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Re-afferent effects of individual static and dynamic gamma-stimuli during maintained fusimotor stimulation.

The ability of maintained dynamic and static fusimotor stimulation to modulate the primary afferent response of the muscle spindle in the rhythm of gamma-stimulation was investigated using a highly sensitive method for modulation detection. The effect of 41 gamma-fibers (13 dynamic; 28 static) on 38 primary afferents obtained from the tibialis anterior muscle of the cat was studied. It was found that maintained stimulation of 10 out of the 13 dynamic (77%) and of 25 out of the 28 static (89%) gamma-fibers could evoke significant modulations of the primary afferent response in the rhythm of fusimotor stimulation at a minimum of one stimulation rate. Moreover, both static and dynamic gamma-stimulations could evoke significant primary afferent modulations almost over the entire range of stimulation rates studied (30-300 stimuli per second). These results show that both gamma-systems can modulate the primary afferent response in the rhythm of fusimotor stimulation over a wide range of stimulation rates; thus the central nervous system may be provided with re-afferent information about the effect of each individual gamma-motoneuron discharge. Some hypotheses for the internal spindle mechanism responsible for the afferent modulations are discussed.

Action Potentials↗

Snoezelen for dementia.

BACKGROUND: Snoezelen, multi-sensory stimulation, provides sensory stimuli to stimulate the primary senses of sight, hearing, touch, taste and smell, through the use of lighting effects, tactile surfaces, meditative music and the odour of relaxing essential oils (Pinkney 1997). The clinical application of snoezelen has been extended from the field of learning disability to dementia care over the past decade. The rationale for its use lies in providing a sensory environment that places fewer demands on intellectual abilities but capitalizes on the residual sensorimotor abilities of people with dementia (e.g. Buettner 1999, Hope 1998). Practitioners are keen to use snoezelen in dementia care, and some encouraging results have been documented in the area of promoting adaptive behaviours (e.g. Baker, Long 1992, Spaull 1998). However, the clinical application of snoezelen often varies in form, nature, principles and procedures. Such variations not only make examination of the therapeutic values of Snoezelen difficult, but also impede the clinical development of snoezelen in dementia care. A systematic review of evidence for the efficacy of snoezelen in the care of people with dementia is therefore needed to inform future clinical applications and research directions. OBJECTIVES: This review aims to examine the clinical efficacy of snoezelen for older people with dementia. SEARCH STRATEGY: "Snoezelen", "multi-sensory", "dement*", "Alzheimer*", "randomized control/single control/double control" were used as keywords to search seven electronic databases (e.g. MEDLINE, PsyLIT). The list of trials was compared with those identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group. SELECTION CRITERIA: All RCTs in which Snoezelen or multi-sensory programmes were used as an intervention for people with dementia were included in the review. Trial data included in the review were restricted to those involving people aged over 60 years suffering from any type of dementia, except one subject of Baker's study was aged below 60 years. DATA COLLECTION AND ANALYSIS: Only two RCTs fulfill the inclusion criteria for this systematic review. Two reviewers independently extracted the data from these two inclusion studies. Quantitative synthesis of the comparable data from the two trials was performed. MAIN RESULTS: Two trials were included. Both Baker (and Kragt examined the short-term values of snoezelen on the behaviours of people with dementia. Although the pooled results were insignificant, the trend was in the direction of favouring treatment (hence a negative value of the SMD). The standardized mean difference (SMD) was -1.22, with a 95% confidence interval (CI) (-4.08, 1.64). Kragt's result, weighted 47%, was significant in favour of treatment, with a SMD of -2.77 and a 95% CI (-4.24, -1.29). During the snoezelen session, Kragt's subjects presented significantly fewer apathetic behaviours (t=-8.22, p<0.01), fewer restless behaviours (t=-3.00, p=0.01), fewer repetitive behaviours (t=-.822, p<0.01), and fewer disturbances (t=-4.91, p<0.01). Baker's result was slightly not in favour of the treatment, with a SMD of 0.16 and a 95% CI (-0.41, 0.73). The control subjects touched objects/equipment more appropriately within the activity sessions than the subjects who participated in snoezelen sessions (F(1,47)=5.96, p=.001). Kragt did not examine the carryover and long-term effects of snoezelen, so only Baker's results were analysed. Baker used the Behavioural and Mood Disturbance scale (BMD), the REHAB, the CAPE and MMSE to assess patients mood, behaviour and cognition after (but not immediately after) four treatment sessions and eight treatment sessions. Some assessments were carried at home, some at day hospital. There were many subscores and mostly there were no differences between treatment and control. The following significant differences were found with benefit in favour of snoezelen compared with control after four sessions: apathy ezelen compared with control after four sessions: apathy score of the BRS (CAPE) (MD -3.00, 95%CIs -5.87 to -0.13, P=0.04), after eight sessions: mood score of the BRS (CAPE) (MD -2.60, 95%CIs -4.92 to -0.28, P=0.03), total score of the BRS (CAPE) (MD -6.92, 95%CIs -13.13 to -0.7, P=0.03), speech skills of the REHAB (MD 1.46, 95%CIs 0.01 to 2.82, P=0.03), psychomotor subscore of the cognitive assessment scale of CAPE (MD -3.12, 95%CIs -5.31 to -0.93, P<0.01). REVIEWER'S CONCLUSIONS: Two trials were reviewed. Although both studies examined the short-term values of snoezelen on people with dementia, it is not feasible to draw a firm conclusion at this stage, for two main reasons. Firstly, very limited data were available for analysis, thus limiting data inference and generalization. Secondly, different methodology and control conditions were adopted in the two trials. Such variations not only require a careful interpretation of results but also make the comparison of results across studies less valid. Hence, there is an urgent need for more systematic and scientific research studies to examine the clinical value of snoezelen for people with dementia. To our knowledge, there are four RCTs currently in progress. It is hoped that the data and results of these trials will enrich the systematic review of snoezelen for dementia in the next update.

Aged↗

Pipradrol enhances reinforcing properties of stimuli paired with brain stimulation.

The hypothesis that a psychomotor stimulant drug (pipradrol) enhances the reinforcing effects of stimuli paired with reinforcing brain stimulation was tested using a conditioned reinforcement paradigm. Rats were trained to discriminate between two stimuli (S+ and S-) to obtain ICS in the lateral hypothalamus by pushing a panel in the presence of S+. In a subsequent preference test, ICS was no longer available, but responding on one of two novel levers now produced S+, whereas responding on the other lever produced S-. Four groups of four rats received 0, 5, 10 or 15 mg/kg pipradrol. Doses of 5 and 10 mg/kg significantly enhanced the preference for S+ over S-. These doses increased responding for S+, but had no effect on responding for S-. These results support the hypothesis tested, and suggest that pipradrol potentiates the effects of conditioned reinforcement.

Animals↗

Sequential immunologic stimuli to the respiratory tract: a paradox in the degree of potentiation of airway responses depending on the sequence of reverse passive and active immunologic stimulation.

Immunologic stimuli to the airway of rhesus monkeys were given by aerosol challenge with ascaris antigen or anti-IgE. Both of these stimuli produce immediate-type airway responses. When 2 sequential aerosol challenges were given during the same experiment, the response following the second stimulus was always less than or equal to the first response following any combination of stimuli except the anti-IgE-ascaris sequence. The second response following the latter challenge was always greater than or equal to the first response. The possibility that this exception was the result of anti-IgE priming mediator releasing cells for antigen was not supported by in vitro experiments. It is suggested that the results obtained with the anti-IgE-ascaris sequence may relate to the presence of intralumenal mast cells in the bronchi and the molecular weights of the 2 immunologic stimuli.

Animals↗

Evidence for direct regulation of myocardial Na+/H+ exchanger isoform 1 phosphorylation and activity by 90-kDa ribosomal S6 kinase (RSK): effects of the novel and specific RSK inhibitor fmk on responses to alpha1-adrenergic stimulation.

Multiple stimuli of physiological and pathophysiological significance, including alpha1-adrenoceptor agonists, stimulate the cardiac sarcolemmal Na+/H+ exchanger isoform 1 (NHE1) through activation of the mitogen-activated or extracellular signal-regulated kinase (ERK) kinase (MEK) ERK-90-kDa ribosomal S6 kinase (RSK) signaling cascade. However, the individual contributions of ERK and RSK, which can each phosphorylate the NHE1 regulatory domain, to such stimulation are unknown. In the present study, we have used the novel RSK inhibitor fmk to determine the role of RSK as a direct regulator of NHE1 phosphorylation and activity in response to alpha1-adrenergic stimulation, in ventricular myocytes isolated from the adult rat heart. Initial experiments confirmed that pretreatment of myocytes with fmk before exposure to the alpha1-adrenoceptor agonist phenylephrine inhibited RSK C-terminal kinase activity and thereby RSK N-terminal kinase activation, without affecting MEK or ERK activation. Pretreatment of myocytes with fmk also inhibited phenylephrine-induced increases in NHE1 phosphorylation and the rate of NHE1-mediated H+ efflux under conditions of intracellular acidosis. These findings reveal, for the first time to our knowledge, that RSK is the principal regulator of NHE1 phosphorylation and activity after alpha1-adrenergic stimulation in adult myocardium.

Animals↗

Topography of occipital EEG-reduction upon visual stimulation.

Visual stimuli were designed to drive a high proportion of the neurons in restricted parts of the human visual cortex. These stimuli were used to examine changes in the ongoing EEG during visual stimulation. The topographic organization of these changes was studied. It was found that the EEG from those parts of the cortex that are exposed to the stimulus is strongly reduced in amplitude. This stimulus dependency is indicative that cortical processing results itself in a reduction of the ongoing EEG, presumably due to desynchronization of neurons. The method shows that ongoing EEG can be used for functional mapping of cortical areas and is therefore valuable in situations where stimulus locked activity can not be measured.

Brain Mapping↗

[Studies on the perception of periodontal stimuli].

The stimulation of the periodontium causes a reflex response of the jaw muscles and at the same time a perceptive reaction of the central nervous system. The aim of our study was to develop a method for the objective assessment of the subjective perception experienced after stimulating the periodontium. Seven healthy volunteers took part in these experiments in the course of which mechanical stimuli (2.5 N, 750 microseconds) were applied perpendicular to the tooth, thus leading to a stimulation of the periodontium. Sensory evoked potentials of the periodontium (SEP-PA) elicited from the EEG served as an objective measure of perception. A computerized analysis of the data thus obtained allows an assessment of the change in perception following repeated periodontal stimulation at different rates.

Electroencephalography↗

Nociceptive masseter inhibitory reflexes evoked by laser radiant heat and electrical stimuli.

Electrical stimulation of the mental nerve evokes two suppression periods SP1 and SP2 in masseter muscle activity bilaterally. In order to investigate a possible nociceptive origin of the suppression periods, we compared the reflex responses evoked by electrical stimulation and by selective activation of nociceptors in hairy skin using painful infrared laser stimuli. The SP was elicited during more than 90% maximal voluntary contraction. Thresholds for detection, pain, and SP in the mental nerve area were determined by the method of limits. A suppression period was evoked by laser stimuli in nine of ten subjects bilaterally. The mean onset latency was 46.9 ms, the mean duration 58.9 ms. The electrical threshold of SP1 (9 mA) was 7.7 x I(0), about 20% smaller than I(P), and significantly higher than I(SP2) (4.7 mA). The onset latencies and durations were 11.7 ms and 21 ms for SP1, and 45 ms and 42.7 ms for SP2 (stimulus intensity 2 x I(P)). The mean difference in onset latencies between laser SP and electrically evoked SP1 was 35.1 +/- 6.2 ms, which closely matches the nociceptor response latency to a laser heat pulse. Based on the threshold and the onset latency we conclude that at least SP1 and laser SP are nociceptive in origin and mediated by group III fibers.

Adult↗

Enhanced de novo synthesis of phosphatidic acid and phosphatidylinositol in rat pancreatic islets exposed to nutrient or neurotransmitter stimuli.

A stimulation of [3H]glycerol incorporation into phosphatidic acid and phosphatidylinositol was observed upon exposure of rat pancreatic islets to the nutrient secretagogues alpha-ketoisocaproate and glucose, or to the neurotransmitter stimuli carbamylcholine and cholecystokinin. These effects were associated with reduced labeling of phosphatidylcholine and, in some cases, phosphatidylethanolamine. The modified patterns of [3H]glycerol incorporation into islet phospholipids persisted in the absence of added Ca2+, but were abolished by excess EDTA. Nutrient, but not neurotransmitter, secretagogues also stimulated the incorporation of [3H]glycerol into triacylglycerols. The results suggest that the stimulation of islets with the above classes of secretagogues is accompanied by enhanced de novo synthesis of acidic phospholipids.

Animals↗

Human jaw-opening muscle responses elicited by multiple-site electrical stimulation.

Electrical stimuli were applied to subjects' upper and/or lower gingivae around the right canines; (i) during maintained relaxation of masticatory muscles; (ii) at an active opening position; (iii) while clenching in an incisal edge-to-edge contact (IEC) position; and (iv) at the wide-open position. Reflex responses of the suprahyoid and jaw-closing muscles were obtained using surface electrodes. The electrical stimulation produced segmented reflex excitation(s) in the suprahyoid muscle and conventional reflex excitation and/or inhibition in the jaw-closing muscles when some background activity was maintained in the muscle(s). The excitatory reflex in the suprahyoid muscle responded to multiple site electrical stimulation which was delivered on both the upper and lower jaw simultaneously rather than to single site stimulation. Also, the responses depended on the intensity of the electrical stimulation. In particular, stronger intensities resulted in longer latencies. The results support the suggestions in our previous studies with mechanical stimuli, i.e. that the human jaw-opening reflex can be obtained only when some background activity is maintained in the jaw openers, perhaps due to low threshold afferent input, and that spatial summation may be effective for the reflex.

Adult↗

Cochlear pathology following chronic electrical stimulation using non charge balanced stimuli.

During the course of a chronic intracochlear electrical stimulation study using charge balanced biphasic current pulses, one animal inadvertently received a short period of direct current (DC) stimulation at a level of approximately 1 microA. Subsequent, the animal was chronically stimulated using a poorly charge balanced waveform that produced a DC level of approximately 2 microA. Extensive pathological changes were observed within the cochlea. These changes included widespread spiral ganglion cell loss and new bone growth that extended throughout all turns of the cochlea. Significant changes in the morphology of the electrically evoked auditory brainstem response (EABR) were associated with these pathological changes. EABRs recorded prior to the DC stimulation exhibited a normal waveform morphology. However, responses recorded during the course of the DC stimulation were dominated by a short latency response believed to be vestibular in origin. The response thresholds were also significantly higher than levels recorded before the DC stimulation. In contrast, the contralateral cochlea, stimulated using charge balanced stimuli, showed no evidence of adverse pathological changes. Furthermore, EABRs evoked from this cochlea remained stable throughout the chronic stimulation period. Although preliminary, the present results illustrate the adverse nature of poorly charge balanced electrical stimuli. These results have important implications for both the design of neural prostheses and the use of DC stimuli to suppress tinnitus in patients.

Animals↗

Cocaine- and amphetamine-regulated transcript (CART) expression is differentially regulated in the hypothalamic paraventricular nucleus of lactating rats exposed to suckling or cold stimulation.

Neural stimuli, such as suckling or cold exposure, increase TRH mRNA in the paraventricular nucleus (PVN) of the rat hypothalamus, yet only suckling induces prolactin secretion. As TRH co-localizes with cocaine- and amphetamine-regulated transcript (CART) in hypophysiotropic neurons of the PVN, and CART inhibits TRH-induced prolactin release but not TRH-induced TSH release in adenohypophyseal cell cultures, we raised the possibility that differential regulation of CART gene expression in the PVN may explain the differences in prolactin secretion following each of the two stimuli. Primiparous female rats were mated and handled daily during the pre- and postpartum periods. After delivery, the litter was adjusted to 8 pups and at mid-lactation, dams were separated from their pups for 8 h and exposed to either 1 h of cold or 30 min of suckling. Long-term effects of suckling were studied by separating pups from their mothers for 24 h, followed by a 12 h period of continuous suckling. Serum TSH levels increased in response to cold exposure, while prolactin levels were increased by suckling and diminished by cold exposure. CART mRNA levels increased in rostral and mid parts of the medial parvocellular PVN following cold exposure but not after suckling stimulation. These data demonstrate a differential regulation of CART gene expression in hypophysiotropic neurons in response to stimuli that increase TRH mRNA levels, and suggest that CART activation in the PVN may contribute to the decrease in PRL release when the thyroid axis is activated by cold exposure.

Animals↗