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  • Short exposure to an enriched environment accelerates plasticity in the barrel cortex of adult rats.

    7 February 2018

    Cortical sensory neurons adapt their response properties to use and disuse of peripheral receptors in their receptive field. Changes in synaptic strength can be generated in cortex by simply altering the balance of input activity, so that a persistent bias in activity levels modifies cortical receptive field properties. Such activity-dependent plasticity in cortical cell responses occurs in rat cortex when all but two whiskers are trimmed for a period of time at any age. The up-regulation of evoked responses to the intact whiskers is first seen within 24 h in the supragranular layers [Laminar comparison of somatosensory cortical plasticity. Science 265(5180):1885-1888] and continues until a new stable state is achieved [Experience-dependent plasticity in adult rat barrel cortex. Proc Natl Acad Sci U S A 90(5):2082-2086; Armstrong-James M, Diamond ME, Ebner FF (1994) An innocuous bias in whisker use in adult rat modifies receptive fields of barrel cortex neurons. J Neurosci 14:6978-6991]. These and many other results suggest that activity-dependent changes in cortical cell responses have an accumulation threshold that can be achieved more quickly by increasing the spike rate arising from the active region of the receptive field. Here we test the hypothesis that the rate of neuronal response change can be accelerated by placing the animals in a high activity environment after whisker trimming. Test stimuli reveal an highly significant receptive field bias in response to intact and trimmed whiskers in layer IV as well as in layers II-III neurons in only 15 h after whisker trimming. Layer IV barrel cells fail to show plasticity after 15-24 h in a standard cage environment, but produce a response bias when activity is elevated by the enriched environment. We conclude that elevated activity achieves the threshold for response modification more quickly, and this, in turn, accelerates the rate of receptive field plasticity.

  • Stimulus frequency processing in awake rat barrel cortex.

    2 February 2018

    In awake rats, we examined the relationship between neural spiking activity in primary somatic sensory cortex and the frequency of whisker stimulation. Neural responses were recorded extracellularly in barrel cortex while single whiskers were deflected with 0.5-18 air puffs per second (apps), a range that includes the whisk rates observed when rats explore their environment and discriminate surfaces with their whiskers. Twenty-nine neurons in layers III and IV were isolated in three rats (23 in barrel columns and 6 in septum columns). At < or = 9 apps, cortical neurons responded with one to two spikes per stimulus, whereas at > 9 apps, the response efficacy was reduced to only 0.2-0.4 spikes per stimulus. Several mechanisms are discussed that could account for the decrement in responsiveness. Despite this adaptation, neural spike rates increased in direct proportion with stimulus frequency when cast on logarithmic scales. At > 9 apps, however, this relationship deteriorated in barrel columns in which the response approximately halved. In contrast, septum column cells continued to increase their spike rates linearly up to 18 apps, although they responded at lower magnitude than the barrel column cells. Our findings suggest that septum column neurons are potential candidates to encode stimulus frequency using spike rate across the entire frequency range relevant to rats' whisking behavior.

  • Optimal spectral tracking--with application to speed dependent neural modulation of tibialis anterior during human treadmill walking.

    20 March 2018

    A novel method of optimal spectral tracking is presented which permits the characterisation of trial-varying parameters. Many experimental studies suffer from the limitations of available analysis methodologies, which often impose a condition of stationarity. This severely limits our ability to track slow varying or dynamic responses with any statistical certainty. Presented is a complete framework for the non-stationary analysis of trial-varying data. Theory is introduced and developed in the characterisation of speed dependent neural modulation of the locomotor drive to tibialis anterior (TA) during healthy treadmill locomotion. The approach adopts adaptive filter theory while retaining a spectral focus, thus remaining compatible with much of the current literature. Spectral tracking procedures are evaluated using both surrogate and neurophysiological time-series. Confidence intervals are derived in both empiric and numerical form. Analysis of the pre-synaptic drive to TA under the modulation of treadmill belt speed follows, with results demonstrating clear speed dependent influences on the spectral content of TA, suggesting dynamic neural modulation of the locomotor drive. Findings include speed-modulated components at 7-12Hz (early swing) and 15-20Hz (pre-stance). Speed invariant components were identified at 8-15 and 15-20Hz during early and late swing, in agreement with previous studies. Modification to the method permits a sub-optimal alternative, encouraging the exploration of short epoched data.

  • Driving oscillatory activity in the human cortex enhances motor performance.

    16 March 2018

    Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior.

  • Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease.

    20 March 2018

    BACKGROUND: Previous Cochrane reviews have considered the use of cholinesterase inhibitors in both Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The clinical features of DLB and PDD have much in common and are distinguished primarily on the basis of whether or not parkinsonism precedes dementia by more than a year. Patients with both conditions have particularly severe deficits in cortical levels of the neurotransmitter acetylcholine. Therefore, blocking its breakdown using cholinesterase inhibitors may lead to clinical improvement. OBJECTIVES: To assess the efficacy, safety and tolerability of cholinesterase inhibitors in dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and cognitive impairment in Parkinson's disease falling short of dementia (CIND-PD) (considered as separate phenomena and also grouped together as Lewy body disease). SEARCH METHODS: The trials were identified from a search of ALOIS, the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (on 30 August 2011) using the search terms Lewy, Parkinson, PDD, DLB, LBD. This register consists of records from major healthcare databases (MEDLINE, EMBASE, PsycINFO, CINAHL) and many ongoing trial databases and is updated regularly.Reference lists of relevant studies were searched for additional trials. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials assessing the efficacy of treatment with cholinesterase inhibitors in DLB, PDD and cognitive impairment in Parkinson's disease (CIND-PD). DATA COLLECTION AND ANALYSIS: Data were extracted from published reports by one review author (MR). The data for each 'condition' (that is DLB, PDD or CIND-PD) were considered separately and, where possible, also pooled together. Statistical analysis was conducted using Review Manager version 5.0. MAIN RESULTS: Six trials met the inclusion criteria for this review, in which a total of 1236 participants were randomised. Four of the trials were of a parallel group design and two cross-over trials were included. Four of the trials included participants with a diagnosis of Parkinson's disease with dementia (Aarsland 2002a; Dubois 2007; Emre 2004; Ravina 2005), of which Dubois 2007 remains unpublished. Leroi 2004 included patients with cognitive impairment and Parkinson's disease (both with and without dementia). Patients with dementia with Lewy bodies (DLB) were included in only one of the trials (McKeith 2000).For global assessment, three trials comparing cholinesterase inhibitor treatment to placebo in PDD (Aarsland 2002a; Emre 2004; Ravina 2005) reported a difference in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the cholinesterase inhibitors (95% CI -0.56 to -0.24, P < 0.0001).For cognitive function, a pooled estimate of the effect of cholinesterase inhibitors on cognitive function measures was consistent with the presence of a therapeutic benefit (standardised mean difference (SMD) -0.34, 95% CI -0.46 to -0.23, P < 0.00001). There was evidence of a positive effect of cholinesterase inhibitors on the Mini-Mental State Examination (MMSE) in patients with PDD (WMD 1.09, 95% CI 0.45 to 1.73, P = 0.0008) and in the single PDD and CIND-PD trial (WMD 1.05, 95% CI 0.42 to 1.68, P = 0.01) but not in the single DLB trial.For behavioural disturbance, analysis of the pooled continuous data relating to behavioural disturbance rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.36 to -0.04, P = 0.01).For activities of daily living, combined data for the ADCS and the Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.38 to -0.02, P = 0.03).For safety and tolerability, those taking a cholinesterase inhibitor were more likely to experience an adverse event (318/452 versus 668/842; odds ratio (OR) 1.64, 95% CI 1.26 to 2.15, P = 0.0003) and to drop out (128/465 versus 45/279; OR 1.94, 95% CI 1.33 to 2.84, P = 0.0006). Adverse events were more common amongst those taking rivastigmine (357/421 versus 173/240; OR 2.28, 95% CI 1.53 to 3.38, P < 0.0001) but not those taking donepezil (311/421 versus 145/212; OR 1.24, 95% CI 0.86 to 1.80, P = 0.25). Parkinsonian symptoms in particular tremor (64/739 versus 12/352; OR 2.71, 95% CI 1.44 to 5.09, P = 0.002), but not falls (P = 0.39), were reported more commonly in the treatment group but this did not have a significant impact on the UPDRS (total and motor) scores (P = 0.71). Fewer deaths occurred in the treatment group than in the placebo group (4/465 versus 9/279; OR 0.28, 95% CI 0.09 to 0.84, P = 0.03). AUTHORS' CONCLUSIONS: The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD.

  • Tackling dementia in patients with Parkinson's disease.

    12 December 2017

    Dementia more than one year after the onset of motor features associated with Parkinson's disease is defined as Parkinson's disease with dementia (PDD). If it develops within one year of the motor features, the term dementia with Lewy bodies (DLB) is used. Since clinical and pathological features are similar, it is generally accepted that both represent a continuum of the same disorder. PDD together with DLB account for around one fifth of all cases of dementia in the elderly. Studies suggest that most patients with Parkinson's disease would eventually develop dementia if they lived long enough. The diagnosis of PDD in the presence of long-standing pronounced motor features rarely poses a diagnostic dilemma. However, the diagnosis of DLB may be more difficult. It relies on the revised consensus clinical criteria which require the presence of at least two of the following three syndromes: persistent visual hallucinations, fluctuating defects in cognitive and functional ability, and parkinsonism. An early referral to a specialist clinic may not only help to confirm the diagnosis, but also to co-ordinate the group of professionals working with the patient. Well lit rooms and the use of glasses and hearing aids can help to reduce hallucinations. Cholinesterase inhibitors used in Alzheimer's disease have a role in DLB and PDD. Trials show moderate improvements in cognitive function in patients treated with rivastigmine. The greatest impact, however, seems to be on the psychotic features of the disease. Patients with DLB are less likely to have a good motor response from L-dopa than patients with Parkinson's disease or PDD.