Linear ensemble-coding in midbrain superior colliculus specifies the saccade kinematics

Recently, we proposed an ensemble-coding scheme of the midbrain superior colliculus (SC) in which, during a saccade, each spike emitted by each recruited SC neuron contributes a fixed minivector to the gaze-control motor output. The size and direction of this ‘spike vector’ depend exclusively on a cell’s location within the SC motor map (Goossens and Van Opstal, in J Neurophysiol 95: 2326–2341, 2006). According to this simple scheme, the planned saccade trajectory results from instantaneous linear summation of all spike vectors across the motor map. In our simulations with this model, the brainstem saccade generator was simplified by a linear feedback system, rendering the total model (which has only three free parameters) essentially linear. Interestingly, when this scheme was applied to actually recorded spike trains from 139 saccade-related SC neurons, measured during thousands of eye movements to single visual targets, straight saccades resulted with the correct velocity profiles and nonlinear kinematic relations (‘main sequence properties– and ‘component stretching’) Hence, we concluded that the kinematic nonlinearity of saccades resides in the spatial-temporal distribution of SC activity, rather than in the brainstem burst generator. The latter is generally assumed in models of the saccadic system. Here we analyze how this behaviour might emerge from this simple scheme. In addition, we will show new experimental evidence in support of the proposed mechanism

Prevalence of age-related hearing loss in Europe: a review

Populations are becoming progressively older thus presenting symptoms of diminished organ function due to degenerative processes. These may be physiological or caused by additional factors damaging the organ. Presbyacusis refers to the physiological age-related changes of the peripheral and central auditory system leading to hearing impairment and difficulty understanding spoken language. In contrast to epidemiological data of other continents, the prevalence of age-related hearing loss (ARHL) in Europe is not well defined, due in part to the use of different classification systems. We performed a systematic literature review with the aim of gaining a picture of the prevalence of ARHL in Europe. The review included only population and epidemiological studies in English since 1970 with samples in European countries with subjects aged 60 years and above. Nineteen studies met our selection criteria and additional five studies reported self-reported hearing impairment. When these data were crudely averaged and interpolated, roughly 30% of men and 20% of women in Europe were found to have a hearing loss of 30 dB HL or more by age 70 years, and 55% of men and 45% of women by age 80 years. Apparent problems in comparing the available data were the heterogeneity of measures and cut-offs for grades of hearing impairment. Our systematic review of epidemiological data revealed more information gaps than information that would allow gaining a meaningful picture of prevalence of ARHL. The need for standardized procedures when collecting and reporting epidemiological data on hearing loss has become evident. Development of hearing loss over time in conjunction with the increase in life expectancy is a major factor determining strategies of detection and correction of ARHL. Thus, we recommend using the WHO classification of hearing loss strictly and including standard audiometric measures in population-based health surveys

Community based intervention to optimize osteoporosis management: randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis are underutilized. This pragmatic randomised study was done to evaluate the impact of a multifaceted community-based care program aimed at optimizing evidence-based management in patients at risk for osteoporosis and fractures.</p> <p>Methods</p> <p>This was a 12-month randomized trial performed in Ontario, Canada. Eligible patients were community-dwelling, aged ≥55 years, and identified to be at risk for osteoporosis-related fractures. Two hundred and one patients were allocated to the intervention group or to usual care. Components of the intervention were directed towards primary care physicians and patients and included facilitated bone mineral density testing, patient education and patient-specific recommendations for osteoporosis treatment. The primary outcome was the implementation of appropriate osteoporosis management.</p> <p>Results</p> <p>101 patients were allocated to intervention and 100 to control. Mean age of participants was 71.9 ± 7.2 years and 94% were women. Pharmacological treatment (alendronate, risedronate, or raloxifene) for osteoporosis was increased by 29% compared to usual care (56% [29/52] vs. 27% [16/60]; relative risk [RR] 2.09, 95% confidence interval [CI] 1.29 to 3.40). More individuals in the intervention group were taking calcium (54% [54/101] vs. 20% [20/100]; RR 2.67, 95% CI 1.74 to 4.12) and vitamin D (33% [33/101] vs. 20% [20/100]; RR 1.63, 95% CI 1.01 to 2.65).</p> <p>Conclusions</p> <p>A multi-faceted community-based intervention improved management of osteoporosis in high risk patients compared with usual care.</p> <p>Trial Registration</p> <p>This trial has been registered with clinicaltrials.gov (ID: NCT00465387)</p

Impact of early applied upper limb stimulation: The EXPLICIT-stroke programme design

Main claims of the literature are that functional recovery of the paretic upper limb is mainly defined within the first month post stroke and that rehabilitation services should preferably be applied intensively and in a task-oriented way within this particular time window. EXplaining PLastICITy after stroke (acronym EXPLICIT-stroke) aims to explore the underlying mechanisms of post stroke upper limb recovery. Two randomized single blinded trials form the core of the programme, investigating the effects of early modified Constraint-Induced Movement Therapy (modified CIMT) and EMG-triggered Neuro-Muscular Stimulation (EMG-NMS) in patients with respectively a favourable or poor probability for recovery of dexterity.BioMechanical EngineeringMechanical, Maritime and Materials Engineerin

Optimal Control of Saccades by Spatial-Temporal Activity Patterns in the Monkey Superior Colliculus

A major challenge in computational neurobiology is to understand how populations of noisy, broadly-tuned neurons produce accurate goal-directed actions such as saccades. Saccades are high-velocity eye movements that have stereotyped, nonlinear kinematics; their duration increases with amplitude, while peak eye-velocity saturates for large saccades. Recent theories suggest that these characteristics reflect a deliberate strategy that optimizes a speed-accuracy tradeoff in the presence of signal-dependent noise in the neural control signals. Here we argue that the midbrain superior colliculus (SC), a key sensorimotor interface that contains a topographically-organized map of saccade vectors, is in an ideal position to implement such an optimization principle. Most models attribute the nonlinear saccade kinematics to saturation in the brainstem pulse generator downstream from the SC. However, there is little data to support this assumption. We now present new neurophysiological evidence for an alternative scheme, which proposes that these properties reside in the spatial-temporal dynamics of SC activity. As predicted by this scheme, we found a remarkably systematic organization in the burst properties of saccade-related neurons along the rostral-to-caudal (i.e., amplitude-coding) dimension of the SC motor map: peak firing-rates systematically decrease for cells encoding larger saccades, while burst durations and skewness increase, suggesting that this spatial gradient underlies the increase in duration and skewness of the eye velocity profiles with amplitude. We also show that all neurons in the recruited population synchronize their burst profiles, indicating that the burst-timing of each cell is determined by the planned saccade vector in which it participates, rather than by its anatomical location. Together with the observation that saccade-related SC cells indeed show signal-dependent noise, this precisely tuned organization of SC burst activity strongly supports the notion of an optimal motor-control principle embedded in the SC motor map as it fully accounts for the straight trajectories and kinematic nonlinearity of saccades

Reconciling disparate prevalence rates of PTSD in large samples of US male Vietnam veterans and their controls

BACKGROUND: Two large independent studies funded by the US government have assessed the impact of the Vietnam War on the prevalence of PTSD in US veterans. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the current PTSD prevalence to be 15.2% while the Vietnam Experience Study (VES) estimated the prevalence to be 2.2%. We compared alternative criteria for estimating the prevalence of PTSD using the NVVRS and VES public use data sets collected more than 10 years after the United States withdrew troops from Vietnam. METHODS: We applied uniform diagnostic procedures to the male veterans from the NVVRS and VES to estimate PTSD prevalences based on varying criteria including one-month and lifetime prevalence estimates, combat and non-combat prevalence estimates, and prevalence estimates using both single and multiple indicator models. RESULTS: Using a narrow and specific set of criteria, we derived current prevalence estimates for combat-related PTSD of 2.5% and 2.9% for the VES and the NVVRS, respectively. Using a more broad and sensitive set of criteria, we derived current prevalence estimates for combat-related PTSD of 12.2% and 15.8% for the VES and NVVRS, respectively. CONCLUSION: When comparable methods were applied to available data we reconciled disparate results and estimated similar current prevalences for both narrow and broad definitions of combat-related diagnoses of PTSD

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05–9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34–1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59–0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD

Bipolar disorders

Bipolar disorder is characterized by (hypo)manic episodes and depressive episodes which alternate with euthymic periods. It causes serious disability with poor outcome, increased suicidality risk, and significant societal costs. This chapter describes the findings of the PET/SPECT research efforts and the current ideas on the pathophysiology of bipolar disorder. First, the cerebral blood flow and cerebral metabolism findings in the prefrontal cortex, limbic system, subcortical structures, and other brain regions are discussed, followed by an overview of the corticolimbic theory of mood disorders that explains these observations. Second, the neurotransmitter studies are discussed. The serotonin transporter alterations are described, and the variation in study results is explained, followed by an overview of the results of the various dopamine receptor and transporter molecules studies, taking into account also the relation to psychosis. Third, a concise overview is given of dominant bipolar disorder pathophysiological models, proposing starting points for future molecular imaging studies. Finally, the most important conclusions are summarized, followed by remarks about the observed molecular imaging study designs specific for bipolar disorder.</p