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY Fineberg, N. A., Apergis-Schoute, A. M., Vaghi, M. M., Banca, P., Gillan, C. M., Voon, V., Chamberlain, S. R., Cinosi, E., Reid, J., Shahper, S., Bullmore, E. T., Sahakian, B. J., Robbins, T. W. 2018; 21 (1): 42–58


    Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder.

    View details for DOI 10.1093/ijnp/pyx088

    View details for Web of Science ID 000423311100006

    View details for PubMedID 29036632

    View details for PubMedCentralID PMC5795357

  • Effective connectivity gateways to the Theory of Mind network in processing communicative intention NEUROIMAGE Tettamanti, M., Vaghi, M. M., Bara, B. G., Cappa, S. F., Enrici, I., Adenzato, M. 2017; 155: 169–76


    An Intention Processing Network (IPN), involving the medial prefrontal cortex, precuneus, bilateral posterior superior temporal sulcus, and temporoparietal junctions, plays a fundamental role in comprehending intentions underlying action goals. In a previous fMRI study, we showed that, depending on the linguistic or extralinguistic (gestural) modality used to convey the intention, the IPN is complemented by activation of additional brain areas, reflecting distinct modality-specific input gateways to the IPN. These areas involve, for the linguistic modality, the left inferior frontal gyrus (LIFG), and for the extralinguistic modality, the right inferior frontal gyrus (RIFG). Here, we tested the modality-specific gateway hypothesis, by using DCM to measure inter-regional functional integration dynamics between the IPN and LIFG/RIFG gateways. We found strong evidence of a well-defined effective connectivity architecture mediating the functional integration between the IPN and the inferior frontal cortices. The connectivity dynamics indicate a modality-specific propagation of stimulus information from LIFG to IPN for the linguistic modality, and from RIFG to IPN for the extralinguistic modality. Thus, we suggest a functional model in which the modality-specific gateways mediate the structural and semantic decoding of the stimuli, and allow for the modality-specific communicative information to be integrated in Theory of Mind inferences elaborated through the IPN.

    View details for DOI 10.1016/j.neuroimage.2017.04.050

    View details for Web of Science ID 000405460900014

    View details for PubMedID 28438665

  • Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry Bandelow, B. n., Baldwin, D. n., Abelli, M. n., Bolea-Alamanac, B. n., Bourin, M. n., Chamberlain, S. R., Cinosi, E. n., Davies, S. n., Domschke, K. n., Fineberg, N. n., Grünblatt, E. n., Jarema, M. n., Kim, Y. K., Maron, E. n., Masdrakis, V. n., Mikova, O. n., Nutt, D. n., Pallanti, S. n., Pini, S. n., Ströhle, A. n., Thibaut, F. n., Vaghi, M. M., Won, E. n., Wedekind, D. n., Wichniak, A. n., Woolley, J. n., Zwanzger, P. n., Riederer, P. n. 2017; 18 (3): 162–214


    Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD).Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network.The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO2 hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics.Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.

    View details for DOI 10.1080/15622975.2016.1190867

    View details for PubMedID 27419272

    View details for PubMedCentralID PMC5341771

  • Biological markers for anxiety disorders, OCD and PTSD - a consensus statement. Part I: Neuroimaging and genetics WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY Bandelow, B., Baldwin, D., Abelli, M., Altamura, C., Dell'Osso, B., Domschke, K., Fineberg, N. A., Gruenblatt, E., Jarema, M., Maron, E., Nutt, D., Pini, S., Vaghi, M. M., Wichniak, A., Zai, G., Riederer, P. 2016; 17 (5): 321–65


    Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network.The present article (Part I) summarises findings on potential biomarkers in neuroimaging studies, including structural brain morphology, functional magnetic resonance imaging and techniques for measuring metabolic changes, including positron emission tomography and others. Furthermore, this review reports on the clinical and molecular genetic findings of family, twin, linkage, association and genome-wide association studies. Part II of the review focuses on neurochemistry, neurophysiology and neurocognition.Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high-quality research has accumulated that will improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.

    View details for DOI 10.1080/15622975.2016.1181783

    View details for Web of Science ID 000382536100003

    View details for PubMedID 27403679

  • Decoding the neural representation of fine-grained conceptual categories NEUROIMAGE Ghio, M., Vaghi, M., Perani, D., Tettamanti, M. 2016; 132: 93–103


    Neuroscientific research on conceptual knowledge based on the grounded cognition framework has shed light on the organization of concrete concepts into semantic categories that rely on different types of experiential information. Abstract concepts have traditionally been investigated as an undifferentiated whole, and have only recently been addressed in a grounded cognition perspective. The present fMRI study investigated the involvement of brain systems coding for experiential information in the conceptual processing of fine-grained semantic categories along the abstract-concrete continuum. These categories consisted of mental state-, emotion-, mathematics-, mouth action-, hand action-, and leg action-related meanings. Thirty-five sentences for each category were used as stimuli in a 1-back task performed by 36 healthy participants. A univariate analysis failed to reveal category-specific activations. Multivariate pattern analyses, in turn, revealed that fMRI data contained sufficient information to disentangle all six fine-grained semantic categories across participants. However, the category-specific activity patterns showed no overlap with the regions coding for experiential information. These findings demonstrate the possibility of detecting specific patterns of neural representation associated with the processing of fine-grained conceptual categories, crucially including abstract ones, though bearing no anatomical correspondence with regions coding for experiential information as predicted by the grounded cognition hypothesis.

    View details for DOI 10.1016/j.neuroimage.2016.02.009

    View details for Web of Science ID 000374832200011

    View details for PubMedID 26883065

  • Fine-Grained Semantic Categorization across the Abstract and Concrete Domains PLOS ONE Ghio, M., Vaghi, M., Tettamanti, M. 2013; 8 (6): e67090


    A consolidated approach to the study of the mental representation of word meanings has consisted in contrasting different domains of knowledge, broadly reflecting the abstract-concrete dichotomy. More fine-grained semantic distinctions have emerged in neuropsychological and cognitive neuroscience work, reflecting semantic category specificity, but almost exclusively within the concrete domain. Theoretical advances, particularly within the area of embodied cognition, have more recently put forward the idea that distributed neural representations tied to the kinds of experience maintained with the concepts' referents might distinguish conceptual meanings with a high degree of specificity, including those within the abstract domain. Here we report the results of two psycholinguistic rating studies incorporating such theoretical advances with two main objectives: first, to provide empirical evidence of fine-grained distinctions within both the abstract and the concrete semantic domains with respect to relevant psycholinguistic dimensions; second, to develop a carefully controlled linguistic stimulus set that may be used for auditory as well as visual neuroimaging studies focusing on the parametrization of the semantic space beyond the abstract-concrete dichotomy. Ninety-six participants rated a set of 210 sentences across pre-selected concrete (mouth, hand, or leg action-related) and abstract (mental state-, emotion-, mathematics-related) categories, with respect either to different semantic domain-related scales (rating study 1), or to concreteness, familiarity, and context availability (rating study 2). Inferential statistics and correspondence analyses highlighted distinguishing semantic and psycholinguistic traits for each of the pre-selected categories, indicating that a simple abstract-concrete dichotomy is not sufficient to account for the entire semantic variability within either domains.

    View details for DOI 10.1371/journal.pone.0067090

    View details for Web of Science ID 000321223000077

    View details for PubMedID 23825625

    View details for PubMedCentralID PMC3692433