Articulation lost in space. The effects of local orobuccal anesthesia on articulation and intelligibility of phonemes.

Motor speech requires numerous neural computations including feedforward and feedback control mechanisms. A reduction of auditory or somatosensory feedback may be implicated in disorders of speech, as predicted by various models of speech control. In this paper the effects of reduced somatosensory feedback on articulation and intelligibility of individual phonemes was evaluated by using topical anesthesia of orobuccal structures in 24 healthy subjects. The evaluation was done using a combination of perceptual intelligibility estimation of consonants and vowels and acoustic analysis of motor speech. A significantly reduced intelligibility was found, with a major impact on consonant formation. Acoustic analysis demonstrated disturbed diadochokinesis. These results underscore the clinical importance of somatosensory feedback in speech control. The interpretation of these findings in the context of speech control models, neuro-anatomy and clinical neurology may have implications for subtyping of dysarthria.

Theoretical implications and clinical support for heart rate variability biofeedback for substance use disorders.

Heart rate variability (HRV) biofeedback is an accessible, cost-effective intervention that has demonstrated clinical value for numerous physical and mental health conditions; however, research on HRV biofeedback in substance use disorders (SUD) is in its nascence. We argue that HRV biofeedback may be particularly beneficial as an adjunct treatment for SUD by targeting bodily systems that are known to be disrupted by chronic substance use and are not historically the focus of psychosocial or pharmacological SUD treatment approaches. In addition to advocating for HRV biofeedback applications in SUD, we identify several gaps within the existing experimental literature, and propose new studies that could accelerate understanding of how and for whom HRV biofeedback is most likely to promote positive behavior change.

Propofol-induced unresponsiveness is associated with impaired feedforward connectivity in cortical hierarchy.

BACKGROUND: Impaired consciousness has been associated with impaired cortical signal propagation after transcranial magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy. METHODS: Eight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced time-frequency responses and evoked response potentials were used to investigate propofol's effects on connectivity between regions. RESULTS: Sensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital, parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward responses in cross-frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, family-wise error corrected P<0.05). An exploratory analysis (thresholded at uncorrected P<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Post hoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left-sided occipital and parietal cortex (T contrast P=0.004, Bonferroni corrected). CONCLUSIONS: Propofol-induced loss of consciousness is associated with impaired hierarchical feedforward connectivity assessed by EEG after occipital TMS.

Ten Mistakes To Avoid When Injecting Botulinum Toxin.

Injection of botulinum toxin is currently the most common cosmetic procedure in the United States, and in recent years it has become-together with dermal fillers-the mainstay of therapy for the prevention and treatment of facial aging. However, in some cases the treatment may lead to a somewhat unnatural appearance, usually caused by loss of facial expression or other telltale signs. In the present article, we review the 10 mistakes that should be avoided when injecting botulinum toxin. We also reflect on how treatment with botulinum toxin influences us through our facial expressions, both in terms of how we feel and what others perceive.

Mirror biofeedback rehabilitation after administration of single-dose botulinum toxin for treatment of facial synkinesis.

OBJECTIVE: The efficacy of facial biofeedback rehabilitation with a mirror after administration of a single dose of botulinum A toxin on facial synkinesis was examined in patients with chronic facial palsy. STUDY DESIGN: Prospective clinical study. SETTING: University hospital. SUBJECTS AND METHODS: The present study includes 8 patients with Bell palsy and 5 with herpes zoster oticus showing facial synkinesis. A single dose of botulinum A toxin was used as the initial process of facial rehabilitation. Patients then continued a daily facial biofeedback rehabilitation with a mirror at home. They were instructed to keep their eyes symmetrically open using a mirror during mouth movements. The degree of oral-ocular synkinesis was evaluated by the degree of asymmetry of eye opening width during mouth movements (% eye opening). RESULTS: After administration of a single dose of botulinum A toxin, temporary relief of facial synkinesis was observed in all patients. Patients were then instructed to continue the facial biofeedback rehabilitation with a mirror for 10 months. The mean values of the percent of eye opening during 3 designated mouth movements that included lip pursing /u:/, teeth baring /i:/, and cheek puffing /pu:/ increased significantly after 10 months when the effects of botulinum A toxin had completely disappeared. CONCLUSION: These findings demonstrate that facial biofeedback rehabilitation with a mirror after administration of a single dose of botulinum A toxin is a long-lasting treatment of established facial synkinesis in patients with chronic facial palsy.

Dynamic assessment of baroreflex control of heart rate during induction of propofol anesthesia using a point process method.

In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R-R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RR-->BP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care.

Differential effects of acute and chronic ethanol exposure on orexin expression in the perifornical lateral hypothalamus.

BACKGROUND: Recent reports support the involvement of hypothalamic orexigenic peptides in stimulating ethanol intake. Our previous studies have examined the effects of ethanol on hypothalamic peptide systems of the paraventricular nucleus (PVN) and identified a positive feedback loop in which PVN peptides, such as enkephalin and galanin, stimulate ethanol intake and ethanol, in turn, stimulates the expression of these peptides. Recently, orexin (OX), a peptide produced mainly by cells in the perifornical lateral hypothalamus (PFLH), has been shown to play an important role in mediating the rewarding aspects of ethanol intake. However, there is little evidence showing the effects that ethanol itself may have on the OX peptide system. In order to understand the feedback relationship between ethanol and the OX system, the current investigation was designed to measure OX gene expression in the PFLH following acute as well as chronic ethanol intake. METHODS: In the first experiment, Sprague-Dawley rats were trained to voluntarily consume a 2 or 9% concentration of ethanol, and the expression of OX mRNA in the PFLH was measured using quantitative real-time polymerase chain reaction (qRT-PCR). The second set of experiments tested the impact of acute oral gavage of 0.75 and 2.5 g/kg ethanol solution on OX expression in the PFLH using qRT-PCR, as well as radiolabeled in situ hybridization. Further tests using digoxigenin-labeled in situ hybridization and immunofluorescence histochemistry allowed us to more clearly distinguish the effects of acute ethanol on OX cells in the lateral hypothalamic (LH) versus perifornical (PF) regions. RESULTS: The results showed chronic consumption of ethanol versus water to dose-dependently reduce OX mRNA in the PFLH, with a larger effect observed in rats consuming 2.5 g/kg/d (-70%) or 1.0 g/kg/d (-50%) compared to animals consuming 0.75 g/kg/d (-40%). In contrast to chronic intake, acute oral ethanol compared to water significantly enhanced OX expression in the PFLH, and this effect occurred at the lower (0.75 g/kg) but not higher (2.5 g/kg) dose of ethanol. Additional analyses of the OX cells in the LH versus PF regions identified the former as the primary site of ethanol's stimulatory effect on the OX system. In the LH but not the PF, acute ethanol increased the density of OX-expressing and OX-immunoreactive neurons. The increase in gene expression was detected only at the lower dose of ethanol (0.75 g/kg), whereas the increase in OX peptide was seen only at the higher dose of ethanol (2.5 g/kg). CONCLUSION: These results lead us to propose that OX neurons, while responsive to negative feedback signals from chronic ethanol consumption, are stimulated by acute ethanol administration, most potently in the LH where OX may trigger central reward mechanisms that promote further ethanol consumption.

Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats.

Depressed patients show cognitive deficits that may depend on an abnormal reaction to positive and negative feedback. The precise neurochemical mechanisms responsible for such cognitive abnormalities have not yet been clearly characterized, although serotoninergic dysfunction is frequently associated with depression. In three experiments described here, we investigated the effects of different manipulations of central serotonin (5-hydroxytryptamine, 5-HT) levels in rats performing a probabilistic reversal learning task that measures response to feedback. Increasing or decreasing 5-HT tone differentially affected behavioral indices of cognitive flexibility (reversals completed), reward sensitivity (win-stay), and reaction to negative feedback (lose-shift). A single low dose of the selective serotonin reuptake inhibitor citalopram (1 mg/kg) resulted in fewer reversals completed and increased lose-shift behavior. By contrast, a single higher dose of citalopram (10 mg/kg) exerted the opposite effect on both measures. Repeated (5 mg/kg, daily, 7 days) and subchronic (10 mg/kg, b.i.d., 5 days) administration of citalopram increased the number of reversals completed by the animals and increased the frequency of win-stay behavior, whereas global 5-HT depletion had the opposite effect on both indices. These results show that boosting 5-HT neurotransmission decreases negative feedback sensitivity and increases reward (positive feedback) sensitivity, whereas reducing it has the opposite effect. However, these effects depend on the nature of the manipulation used: acute manipulations of the 5-HT system modulate negative feedback sensitivity, whereas long-lasting treatments specifically affect reward sensitivity. These results parallel some of the findings in humans on effects of 5-HT manipulations and are relevant to hypotheses of altered response to feedback in depression.

Altered protein synthesis is a trigger for long-term memory formation.

There is ongoing debate concerning whether new protein synthesis is necessary for, or even contributes to, memory formation and storage. This review summarizes a contemporary model proposing a role for altered protein synthesis in memory formation and its subsequent stabilization. One defining aspect of the model is that altered protein synthesis serves as a trigger for memory consolidation. Thus, we propose that specific alterations in the pattern of neuronal protein translation serve as an initial event in long-term memory formation. These specific alterations in protein readout result in the formation of a protein complex that then serves as a nidus for subsequent perpetuating reinforcement by a positive feedback mechanism. The model proposes this scenario as a minimal but requisite component for long-term memory formation. Our description specifies three aspects of prevailing scenarios for the role of altered protein synthesis in memory that we feel will help clarify what, precisely, is typically proposed as the role for protein translation in memory formation. First, that a relatively short initial time window exists wherein specific alterations in the pattern of proteins translated (not overall protein synthesis) is involved in initializing the engram. Second, that a self-perpetuating positive feedback mechanism maintains the altered pattern of protein expression (synthesis or recruitment) locally. Third, that other than the formation and subsequent perpetuation of the unique initializing proteins, ongoing constitutive protein synthesis is all that is minimally necessary for formation and maintenance of the engram. We feel that a clear delineation of these three principles will assist in interpreting the available experimental data, and propose that the available data are consistent with a role for protein synthesis in memory.

Can behavioural therapy influence neuromodulation?

This paper reviews non-invasive behavioural approaches - broadly construed as cognitive, affective, behavioural and psychophysiological interventions - and examines whether they can impact central, peripheral or autonomic nervous system components responsive to pain in general and headache in particular. It focuses on two developing bodies of literature - neurophysiology of migraine and fMRI studies of pain networks. The available literature suggests behavioural interventions can affect neuromodulation, although further research is clearly warranted.

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons.

BDNF, a member of the neurotrophin family, is emerging as a key modulator of synaptic structure and function in the CNS. Due to the critical role of postsynaptic Ca(2+) signals in dendritic development and synaptic plasticity, we tested whether long-term exposure to BDNF affects Ca(2+) elevations evoked by coincident excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (bAPs) in spiny dendrites of CA1 pyramidal neurons within hippocampal slice cultures. In control neurons, a train of 5 coincident EPSPs and bAPs evoked Ca(2+) elevations in oblique radial branches of the main apical dendrite that were of similar amplitude than those evoked by a train of 5 bAPs alone. On the other hand, dendritic Ca(2+) signals evoked by coincident EPSPs and bAPs were always larger than those triggered by bAPs in CA1 neurons exposed to BDNF for 48 h. This difference was not observed after blockade of NMDA receptors (NMDARs) with D,L-APV, but only in BDNF-treated neurons, suggesting that Ca(2+) signals in oblique radial dendrites include a synaptic NMDAR-dependent component. Co-treatment with the receptor tyrosine kinase inhibitor k-252a prevented the effect of BDNF on coincident dendritic Ca(2+) signals, suggesting the involvement of neurotrophin Trk receptors. These results indicate that long-term exposure to BDNF enhances Ca(2+) signaling during coincident pre- and postsynaptic activity in small spiny dendrites of CA1 pyramidal neurons, representing a potential functional consequence of neurotrophin-mediated dendritic remodeling in developing neurons.

Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning.

Although there is consensus that instrumental conditioning depends on the encoding of action-outcome associations, it is not known where this learning process is localized in the brain. Recent research suggests that the posterior dorsomedial striatum (pDMS) may be the critical locus of these associations. We tested this hypothesis by examining the contribution of N-methyl-D-aspartate receptors (NMDARs) in the pDMS to action-outcome learning. Rats with bilateral cannulae in the pDMS were first trained to perform two actions (left and right lever presses), for sucrose solution. After the pre-training phase, they were given an infusion of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (APV, 1 mg/mL) or artificial cerebral spinal fluid (ACSF) before a 30-min session in which pressing one lever delivered food pellets and pressing the other delivered fruit punch. Learning during this session was tested the next day by sating the animals on either the pellets or fruit punch before assessing their performance on the two levers in extinction. The ACSF group selectively reduced responding on the lever that, in training, had earned the now devalued outcome, whereas the APV group did not. Experiment 2 replicated the effect of APV during the critical training session but found no effect of APV given after acquisition and before test. Furthermore, Experiment 3 showed that the effect of APV on instrumental learning was restricted to the pDMS; infusion into the dorsolateral striatum did not prevent learning. These experiments provide the first direct evidence that, in instrumental conditioning, NMDARs in the dorsomedial striatum are involved in encoding action-outcome associations.

[Clinico-neurological and stabilometric analysis of betahistine (betaserc) efficacy in the patients with vertigo in the rehabilitation period of ischemic stroke].

A study of betahistine (betaserc) in 65 patients aged 59,48 +/- 8,63 years with vertigo in early rehabilitation period of ischemic stroke has been carried out. Thirty-five patients got atiplatelet and antihypertensive therapy and were also treated by betaserc--8-16 mg 3 times per day for 14 days per os, after meals. The control group of 30 patients received only atiplatelet and antihypertensive therapy. Both groups were similar in demographic and clinical characteristics. The treatment with betahistine reduced the intensity and duration of vertigo, led to improvement of coordination and equilibrium, increase stability of a vertical posture that was accompanied by significant (p<0,05) improvement of the values on the Hoffenberth and Bohannon scales. Betahistine treatment also resulted in marked authentic (p<0,05) improvement of stabilometric parameters in biological feedback task that might be explained by activation of the mechanisms maintaining vertical balance. An improvement of clinical and neurophysiologic traits was more pronounced in the group treated with betaserc as compared to the control group.

The role of cutaneous feedback for anticipatory grip force adjustments during object movements and externally imposed variation of the direction of gravity.

Grip force adjustments to changes of object loading induced by external changes of the direction of gravity during discrete arm movements with a grasped object were analyzed during normal and anesthetized finger sensibility. Two subjects were seated upright in a rotatable chair and rotated backwards into a horizontal position during discrete movements with a hand-held instrumented object. The movement direction varied from vertical to horizontal inducing corresponding changes in the direction of gravity, but the orientation of the movement in relation to the body remained unaffected. During discrete vertical movements a maximum of load force occurs early in upward and late in downward movements; during horizontal movements two load force peaks result from both acceleratory and deceleratory phases of the movement. During performance with normal finger sensibility grip force was modulated in parallel with fluctuations of load force during vertical and horizontal movements. The grip force profile adopted to the varying load force profile during the transition from the vertical to the horizontal position. The maximum grip force occurred at the same time of maximum load force irrespective of the movement plane. During both subjects' first experience of digital anesthesia the object slipped from the grasp during rotation to the horizontal plane. During the following trials with anesthetized fingers subjects substantially increased their grip forces, resulting in elevated force ratios between maximum grip and load force. However, grip force was still modulated with the movement-induced load fluctuations and maximum grip force coincided with maximum load force during vertical and horizontal movements. This implies that the elevated force ratio between maximum grip and load force does not alter the feedforward system of grip force control. Cutaneous afferent information from the grasping digits seems to be important for the economic scaling of the grip force magnitude according to the actual loading conditions and for reactive grip force adjustments in response to load perturbations. However, it plays a subordinate role for the precise anticipatory temporal coupling between grip and load forces during voluntary object manipulation.

Caffeine enhances initial but not extended learning of a proprioceptive-based discrimination task in nonsmoking moderate users.

We examined the effects of caffeine on fine motor performance and learning using a multiple-force discrimination task. 93 college-aged subjects performed this task on which multiple measurements were made in an operant response paradigm. Quantitative measures of accuracy of response, duration of response, latency of response, force, and variability of force were examined. Significant interactions for caffeine dose by session on accuracy of response and latency of response indicated that caffeine enhanced the initial learning of a proprioceptive motor task but did not improve performance beyond that of normal practice.

Enhancing the effectiveness of relaxation-thermal biofeedback training with propranolol hydrochloride.

This article evaluated the ability of propranolol to enhance results achieved with relaxation-biofeedback training. Thirty-three patients were randomized to relaxation-biofeedback training alone (administered in a limited-contact treatment format), or to relaxation-biofeedback training accompanied by long-acting propranolol (with dosage individualized at 60, 120, or 180 mg/day). Concomitant propranolol therapy significantly enhanced the effectiveness of relaxation-biofeedback training when either daily headache recordings (79% vs. 54% reduction in migraine activity) or neurologist clinical evaluations (90% vs. 66% reduction) were used to assess treatment outcome. Concomitant propranolol therapy also yielded larger reductions in analgesic medication use and greater improvements of quality of life measures than relaxation-biofeedback training alone but was more frequently associated with side effects.

[The neuroregulatory modulation of the hemodynamic reactions to physical loading in patients with cardiac arrhythmias]. / Neiroreguliatornaia moduliatsiia gemodinamicheskikh reaktsii na fizicheskuiu nagruzku u bol'nykh s aritmiiami serdtsa.

Course activations of artificial stable functional links (ASFL-II) simulating tranquilizer hidazepam were given to 36 arrhythmic patients with effort syndrome (ES) and coronary heart disease. Hemodynamic responses to ASFL-II at bicycle exercise were evaluated. It was found that ASFL diminish pressor vascular reactions and increase hemodynamic resources at bicycle exercise, especially of ES patients. The modulating activity of ASFL-II in relation to hemocirculation is attributed to alterations in the central neuromediator mechanisms.

Nicotine effects on biofeedback training.

Biofeedback involving hand warming has become a frequently used procedure in health and stress management programs. The present research examined the effects of smoking on the ability to learn temperature control during biofeedback training. Three groups of female college students were compared: groups of smokers who smoked prior to the biofeedback session were compared to smokers who did not smoke and to nonsmokers. The results showed that the greatest increase in skin temperature was for nonsmokers, followed by smokers who did not smoke for at least 1 hr before the biofeedback session. The group of smokers who smoked just prior to the biofeedback were not able to increase their skin temperature. The basal skin temperature measured before treatment was higher for smokers than nonsmokers. The results are discussed in terms of the paradoxical physiological arousing effects and the self-reported tranquilizing effects of smoking.

Blood glucose discrimination training in patients with type II diabetes.

This study was designed to determine whether patients with Type II diabetes could be taught to discriminate blood glucose after experiencing a variety of blood glucose levels and receiving feedback on the accuracy of their estimates. Thirty-six subjects (18 on oral agents and 18 on insulin) were randomly assigned to one of two feedback conditions: (1) current feedback, which received accurate information regarding their blood glucose levels, (2) noncurrent feedback, which received blood glucose levels from the preceding session. Subjects were exposed to a wide range of blood glucose values in six training sessions by ingesting drinks with three different caloric loads. In pre/post comparisons using several indices of accuracy, both groups showed significant improvement in estimating blood glucose levels. However, feedback on current blood glucose levels did not produce greater improvement than noncurrent. Accuracy was unrelated to the degree to which subjects reported associating internal sensations to their estimates. Failure to find differences between the two feedback conditions may have been due to the noncurrent feedback group's receiving fairly accurate information, to the difficulty of the discrimination task, and to the limited number of training trials.

Regulation of bile acid synthesis. III. Correlation between biliary bile salt hydrophobicity index and the activities of enzymes regulating cholesterol and bile acid synthesis in the rat.

Hepatic bile acid synthesis is thought to be under negative feedback control by bile salts in the enterohepatic circulation, acting at the level of cholesterol 7 alpha-hydroxylase (C7 alpha H), the initial and rate-limiting step in the bile acid biosynthetic pathway. Bile salts also suppress the activity of the rate-limiting enzyme for cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R). The mechanisms of these regulatory effects are poorly understood, and one or both may be indirect. Previous data suggest that the hydrophilic-hydrophobic balance of bile salts, a major determinant of their cholesterol solubilizing properties, also determines their potency as regulators of bile acid and cholesterol synthesis. To further evaluate the relationship between the physicochemical and regulatory properties of bile acids, we altered the composition of the bile salt pool of rats by feeding one or more of seven different bile acids (1% w/w for 14 days). We then determined the mean hydrophilic-hydrophobic balance (hydrophobicity index) of the bile salts in bile, and correlated this with the specific activities of C7 alpha H and HMG-CoA-R, and of acyl-CoA:cholesterol acyltransferase (ACAT), a third hepatic microsomal enzyme which regulates cholesterol esterification. In all instances following bile acid feeding, conjugates of the fed bile acid(s) became the predominant bile salts in bile. Highly significant negative linear correlations (each P less than 0.0001) were found between the hydrophobicity indices of biliary bile salts and the activities of C7 alpha H (r = 0.79) or HMG-CoA-R (r = 0.63). By contrast, no significant correlation could be demonstrated between ACAT activity and the hydrophobicity index of biliary bile salts. The correlation between activities of HMG-CoA-R and C7 alpha H was also highly significant (r = 0.81; P less than 0.0001). No significant correlation existed between ACAT and either HMG-CoA-R or C7 alpha H. Microsomal free cholesterol was not consistently altered by bile acid feeding. Thus, the potency of circulating bile salts as suppressors of the enzymes regulating bile acid and cholesterol synthesis increases with increasing hydrophobicity. The hydrophobic-hydrophilic balance of the bile salt pool may play an important role in the regulation of cholesterol and bile acid synthesis.