Medium-term outcomes in single anaesthetic bilateral total knee replacement surgery: a single surgeon series.

BACKGROUND: The lifetime risk of developing symptomatic knee osteoarthritis (OA) is estimated to be 45%, with up to two thirds of patients presenting with bilateral knee symptoms. Patients presenting with end stage bilateral knee OA may benefit from single anaesthetic bilateral total knee replacement (SABTKR). Our study aim was to compare the outcomes of SABTKR with unilateral total knee arthroplasty (TKA) in a single surgeon series over a 20 year period. METHODS: We performed a retrospective review of a single surgeon's data from the New Zealand Joint Registry (NZJR) over a 20-year period from January 1999 to December 2018. This review reports on patient demographics, functional outcomes, revision rates and mortality rates. RESULTS: 1225 total knee replacements were performed by the senior author (995 TKAs and 115 patients underwent SABTKRs) over the 20 year period reviewed. The mean ages of the TKA and SABTKR groups were 67.7 and 66.7 years, respectively. There was 16.9% mortality rate for the TKA group versus 7.8% in SABTKR group. There were no revisions in the SABTKR group versus 17 revisions in the TKA group representing a revision rate of 0.23/100 component years which can be viewed against a 20 year revision rate of 0.48/100 component years (p < 0.05) for all comers in the NZJR. CONCLUSION: This NZJR study demonstrates excellent medium term survival outcomes for selected patients having simultaneous bilateral total knee replacements.

Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness.SIGNIFICANCE STATEMENT To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that are modulated by the brain chemical dopamine are sensitive to reward variability. Here, we aimed to directly relate dopamine to learning about variable rewards, and the neural encoding of associated teaching signals. We perturbed dopamine in healthy individuals using dopaminergic medication and asked them to predict variable rewards while we made brain scans. Dopamine perturbations impaired learning and the neural encoding of reward variability, thus establishing a direct link between dopamine and adaptation to reward variability. These results aid our understanding of clinical conditions associated with dopaminergic dysfunction, such as psychosis.

Diversity of Salmonella serotypes from humans, food, domestic animals and wildlife in New South Wales, Australia.

BACKGROUND: Salmonella is an important human pathogen in Australia and annual case rates continue to increase. In addition to foodborne exposures, cases have been associated with animal and contaminated environment contact. However, routine surveillance in Australia has tended to focus on humans and food, with no reported attempts to collate and compare Salmonella data from a wider range of potential sources of exposure. METHODS: Salmonella data from humans, food, animals and environments were collated from a range of surveillance and diagnostic sources in New South Wales (NSW). Data were categorised to reflect one of 29 sample origins. Serotype diversity was described for each category, and the distribution of serotypes commonly isolated from humans was examined for each sample origin. The distribution of serotypes along the livestock-food-human continuum and at the companion animal-wildlife interface was also examined. RESULTS: In total, 49,872 Salmonella isolates were included in this analysis, comprising 325 serotypes. The vast majority of these isolates were from humans (n = 38,106). Overall S. Typhimurium was the most frequently isolated serotype and was isolated from all sample categories except natural environment and game meat. S. Enteriditis was not isolated from any livestock animal, however sporadic cases were documented in food, companion animals and a reptile. Many serotypes that were frequently isolated from livestock animals and associated food products were only rarely isolated from humans. In addition, a number of key human serotypes were only sporadically isolated from livestock and food products, suggesting alternative sources of infection. In particular, S. Paratyphi B Java and S. Wangata were more often isolated from wild animals. Finally, there was some overlap between serotypes in companion animals and wildlife, with cats in particular having a large number of serotypes in common with wild birds. CONCLUSIONS: This is the most comprehensive description of Salmonella data from humans, food, livestock, wildlife, companion animals and various environments in Australia reported to date. Results confirm that livestock and food are important sources of salmonellosis in humans but that alternative sources - such as contact with wildlife and environments - warrant further investigation. Surveillance in NSW is largely human-focussed: major knowledge gaps exist regarding the diversity and frequency of serotypes in animals. More systematic surveillance of domestic animals and wildlife is needed to inform targeted control strategies and quantitative source attribution modelling in this state.

Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken.

A specific nanomanufacturing challenge.

For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO(®) brick scaled down by a factor of 10(n) for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

Accuracy of genomic selection for age at puberty in a multi-breed population of tropically adapted beef cattle.

Genomic selection is becoming a standard tool in livestock breeding programs, particularly for traits that are hard to measure. Accuracy of genomic selection can be improved by increasing the quantity and quality of data and potentially by improving analytical methods. Adding genotypes and phenotypes from additional breeds or crosses often improves the accuracy of genomic predictions but requires specific methodology. A model was developed to incorporate breed composition estimated from genotypes into genomic selection models. This method was applied to age at puberty data in female beef cattle (as estimated from age at first observation of a corpus luteum) from a mix of Brahman and Tropical Composite beef cattle. In this dataset, the new model incorporating breed composition did not increase the accuracy of genomic selection. However, the breeding values exhibited slightly less bias (as assessed by deviation of regression of phenotype on genomic breeding values from the expected value of 1). Adding additional Brahman animals to the Tropical Composite analysis increased the accuracy of genomic predictions and did not affect the accuracy of the Brahman predictions.

Scaling prediction errors to reward variability benefits error-driven learning in humans.

Effective error-driven learning requires individuals to adapt learning to environmental reward variability. The adaptive mechanism may involve decays in learning rate across subsequent trials, as shown previously, and rescaling of reward prediction errors. The present study investigated the influence of prediction error scaling and, in particular, the consequences for learning performance. Participants explicitly predicted reward magnitudes that were drawn from different probability distributions with specific standard deviations. By fitting the data with reinforcement learning models, we found scaling of prediction errors, in addition to the learning rate decay shown previously. Importantly, the prediction error scaling was closely related to learning performance, defined as accuracy in predicting the mean of reward distributions, across individual participants. In addition, participants who scaled prediction errors relative to standard deviation also presented with more similar performance for different standard deviations, indicating that increases in standard deviation did not substantially decrease "adapters'" accuracy in predicting the means of reward distributions. However, exaggerated scaling beyond the standard deviation resulted in impaired performance. Thus efficient adaptation makes learning more robust to changing variability.

Cortical thickness in individuals with non-clinical and clinical psychotic symptoms.

Symptoms that are linked to psychosis are also experienced by individuals who are not in need of care. In the present study, cortical thickness was investigated in these individuals. Fifty individuals with non-clinical auditory verbal hallucinations (most of them also experienced other non-clinical psychotic symptoms), 50 patients with a psychotic disorder and auditory verbal hallucinations, and 50 healthy control subjects underwent structural magnetic resonance imaging. Data were analysed using FreeSurfer. Cortical thickness in the pars orbitalis, paracentral lobule, fusiform gyrus and inferior temporal gyrus was lowest in patients, intermediate in the non-clinical hallucinating group, and highest in control subjects. The patients also showed thinning in widespread additional areas compared to the two other groups, whereas both hallucinating groups showed similar levels of thinning in the insula. Ranking the levels of cortical thickness per brain region across groups revealed that for 88% of brain regions, cortical thickness was lowest in patients, intermediate in the non-clinical hallucinating group, and highest in controls. These findings show that individuals with non-clinical psychotic symptoms show a similar but less pronounced pattern of cortical thinning as patients with a psychotic disorder, which is suggestive of a similar, but milder underlying pathophysiology in this group compared to the psychosis group.

Network analysis of auditory hallucinations in nonpsychotic individuals.

BACKGROUND: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia and can severely disrupt behavior and decrease quality of life. Identification of areas with high functional connectivity (so-called hub regions) that are associated with the predisposition to hallucinate may provide potential targets for neuromodulation in the treatment of AVH. METHODS: Resting-state fMRI scans during which no hallucinations had occurred were acquired from 29 nonpsychotic individuals with AVH and 29 matched controls. These nonpsychotic individuals with AVH provide the opportunity to study AVH without several confounds associated with schizophrenia, such as antipsychotic medication use and other symptoms related to the illness. Hub regions were identified by assessing weighted connectivity strength and betweenness centrality across groups using a permutation analysis. RESULTS: Nonpsychotic individuals with AVH exhibited increased functioning as hub regions in the temporal cortices and the posterior cingulate/precuneus, which is an important area in the default mode network (DMN), compared to the nonhallucinating controls. In addition, the right inferior temporal gyrus, left paracentral lobule and right amygdala were less important as a hub region in the AVH group. CONCLUSIONS: These results suggest that the predisposition to hallucinate may be related to aberrant functioning of the DMN and the auditory cortices.

Supervised independent component analysis as an alternative method for genomic selection in pigs.

The objective of this work was to evaluate the efficiency of the supervised independent component regression (SICR) method for the estimation of genomic values and the SNP marker effects for boar taint and carcass traits in pigs. The methods were evaluated via the agreement between the predicted genetic values and the corrected phenotypes observed by cross-validation. These values were also compared with other methods generally used for the same purposes, such as RR-BLUP, SPCR, SPLS, ICR, PCR and PLS. The SICR method was found to have the most accurate prediction values.

The membrane estrogen receptor ligand STX rapidly enhances GABAergic signaling in NPY/AgRP neurons: role in mediating the anorexigenic effects of 17ß-estradiol.

Besides its quintessential role in reproduction, 17ß-estradiol (E2) is a potent anorexigenic hormone. E2 and the selective Gq-coupled membrane estrogen receptor (Gq-mER) ligand STX rapidly increase membrane excitability in proopiomelanocortin (POMC) neurons by desensitizing the coupling of GABAB receptors to G protein-coupled inwardly rectifying K(+) channels (GIRKs), which upon activation elicit a hyperpolarizing outward current. However, it is unknown whether E2 and STX can modulate GABAB signaling in neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. We used single-cell RT-PCR and whole cell patch clamping with selective pharmacological reagents to show that NPY/AgRP cells of mice express the GABAB-R1 and -R2 receptors and are hyperpolarized by the GABAB agonist baclofen in an E2-dependent manner. In males, E2 rapidly attenuated the coupling of GABAB receptors to GIRKs, which was blocked by the general PI3K inhibitors wortmannin and LY-294002 or the selective p110ß subunit inhibitor TGX-221. The ERα-selective agonist propyl pyrazole triol mimicked the effects of E2. STX, in contrast, enhanced the GABAB response in males, which was abrogated by the estrogen receptor (ER) antagonist ICI 182,780. In gonadectomized mice of both sexes, E2 enhanced or attenuated the GABAB response in different NPY/AgRP cells. Coperfusing wortmannin with E2 or simply applying STX always enhanced the GABAB response. Thus, in NPY/AgRP neurons, activation of the Gq-mER by E2 or STX enhances the GABAergic postsynaptic response, whereas activation of ERα by E2 attenuates it. These findings demonstrate a clear functional dichotomy of rapid E2 membrane-initiated signaling via ERα vs. Gq-mER in a CNS neuron vital for regulating energy homeostasis.

Does tuition for journal referees work? A quantitative evaluation of a half-day tuition course.

AIM: Most consultants participating as referees in the peer review process of papers submitted to scholarly journals have had no training or tuition. This study attempted to evaluate the effect on reviewing of a half-day course held at the Royal Society of Medicine. METHOD: Registered consultant delegates were sent two 'doctored' papers, a case report and an original paper, well before the meeting to review at home using the standard computerized score sheet issued with referee requests by Colorectal Disease. At the start of the meeting the scores were entered into a computer as 'Before'. After each paper had been presented and then discussed, it was re-marked to give the 'After' score. The Before and After scores were compared with the post-meeting feedback forms. RESULTS: The Before and After scores provided by the participants for the two papers each reviewed were not significantly different for the questions relating to the publication/rejection decision. The Before score was higher than the After score for questions relating to the Abstract, Introduction and Method sections. Feedback forms regarding the tuition were universally positive and appreciative. CONCLUSION: Consultants already have the expertise to decide whether a paper should be rejected. The study day appears to give an additional insight that may change an initial opinion. In general a paper scored before the meeting was scored lower after it was presented and discussed at the meeting (the tuition).

Serotonin 5-HT2C receptor-mediated inhibition of the M-current in hypothalamic POMC neurons.

Hypothalamic proopiomelanocortin (POMC) neurons are controlled by many central signals, including serotonin. Serotonin increases POMC activity and reduces feeding behavior via serotonion [5-hydroxytryptamine (5-HT)] receptors by modulating K(+) currents. A potential K(+) current is the M-current, a noninactivating, subthreshold outward K(+) current. Previously, we found that M-current activity was highly reduced in fasted vs. fed states in neuropeptide Y neurons. Because POMC neurons also respond to energy states, we hypothesized that fasting may alter the M-current and/or its modulation by serotonergic input to POMC neurons. Using visualized-patch recording in neurons from fed male enhanced green fluorescent protein-POMC transgenic mice, we established that POMC neurons expressed a robust M-current (102.1 ± 6.7 pA) that was antagonized by the selective KCNQ channel blocker XE-991 (40 µM). However, the XE-991-sensitive current in POMC neurons did not differ between fed and fasted states. To determine if serotonin suppresses the M-current via the 5-HT(2C) receptor, we examined the effects of the 5-HT(2A)/5-HT(2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on the M-current. Indeed, DOI attenuated the M-current by 34.5 ± 6.9% and 42.0 ± 5.3% in POMC neurons from fed and fasted male mice, respectively. In addition, the 5-HT(1B)/5-HT(2C) receptor agonist m-chlorophenylpiperazine attenuated the M-current by 42.4 ± 5.4% in POMC neurons from fed male mice. Moreover, the selective 5-HT(2C) receptor antagonist RS-102221 abrogated the actions of DOI in suppressing the M-current. Collectively, these data suggest that although M-current expression does not differ between fed and fasted states in POMC neurons, serotonin inhibits the M-current via activation of 5-HT(2C) receptors to increase POMC neuronal excitability and, subsequently, reduce food intake.

Predicting benign course and prolonged illness in lower respiratory tract infections: a 13 European country study.

BACKGROUND: Clinicians and patients are often uncertain about the likely clinical course of community-acquired lower respiratory tract infection (LRTI) in individual patients. We therefore set out to develop a prediction rule to identify patients at risk of prolonged illness and those with a benign course. METHODS: We determined which signs and symptoms predicted prolonged illness (moderately bad symptoms lasting >3 weeks after consultation) in 2690 adults presenting in primary care with LRTI in 13 European countries by using multilevel modelling. RESULTS: 212 (8.1%) patients experienced prolonged illness. Illness that had lasted >5 days at the time of presentation, >1 episode of cough in the preceding year, chronic use of inhaled pulmonary medication and diarrhoea independently predicted prolonged illness. Applying a rule based on these four variables, 3% of the patients with ≤ 1 variable present (n = 955, 37%) had prolonged illness. Patients with all four variables present had a 30% chance of prolonged illness (n = 71, 3%). CONCLUSIONS: Most patients with acute cough (>90%) recover within 3 weeks. A prediction rule containing four clinical items had predictive value for the risk of prolonged illness, but given its imprecision, appeared to have little clinical utility. Patients should be reassured that they are most likely to recover within three weeks and advised to re-consult if their symptoms persist beyond that period.

Navigated knee kinematics after cutting of the ACL and its secondary restraint.

PURPOSE: The purpose of this study is to evaluate the kinematics changes of the knee after cutting of the ACL with or without injury of the anterolateral structures. METHODS: In this study, the role of the ACL and one of the secondary restraints in controlling knee stability using a navigation system was evaluated. The kinematics of the knee was evaluated in different conditions of instability: ACL intact, after dissection of the posterolateral (PL) bundle, after dissection of the anteromedial (AM) bundle, and after lesion of the lateral capsular ligament (LCL). Anterior tibial translation and rotation were measured with a computer navigation system in 10 fresh-frozen cadaveric knees by use of a manual maximum load. Anterior translation was evaluated at 30°, 60°, and 90° of flexion; rotation at 0°, 15°, 30°, 45°, 60°, and 90°. RESULTS: Cutting the PL bundle does not increase anterior translation and rotation of the knee. Cutting the AM bundle significantly increased the anteroposterior (AP) translation at 30° and 60° (P = 0.01), but does not increase rotation of the knee. Cutting the LCL increased anterior translation at 60° (P = 0.04) and rotation at 30°, 45°, and 60° (P = 0.03). CONCLUSIONS: Within the testing conditions of this study, the PL bundle does not affect anterior translation and rotation of the knee; the AM bundle is the primary restraint of the anterior translation but does not affect rotation of the knee while the lesion of the LCL increases tibial rotation and could be related to the pivot shift phenomenon, so it is more correct and biomechanical valid to assess and repair the associated lesion of the antero-lateral structure of the knee at the time of ACL surgery.

Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior.

Anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown. We therefore used single-voxel proton magnetic resonance spectroscopy to measure glutamate, myo-inositol, and NAA in the right inferior lateral prefrontal cortex and the right occipital cortex of 85 women [n = 22 AN (binge-eating/purging subtype; AN-BP), n = 33 BN, n = 30 controls]. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Women with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both regions. Although patient groups had intact instrumental learning task performance, both groups reported increased routine behaviors compared to controls, and automaticity was related to reduced prefrontal glutamate and NAA participants with AN-BP. Our findings extend previous reports of reduced myo-inositol and NAA levels in restrictive AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.

Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines.

European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription.

Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection.

We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p = 0.68) or green (coefficient -0.01; p = 0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p = 0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.

Intrinsic top-down unmanufacturability.

Although small structures can be fabricated by deposition, lithography and etching, in some cases their intrinsic variability precludes their use as elements in useful arrays. Manufacture is a proper subset of fabrication. We show that structures with 3 nm design rules can be fabricated but not manufactured in a top-down approach-they do not have the reproducibility to give a satisfactory yield to a pre-ordained specification. It is also shown that the transition from manufacturability to intrinsic unmanufacturability takes place at nearer 7 nm design rules.

Decreased language lateralization is characteristic of psychosis, not auditory hallucinations.

Decreased language lateralization is a well-replicated finding in psychotic patients. It is currently unclear, however, whether this abnormality is related to a particular symptom of psychosis or to psychosis in general. It has been argued that decreased language lateralization may be related to auditory verbal hallucinations. To elucidate this, these hallucinations should be studied in isolation. Thirty-five patients with a psychotic disorder, 35 non-psychotic subjects with relatively isolated auditory verbal hallucinations and 35 healthy control subjects participated in this study. All subjects were scanned on a 3T magnetic resonance imaging scanner, while covertly performing a paced verbal fluency task. In order to measure performance on the task, one additional task block was presented during which subjects had to generate words overtly. In addition to calculating language lateralization indices, group-wise brain activation during verbal fluency was compared between the three groups. Task performance was nearly maximal for all groups and did not differ significantly between the groups. Compared with the healthy control subjects and non-psychotic subjects with auditory verbal hallucinations, language lateralization was significantly reduced for the patient group. In addition, the patients displayed significantly greater activity in the right precentral gyrus and left insula when compared with the healthy control subjects and the non-psychotic subjects with auditory verbal hallucinations. Furthermore, the patients showed greater activity in the right superior parietal lobule when compared with the healthy control subjects. Lateralization indices did not differ significantly between the non-psychotic subjects with auditory verbal hallucinations and the healthy control subjects. Moreover, there were no significant differences in brain activation during verbal fluency between the two non-psychotic groups. As language lateralization was not significantly reduced in the non-psychotic individuals with auditory verbal hallucinations, a direct relationship between auditory verbal hallucinations and decreased language lateralization can not be established at present.