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See Vidailhet et al. (doi:10.1093/brain/awx140) for a scientific commentary on this article. Misdiagnosis among tremor syndromes is common, and can impact on both clinical care and research. To date no validated neurophysiological technique is available that has proven to have good classification performance, and the diagnostic gold standard is the clinical evaluation made by a movement disorders expert. We present a robust new neurophysiological measure, the tremor stability index, which can discriminate Parkinson’s disease tremor and essential tremor with high diagnostic accuracy. The tremor stability index is derived from kinematic measurements of tremulous activity. It was assessed in a test cohort comprising 16 rest tremor recordings in tremor-dominant Parkinson’s disease and 20 postural tremor recordings in essential tremor, and validated on a second, independent cohort comprising a further 55 tremulous Parkinson’s disease and essential tremor recordings. Clinical diagnosis was used as gold standard. One hundred seconds of tremor recording were selected for analysis in each patient. The classification accuracy of the new index was assessed by binary logistic regression and by receiver operating characteristic analysis. The diagnostic performance was examined by calculating the sensitivity, specificity, accuracy, likelihood ratio positive, likelihood ratio negative, area under the receiver operating characteristic curve, and by cross-validation. Tremor stability index with a cut-off of 1.05 gave good classification performance for Parkinson’s disease tremor and essential tremor, in both test and validation datasets. Tremor stability index maximum sensitivity, specificity and accuracy were 95%, 95% and 92%, respectively. Receiver operating characteristic analysis showed an area under the curve of 0.916 (95% confidence interval 0.797–1.000) for the test dataset and a value of 0.855 (95% confidence interval 0.754–0.957) for the validation dataset. Classification accuracy proved independent of recording device and posture. The tremor stability index can aid in the differential diagnosis of the two most common tremor types. It has a high diagnostic accuracy, can be derived from short, cheap, widely available and non-invasive tremor recordings, and is independent of operator or postural context in its interpretation. [ABSTRACT FROM AUTHOR]

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered. [ABSTRACT FROM AUTHOR]

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. [ABSTRACT FROM AUTHOR]

Adaptive behaviour entails the capacity to select actions as a function of their energy cost and expected value and the disruption of this faculty is now viewed as a possible cause of the symptoms of Parkinson's disease. Indirect evidence points to the involvement of the subthalamic nucleus-the most common target for deep brain stimulation in Parkinson's disease-in cost-benefit computation. However, this putative function appears at odds with the current view that the subthalamic nucleus is important for adjusting behaviour to conflict. Here we tested these contrasting hypotheses by recording the neuronal activity of the subthalamic nucleus of patients with Parkinson's disease during an effort-based decision task. Local field potentials were recorded from the subthalamic nucleus of 12 patients with advanced Parkinson's disease (mean age 63.8 years ± 6.8; mean disease duration 9.4 years ± 2.5) both OFF and ON levodopa while they had to decide whether to engage in an effort task based on the level of effort required and the value of the reward promised in return. The data were analysed using generalized linear mixed models and cluster-based permutation methods. Behaviourally, the probability of trial acceptance increased with the reward value and decreased with the required effort level. Dopamine replacement therapy increased the rate of acceptance for efforts associated with low rewards. When recording the subthalamic nucleus activity, we found a clear neural response to both reward and effort cues in the 1-10 Hz range. In addition these responses were informative of the subjective value of reward and level of effort rather than their actual quantities, such that they were predictive of the participant's decisions. OFF levodopa, this link with acceptance was weakened. Finally, we found that these responses did not index conflict, as they did not vary as a function of the distance from indifference in the acceptance decision. These findings show that low-frequency neuronal activity in the subthalamic nucleus may encode the information required to make cost-benefit comparisons, rather than signal conflict. The link between these neural responses and behaviour was stronger under dopamine replacement therapy. Our findings are consistent with the view that Parkinson's disease symptoms may be caused by a disruption of the processes involved in balancing the value of actions with their associated effort cost. [ABSTRACT FROM AUTHOR]

Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. [ABSTRACT FROM AUTHOR]

Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6-20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL. [ABSTRACT FROM AUTHOR]

The process of invasion and the desire to predict the invasiveness (and associated impacts) of new arrivals has been a focus of attention for ecologists over centuries. The volunteer recording community has made unique and inspiring contributions to our understanding of invasion biology within Britain. Indeed information on non-native species ( NNS) compiled within the GB Non- Native Species Information Portal ( GB-NNSIP) would not have been possible without the involvement of volunteer experts from across Britain. Here we review examples of ways in which biological records have informed invasion biology. We specifically examine NNS information available within the GB-NNSIP to describe patterns in the arrival and establishment of NNS providing an overview of habitat associations of NNS in terrestrial, marine and freshwater environments. Monitoring and surveillance of the subset of NNS that are considered to be adversely affecting biodiversity, society or the economy, termed invasive non-native species ( INNS), is critical for early warning and rapid response. Volunteers are major contributors to monitoring and surveillance of INNS and not only provide records from across Britain but also underpin the system of verification necessary to confirm the identification of sightings. Here we describe the so-called 'alert system' which links volunteer experts with the wider recording community to provide early warning of INNS occurrence. We highlight the need to increase understanding of community and ecosystem-level effects of invasions and particularly understanding of ecological resilience. Detailed field observations, through biological recording, will provide the spatial, temporal and taxonomic breadth required for such research. The role of the volunteer recording community in contributing to the understanding of invasion biology has been invaluable and it is clear that their expertise and commitment will continue to be so. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, ●●, ●●-●●. [ABSTRACT FROM AUTHOR]

We present observations of SN Hunt 248, a new supernova (SN) impostor in NGC 5806, which began a multistage outburst in 2014 May. The '2014a' discovery brightening exhibited an absolute magnitude of M ≈ - 12 and the spectral characteristics of a cool, dense outflow, including P Cygni lines of FeII, HI, and NaI, and line blanketing from metals. The source rapidly climbed and peaked at M ≈ 15 mag after two additional weeks. During this bright '2014b' phase the spectrum became dominated by Balmer emission and a stronger blue continuum, similar to the SN impostor SN 1997bs. Archival images from the Hubble Space Telescope between 1997 and 2005 reveal a luminous (4 x 105 L⊙) variable precursor star. Its location on the Hertzsprung-Russell diagram is consistent with a massive (Minit ≈ 30 M⊙) cool hypergiant having an extremely dense wind and an Eddington ratio (Γ) just below unity. At the onset of the 2014a brightening, however, the object was super-Eddington (Γ = 4-12). The subsequent boost in luminosity during the 2014b phase probably resulted from circumstellar interaction. SN Hunt 248 provides the first case of a cool hypergiant undergoing a giant eruption reminiscent of outbursts from luminous blue variable stars (LBVs). This lends support to the hypothesis that some cool hypergiants, such as ρ Cas, could be LBVs masquerading under a pseudo-photosphere created by their extremely dense winds. Moreover, SN Hunt 248 demonstrates that eruptions stemming from such stars can rival in peak luminosity the giant outbursts of much more massive systems like η Car. [ABSTRACT FROM AUTHOR]

See Arkadir et al. (doi:10.1093/brain/awu285) for a scientific commentary on this article. The mechanisms underlying tremor generation remain unclear. Cagnan et al. use deep brain stimulation of the thalamus or subthalamic nucleus at/near a patient's own tremor frequency to investigate the networks responsible for parkinsonian and essential tremor. The results reveal differences in the circuitry underlying these two tremor types.Tremor is a cardinal feature of Parkinson’s disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient’s own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson’s disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50–77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34–74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson’s disease, P = 0.0078, subthalamic stimulation in Parkinson’s disease, P = 0.0312; ventrolateral thalamic stimulation in essential tremor, P = 0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P = 0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that parkinsonian rest tremor is driven by a neural network, which includes the subthalamic nucleus and ventrolateral thalamus and has broad frequency-amplitude tolerance. We propose that it is this tolerance to changes in tremor frequency that dictates that parkinsonian rest tremor may be significantly entrained by low frequency stimulation without stimulation timing-dependent amplitude modulation. In contrast, the circuit influenced by low frequency thalamic stimulation in essential tremor has a narrower frequency-amplitude tolerance so that tremor entrainment through extrinsic driving is necessarily accompanied by amplitude modulation. Such differences in parkinsonian rest and essential tremor will be important in selecting future strategies for closed loop deep brain stimulation for tremor control. [ABSTRACT FROM AUTHOR]

Deep brain stimulation of the globus pallidus internus alleviates involuntary movements in patients with dystonia. However, the mechanism is still not entirely understood. One hypothesis is that deep brain stimulation suppresses abnormally enhanced synchronized oscillatory activity within the motor cortico-basal ganglia network. Here, we explore deep brain stimulation-induced modulation of pathological low frequency (4-12 Hz) pallidal activity that has been described in local field potential recordings in patients with dystonia. Therefore, local field potentials were recorded from 16 hemispheres in 12 patients undergoing deep brain stimulation for severe dystonia using a specially designed amplifier allowing simultaneous high frequency stimulation at therapeutic parameter settings and local field potential recordings. For coherence analysis electroencephalographic activity (EEG) over motor areas and electromyographic activity (EMG) from affected neck muscles were recorded before and immediately after cessation of high frequency stimulation. High frequency stimulation led to a significant reduction of mean power in the 4-12 Hz band by 24.8 ± 7.0% in patients with predominantly phasic dystonia. A significant decrease of coherence between cortical EEG and pallidal local field potential activity in the 4-12 Hz range was revealed for the time period of 30 s after switching off high frequency stimulation. Coherence between EMG activity and pallidal activity was mainly found in patients with phasic dystonic movements where it was suppressed after high frequency stimulation. Our findings suggest that high frequency stimulation may suppress pathologically enhanced low frequency activity in patients with phasic dystonia. These dystonic features are the quickest to respond to high frequency stimulation and may thus directly relate to modulation of pathological basal ganglia activity, whereas improvement in tonic features may depend on long-term plastic changes within the motor network. [ABSTRACT FROM AUTHOR]

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound. [ABSTRACT FROM PUBLISHER]

The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson’s disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson’s disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5–12 Hz) and high-gamma/high-frequency (55–375 Hz) subthalamic nucleus activity and force measures, which explained close to 70% of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (≤13%). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual’s peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli. [ABSTRACT FROM AUTHOR]

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral. [ABSTRACT FROM PUBLISHER]

Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as ‘slowness of initiation with progressive reduction in speed and amplitude of repetitive action’. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (−0.20°/cycle, P = 0.002). ‘Hypokinesia’, defined as <50% of control group's mean amplitude, combined with ‘absence of decrement’, defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria-defined bradykinesia, characterized by slowness with progressive reduction in amplitude and speed and increased variability in speed throughout the tap trial. In Parkinson's disease, smaller amplitude, slower speed and greater speed variability were all associated with a more severe Unified Parkinson's Disease Rating Scale motor score. Analyses of handwriting showed that micrographia, defined as smaller than 50% of the control group's mean script size, was present in 75% of patients with progressive supranuclear palsy and 15% of patients with Parkinson's disease (P = 0.022). Most scripts performed by patients with progressive supranuclear palsy did not exhibit decrements in script size. In conclusion, patients with progressive supranuclear palsy have a specific finger tap pattern of ‘hypokinesia without decrement’ and they do not have criteria-defined limb bradykinesia. Similarly, ‘micrographia’ and ‘lack of decrement in script size’ are also more common in progressive supranuclear palsy than in Parkinson's disease. [ABSTRACT FROM AUTHOR]

The pedunculopontine nucleus, a component of the reticular formation, is topographically organized in animal models and implicated in locomotor control. In Parkinson's disease, pedunculopontine nucleus stimulation is an emerging treatment for gait freezing. Local field potentials recorded from pedunculopontine nucleus electrodes in such patients have demonstrated oscillations in the alpha and beta frequency bands, reactive to self-paced movement. Whether these oscillations are topographically organized or relevant to locomotion is unknown. Here, we recorded local field potentials from the pedunculopontine nucleus in parkinsonian patients during rest and unconstrained walking. Relative gait speed was assessed with trunk accelerometry. Peaks of alpha power were present at rest and during gait, when they correlated with gait speed. Gait freezing was associated with attenuation of alpha activity. Beta peaks were less consistently observed across rest and gait, and did not correlate with gait speed. Alpha power was maximal in the caudal pedunculopontine nucleus region and beta power was maximal rostrally. These results indicate a topographic distribution of neuronal activity in the pedunculopontine nucleus region and concur with animal data suggesting that the caudal subregion has particular relevance to gait. Alpha synchronization, proposed to suppress ‘task irrelevant’ distraction, has previously been demonstrated to correlate with performance of cognitive tasks. Here, we demonstrate a correlation between alpha oscillations and improved gait performance. The results raise the possibility that stimulation of caudal and rostral pedunculopontine nucleus regions may differ in their clinical effects. [ABSTRACT FROM PUBLISHER]

Objective: To quantify the health, fitness, and physiological responses to military training of Officer Cadets from a Gulf Cooperation Council country.Methods: One hundred and nineteen Officer Cadets volunteered; body composition, core body temperature, aerobic fitness, hydration status (urine osmolality), cardiovascular strain, physical activity (3-dimensional accelerometry), and energy expenditure (doubly labelled water) were measured over 5-days of Basic Training (BT), Army Training (AT), Navy Training (NT), and Air Force Training (AFT).Results: There were no differences between courses for body mass index (mean all courses: 24.1 +/- 4.1 kg x m2) or peak core body temperature (mean all courses: 38.1 +/- 0.4 degrees C) (p > 0.05). AT body fat (19.8 +/- 3.6%) and BT VO2 max (36.8 +/- 11.6 mL x kg(-1) x min(-1)) were lower than the other courses (BT, 26.1 +/- 8.1; NT, 26.0 +/- 6.0; AFT, 24.7 +/- 6.1%) and (AT, 44.8 +/- 9.6; NT, 45.0 +/- 7.5; AFT, 44.6 +/- 5.2 mL x kg(-1) x min(-1)), respectively (p < 0.05). NT urine osmolality (979 +/- 90 mOsmol x kg(-1)) was similar to BT (946 +/- 181 mOsmol x kg(-1) p > 0.05) but lower in AT (868 +/- 144 mOsmol x kg(-1), p < 0.05) and AFT (883 +/- 121 mOsmol x kg(-1), p < 0.05). Cardiovascular strain during NT (22 +/- 5% HRR) was lower than other courses (range, 25 +/- 4-29 +/- 3% Heart Rate Reserve) (p < 0.05). Physical activity level during AFT (1.70 +/- 0.18 AU) was lower than other courses (range, 1.86 +/- 0.21-1.92 +/- 0.18 AU) (p > 0.05).Conclusion: Positive developments were apparent from BT leading into other courses. Potential exists to increase physical training volume on all courses, which may improve participants' aerobic fitness, body composition, and health. [ABSTRACT FROM AUTHOR]

Gait freezing and postural instability are disabling features of Parkinsonian disorders, treatable with pedunculopontine nucleus stimulation. Both features are considered deficits of proximal and axial musculature, innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment. Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release. Experimentally, such accelerated release can be elicited by loud auditory stimuli—a phenomenon known as ‘StartReact’. We observed StartReact in healthy and Parkinsonian controls. However, StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability. Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance. These findings suggest a relative block to triggered, pre-prepared movement in gait freezing and postural instability, relieved by pedunculopontine nucleus stimulation. [ABSTRACT FROM AUTHOR]

Both phenotype and treatment response vary in patients with Parkinson's disease. Anatomical and functional imaging studies suggest that individual symptoms may represent malfunction of different segregated networks running in parallel through the basal ganglia. In this study, we use a newly described, electrophysiological method to describe cortico-subthalamic networks in humans. We performed combined magnetoencephalographic and subthalamic local field potential recordings in thirteen patients with Parkinson's disease at rest. Two spatially and spectrally separated networks were identified. A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7-13 Hz) band, whilst a predominantly frontal network was coherent in the beta (15-35 Hz) band. Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex. Subthalamic activity was predominantly led by activity in the cortex in both frequency bands. The cortical topography and frequencies involved in the alpha and beta networks suggest that these networks may be involved in attentional and executive, particularly motor planning, processes, respectively. [ABSTRACT FROM AUTHOR]

Both phenotype and treatment response vary in patients with Parkinson’s disease. Anatomical and functional imaging studies suggest that individual symptoms may represent malfunction of different segregated networks running in parallel through the basal ganglia. In this study, we use a newly described, electrophysiological method to describe cortico-subthalamic networks in humans. We performed combined magnetoencephalographic and subthalamic local field potential recordings in thirteen patients with Parkinson’s disease at rest. Two spatially and spectrally separated networks were identified. A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7–13 Hz) band, whilst a predominantly frontal network was coherent in the beta (15–35 Hz) band. Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex. Subthalamic activity was predominantly led by activity in the cortex in both frequency bands. The cortical topography and frequencies involved in the alpha and beta networks suggest that these networks may be involved in attentional and executive, particularly motor planning, processes, respectively. [ABSTRACT FROM AUTHOR]

Neuronal activity within and across the cortex and basal ganglia is pathologically synchronized, particularly at approximately 20 Hz in patients with Parkinson's disease. Defining how activities in spatially distributed brain regions overtly synchronize in narrow frequency bands is critical for understanding disease processes like Parkinson's disease. To address this, we studied cortical responses to electrical stimulation of the subthalamic nucleus (STN) at various frequencies between 5 and 30 Hz in two cohorts of eight patients with Parkinson's disease from two different surgical centres. We found that evoked activity consisted of a series of diminishing waves with a peak latency of 21 ms for the first wave in the series. The cortical evoked potentials (cEPs) averaged in each group were well fitted by a damped oscillator function (r > or = 0.9, P < 0.00001). Fits suggested that the natural frequency of the subthalamo-cortical circuit was around 20 Hz. When the system was forced at this frequency by stimulation of the STN at 20 Hz, the undamped amplitude of the modelled cortical response increased relative to that with 5 Hz stimulation in both groups (P < or = 0.005), consistent with resonance. Restoration of dopaminergic input by treatment with levodopa increased the damping of oscillatory activity (as measured by the modelled damping factor) in both patient groups (P < or = 0.001). The increased damping would tend to limit resonance, as confirmed in simulations. Our results show that the basal ganglia-cortical network involving the STN has a tendency to resonate at approximately 20 Hz in Parkinsonian patients. This resonance phenomenon may underlie the propagation and amplification of activities synchronized around this frequency. Crucially, dopamine acts to increase damping and thereby limit resonance in this basal ganglia-cortical network. [ABSTRACT FROM AUTHOR]

Photographs from a cardiac computed tomography showing an internal mammary arterio-venous fistula from a 73-year old female patient with continuous heart murmur are presented.

Whilst urban-dwelling individuals who seek out parks and gardens appear to intuitively understand the personal health and well-being benefits arising from 'contact with nature', public health strategies are yet to maximize the untapped resource nature provides, including the benefits of nature contact as an upstream health promotion intervention for populations. This paper presents a summary of empirical, theoretical and anecdotal evidence drawn from a literature review of the human health benefits of contact with nature. Initial findings indicate that nature plays a vital role in human health and well-being, and that parks and nature reserves play a significant role by providing access to nature for individuals. Implications suggest contact with nature may provide an effective population-wide strategy in prevention of mental ill health, with potential application for sub-populations, communities and individuals at higher risk of ill health. Recommendations include further investigation of 'contact with nature' in population health, and examination of the benefits of nature-based interventions. To maximize use of 'contact with nature' in the health promotion of populations, collaborative strategies between researchers and primary health, social services, urban planning and environmental management sectors are required. This approach offers not only an augmentation of existing health promotion and prevention activities, but provides the basis for a socio-ecological approach to public health that incorporates environmental sustainability. [ABSTRACT FROM AUTHOR]

The prevalence of post-traumatic stress disorder (PTSD) has reached epidemic proportions among U.S. veterans, many of whom also have concurrent alcohol use disorder. This case report describes improvements in PTSD symptom severity and memory dysfunction in a combat-exposed veteran with persistent PTSD and alcohol use disorder following two treatments of stellate ganglion block (SGB). PTSD severity was measured using the PTSD Checklist, Military Version. Memory function was evaluated using the Rey Auditory Verbal Learning Test. One month after the first SGB, a 43.6% reduction in PTSD severity was observed along with increases in immediate memory (50%), recent memory (28%), and recognition memory (25%). Following a second SGB, PTSD severity decreased by 57.7% and memory function substantially improved, with pronounced changes in immediate memory (50%), recent memory (58%), and recognition memory (36%). One year after SGB treatments, the patient has stopped drinking alcohol, continues to have sustained relief from PTSD, has improved memory function, and has become gainfully employed. Future studies that employ robust epidemiologic methodologies are needed to generate confirmatory evidence that would substantiate SGB's clinical utility as an adjunctive treatment option for PTSD. [ABSTRACT FROM AUTHOR]

Background: Prior to the introduction of combination antiretroviral therapy (cART), cytopenias were common in people with human immunodeficiency virus (PWH), but it is unknown if well-controlled HIV infection is a risk factor for cytopenia. In this study we aimed to determine if HIV infection is an independent risk factor for anemia, neutropenia, lymphocytopenia, and thrombocytopenia.Methods: PWH with undetectable viral replication and absence of chronic hepatitis infection (n = 796) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) study and matched uninfected controls from the Copenhagen General Population Study (n = 2388). Hematology was analyzed in venous blood samples. Logistic regression analyses adjusted for age, sex, ethnicity, smoking status, alcohol, and high-sensitivity C-reactive protein were performed to determine possible associations between HIV and cytopenias.Results: PWH had a higher prevalence of anemia (6.9% vs 3.4%, P < .001), neutropenia (1.3% vs 0.2%, P < .001), and thrombocytopenia (5.5% vs 2.7%, P < .001) compared with uninfected controls. HIV was independently associated with anemia-adjusted odds ratio (aOR) of 2.0 (95% confidence interval [CI], 1.4-3.0); neutropenia aOR, 6.3 (95% CI, 2.0-19.6); and thrombocytopenia aOR, 2.7 (95% CI, 1.8-4.2). No association was found between HIV and lymphocytopenia.Conclusions: Cytopenia is rare in people with well-controlled HIV, but HIV remains a risk factor for anemia, neutropenia, and thrombocytopenia and requires ongoing attention and monitoring. [ABSTRACT FROM AUTHOR]

Background Febrile neutropenia (FN) is a common complication to chemotherapy, associated with increased short-term morbidity and mortality. However, the long-term outcomes after FN are poorly elucidated. We examined the long-term risk of infection and mortality rates in cancer patients with and without FN. Methods Patients aged >16 years treated with firstline chemotherapy were followed from 180 days after initiating chemotherapy until first infection, a new treatment with chemotherapy, death, or end of follow-up. Risk factors for infections were analyzed by competing risks regression, with death or another treatment with chemotherapy as competing events. Adjusted incidence rate ratios (aIRRs) of infection and death were analyzed using Poisson regression. In analyses of mortality, infection was included as a time-updated variable. Results We included 7190 patients with a median follow-up (interquartile range) of 0.58 (0.20–1.71) year. A total of 1370 patients had an infection during follow-up. The aIRRs of infection were 1.86 (95% confidence interval [CI], 1.56–2.22) and 2.19 (95% CI, 1.54–3.11) for patients with 1 or >1 episode of FN compared with those without FN. Mortality rate ratios were 7.52 (95% CI, 6.67–8.48) <1 month after, 4.24 (95% CI, 3.80–4.75) 1–3 months after, 2.33 (95% CI, 1.63–3.35) 3–6 months after, and 1.09 (95% CI, 0.93–1.29) >6 months after an infection, compared with the time before infection. Conclusions FN during chemotherapy is associated with a long-term increased risk of infection. Mortality rates are substantially increased for 6 months following an infection. [ABSTRACT FROM AUTHOR]

Neuronal activity within and across the cortex and basal ganglia is pathologically synchronized, particularly at ∼ 20 Hz in patients with Parkinsons disease. Defining how activities in spatially distributed brain regions overtly synchronize in narrow frequency bands is critical for understanding disease processes like Parkinsons disease. To address this, we studied cortical responses to electrical stimulation of the subthalamic nucleus (STN) at various frequencies between 5 and 30 Hz in two cohorts of eight patients with Parkinsons disease from two different surgical centres. We found that evoked activity consisted of a series of diminishing waves with a peak latency of 21 ms for the first wave in the series. The cortical evoked potentials (cEPs) averaged in each group were well fitted by a damped oscillator function (r ≥0.9, P < 0.00001). Fits suggested that the natural frequency of the subthalamo-cortical circuit was around 20 Hz. When the system was forced at this frequency by stimulation of the STN at 20 Hz, the undamped amplitude of the modelled cortical response increased relative to that with 5 Hz stimulation in both groups (P ≤ 0.005), consistent with resonance. Restoration of dopaminergic input by treatment with levodopa increased the damping of oscillatory activity (as measured by the modelled damping factor) in both patient groups (P ≤0.001). The increased damping would tend to limit resonance, as confirmed in simulations. Our results show that the basal ganglia–cortical network involving the STN has a tendency to resonate at ∼ 20 Hz in Parkinsonian patients. This resonance phenomenon may underlie the propagation and amplification of activities synchronized around this frequency. Crucially, dopamine acts to increase damping and thereby limit resonance in this basal ganglia–cortical network. [ABSTRACT FROM AUTHOR]