James Stanley

Disruption of State Estimation in the Human Lateral Cerebellum

The cerebellum has been proposed to be a crucial component in the state estimation process that combines information from motor efferent and sensory afferent signals to produce a representation of the current state of the motor system. Such a state estimate of the moving human arm would be expected to be used when the arm is rapidly and skillfully reaching to a target. We now report the effects of transcranial magnetic stimulation (TMS) over the ipsilateral cerebellum as healthy humans were made to interrupt a slow voluntary movement to rapidly reach towards a visually defined target. Errors in the initial direction and in the final finger position of this reach-to-target movement were significantly higher for cerebellar stimulation than they were in control conditions. The average directional errors in the cerebellar TMS condition were consistent with the reaching movements being planned and initiated from an estimated hand position that was 138 ms out of date. We suggest that these results demonstrate that the cerebellum is responsible for estimating the hand position over this time interval and that TMS disrupts this state estimate.

Effects of agency on movement interference during observation of a moving dot stimulus.

Human movement performance is subject to interference if the performer simultaneously observes an incongruent action. It has been proposed that this phenomenon is due to motor contagion during simultaneous movement performance–observation, with coactivation of shared action performance and action observation circuitry in the premotor cortex. The present experiments compared the interference effect during observation of a moving person with observation of moving dot stimuli: The dot display followed either a biologically plausible or implausible velocity profile. Interference effects due to dot observation were present for both biological and nonbiological velocity profiles when the participants were informed that they were observing prerecorded human movement and were absent when the dot motion was described as computer generated. These results suggest that the observers belief regarding the origin of the dot motion (human–computer generated) modulates the processing of the dot movement stimuli on their later integration within the motor system, such that the belief regarding their biological origin is a more important determinant of interference effects than the stimulus kinematics.

Movement interference in autism-spectrum disorder

Movement interference occurs when concurrently observing and executing incompatible actions and is believed to be due to co-activation of conflicting populations of mirror neurons. It has also been suggested that mirror neurons contribute towards the imitation of observed actions. However, the exact neural substrate of imitation may depend on task demands: a processing route for goal-directed meaningful actions may be distinct from one for non-goal-directed actions. A more controversial role proposed for these neurons is in theory of mind processing, along with the subsequent suggestion that impairment in the mirror neuron circuit can contribute to autism-spectrum disorder (ASD) where individuals have theory of mind deficits. We have therefore examined movement interference in nine ASD participants and nine matched controls while performing actions congruent and incongruent with observed meaningless arm movements. We hypothesised that if the mirror neuron system was impaired, reduced interference should be observed in the ASD group. However, control and ASD participants demonstrated an equivalent interference effect in an interpersonal condition, with greater movement variability in the incongruent compared to the congruent condition. A component of movement interference which is independent of congruency did differ between groups: ASD participants made generally more variable movements for the interpersonal task than for biological dot-motion task, while the reverse was true for the control participants. We interpret these results as evidence that the ASD participant group either rely to a greater extent on the goal-directed imitation pathway, supporting claims that they have a specific deficit of the non-goal-directed imitation pathway, or exhibit reduced visuomotor integration.

The relationship between socially-assigned ethnicity, health and experience of racial discrimination for Māori: analysis of the 2006/07 New Zealand Health Survey.

BackgroundIn New Zealand, there are significant and long-standing inequalities in a range of health outcomes, risk factors and healthcare measures between Māori (indigenous peoples) and Pākehā (European). This study expands our understanding of racism as a determinant of such inequalities to examine the concept of socially-assigned ethnicity (how an individual is classified by others ethnically/racially) and its relationship to health and racism for Māori. There is some evidence internationally that being socially-assigned as the dominant ethnic group (in this case European) offers health advantage.MethodsWe analysed data from the 2006/07 New Zealand Health Survey for adult participants who self-identified their ethnicity as Māori (n = 3160). The association between socially-assigned ethnicity and individual experience of racial discrimination, and socially-assigned ethnicity and health (self-rated health, psychological distress [Kessler 10-item scale]) was assessed using logistic and linear regression analyses, respectively.ResultsMāori who were socially-assigned as European-only had significantly lower experience of racial discrimination (adjusted odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.44, 0.78) than Māori who were socially-assigned as non-European. Being socially-assigned as European-only was also associated with health advantage compared to being socially-assigned non-European: more likely to respond with self-rated very good/excellent health (age, sex adjusted OR = 1.39, 95% CI = 1.10, 1.74), and lower Kessler 10 scores (age, sex adjusted mean difference = -0.66, 95% C I = -1.22, -0.10). These results were attenuated following adjustment for socioeconomic measures and experience of racial discrimination.ConclusionsResults suggest that, in a race conscious society, the way people’s ethnicities are viewed by others is associated with tangible health risk or advantage, and this is consistent with an understanding of racism as a health determinant.

The quick and the dead: when reaction beats intention

Everyday behaviour involves a trade-off between planned actions and reaction to environmental events. Evidence from neurophysiology, neurology and functional brain imaging suggests different neural bases for the control of different movement types. Here we develop a behavioural paradigm to test movement dynamics for intentional versus reaction movements and provide evidence for a ‘reactive advantage’ in movement execution, whereby the same action is executed faster in reaction to an opponent. We placed pairs of participants in competition with each other to make a series of button presses. Within-subject analysis of movement times revealed a 10 per cent benefit for reactive actions. This was maintained when opponents performed dissimilar actions, and when participants competed against a computer, suggesting that the effect is not related to facilitation produced by action observation. Rather, faster ballistic movements may be a general property of reactive motor control, potentially providing a useful means of promoting survival.

Cancer-specific administrative data–based comorbidity indices provided valid alternative to Charlson and National Cancer Institute Indices

OBJECTIVE We aimed to develop and validate administrative data-based comorbidity indices for a range of cancer types that included all relevant concomitant conditions. STUDY DESIGN AND SETTINGS Patients diagnosed with colorectal, breast, gynecological, upper gastrointestinal, or urological cancers identified from the National Cancer Registry between July 1, 2006 and June 30, 2008 for the development cohort (n=14,096) and July 1, 2008 to December 31, 2009 for the validation cohort (n=11,014) were identified. A total of 50 conditions were identified using hospital discharge data before cancer diagnosis. Five site-specific indices and a combined site index were developed, with conditions weighted according to their log hazard ratios from age- and stage-adjusted Cox regression models with noncancer death as the outcome. We compared the performance of these indices (the C3 indices) with the Charlson and National Cancer Institute (NCI) comorbidity indices. RESULTS The correlation between the Charlson and C3 index scores ranged between 0.61 and 0.78. The C3 index outperformed the Charlson and NCI indices for all sites combined, colorectal, and upper gastrointestinal cancer, performing similarly for urological, breast, and gynecological cancers. CONCLUSION The C3 indices provide a valid alternative to measuring comorbidity in cancer populations, in some cases providing a modest improvement over other indices.

Clozapine-treated Patients Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-threatening Gastrointestinal Complications: A Cross Sectional Study.

Background Gastrointestinal side effects are particularly common with clozapine and occur with other antipsychotics, ranging from mild constipation to fatal bowel obstruction and/or ischemia. While this adverse-effect spectrum has been attributed to ‘gastrointestinal hypomotility’, gastrointestinal transit times in antipsychotic-treated patients have not previously been measured, making this mechanism speculative. Methods Using standardized radiopaque marker (‘Metcalf’) methods we established colonic transit times of antipsychotic-treated psychiatric inpatients and compared them with population normative values. We analyzed results by antipsychotic type, antipsychotic dose equivalent, anticholinergic load, duration of treatment, gender, ethnicity, and age. Outcomes For patients not prescribed clozapine, median colonic transit time was 23 h. For patients prescribed clozapine, median transit time was 104.5 h, over four times longer than those on other antipsychotics or normative values (p < 0.0001). Eighty percent of clozapine-treated patients had colonic hypomotility, compared with none of those prescribed other antipsychotics (olanzapine, risperidone, paliperidone aripiprazole, zuclopenthixol or haloperidol). In the clozapine group, right colon, left colon and rectosigmoid transit times were all markedly abnormal suggesting pan-colonic pathology. Hypomotility occurred irrespective of gender, age, ethnicity, or length of clozapine treatment. Transit times were positively correlated with clozapine plasma level (rho = 0.451, p = 0.045), but not with duration of treatment, total antipsychotic load or demographic factors. Interpretation Clozapine, unlike the other antipsychotics examined, causes marked gastrointestinal hypomotility, as previously hypothesized. Pre-emptive laxative treatment is recommended when starting clozapine.

Preventability of severe acute maternal morbidity

OBJECTIVE We sought to assess potential preventability of severe acute maternal morbidity (SAMM) cases admitted to intensive-care units (ICUs) or high-dependency units (HDUs). STUDY DESIGN Inclusion criteria were admissions to ICUs or HDUs of women who were pregnant or within 42 days of delivery in 4 District Health Board areas (accounting for a third of annual births in New Zealand) during a 17-month period. Cases were reviewed by external multidisciplinary panels using a validated model for assessing preventability. RESULTS In all, 98 SAMM cases were assessed; 38 (38.8%) cases were deemed potentially preventable, 36 (36.7%) not preventable but improvement in care was needed, and 24 (24.5%) not preventable. The most frequent preventable factors were clinician related: delay or failure in diagnosis or recognition of high-risk status (51%); and delay or inappropriate treatment (70%). The most common causes of preventable severe morbidity were blood loss and septicemia. CONCLUSION The majority of SAMM cases were potentially preventable or required improvement in care. Themes around substandard care related to delay in diagnosis and treatment for postpartum hemorrhage and septicemia. These findings can inform clinical educational programs and policies to improve maternal outcomes. This study has now been expanded to a national New Zealand audit of all SAMM cases admitted to an ICU/HDU.

Cancer survival in the context of mental illness: a national cohort study

OBJECTIVE To explore the reasons for worse cancer survival in people with experience of mental illness, including differences by cancer type and psychiatric diagnosis. METHOD New Zealand breast and colorectal cancer registrations (2006-2010) were linked to psychiatric hospitalization records for adults (18-64 years). Cancer-specific survival was compared for recent psychiatric service users and nonusers using Cox regression. The contributions of deprivation, comorbidity and stage at diagnosis were assessed for those with schizophrenia or bipolar affective disorder (Group A) and others using mental health services (Group B). RESULTS Of 8762 and 4022 people with breast and colorectal cancer respectively, 440 (breast) and 190 (colorectal) had recent contact with psychiatric services. After adjusting for confounding, risk of death from breast cancer was increased for Group A [Hazard Ratio (HR) 2.55 (95% confidence interval 1.49-4.35)] and B [HR 1.62 (1.09-2.39)] and from colorectal cancer for Group A [HR 2.92 (1.75-4.87)]. Later stage at diagnosis contributed to survival differences for Group A, and comorbidity contributed for both groups. Fully adjusted HR estimates were breast: Group A 1.65 (0.96-2.84), B 1.41 (0.95-2.09); colorectal: Group A 1.89 (1.12-3.17), B 1.25 (0.89-1.75)]. CONCLUSIONS The high burden of physical disease and delayed cancer diagnosis in those with psychotic disorders contributes to worse cancer survival in New Zealand psychiatric service users.

Immediate postabortion initiation of levonorgestrel implants reduces the incidence of births and abortions at 2 years and beyond

OBJECTIVES The aims of this study were to compare immediate postabortion uptake of recently subsidized (no-cost) levonorgestrel-releasing implants with already available intrauterine and shorter-acting methods and to compare the incidence of subsequent pregnancies (ending in birth or abortion) within 2 years. STUDY DESIGN Retrospective chart review of 4698 women attending a New Zealand public hospital abortion clinic over 2 years (2010-2012) to describe postabortion contraceptive choice, with follow-up via clinic and national births records to assess subsequent pregnancies at 12, 24, 36, and 48 months. RESULTS Twenty percent of the cohort (934/4698) received an implant, 26% an intrauterine method (927 copper intrauterine device, 301 levonorgestrel-releasing intrauterine system [LNG-IUS]), and 54% chose other shorter-acting methods (2536/4698). Method choice was significantly associated with age, ethnicity, and pregnancy history (p < .001). At 24 months, the unadjusted incidence of subsequent abortion for implant users was 3.8% (95% confidence interval [CI] = 2.5-5.0) and 11.6% (95% CI = 10.3-12.8) for those choosing other short-acting methods. By 48 months, 6.6% of implant users had a subsequent abortion (compared with 18.3% for short-acting methods). The incidence of continued pregnancy at 24 months was 6.3% (95% CI = 4.4-8.1) for implant users and 15.7% (95% CI = 14-17.2) for those choosing other short-acting methods. Adjusted hazard ratios (HRs) for subsequent abortion were lowest for women initiating an implant (HR = 0.26, 95% CI = 0.20-0.35) or LNG-IUS (HR = 0.26, 0.16-0.44, reference group: short-acting methods). CONCLUSIONS Immediate postabortion insertion of an implant significantly reduced rates of subsequent pregnancy for at least 2 years. Abortion service providers should ensure women have barrier-free access to all long-acting reversible contraceptions to delay or prevent pregnancy. IMPLICATIONS Initiation of an levonorgestrel implant immediately postabortion was associated with a 74% reduction in subsequent abortion over the next 4 years compared with use of short-acting methods. Implants were popular among adolescents-a group at high-risk of subsequent pregnancy, and who have not historically been considered appropriate candidates for intrauterine contraceptive methods.