Longitudinal Stability of Vitamin D Status and Its Association With Bone Mineral Density in Middle-aged Australians.

Context: The skeletal effects of vitamin D remain controversial and it is uncertain whether variation in serum 25-hydroxyvitamin D (25OHD) levels over time influences bone mineral density (BMD). Objective: We evaluated longitudinal stability of serum 25OHD and associations with changes in BMD in participants aged 46-70 years at baseline. Methods: We studied 3698 Busselton Healthy Ageing Study participants (2040 female) with serum 25OHD and dual-energy x-ray absorptiometry (DXA) BMD assessments at baseline and at ∼6 years follow-up. Restricted cubic splines were used to evaluate associations between changes in 25OHD and BMD. Results: Mean season-corrected serum 25OHD was 81.3 ± 22.7 and 78.8 ± 23.1 nmol/L at baseline and 6 years, respectively, and showed moderate correlation (intraclass correlation coefficient: 0.724). Significant predictors of change in 25OHD concentration (Δ25OHD) included baseline 25OHD, change in body mass index and vitamin D supplementation at follow-up. Greater decline in serum 25OHD over time was associated with significantly greater reduction in BMD at total hip and femoral neck, but the magnitude of the differences was small (estimated differences 0.004 g/cm2 and 0.005-0.007 g/cm2, respectively, for lowest quartile of Δ25OHD compared with higher quartiles, adjusted for sex, baseline BMD, 25OHD, and demographics). No significant associations between Δ25OHD and lumbar spine BMD were observed. Increase in 25OHD levels was not associated with change in BMD. Conclusions: In this predominantly vitamin D-replete middle-aged cohort, serum 25OHD showed moderate longitudinal stability. Declining serum 25OHD over time was associated with greater reduction in BMD at the total hip and femoral neck.

Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study.

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

Modulating affective experience and emotional intelligence with loving kindness meditation and transcranial direct current stimulation: A pilot study.

Positive emotional perceptions and healthy emotional intelligence (EI) are important for social functioning. In this study, we investigated whether loving kindness meditation (LKM) combined with anodal transcranial direct current stimulation (tDCS) would facilitate improvements in EI and changes in affective experience of visual stimuli. LKM has been shown to increase positive emotional experiences and we hypothesized that tDCS could enhance these effects. Eighty-seven undergraduates were randomly assigned to 30 minutes of LKM or a relaxation control recording with anodal tDCS applied to the left dorsolateral prefrontal cortex (left dlPFC) or right temporoparietal junction (right TPJ) at 0.1 or 2.0 milliamps. The primary outcomes were self-reported affect ratings of images from the International Affective Picture System and EI as measured by the Mayer, Salovey and Caruso Emotional Intelligence Test. Results indicated no effects of training on EI, and no main effects of LKM, electrode placement, or tDCS current strength on affect ratings. There was a significant interaction of electrode placement by meditation condition (p = 0.001), such that those assigned to LKM and right TPJ tDCS, regardless of current strength, rated neutral and positive images more positively after training. Results suggest that LKM may enhance positive affective experience.

Mindfulness-based training with transcranial direct current stimulation modulates neuronal resource allocation in working memory: A randomized pilot study with a nonequivalent control group.

Mindfulness-based training (MBT) and transcranial electrical stimulation (TES) methods such as direct current stimulation (tDCS) have demonstrated promise for the augmentation of cognitive abilities. The current study investigated the potential compatibility of concurrent "electrical" MBT and tDCS (or eMBT) by testing its combined effects on behavioral and neurophysiological indices of working memory (WM) and attentional resource allocation. Thirty-four healthy participants were randomly assigned to either a MBT task with tDCS group (eMBT) or an active control training task with sham tDCS (Control) group. Training lasted 4-weeks, with up to twenty MBT sessions and with up to eight of those sessions that were eMBT sessions. Electroencephalography was acquired during varying WM load conditions using the n-back task (1-, 2-, 3-back), along with performance on complex WM span tasks (operation and symmetry span) and fluid intelligence measures (Ravens and Shipley) before and after training. Improved performance was observed only on the 3-back and spatial span tasks for eMBT but not the Control group. During 3-back performance in the eMBT group, an increase in P3 amplitude and theta power at electrode site Pz was also observed, along with a simultaneous decrease in frontal midline P3 amplitude and theta power compared to the Control group. These results are consistent with the neural efficiency hypothesis, where higher cognitive capacity was associated with more distributed brain activity (i.e., increase in parietal and decrease in frontal amplitudes). Future longitudinal studies are called upon to further examine the direct contributions of tDCS on MBT by assessing the differential effects of electrode montage, polarity, current strength and a direct contrast between the eMBT and MBT conditions on performance and neuroimaging outcome data. While preliminary, the current results provided evidence for the potential compatibility of using eMBT to modulate WM capacity through the allocation of attention and its neurophysiological correlates.

Vitamin D and respiratory health in the Busselton Healthy Ageing Study.

BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). CONCLUSION: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.

By our bootstraps: Comparing methods for measuring auditory 40 Hz steady-state neural activity.

Although the 40 Hz auditory steady-state response (ASSR) is of clinical interest, the construct validity of EEG and MEG measures of 40 Hz ASSR cortical microcircuits is unclear. This study evaluated several MEG and EEG metrics by leveraging findings of (a) an association between the 40 Hz ASSR and age in the left but not right hemisphere, and (b) right- > left-hemisphere differences in the strength of the 40 Hz ASSR. The contention is that, if an analysis method does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere differences, then the obtained measures likely have low validity. Fifty-three adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were collected. ASSR activity was examined as a function of phase similarity (intertrial coherence) and percent change from baseline (total power). A variety of head models (spherical and realistic) and a variety of dipole source modeling strategies (dipole source localization and dipoles fixed to Heschl's gyri) were compared. Several sensor analysis strategies were also tested. EEG sensor measures failed to detect left 40 Hz ASSR and age associations or hemisphere differences. A comparison of MEG and EEG head-source models showed similarity in the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations, indicating good construct validity across models. Given a goal of measuring the 40 Hz ASSR cortical microcircuits, a source-modeling approach was shown to be superior in measuring this construct versus methods that rely on EEG sensor measures.

Practice makes imperfect: Working memory training can harm recognition memory performance.

There is a great deal of debate concerning the benefits of working memory (WM) training and whether that training can transfer to other tasks. Although a consistent finding is that WM training programs elicit a short-term near-transfer effect (i.e., improvement in WM skills), results are inconsistent when considering persistence of such improvement and far transfer effects. In this study, we compared three groups of participants: a group that received WM training, a group that received training on how to use a mental imagery memory strategy, and a control group that received no training. Although the WM training group improved on the trained task, their posttraining performance on nontrained WM tasks did not differ from that of the other two groups. In addition, although the imagery training group's performance on a recognition memory task increased after training, the WM training group's performance on the task decreased after training. Participants' descriptions of the strategies they used to remember the studied items indicated that WM training may lead people to adopt memory strategies that are less effective for other types of memory tasks. These results indicate that WM training may have unintended consequences for other types of memory performance.

Mismatch negativity (MMN) in freely-moving rats with several experimental controls.

Mismatch negativity (MMN) is a scalp-recorded electrical potential that occurs in humans in response to an auditory stimulus that defies previously established patterns of regularity. MMN amplitude is reduced in people with schizophrenia. In this study, we aimed to develop a robust and replicable rat model of MMN, as a platform for a more thorough understanding of the neurobiology underlying MMN. One of the major concerns for animal models of MMN is whether the rodent brain is capable of producing a human-like MMN, which is not a consequence of neural adaptation to repetitive stimuli. We therefore tested several methods that have been used to control for adaptation and differential exogenous responses to stimuli within the oddball paradigm. Epidural electroencephalographic electrodes were surgically implanted over different cortical locations in adult rats. Encephalographic data were recorded using wireless telemetry while the freely-moving rats were presented with auditory oddball stimuli to assess mismatch responses. Three control sequences were utilized: the flip-flop control was used to control for differential responses to the physical characteristics of standards and deviants; the many standards control was used to control for differential adaptation, as was the cascade control. Both adaptation and adaptation-independent deviance detection were observed for high frequency (pitch), but not low frequency deviants. In addition, the many standards control method was found to be the optimal method for observing both adaptation effects and adaptation-independent mismatch responses in rats. Inconclusive results arose from the cascade control design as it is not yet clear whether rats can encode the complex pattern present in the control sequence. These data contribute to a growing body of evidence supporting the hypothesis that rat brain is indeed capable of exhibiting human-like MMN, and that the rat model is a viable platform for the further investigation of the MMN and its associated neurobiology.

Repetition suppression of the rat auditory evoked potential at brief stimulus intervals.

An important prerequisite for the development of animal models of human auditory evoked potentials (AEP) is the accurate identification of homology. Prior research has revealed some remarkably similar response properties between rat and human AEPs, although there remains little consensus regarding the nature or validity of this correspondence. In the present study we seek to extend this research by examining the response properties of rat AEP as a function of stimulus repetition and interval. The aim being to determine whether rat AEP components show the same paradoxical reversal of repetition suppression observed for the human N100 AEP component at brief stimulus intervals. To achieve this, AEPs were recorded epidurally at the vertex in the freely moving rat in response to acoustic stimuli presented at random stimulus intervals between 50 and 5,000 ms. Using stimulation and analysis techniques to remove AEP waveform distortion due to overlapping AEP responses, the present results show that rat AEP components can be successfully resolved at intervals as brief as 50 ms. The results also demonstrate several fundamental types of correspondence between human and rat AEP components in terms of the sensitivity to stimulus interval and acoustic stimulus type. However the results found no evidence that rat AEP components show the reversal of repetition suppression at brief, relative to long, stimulus intervals as demonstrated for the N100 component in humans. The results are discussed in terms of EEG recording and AEP analysis procedures that provide promising avenues for future research.

Temporal and frontal cortical thickness associations with M100 auditory activity and attention in healthy controls and individuals with schizophrenia.

BACKGROUND: Although gray matter (GM) abnormalities are frequently observed in individuals with schizophrenia (SCZ), the functional consequences of these structural abnormalities are not yet understood. The present study sought to better understand GM abnormalities in SCZ by examining associations between GM and two putative functional SCZ biomarkers: weak 100 ms (M100) auditory responses and impairment on tests of attention. METHODS: Data were available from 103 subjects (healthy controls=52, SCZ=51). GM cortical thickness measures were obtained for superior temporal gyrus (STG) and prefrontal cortex (PFC). Magnetoencephalography (MEG) provided measures of left and right STG M100 source strength. Subjects were administered the Trail Making Test A and the Connors' Continuous Performance Test to assess attention. RESULTS: A strong trend indicated less GM cortical thickness in SCZ than controls in both regions and in both hemispheres (p=0.06). Individuals with SCZ had weaker M100 responses than controls bilaterally, and individuals with SCZ performed more poorly than controls on tests of attention. Across groups, left STG GM was positively associated with left M00 source strength. In SCZ only, less left and right STG and PFC GM predicted poorer performance on tests of attention. After removing variance in attention associated with age, associations between GM and attention remained significant only in left and right STG. CONCLUSIONS: Reduced GM cortical thickness may serve as a common substrate for multiple functional abnormalities in SCZ, with structural-functional abnormalities in STG GM especially prominent. As suggested by others, functional abnormalities in SCZ may be a consequence of elimination of the neuropil (dendritic arbors and associated synaptic infrastructure) between neuron bodies.

The Royal Society and the decline of magic.

Whereas some have asserted that the early Royal Society actively sought to discredit magical beliefs, others have seen ideas of this kind as integral to the Society's 'nature' in its early years. This paper argues that, whatever the magical commitments of individual Fellows, the Society's corporate policy simply sidelined such pursuits. Yet, insofar as the result was that magic was excluded by default from the proper realm of scientific enquiry, this attitude was to prove paradoxically influential (although its roots have been retrospectively misconstrued to an extent that is significant in itself).

Enhanced cortical effects of auditory stimulation and auditory attention in healthy individuals prone to auditory hallucinations during partial wakefulness.

Investigating auditory hallucinations that occur in health may help elucidate brain mechanisms which lead to the pathological experience of auditory hallucinations in neuropsychiatric disorders such as schizophrenia. In this study, we investigated healthy individuals who reported auditory hallucinations whilst falling asleep (hypnagogic hallucinations; HG) and waking up (hypnopompic hallucinations; HP). In an initial behavioural study, we found that subjects with a history of auditory HG/HP hallucinations (n = 26) reported significantly greater subjective sensitivity to environmental sounds than non-hallucinator controls (n = 74). Then, two fMRI experiments were performed. The first examined speech-evoked brain activation in 12 subjects with a history of auditory HG/HP hallucinations and 12 non-hallucinator controls matched for age, gender and IQ. The second fMRI experiment, in the same subjects, probed how brain activation was modulated by auditory attention using a bimodal selective attention paradigm. In the first experiment, the hallucinator group demonstrated significantly greater speech-evoked activation in the left supramarginal gyrus than the control group. In the second experiment, directing attention towards the auditory (vs. visual) modality induced significantly greater activation of the anterior cingulate gyrus in the hallucinator group than in the control group. These results suggest that hallucination proneness is associated with increased sensitivity of auditory and polysensory association cortex to auditory stimulation, an effect which might arise due to enhanced attentional bias from the anterior cingulate gyrus. Our data support the overarching hypothesis that top-down modulation of auditory cortical response characteristics may be a key mechanistic step in the generation of auditory hallucinations.

Lateralized abnormalities in auditory M50 sensory gating and cortical thickness of the superior temporal gyrus in post-traumatic stress disorder: preliminary results.

Auditory sensory gating deficits have been reported in subjects with post-traumatic stress disorder (PTSD), but the hemispheric and neuronal origins of this deficit are not well understood. The objectives of this study were to: (1) investigate auditory sensory gating of the 50-ms response (M50) in patients diagnosed with PTSD by utilizing magnetoencephalography (MEG); (2) explore the relationship between M50 sensory gating and cortical thickness of the superior temporal gyrus (STG) measured with structural magnetic resonance imaging (MRI); and (3) examine the association between PTSD symptomatology and bilateral sensory gating. Seven participants with combat-related PTSD and eleven controls underwent the paired-click sensory gating paradigm. MEG localized M50 neuronal generators to the STG in both groups. The PTSD group displayed impaired M50 gating in the right hemisphere. Thinner right STG cortical thickness was associated with worse right sensory gating in the PTSD group. The right S1 M50 source strength and gating ratio were correlated with PTSD symptomatology. These findings suggest that the structural integrity of right hemisphere STG cortices play an important role in auditory sensory gating deficits in PTSD.

Voice familiarity engages auditory cortex.

Familiarity with a speaker's voice has been shown to enhance its auditory processing, implicating physiological effects at the level of the auditory cortex, although auditory cortical involvement has not previously been demonstrated. Eleven healthy right-handed male participants performed two tasks during blood oxygenation level-dependent functional MRI at 1.5 T. Both tasks used the same vocal stimuli. In task 1, they classified speakers as familiar or unfamiliar. In task 2, they judged stimuli as being in the right or left auditory field. Our analysis showed an area of auditory cortex on the lower bank of the superior temporal sulcus that was preferentially activated by familiar voices in both tasks. Familiar voices may elicit access to detailed sensory expectations, allowing enhanced auditory cortical processing.

Lateral response dynamics and hemispheric dominance for speech perception.

In this study, we investigated the mechanism for the left cerebral hemisphere's dominance for speech perception. We utilized the crossover of auditory pathways in the central nervous system to present speech stimuli more directly to the left hemisphere (via the right ear) and right hemisphere (via the left ear). Using functional MRI, we found that estimated duration of neural response in the left auditory cortex increased as more speech information was directly received from the right ear. Conversely, response duration in the right auditory cortex was not modulated when more speech information was directly received from the left ear. These data suggest that selective temporal responding distinguishes the dominant from nondominant hemisphere of the human brain during speech perception.

Male and female voices activate distinct regions in the male brain.

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.