Short-term safety and effectiveness of sugammadex for surgical patients with end-stage renal disease: a two-centre retrospective study.

Sugammadex is a novel reversal agent for aminosteroid neuromuscular blocking drugs, especially rocuronium. Given its renal excretion, sugammadex is not recommended for patients with end-stage renal disease; however, reports exist of its use in this group of patients. This two-institutional retrospective observational study aimed to review the safety profile and effectiveness of sugammadex in surgical patients with end-stage renal disease who required pre-operative renal replacement therapy. Adult surgical patients with end-stage renal disease requiring pre-operative renal replacement therapy, who received sugammadex between April 2016 and January 2019, were studied. The primary outcome was the incidence of postoperative tracheal re-intubation within 48 h. The secondary outcome was the incidence of deferred tracheal extubation in the operating theatre. One hundred and fifty-eight patients were identified from 125,653 surgical patients: 48 patients (30%) underwent renal transplantation and 110 (70%) underwent non-renal transplantation procedures. There were 22 instances (14%) of deferred tracheal extubation due to surgical and/or pre-existing medical conditions. Out of the 136 patients who had the tracheal tube removed at the end of the procedure, three patients had their trachea re-intubated within 48 h: two patients developed pulmonary oedema resulting from volume overload; and one patient had worsening sepsis. No incidence of recurrence of neuromuscular blockade was observed. Of note, 24 (18%) patients were found to have incomplete neuromuscular blockade reversal with neostigmine but administration of sugammadex led to successful tracheal extubation. In conclusion, sugammadex appears to be safe and effective in adult patients with end-stage renal disease receiving pre-operative renal replacement therapy.

What do Vitiligo Impact Scale-22 scores mean? Studying the clinical interpretation of scores using an anchor-based approach.

BACKGROUND: The Vitiligo Impact Scale (VIS)-22 is a vitiligo-specific quality-of-life instrument. Its criterion, convergent and known-groups validity, test-retest reliability and responsiveness have been studied previously in an Indian population. The clinical meaning of VIS-22 scores has not yet been analysed. OBJECTIVES: To assign clinical meaning to VIS-22 scores using anchor-based methods. METHODS: This was a cross-sectional study conducted in a large teaching hospital in North India. Patients with vitiligo > 15 years of age (n = 391) completed the VIS-22 and Dermatology Life Quality Index (DLQI) questionnaires, and answered a Global Question (GQ) on the effect of vitiligo on their lives on a five-point Likert scale. Multiple band sets of VIS-22 scores were devised using GQ as the anchor. A weighted kappa-coefficient was calculated to estimate the level of agreement between different band sets of VIS-22 and GQ. VIS-22 and DLQI were compared based on their degree of correlation and agreement with GQ. RESULTS: The mean ± SD of VIS-22 scores was 24·8 ± 14·0 (range 0-61). VIS-22 scores showed good correlation with GQ (r = 0·76). Of the various VIS-22 band sets tested, the following was chosen: 0-5, 6-15, 16-25, 26-40 and 41-66 (weighted κ = 0·57), corresponding to the five categories of GQ. The degree of correlation (VIS-22, r = 0·77; DLQI, r = 0·69) and agreement (VIS-22, 51·6%; DLQI, 36·1%; P < 0·001) of VIS-22 with GQ was higher than that with DLQI. CONCLUSIONS: VIS-22 scores can be used to stratify the impairment of vitiligo-related quality of life.

Altered fear processing in adolescents with a history of severe childhood maltreatment: an fMRI study.

BACKGROUND: Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse. METHOD: Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions. RESULTS: Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls. CONCLUSIONS: The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.

Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.

BACKGROUND: Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. METHODS: Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. RESULTS: For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. CONCLUSIONS: Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.

Feasibility of measuring memory response to increasing dexmedetomidine sedation in children.

BACKGROUND: The memory effect of dexmedetomidine has not been prospectively evaluated in children. We evaluated the feasibility of measuring memory and sedation responses in children during dexmedetomidine sedation for non-painful radiological imaging studies. Secondarily, we quantified changes in memory in relation to the onset of sedation. METHODS: A 10 min bolus of dexmedetomidine (2 mcg kg-1) was given to children as they named simple line drawings every five s. The absence of sedation was identified as any verbal response, regardless of correctness. After recovery, recognition memory was tested with correct Yes/No recognitions (50% novel pictures) and was matched to sedation responses during the bolus period (subsequent memory paradigm). RESULTS: Of 64 accruals, 30 children (mean [SD]6.1 (1.2) yr, eight male) received dexmedetomidine and completed all study tasks. Individual responses were able to be modelled successfully in the 30 children completing all the study tasks, demonstrating feasibility of this approach. Children had 50% probability of verbal response at five min 40 s after infusion start, whereas 50% probability of subsequent recognition memory occurred sooner at four min five s. CONCLUSIONS: Quantifying memory and sedation effects during dexmedetomidine infusion in verbal children was possible and demonstrated that memory function was present until shortly before verbal unresponsiveness occurred. This is the first study to investigate the effect of dexmedetomidine on memory in children. CLINICAL TRIAL REGISTRATION: NCT 02354378.

Prefrontal cortex dopamine release measured in vivo with positron emission tomography: Implications for the stimulant paradigm.

Experimental tasks and stimulant paradigms in combination with D2/3 emission tomography have been essential in understanding the dopamine (DA) system. However, whereas task-induced DA release is dependent on a mechanism that is largely similar throughout the brain, the DA-increasing stimulant mechanism of action changes drastically from striatum to cortex. We posit the problems that may be encountered when translating the stimulant emission tomography paradigm from striatum to PFC. After comparing the available human data on task- and stimulant-induced changes in extracellular PFC DA assessed with PET, we hypothesize that the stimulant paradigm in the PFC, even with high affinity tracers, may not completely capture the true effect of stimulants on extracellular PFC DA levels. Task-induced and stimulant-induced effects on extracellular PFC DA measured with emission tomography should therefore be regarded as different phenomena. We conclude with future directions and alternative probes to measure PFC DA transmission with emission tomography.

Effects of ketamine on brain function during smooth pursuit eye movements.

The uncompetitive NMDA receptor antagonist ketamine has been proposed to model symptoms of psychosis. Smooth pursuit eye movements (SPEM) are an established biomarker of schizophrenia. SPEM performance has been shown to be impaired in the schizophrenia spectrum and during ketamine administration in healthy volunteers. However, the neural mechanisms mediating SPEM impairments during ketamine administration are unknown. In a counter-balanced, placebo-controlled, double-blind, within-subjects design, 27 healthy participants received intravenous racemic ketamine (100 ng/mL target plasma concentration) on one of two assessment days and placebo (intravenous saline) on the other. Participants performed a block-design SPEM task during functional magnetic resonance imaging (fMRI) at 3 Tesla field strength. Self-ratings of psychosis-like experiences were obtained using the Psychotomimetic States Inventory (PSI). Ketamine administration induced psychosis-like symptoms, during ketamine infusion, participants showed increased ratings on the PSI dimensions cognitive disorganization, delusional thinking, perceptual distortion and mania. Ketamine led to robust deficits in SPEM performance, which were accompanied by reduced blood oxygen level dependent (BOLD) signal in the SPEM network including primary visual cortex, area V5 and the right frontal eye field (FEF), compared to placebo. A measure of connectivity with V5 and FEF as seed regions, however, was not significantly affected by ketamine. These results are similar to the deviations found in schizophrenia patients. Our findings support the role of glutamate dysfunction in impaired smooth pursuit performance and the use of ketamine as a pharmacological model of psychosis, especially when combined with oculomotor biomarkers. Hum Brain Mapp 37:4047-4060, 2016. © 2016 Wiley Periodicals, Inc.

Comparing clinical outcomes in HIV-infected and uninfected older men hospitalized with community-acquired pneumonia.

OBJECTIVES: Outcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear. METHODS: Associations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models. RESULTS: Among 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94 [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65, 4.73]; P = 0.008), after accounting for VACS Index. Readmission was not associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714). CONCLUSION: Among HIV-infected and uninfected older adults hospitalized for CAP, organ system components of the VACS Index were associated with adverse CAP outcomes. Among HIV-infected individuals, ART was associated with decreased 30-day mortality and LOS.

Disorder-specific grey matter deficits in attention deficit hyperactivity disorder relative to autism spectrum disorder.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two common childhood disorders that exhibit genetic and behavioural overlap and have abnormalities in similar brain systems, in particular in frontal and cerebellar regions. This study compared the two neurodevelopmental disorders to investigate shared and disorder-specific structural brain abnormalities. METHOD: Forty-four predominantly medication-naïve male adolescents with ADHD, 19 medication-naïve male adolescents with ASD and 33 age-matched healthy male controls were scanned using high-resolution T1-weighted volumetric imaging in a 3-T magnetic resonance imaging (MRI) scanner. Voxel-based morphometry (VBM) was used to test for group-level differences in structural grey matter (GM) and white matter (WM) volumes. RESULTS: There was a significant group difference in the GM of the right posterior cerebellum and left middle/superior temporal gyrus (MTG/STG). Post-hoc analyses revealed that this was due to ADHD boys having a significantly smaller right posterior cerebellar GM volume compared to healthy controls and ASD boys, who did not differ from each other. ASD boys had a larger left MTG/STG GM volume relative to healthy controls and at a more lenient threshold relative to ADHD boys. CONCLUSIONS: The study shows for the first time that the GM reduction in the cerebellum in ADHD is disorder specific relative to ASD whereas GM enlargement in the MTG/STG in ASD may be disorder specific relative to ADHD. This study is a first step towards elucidating disorder-specific structural biomarkers for these two related childhood disorders.

Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.

BACKGROUND: Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects. METHODS: Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 µg ml(-1), or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models. RESULTS: Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia. CONCLUSIONS: Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder. CLINICAL TRIAL REGISTRATION: NCT00504894.

Alginate microparticles loaded with lipopolysaccharide subunit antigen for mucosal vaccination against Klebsiella pneumoniae.

Klebsiella pneumoniae (K. pneumoniae) is one of the commonest causes of nosocomial infections in human beings. Since K. pneumoniae infections are air borne type, controlling it by mucosal vaccination through nasal and pulmonary route could be a promising approach in order to simulate the natural infection. New vaccines such as subunit vaccines are safer than traditional vaccines, but they are less immunogenic. Therefore to enhance their immunogenicity, there is a need to develop potent and safe adjuvants and delivery systems. It has been established that micro-particles are one of the most potent adjuvants available for mucosal delivery of vaccines and they do so by improving uptake of encapsulated antigen by antigen presenting cells (APCs). Lipopolysaccharide (LPS), the antigenic fraction was extracted from K. pneumoniae by hot phenol extraction method. LPS loaded sodium alginate microparticles were prepared by emulsion ionic gelation method. Microparticles with particle size less than 5 µm were obtained. Loading efficiency of the LPS loaded microparticles ranged from 76 to 82 %. Comparative in vivo immunogenicity studies were carried for free LPS and encapsulated LPS, administered via intramuscular, intratracheal and intranasal routes in Swiss albino mice. The study revealed that LPS encapsulated microparticles exhibit greater efficacy when administered by intra-tracheal route as compared to free LPS vaccine.

Measurement properties of the Vitiligo Impact Scale-22 (VIS-22), a vitiligo-specific quality-of-life instrument.

BACKGROUND: Vitiligo has a significant psychological impact which needs to be evaluated separately from the extent of depigmentation. We have developed a vitiligo-specific quality-of-life (QoL) instrument, Vitiligo Impact Scale-22 (VIS-22) for this purpose. OBJECTIVES: To study the measurement properties of VIS-22 and compare it with the Dermatology Life Quality Index (DLQI) and Skindex-16. METHODS: Item-reduction analysis was used to reduce the number of items in the original VIS from 27 to 22. The 5-point Physician's Global Assessment (PGA) was used to evaluate the QoL followed by a Visual Analogue Scale (VAS) to assess patient-perceived severity. VIS-22, DLQI and Skindex-16 were self-administered. The validity of the VIS-22 was assessed in 161 patients, reliability in 69 patients and responsiveness in 72 patients and compared with DLQI and Skindex-16. RESULTS: Criterion validity was shown by strong correlation of VIS-22 with VAS (r = 0·7076). Convergent validity was evidenced by strong correlations with DLQI (r = 0·71) and Skindex-16 (r = 0·72). Known-groups validity was demonstrated by significantly higher scores in females, those with less education, patients with progressive disease and patients with vitiligo compared with controls (P < 0·001). Reliability was shown by excellent correlation of the scores between baseline and 2 weeks (r = 0·9053). VIS-22 was found to be responsive with scores at 12 weeks moving parallel to scores on VAS. Similar trends were noted with DLQI and Skindex-16. CONCLUSIONS: VIS-22 is a valid, reliable and responsive QoL instrument. It is comparable to DLQI and Skindex-16 in its measurement properties, while being specific to the needs of patients with vitiligo.

Using suggestion to model different types of automatic writing.

Our sense of self includes awareness of our thoughts and movements, and our control over them. This feeling can be altered or lost in neuropsychiatric disorders as well as in phenomena such as "automatic writing" whereby writing is attributed to an external source. Here, we employed suggestion in highly hypnotically suggestible participants to model various experiences of automatic writing during a sentence completion task. Results showed that the induction of hypnosis, without additional suggestion, was associated with a small but significant reduction of control, ownership, and awareness for writing. Targeted suggestions produced a double dissociation between thought and movement components of writing, for both feelings of control and ownership, and additionally, reduced awareness of writing. Overall, suggestion produced selective alterations in the control, ownership, and awareness of thought and motor components of writing, thus enabling key aspects of automatic writing, observed across different clinical and cultural settings, to be modelled.

D2/D3 dopamine supports the precision of mental state inferences and self-relevance of joint social outcomes.

Striatal dopamine is important in paranoid attributions, although its computational role in social inference remains elusive. We employed a simple game-theoretic paradigm and computational model of intentional attributions to investigate the effects of dopamine D2/D3 antagonism on ongoing mental state inference following social outcomes. Haloperidol, compared with the placebo, enhanced the impact of partner behaviour on beliefs about the harmful intent of partners, and increased learning from recent encounters. These alterations caused substantial changes to model covariation and negative correlations between self-interest and harmful intent attributions. Our findings suggest that haloperidol improves belief flexibility about others and simultaneously reduces the self-relevance of social observations. Our results may reflect the role of D2/D3 dopamine in supporting self-relevant mentalising. Our data and model bridge theory between general and social accounts of value representation. We demonstrate initial evidence for the sensitivity of our model and short social paradigm to drug intervention and clinical dimensions, allowing distinctions between mechanisms that operate across traits and states.

Profiles of objective and subjective cognitive function in Post-COVID Syndrome, COVID-19 recovered, and COVID-19 naïve individuals.

Post-COVID Syndrome has emerged as a significant public health concern worldwide with increasing evidence to suggest that individuals who have had an acute COVID-19 infection report lingering memory and attention difficulties, even in individuals who have fully recovered and no longer experiencing symptoms of COVID-19. The present study sought to investigate the profile of objective and subjective cognitive difficulties in people who have Post-COVID Syndrome, people who have fully recovered from an acute COVID infection and people who have never had COVID-19. We further sought to explore the extent to which self-reported fatigue and stress are related to subjective and objective cognitive difficulties. 162 participants including 50 people living with Post-COVID Syndrome, 59 people who have had COVID-19 but have fully recovered and 53 people who have never experienced symptoms of COVID-19 and had never tested positive for COVID-19 were recruited from Academic Prolific to complete a series of online questionnaires and neurocognitive tasks. Subjective cognitive function was measured using the Cognitive Failures Questionnaire and objective cognitive function was measured using the Cognitron cognitive test battery. We found that objective and subjective measures of cognitive function were not significantly related, suggesting that self-reports of "brain fog" are not reflecting objectively measured cognitive dysfunction. A MANOVA revealed that subjective cognitive deficits were driven by heightened perceived stress and fatigue and not significantly related to COVID-19 status. Objective cognitive function, however, was significantly related to perceived stress and COVID status whereby we observed significant objective cognitive deficits in people who have been exposed to an acute COVID-19 infection regardless of whether they had Post-COVID Syndrome or had fully recovered, as compared to people who had never had COVID-19. This suggests that an acute infection can have long term effects on cognitive function, even without persistent COVID-19 symptoms. Encouragingly, objective cognitive function was significantly associated with time since initial infection showing that cognitive deficits improved over time for people who had recovered from COVID-19. However, we did not observe the same improvement in individuals with Post-COVID Syndrome and observed that cognitive dysfunction was significantly related to the number of neurological symptoms presently experienced. These results add to the accumulating literature that COVID-19 is associated with significant cognitive difficulties following a COVID-19 infection, which appear to improve over time for those who have recovered from COVID-19 yet persist in people living with Post-COVID Syndrome.

Effects of triple antioxidant therapy on measures of cardiovascular autonomic neuropathy and on myocardial blood flow in type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: We evaluated the effects of a combination triple antioxidant therapy on measures of cardiovascular autonomic neuropathy (CAN) and myocardial blood flow (MBF) in patients with type 1 diabetes. METHODS: This was a randomised, parallel, placebo-controlled trial. Participants were allocated to interventions by sequentially numbered, opaque, sealed envelopes provided to the research pharmacist. All participants and examiners were masked to treatment allocation. Participants were evaluated by cardiovascular autonomic reflex testing, positron emission tomography with [(11)C]meta-hydroxyephedrine ([(11)C]HED) and [(13)N]ammonia, and adenosine stress testing. Markers of oxidative stress included 24 h urinary F2-isoprostanes. Diabetic peripheral neuropathy (DPN) was evaluated by symptoms, signs, electrophysiology and intra-epidermal nerve fibre density. Randomised participants included 44 eligible adults with type 1 diabetes and mild-to-moderate CAN, who were aged 46 ± 11 years and had HbA1c 58 ± 5 mmol/mol (7.5 ± 1.0%), with no evidence of ischaemic heart disease. Participants underwent a 24-month intervention, consisting of antioxidant treatment with allopurinol, α-lipoic acid and nicotinamide, or placebo. The main outcome was change in the global [(11)C]HED retention index (RI) at 24 months in participants on the active drug compared with those on placebo. RESULTS: We analysed data from 44 participants (22 per group). After adjusting for age, sex and in-trial HbA1c, the antioxidant regimen was associated with a slight, but significant worsening of the global [(11)C]HED left ventricle RI (-0.010 [95% CI -0.020, -0.001] p = 0.045) compared with placebo. There were no significant differences at follow-up between antioxidant treatment and placebo in the global MBF, coronary flow reserve, or in measures of DPN and markers of oxidative stress. The majority of adverse events were of mild-to-moderate severity and did not differ between groups CONCLUSIONS/INTERPRETATION: In this cohort of type 1 diabetes patients with mild-to-moderate CAN, a combination antioxidant treatment regimen did not prevent progression of CAN, had no beneficial effects on myocardial perfusion or DPN, and may have been detrimental. However, a larger study is necessary to assess the underlying causes of these findings.

Multivariate decoding of brain images using ordinal regression.

Neuroimaging data are increasingly being used to predict potential outcomes or groupings, such as clinical severity, drug dose response, and transitional illness states. In these examples, the variable (target) we want to predict is ordinal in nature. Conventional classification schemes assume that the targets are nominal and hence ignore their ranked nature, whereas parametric and/or non-parametric regression models enforce a metric notion of distance between classes. Here, we propose a novel, alternative multivariate approach that overcomes these limitations - whole brain probabilistic ordinal regression using a Gaussian process framework. We applied this technique to two data sets of pharmacological neuroimaging data from healthy volunteers. The first study was designed to investigate the effect of ketamine on brain activity and its subsequent modulation with two compounds - lamotrigine and risperidone. The second study investigates the effect of scopolamine on cerebral blood flow and its modulation using donepezil. We compared ordinal regression to multi-class classification schemes and metric regression. Considering the modulation of ketamine with lamotrigine, we found that ordinal regression significantly outperformed multi-class classification and metric regression in terms of accuracy and mean absolute error. However, for risperidone ordinal regression significantly outperformed metric regression but performed similarly to multi-class classification both in terms of accuracy and mean absolute error. For the scopolamine data set, ordinal regression was found to outperform both multi-class and metric regression techniques considering the regional cerebral blood flow in the anterior cingulate cortex. Ordinal regression was thus the only method that performed well in all cases. Our results indicate the potential of an ordinal regression approach for neuroimaging data while providing a fully probabilistic framework with elegant approaches for model selection.