Integrating multimodal and multiscale connectivity blueprints of the human cerebral cortex in health and disease.

The brain is composed of disparate neural populations that communicate and interact with one another. Although fiber bundles, similarities in molecular architecture, and synchronized neural activity all reflect how brain regions potentially interact with one another, a comprehensive study of how all these interregional relationships jointly reflect brain structure and function remains missing. Here, we systematically integrate 7 multimodal, multiscale types of interregional similarity ("connectivity modes") derived from gene expression, neurotransmitter receptor density, cellular morphology, glucose metabolism, haemodynamic activity, and electrophysiology in humans. We first show that for all connectivity modes, feature similarity decreases with distance and increases when regions are structurally connected. Next, we show that connectivity modes exhibit unique and diverse connection patterns, hub profiles, spatial gradients, and modular organization. Throughout, we observe a consistent primacy of molecular connectivity modes-namely correlated gene expression and receptor similarity-that map onto multiple phenomena, including the rich club and patterns of abnormal cortical thickness across 13 neurological, psychiatric, and neurodevelopmental disorders. Finally, to construct a single multimodal wiring map of the human cortex, we fuse all 7 connectivity modes and show that the fused network maps onto major organizational features of the cortex including structural connectivity, intrinsic functional networks, and cytoarchitectonic classes. Altogether, this work contributes to the integrative study of interregional relationships in the human cerebral cortex.

Metabolic and functional connectivity provide unique and complementary insights into cognition-connectome relationships.

A major challenge in current cognitive neuroscience is how functional brain connectivity gives rise to human cognition. Functional magnetic resonance imaging (fMRI) describes brain connectivity based on cerebral oxygenation dynamics (hemodynamic connectivity), whereas [18F]-fluorodeoxyglucose functional positron emission tomography (FDG-fPET) describes brain connectivity based on cerebral glucose uptake (metabolic connectivity), each providing a unique characterization of the human brain. How these 2 modalities differ in their contribution to cognition and behavior is unclear. We used simultaneous resting-state FDG-fPET/fMRI to investigate how hemodynamic connectivity and metabolic connectivity relate to cognitive function by applying partial least squares analyses. Results revealed that although for both modalities the frontoparietal anatomical subdivisions related the strongest to cognition, using hemodynamic measures this network expressed executive functioning, episodic memory, and depression, whereas for metabolic measures this network exclusively expressed executive functioning. These findings demonstrate the unique advantages that simultaneous FDG-PET/fMRI has to provide a comprehensive understanding of the neural mechanisms that underpin cognition and highlights the importance of multimodality imaging in cognitive neuroscience research.

Diabetes disturbs functional adaptation of the remote myocardium after ischemia/reperfusion.

Diabetes mellitus type 2 is associated with adverse clinical outcome after myocardial infarction. To better understand the underlying causes we here investigated sarcomere protein function and its calcium-dependent regulation in the non-ischemic remote myocardium (RM) of diabetic mice (db/db) after transient occlusion of the left anterior descending coronary artery. Before and 24 h after surgery db/db and non-diabetic db/+ underwent magnetic resonance imaging followed by histological and biochemical analyses of heart tissue. Intracellular calcium transients and sarcomere function were measured in isolated cardiomyocytes. Active and passive force generation was assessed in skinned fibers and papillary muscle preparations. Before ischemia and reperfusion (I/R), beat-to-beat calcium cycling was depressed in diabetic cardiomyocytes. Nevertheless, contractile function was preserved owing to increased myofilament calcium sensitivity and higher responsiveness of myocardial force production to ß-adrenergic stimulation in db/db compared to db/+. In addition, protein kinase C activity was elevated in db/db hearts leading to strong phosphorylation of the titin PEVK region and increased titin-based tension of myofilaments. I/R impaired the function of whole hearts and RM sarcomeres in db/db to a larger extent than in non-diabetic db/+, and we identified several reasons. First, the amplitude and the kinetics of cardiomyocyte calcium transients were further reduced in the RM of db/db. Underlying causes involved altered expression of calcium regulatory proteins. Diabetes and I/R additively reduced phospholamban S16-phosphorylation by 80% (P < 000.1) leading to strong inhibition of the calcium ATPase SERCA2a. Second, titin stiffening was only observed in the RM of db/+, but not in the RM of db/db. Finally, db/db myofilament calcium sensitivity and force generation upon ß-adrenergic stimulation were no longer enhanced over db/+ in the RM. The findings demonstrate that impaired cardiomyocyte calcium cycling of db/db hearts is compensated by increased myofilament calcium sensitivity and increased titin-based stiffness prior to I/R. In contrast, sarcomere function of the RM 24 h after I/R is poor because both these compensatory mechanisms fail and myocyte calcium handling is further depressed.

Neural underpinnings of food choice and consumption in obesity.

BACKGROUND/OBJECTIVES: Obesity is associated with unhealthy food choices. Food selection is driven by the subjective valuation of available options, and the perceived and actual rewards accompanying consumption. These cognitive operations are mediated by brain regions including the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), and ventral striatum (vStr). This study investigated the relationship between body mass index (BMI) and functional activations in the vmPFC, dACC, and vStr during food selection and consumption. SUBJECTS/METHODS: After overnight fasting, 26 individuals (BMI: 18-40 kg/m2) performed a food choice task while being scanned with functional magnetic resonance imaging (fMRI). Each trial involved selecting one beverage from a pair of presented options, followed by delivery of a 3 mL aliquot of the selected option using an MR-compatible gustometer. We also tracked subjective preference for each beverage throughout the experiment. RESULTS: During food choice, individuals with greater BMI had less activation in the dorsolateral prefrontal cortex when selecting a high-value option and less vmPFC activation upon its consumption. Independent of BMI, during food choice the dACC and anterior insula elicited higher activation when a less preferred beverage was selected. Activation of the dACC and a broader frontoparietal network was also observed when deciding between options more similar in value. During consumption, receipt of a more preferred beverage was associated with greater vmPFC response, and attenuation of the dACC. CONCLUSIONS: An individual's preference for a food option modulates the brain activity associated with choosing and consuming it. The relationship between food preference and underlying brain activity is altered in obesity, with reduced engagement of cognition-related regions when presented with a highly valued option, but a blunted response in reward-related regions upon consumption.

Neural network modelling reveals changes in directional connectivity between cortical and hypothalamic regions with increased BMI.

BACKGROUND/OBJECTIVES: Obesity has been ascribed to corticostriatal regions taking control over homeostatic areas. To test this assumption, we applied an effective connectivity approach to reveal the direction of information flow between brain regions and the valence of connections (excitatory versus inhibitory) as a function of increased BMI and homeostatic state. SUBJECTS/METHODS: Forty-one participants (21 overweight/obese) underwent two resting-state fMRI scans: after overnight fasting (hunger) and following a standardised meal (satiety). We used spectral dynamic causal modelling to unravel hunger and increased BMI-related changes in directed connectivity between cortical, insular, striatal and hypothalamic regions. RESULTS: During hunger, as compared to satiety, we found increased excitation of the ventromedial prefrontal cortex over the ventral striatum and hypothalamus, suggesting enhanced top-down modulation compensating energy depletion. Increased BMI was associated with increased excitation of the anterior insula over the hypothalamus across the hunger and satiety conditions. The interaction of hunger and increased BMI yielded decreased intra-cortical excitation from the dorso-lateral to the ventromedial prefrontal cortex. CONCLUSIONS: Our findings suggest that excess weight and obesity is associated with persistent top-down excitation of the hypothalamus, regardless of homeostatic state, and hunger-related reductions of dorso-lateral to ventromedial prefrontal inputs. These findings are compatible with eating without hunger and reduced self-regulation views of obesity.

Hard Decisions Shape the Neural Coding of Preferences.

Hard decisions between equally valued alternatives can result in preference changes, meaning that subsequent valuations for chosen items increase and decrease for rejected items. Previous research suggests that this phenomenon is a consequence of cognitive dissonance reduction after the decision, induced by the mismatch between initial preferences and decision outcomes. In contrast, this functional magnetic resonance imaging and eye-tracking study with male and female human participants found that preferences are already updated online during the process of decision-making. Preference changes were predicted from activity in left dorsolateral prefrontal cortex and precuneus while making hard decisions. Fixation durations during this phase predicted both choice outcomes and subsequent preference changes. These preference adjustments became behaviorally relevant only for choices that were remembered and were in turn associated with hippocampus activity. Our results suggest that preferences evolve dynamically as decisions arise, potentially as a mechanism to prevent stalemate situations in underdetermined decision scenarios.SIGNIFICANCE STATEMENT Most theories of decision-making assume that we always choose the best option available, based on a set of stable preferences. However, what happens for hard decisions when the available options are preferred equally? We show that in such stalemate situations, decision-makers adjust their preferences dynamically during the process of decision-making, and these preference adjustments are predicted by a left prefrontal-parietal network. We also show that eye movements during decision-making are predictive of the magnitude of the upcoming value change. Our results suggest that preferences are dynamic, adjusted every time a hard decision is made, prompting a re-evaluation of existing frameworks of decision-making.

Effective brain connectivity at rest is associated with choice-induced preference formation.

Preferences can change as a consequence of making hard decisions whereby the value of chosen options increases and the value of rejected options decreases. Such choice-induced preference changes have been associated with brain areas detecting choice conflict (anterior cingulate cortex, ACC), updating stimulus value (dorsolateral prefrontal cortex, dlPFC) and supporting memory of stimulus value (hippocampus and ventromedial prefrontal cortex, vmPFC). Here we investigated whether resting-state neuronal activity within these regions is associated with the magnitude of individuals' preference updates. We fitted a dynamic causal model (DCM) to resting-state neuronal activity in the spectral domain (spDCM) and estimated the causal connectivity among core regions involved in preference formation following hard choices. The extent of individuals' choice-induced preference changes were found to be associated with a diminished resting-state excitation between the left dlPFC and the vmPFC, whereas preference consistency was related to a higher resting-state excitation from the ACC to the left hippocampus and vmPFC. Our results point to a model of preference formation during which the dynamic network configurations between left dlPFC, ACC, vmPFC and left hippocampus at rest are linked to preference change or stability.

Development and Validation of the Somatic Symptom Disorder-B Criteria Scale (SSD-12).

OBJECTIVE: To develop and validate a new self-report questionnaire for the assessment of the psychological features of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder. METHODS: The Somatic Symptom Disorder-B Criteria Scale (SSD-12) was developed in several steps from an initial pool of 98 items. The SSD-12 is composed of 12 items; each of the three psychological subcriteria is measured by four items. In a cross-sectional study, the SSD-12 was administered to 698 patients (65.8% female, mean [standard deviation] age = 38.79 [14.15] years) from a psychosomatic outpatient clinic. Item and scale characteristics as well as measures of reliability and validity were determined. RESULTS: The SSD-12 has good item characteristics and excellent reliability (Cronbach α = .95). Confirmatory factor analyses suggested that a three-factorial structure that reflects the three psychological criteria interpreted as cognitive, affective, and behavioral aspects (n = 663, Comparative Fit Index > 0.99, Tucker-Lewis Index > 0.99, Root Mean Square Error of Approximation = 0.06, 90% confidence interval = 0.01-0.08). SSD-12 total sum score was significantly associated with somatic symptom burden (r = 0.47, p < .001) and health anxiety (r = 0.71, p < .001), and moderately associated with general anxiety (r = 0.35, p < .001) and depressive symptoms (r = 0.22, p < .001). Patients with a higher SSD-12 psychological symptom burden reported higher general physical and mental health impairment and significantly higher health care use. CONCLUSIONS: The SSD-12 is the first self-report questionnaire that operationalizes the new psychological characteristics of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder. Initial assessment indicates that the SSD-12 has sufficient reliability and validity to warrant further testing in both research and clinical settings.

Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis.

BACKGROUND & AIMS: Improving health related quality of life (HrQoL) in patients with chronic diseases such as autoimmune hepatitis (AIH) should be a major treatment goal. However, little is known on the HrQoL in patients with AIH, and the topic is not given attention in current practice guidelines. We therefore conducted a single center study evaluating HrQoL in 103 consecutive outpatients with AIH. METHODS: Patient-reported HrQoL data were analysed in relation to clinical disease parameters and compared to representative data of the German population as well as control patients. RESULTS: Based on patient-reported data, a major depressive syndrome (10.8%) was found to be five times more frequent in AIH patients compared to the general population (p<0.001). The rate of severe symptoms of anxiety was also found to be significantly increased compared to the general population (p=0.006). In seven of the eleven patients who scored for a major depressive syndrome a psychiatric comorbidity had not been diagnosed before. Major factors associated with depression and anxiety were concerns with regard to the progression of the liver disease. CONCLUSIONS: This study identified--for the first time--a high rate of previously unrecognized severe symptoms of depression and anxiety in patients with AIH. Of importance for daily clinical practice, the factors associated with these symptoms may in part be amenable to targeted counselling and adequate treatment of the disease, thereby offering the chance to improve the care and HrQoL of AIH-patients.

[The Somatic Symptoms Experiences Questionnaire (SSEQ): a new self-report instrument for the assessment of psychological characteristics of patients with somatoform disorder]. / Der Fragebogen zum Erleben von Körperbeschwerden (SSEQ): Ein neues Selbstbeurteilungsinstrument zur Erfassung der psychischen Merkmale somatoformer Störungen.

Psychological symptoms of somatoform disorders will be part of their new definition in DSM-5. We developed the Somatic Symptoms Experiences Questionnaire (SSEQ) as a self-report questionnaire to assess important psychological characteristics of patients with somatoform disorders. Item selection and identification of factor structure, as well as reliability and validity have been checked in a sample of N=453 psychsomatic outpatients. Results of a principal components analysis with Promax-rotation suggested 4 factors (health worries, illness experience, difficulties in interaction with doctors, impact of illness). Validity analyses confirmed associations between the SSEQ-Scores and the physical disability of patients. Although further assessments of psychometric qualities are needed, the questionnaire appears to be well-suited for future assessment of relevant psychological features of somatoform disorders.

The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance.

Rising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of age and insulin resistance to the association of cerebral blood flow and glucose metabolism; both critical process in the supply of energy for the brain. Thirty-four younger (20-42 years) and 41 older (66-86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Lower cerebral blood flow was also associated with worse working memory and slower reaction time in tasks requiring cognitive flexibility and response inhibition. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive correlation. In insulin resistant younger adults, the association showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates of and associations between cerebral blood flow and glucose metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

Suicidality in primary care patients with somatoform disorders.

OBJECTIVE: To examine rates of suicidality in primary care patients with somatoform disorders and to identify factors that might help to understand and manage active suicidal ideation in these patients. METHODS: We conducted a cross-sectional study screening 1645 primary care patients. In total, 142 patients fulfilled the criteria for a somatoform disorder. Suicidality and illness perceptions were assessed in these patients. RESULTS: Of the 142 patients, 23.9% had active suicidal ideation during the previous 6 months; 17.6% had attempted to commit suicide in the past, the majority after onset of the somatoform symptoms. We tested two models with suicidal ideation as a dependent variable. In the first model, comorbid symptoms of depression (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.03-1.33) and previous suicide attempts (OR= 3.02, 95% CI = 1.06-8.62) were significantly associated with suicidal ideation. Comorbid symptoms of anxiety did not yield significance. Illness perceptions and age of onset of the symptoms were then added to this model to test the role of somatoform-specific factors in addition to previous factors. In the complete model, comorbid symptoms of depression (OR = 1.15, 95% CI = 1.00-1.32) and dysfunctional illness perceptions (OR = 1.06, 95% CI = 1.01-1.11) were independently associated with active suicidal ideation, whereas the other factors did not yield significance. CONCLUSIONS: According to our data, suicidality seems to be a substantial problem in primary care patients with somatoform disorders. Dysfunctional illness perceptions may play a vital role in the understanding and management of active suicidal ideation in these patients, in addition to more established factors.

The maternal brain is more flexible and responsive at rest: effective connectivity of the parental caregiving network in postpartum mothers.

The field of neuroscience has largely overlooked the impact of motherhood on brain function outside the context of responses to infant stimuli. Here, we apply spectral dynamic causal modelling (spDCM) to resting-state fMRI data to investigate differences in brain function between a group of 40 first-time mothers at 1-year postpartum and 39 age- and education-matched women who have never been pregnant. Using spDCM, we investigate the directionality (top-down vs. bottom-up) and valence (inhibition vs excitation) of functional connections between six key left hemisphere brain regions implicated in motherhood: the dorsomedial prefrontal cortex, ventromedial prefrontal cortex, posterior cingulate cortex, parahippocampal gyrus, amygdala, and nucleus accumbens. We show a selective modulation of inhibitory pathways related to differences between (1) mothers and non-mothers, (2) the interactions between group and cognitive performance and (3) group and social cognition, and (4) differences related to maternal caregiving behaviour. Across analyses, we show consistent disinhibition between cognitive and affective regions suggesting more efficient, flexible, and responsive behaviour, subserving cognitive performance, social cognition, and maternal caregiving. Together our results support the interpretation of these key regions as constituting a parental caregiving network. The nucleus accumbens and the parahippocampal gyrus emerging as 'hub' regions of this network, highlighting the global importance of the affective limbic network for maternal caregiving, social cognition, and cognitive performance in the postpartum period.

Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus.

BACKGROUND: A greater understanding of how the brain controls appetite is fundamental to developing new approaches for treating diseases characterized by dysfunctional feeding behavior, such as obesity and anorexia nervosa. METHODS: By modeling neural network dynamics related to homeostatic state and body mass index, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans (n = 53). We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice. RESULTS: In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under nonstressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose seeking in mice. CONCLUSIONS: These studies identify a glutamatergic mPFC-LH circuit as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.

Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers.

Hematologic spread of carcinoma results in incurable metastasis; yet, the basic characteristics and travel mechanisms of cancer cells in the bloodstream are unknown. We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) without using surface protein-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. This 'HD-CTC' assay finds >5 HD-CTCs mL(-1) of blood in 80% of patients with metastatic prostate cancer (n = 20), in 70% of patients with metastatic breast cancer (n = 30), in 50% of patients with metastatic pancreatic cancer (n = 18), and in 0% of normal controls (n = 15). Additionally, it finds HD-CTC clusters ranging from 2 HD-CTCs to greater than 30 HD-CTCs in the majority of these cancer patients. This initial validation of an enrichment-free assay demonstrates our ability to identify significant numbers of HD-CTCs in a majority of patients with prostate, breast and pancreatic cancers.

[Spinal anesthesia for patients harboring a neurostimulator]. / Spinalanästhesie bei vorhandenem Neurostimulator.

This article presents the case of an 82-year-old male patient with an implanted spinal cord stimulation system, who presented to our premedication consultation for a planned knee joint replacement. Spinal anesthesia was preferred because of the previous illnesses. In accordance with the recommendation of the treating pain physician for the puncture site, an uncomplicated L4/5 puncture was performed, and the surgery was performed with the patient under adequate spinal anesthesia. The system was checked postoperatively with regular findings.

Inhibitory Control Development: A Network Neuroscience Perspective.

As one of the core executive functions, inhibition plays an important role in human life through development. Inhibitory control is defined as the ability to suppress actions when they are unlikely to accomplish valuable results. Contemporary neuroscience has investigated the underlying neural mechanisms of inhibitory control. The controversy started to arise, which resulted in two schools of thought: a modulatory and a network account of inhibitory control. In this systematic review, we survey developmental mechanisms in inhibitory control as well as neurodevelopmental diseases related to inhibitory dysfunctions. This evidence stands against the modulatory perspective of inhibitory control: the development of inhibitory control does not depend on a dedicated region such as the right inferior frontal gyrus (rIFG) but relies on a more broadly distributed network.

Hypothalamic effective connectivity at rest is associated with body weight and energy homeostasis.

Hunger and satiety drive eating behaviours via changes in brain function. The hypothalamus is a central component of the brain networks that regulate food intake. Animal research parsed the roles of the lateral hypothalamus (LH) and medial hypothalamus (MH) in hunger and satiety, respectively. Here, we examined how hunger and satiety change information flow between human LH and MH brain networks, and how these interactions are influenced by body mass index (BMI). Forty participants (16 overweight/obese) underwent two resting-state functional MRI scans while being fasted and sated. The excitatory/inhibitory influence of information flow between the MH and LH was modelled using spectral dynamic causal modelling. Our results revealed two core networks interacting across homeostatic state and weight: subcortical bidirectional connections between the LH, MH and the substantia nigra pars compacta (prSN), and cortical top-down inhibition from fronto-parietal and temporal areas. During fasting, we found higher inhibition between the LH and prSN, whereas the prSN received greater top-down inhibition from across the cortex. Individuals with higher BMI showed that these network dynamics occur irrespective of homeostatic state. Our findings reveal fasting affects brain dynamics over a distributed hypothalamic-midbrain-cortical network. This network is less sensitive to state-related fluctuations among people with obesity.

The hypothalamus is a central component of the brain networks regulating food intake. Animal research subdivided the hypothalamus anatomically and functionally into lateral hypothalamus (LH) and medial hypothalamus (MH). This is the first study showing how the LH and MH causally interact with other neural regions and how their dynamics change with weight and homeostasis in humans. Adopting state-of-the-art spectral dynamic causal modelling of resting-state fMRI data, we provide new insights into how homeostasis affect hypothalamic circuit dynamics, which involve a distributed network of midbrain and cortical areas with a key role of the substantia nigra. We identified unique aspects of network organisation associated with obesity involving reciprocal connections between the LH and MH, and input from the substantia nigra to the MH.

A unified online test battery for cognitive impulsivity reveals relationships with real-world impulsive behaviours.

Impulsive behaviours are a major contributor to the global burden of disease, but existing measures of cognitive impulsivity have suboptimal reliability and validity. Here, we introduce the Cognitive Impulsivity Suite, comprising three computerized/online tasks using a gamified interface. We conceptualize rapid-response impulsive behaviours (disinhibition) as arising from the failure of three distinct cognitive mechanisms: attentional control, information gathering and monitoring/shifting. We demonstrate the construct and criterion validity of the Cognitive Impulsivity Suite in an online community sample (N = 1,056), show test-retest reliability and between-subjects variability in a face-to-face community sample (N = 63), and replicate the results in a community and clinical sample (N = 578). The results support the theoretical architecture of the attentional control, information gathering and monitoring/shifting constructs. The Cognitive Impulsivity Suite demonstrated incremental criterion validity for prediction of real-world, addiction-related problems and is a promising tool for large-scale research on cognitive impulsivity.

The Hunger Games: Homeostatic State-Dependent Fluctuations in Disinhibition Measured with a Novel Gamified Test Battery.

Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours.