Inhibitory Reflex Research Articles

Differences Between Natural Sleep and the Anesthetic State

The anesthetic state and natural sleep share many neurobiological features and yet are two distinct states. The hallmarks of general anesthesia include hypnosis, analgesia, akinesia and anxiolysis. These are the principal parameters by which the anesthetic state differs from natural sleep. These properties are mediated by systemic administration of a combination of agents producing balanced anesthesia. The exact nature of anesthetic narcosis is dose dependent and agent specific. It exhibits a relative lack of nociceptive response and active suppression of motor and autonomic reflexes. Surgical anesthesia displays a signature electroencephalogram pattern of burst suppression that differs from rapid eye movement sleep, representing more widespread disruption of thalamocortical connectivity, impairing information integration and processing. These differences underpin successful anesthetic action. This review explores the differences between natural sleep and anesthetic-induced unconsciousness as induced by balanced anesthesia.

Variation in rectoanal inhibitory reflex after laparoscopic intersphincteric resection for ultralow rectal cancer.

The aim was to evaluate the physiological variation in rectoanal inhibitory reflex (RAIR) after laparoscopic intersphincteric resection (Lap-ISR) for ultralow rectal cancer. This was a retrospective study that included 56 patients who underwent Lap-ISR from a prospectively collected database. The RAIR was examined preoperatively and up to 12 months after ileostomy closure. The primary outcome included physiological variation in RAIR and its difference between partial, subtotal and total ISR. The secondary outcome was its correlation with functional outcome. The reflex was present in 95% (53/56) of patients preoperatively, in 36% (20/56) before ileostomy closure, in 48% (27/56) at 3-6months and in 61% (34/56) at 12 months after ileostomy closure. The elicited volume of RAIR was significantly increased at 12 months after ileostomy closure than at baseline (P=0.005), but its duration and amplitude did not differ significantly. There was no significant difference in the reflex recovery between the ISR groups (partial vs. subtotal vs. total: 65% vs. 63% vs. 44%, P=0.61). At 12 months after ileostomy closure, the RAIR-present group had favourable functional results and patient satisfaction (P<0.05). Major faecal incontinence was found in 82% of patients in the RAIR-absent group. The RAIR is abolished in the majority of patients after Lap-ISR, but a time-dependent recovery could be observed in more than half of the patients. The reflex recovery is not influenced by the resection grade of the internal sphincter. However, persistent loss of the RAIR correlates with worse continence.

Attribute capture underlying the precedence effect in rats

In a reverberant environment, humans with normal hearing can perceptually fuse the soundwave from a source with its reflections off nearby surfaces into a single auditory image, whose location appears to be around the source. This phenomenon is called the precedence effect, which is based on the perceptual capture of the reflected (lagging) sounds' attributes by the direct wave from the source. Using the paradigm of attentional modulation of the prepulse inhibition (PPI) of the startle reflex, with both the prepulse-feature specificity and the perceived-prepulse-location specificity, this study was to examine whether the perceptual attribute capture underlying the precedence effect occurs in rats. One broadband continuous noise was delivered by each of two spatially separated left and right loudspeakers with a 1-ms inter-loudspeaker delay. A silent gap was embedded in one of the two noises as the prepulse stimulus. The results showed that regardless of whether the gap was physically in the leading or lagging noise when the leading noise was either the left or right one, fear conditioning the gap enhanced PPI only when the leading noise was delivered from the loudspeaker that was the leading but not the lagging loudspeaker during the conditioning, indicating that due to the spatial specificity (either left or right) in the attentional enhancement of PPI, the perceived location of the conditioned gap was always on the leading side even though the gap was physically on the lagging side. Thus, rats have the same perceptual ability of attribute capture, thereby experiencing the auditory precedence effect as humans.

Effect of age on the gap-prepulse inhibition of the cortical N1-P2 complex in humans as a step towards an objective measure of tinnitus.

The gap-prepulse inhibition of the acoustic startle reflex has been widely used as a behavioral method for tinnitus screening in animal studies. The cortical-evoked potential gap-induced inhibition has also been investigated in animals as well as in human subjects. The present study aimed to investigate the effect of age on the cortical N1-P2 complex in the gap-prepulse inhibition paradigm. Fifty-seven subjects, aged 20 to 68 years, without continuous tinnitus, were tested with two effective gap conditions (embedded gap of 50- or 20-ms duration). Retest sessions were performed within one month. A significant gap-induced inhibition of the N1-P2 complex was found in both gap durations. Age differently affected the inhibition, depending on gap duration. With a 50-ms gap, the inhibition decreased significantly with the increase in age. This age-inhibition relationship was not found when using a 20-ms gap. The results were reproducible in the retest session. Our findings suggest that the interaction between age and gap duration should be considered when applying the gap-induced inhibition of the cortical-evoked potential as an objective measure of tinnitus in human subjects. Further studies with tinnitus patients are warranted to identify gap duration that would minimize the effects of age and maximize the difference in the inhibition between those with and without tinnitus.

Anorectal manometry in pediatric settings: A systematic review of 227 studies.

There is wide variation in the clinical use of diagnostic tools for children with chronic constipation and functional/structural fecal incontinence (CCFSFI). Anorectal manometry (ARM) is a well-recognized technique to assess the function of the anorectum. Our aim was to perform an up-to-date review on ARM in pediatric patients with CCFSFI, with specific focus on the indication of use and protocol. Variation of its use in pediatrics will be explored. A systematic search was conducted for empirical studies utilizing ARM with a pediatric sample. A keyword search of literature published in English before July 2018 was conducted and updated to October 2019. Data on demographics, clinical information, study aims, ARM parameters and use of sedation/anesthesia were collected. A total of 227 studies were included in this systematic review. The age of study participants at the time of ARM ranged from birth to 18years. ARM was most commonly used in patients with organic conditions (65%) compared to functional constipation (41%). In almost half [108/227 (48%)] of the studies, ARM was performed awake. The ARM parameters most frequently assessed were the rectoanal inhibitory reflex, which was evaluated in 198/227 studies (87%) and the anal resting pressure [166/227 studies (73%)]. This systematic review has highlighted the vast variation of ARM use within pediatrics and the need to strive toward standardization and use of consensus guidelines. We anticipate this will further advance our understanding of the pathophysiological mechanisms involved in children with defecation disorders.

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

Prepulse inhibition and recovery of trigemino-cervical reflex in patients with cervical dystonia

ObjectiveWe aimed to analyze the prepulse inhibition (PPI) and recovery rate (R) of the trigeminocervical reflex (TCR) in patients with cervical dystonia (CD). MethodsWe enrolled 15 patients with CD and 16 healthy subjects. TCR was recorded over splenius capitis after infraorbital nerve stimulation. For TCR-PPI, we applied a prepulse stimulus to the left second finger 100 ms prior to the test stimulus and the percentage of change of response to test stimulus was calculated. For TCR-R, we applied paired infraorbital stimuli at interstimulus interval (ISIs) of 300 ms and the percentage of change of the second compared to the first response was calculated. ResultsTCR-PPI and TCR-R values were higher (less inhibition and greater recovery) on both sides in the patient group compared to healthy subjects. There was high correlation between TCR-PPI and TCR-R on both sides in patients with dystonia (p < 0.005). We did not find any significant relationship between TCR-R or TCR-PPI and side of dystonic posture. ConclusionsWe showed disturbed modulation of TCR in CD patients. In CD, a general inhibition of the inhibitory pathways and facilitation of the excitatory pathways occur. Although TCR was recorded directly on the affected muscles in CD, symmetric abnormal TCR findings in CD suggest that these findings are probably secondary to altered function of higher order centers rather than being directly related to the pathophysiological process.

Effect of risperidone on prepulse inhibition of the startle reflex and P50 deficit in patients with first-episode and chronic schizophrenia

Objective: To investigate the effect of antipsychotic medicine risperidone on prepulse inhibition of the startle reflex (PPI) and P50 deficit in patients with first-episode and chronic. Methods: Thirty-eight patients with first-episode schizophrenia and 36 patients with chronic schizophrenia, both in acute stage, were enrolled in the study. All patients were treated with risperidone of different doses (2 to 6mg/d). All patients fulfilled the evaluation of PPI and P50 before treatment and 8 weeks after treatment. The psychotic symptoms were assessed with Positive and Negative Syndrome Scale (PANSS), and the therapeutic effects were evaluated with PANSS reduction rate. Results: (1) There was no significant difference in PPI and P50 parameters between the two groups before treatment (PPI ratio: first group 43%±29%, chronic group 42%±27%, P>0.05; P50 S2/S1 ratio: first group 83%±33%, chronic group 82%±24%, P>0.05). (2) There was no significant correlation between PPI and P50 inhibition parameters and disease course, psychotic episodes and psychiatric symptoms (PANSS total score, positive symptoms score, negative symptoms score and general psychopathology symptoms score) of schizophrenia (P>0.05). (3) Except the group main effect for S2 amplitude (F=5.75, P=0.019), there was no significant change for main effect and interaction of the other P50 and PPI inhibition ratio parameters after treatment (P50 S2/S1 ratio: first group before treatment 83%±33%, after treatment 85%±49%, P>0.05; chronic group before treatment 82%±44%, after treatment 84%±35%, P>0.05. PPI ratio: first group before treatment 43%±29%, after treatment 42%±27%; chronic group before treatment 42%±27%, after treatment 41%±28%,P>0.05). The effect of risperidone on P50 and PPI parameters was not related to the therapeutic effect. Conclusion: Deficit in sensory gating inhibition exists in both first-episode schizophrenia and chronic schizophrenia, and risperidone is not effective in treating the deficit in sensory gating (PPI and P50) inhibition of schizophrenia.

A novel method for measurement of the recto-anal inhibitory reflex using anal acoustic reflectometry.

The recto-anal inhibitory reflex (RAIR) is currently measured using manometry catheters, which potentially distort the anal canal. Anal acoustic reflectometry (AAR) is considered to be a catheter-free technique and primarily measures the function of the internal anal sphincter. We sought to determine if RAIR could be measured using AAR. Patients aged 18 and over attending the hospital for investigation of pelvic floor dysfunction were included. AAR parameters were obtained before (prerectal distension) and after (postrectal distension) inflation of a rectal balloon catheter with 100ml of air. Minimum opening pressure (Op, cmH2 O), opening elastance (Oe, cmH2 O/mm2 ), closing pressure (Cp, cmH2 O), closing elastance (Ce, cmH2 O/mm2 ) and hysteresis (Hys, %) were recorded. The presence of RAIR was defined by a reduction of prerectal distension Op by 20% or more. Thirty-two patients were included, 26 of whom were women. The mean age of patients was 57.5years (SD 11.3years). Nine patients had faecal incontinence, six patients had obstructive defaecation and 17 patients had both. RAIR was seen in 30/32 patients. The mean reduction in Op was 58.8% (range -59.18% to 100%). Three patients had 100% reduction. Comparison of pre- and post-RAIR parameters showed a significant difference in Op (34.44 vs 15.41, P<0.0001), Oe (1.39 vs 1.1, P=0.004), Cp (20.06 vs 8.00, P<0.0001) and Ce (1.31 vs 1.13, P<0.0001) but not Hys (39.71 vs 39.90, P=0.88). We describe a novel method for the measurement of RAIR. Rectal distension appears to alter resting pressure and the resistance of the anal canal to opening and closing, with complete inhibition of the sphincter complex in three patients.

Prefrontal inhibition of neuronal Kv 7 channels enhances prepulse inhibition of acoustic startle reflex and resistance to hypofrontality.

Background and PurposeDysfunction of the prefrontal cortex (PFC) is involved in the cognitive deficits in neuropsychiatric diseases, such as schizophrenia, characterized by deficient neurotransmission known as NMDA receptor hypofrontality. Thus, enhancing prefrontal activity may alleviate hypofrontality‐induced cognitive deficits. To test this hypothesis, we investigated the effect of forebrain‐specific suppression or pharmacological inhibition of native Kv7/KCNQ/M‐current on glutamatergic hypofrontality induced by the NMDA receptor antagonist MK‐801.Experimental ApproachThe forebrain‐specific inhibition of native M‐current was generated by transgenic expression, in mice, of a dominant‐negative pore mutant G279S of Kv7.2/KCNQ2 channels that suppresses channel function. A mouse model of cognitive impairment was established by single i.p. injection of 0.1 mg·kg−1 MK‐801. Mouse models of prepulse inhibition (PPI) of acoustic startle reflex and Y‐maze spontaneous alternation test were used for evaluation of cognitive behaviour. Hippocampal brain slice recordings of LTP were used to assess synaptic plasticity. Hippocampus and cortex were dissected for detecting protein expression using western blot analysis.Key ResultsGenetic suppression of Kv7 channel function in the forebrain or pharmacological inhibition of Kv7 channels by the specific blocker XE991 enhanced PPI and also alleviated MK‐801 induced cognitive decline. XE991 also attenuated MK‐801‐induced LTP deficits and increased basal synaptic transmissions. Western blot analysis revealed that inhibiting Kv7 channels resulted in elevation of pAkt1 and pGSK‐3β expressions in both hippocampus and cortex.Conclusions and ImplicationsBoth genetic and pharmacological inhibition of Kv7 channels alleviated PPI and cognitive deficits. Mechanistically, inhibition of Kv7 channels promotes synaptic transmission and activates Akt1/GSK‐3β signalling.

Bedside examination elderly patient with vertigo and dizziness

Bedside examination is undoubtedly important part of general investigation of elderly patients with vertigo and dizziness. The main purposes of such examination is to confirm the vestibular origin of vertigo, to find out where vestibular system has been damaged and to establish the extent of central vestibular compensation. Bedside examination for vestibular screening consists of an interview, analysis of spontaneous, gaze-evoked and positional nystagmus, Halmagyi head impulse test, vestibule-ocular reflex suppression test and Fukuda stepping test. These tests do not take a lot of time and for this reason can be recommended for neurologists, gerontologists and general practitioners in their everyday practice.

Placement of a fine-bore rectal balloon catheter in the anal canal does not affect anal sphincter pressures: improving our understanding of physiological function with anal acoustic reflectometry.

The recto-anal inhibitory reflex (RAIR) is currently measured using anorectal manometry catheters, which may distort the anal canal. Anal acoustic reflectometry (AAR) is considered a catheter-free technique for evaluating the physiological function of the anal canal; however, it has yet to be used to elicit the RAIR. For the RAIR to be measured with AAR, the effect of placing an additional rectal balloon catheter on the measured AAR parameters needs to be investigated: that is the aim of this work. Patients aged over 18years attending hospital for the investigation of pelvic floor disorders were included. AAR parameters were obtained before and after a rectal balloon catheter was placed alongside the AAR catheter. The following parameters were measured: opening pressure (Op, cmH2 O), opening elastance (Oe, cmH2 O/mm2 ), closing pressure (Cp, cmH2 O), closing elastance (Ce, cmH2 O/mm2 ), hysteresis (Hys, %), squeeze opening pressure (SqOp, cmH2 O) and squeeze opening elastance (SqOe, cmH2 O/mm2 ). Thirty-five patients were included in the analysis, of whom 28 were women. The median age was 58years. Comparison of median AAR parameters before and after catheter placement showed no significant difference: Op (36.36 vs 33.42, P=0.09), Oe (1.27 vs 1.39, P=0.19), Cp (18.62 vs 19.73, P=0.13), Ce (1.2 vs 1.28, P=0.33), Hys (41.08 vs 40.11, P=0.17), SqOp (81.85 vs 81.65, P=0.93) and SqOe (1.44 vs 1.49, P=0.55). Placement of a rectal balloon catheter alongside the AAR catheter has no significant effect on the measured AAR parameters. The results of this study add to the fundamental basic science and understanding of the physiological function of the anal canal.

Sex-dependent aberrant PFC development in the adolescent offspring rats exposed to variable prenatal stress.

Adolescence is a remarkable period of brain development. Prenatal stress can increase the risk of various neuropsychiatric disorders. This research investigated neurochemical and behavioural changes in the offspring rats (especially adolescences) who were treated with repeated variable prenatal stress (PNS) during the third week of gestation. The study tested the concentration of brain-derived neurotrophic factor (BDNF), cluster of differentiation 68 (CD68), synaptotagmin-1(Syt-1), 5-hydroxytryptamine (5-HT), dopamine (DA), glucocorticoid receptors (GRs) and oestrogen receptors (ERs) in the PFC (prefrontal cortex). We also tested prepulse inhibition (PPI) of the acoustic startle reflex (ASR) (a measure of sensorimotor gating). The main results were as follows: PNS increased the BDNF and CD68 concentrations in adolescent females, and increased the Syt-1 concentration in adolescent males. The increases in BDNF/CD68 concentration (in females) and Syt-1/DA concentration (in males) with age were disturbed by PNS, and PNS changed the sex differences in CD68 concentration in adolescence and disturbed the sex differences in the Syt-1 concentration (in adolescence) and DA concentration (in adults). In conclusion, we found that PNS lead to Sex-dependent aberrant PFC development, and might accelerate the development of the adolescent PFC, and so that lessened the age difference (between adolescence and adulthood) and the sex difference.

Postoperative manometric profile in recto-vestibular fistula and rectourethral fistula: A comparative study

The recto-urethral (RUF) and recto-vestibular fistula (RVF) are varieties of anorectal malformation (ARM) with distinct clinical behaviour. In this study post-operative clinico-manometric comparison has been done.The study was conducted for 2 year period and included post-operative cases of RUF and RVF. Post-operative follow up was done clinically and by anal manometry.Kruskal Wallis test, Mann Whitney U test, and Spearman correlation test were done to find out the statistical significance.A total of 21 patients with RUF and RVF were included. The average basal and squeeze pressure of RVF group was (cm H2O) 34.66 ± 13.2 and 89.35 ± 30.8 respectively. These pressures were higher than those of RUF which were 26.74 ± 12.8 and 71.20 ± 42.8 respectively. Rectoanal inhibitory reflex (RAIR) was present in 84.6% cases of RVF in comparison to 62.5% in RUF group. The mean combined (RUF + RVF) basal pressure in RAIR positive group was 32.97 ± 12.2 compared to 24.5 ± 4.6 cm HO in RAIR negative group. The mean combined squeeze pressure in RAIR positive group was 84.34 ± 36.2 compared to 68.83 ± 32.75 cm HO in RAIR negative group.The anal pressures of RVF group were higher than RUF group. Anal pressures also higher in RAIR positive group than the RAIR negative group. Anal pressures and RAIR status may have some role in post-operative outcome in cases of ARM.

NMDAR Antibodies Alter Dopamine Receptors and Cause Psychotic Behavior in Mice.

The aim was to demonstrate that antibodies from patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis alter the levels of dopamine 1 receptor (D1R) and dopamine 2 receptor (D2R) and cause psychotic-like features in mice. Cultured rat hippocampal neurons were treated with cerebrospinal fluid (CSF) from patients with anti-NMDAR encephalitis or controls, and the effects on clusters of D1R and D2R were quantified. In vivo studies included 71 C57BL/6J mice that were chronically infused with CSF from patients or controls through ventricular catheters connected to subcutaneous osmotic pumps. Prepulse inhibition of the acoustic startling reflex (PPI; a marker of psychotic-like behavior), memory, locomotor activity, and the density of cell-surface and synaptic D1R, D2R, and NMDAR clusters were examined at different time points using reported techniques. In cultured neurons, CSF from patients, but not from controls, caused a significant decrease of cell-surface D1R and an increase of D2R clusters. In mice, CSF from patients caused a significant decrease of synaptic and total cell-surface D1R clusters and an increase of D2R clusters associated with a decrease of PPI. These effects were accompanied by memory impairment and a reduction of surface NMDARs, as reported in this model. The psychotic-like features, memory impairment, and changes in levels of D1R, D2R, and NMDAR progressively improved several days after the infusion of CSF from patients stopped. In addition to memory deficits and reduction of NMDARs, CSF antibodies from patients with anti-NMDAR encephalitis cause reversible psychotic-like features accompanied by changes (D1R decrease, D2R increase) in cell-surface dopamine receptor clusters. ANN NEUROL 2020 ANN NEUROL 2020;88:603-613.

Chloroquine for prolonged skin analgesia in rats

The purpose of this study was to investigate the ability of chloroquine and chloroquine in combination with vasoconstrictor epinephrine to act as a local anesthetic in skin analgesia. After subcutaneous injection of drugs in rats, the inhibition of the cutaneous trunci muscle reflex (CTMR) is designed for evaluation of the cutaneous analgesic effect. The analgesic effect of chloroquine was compared with that of bupivacaine or coadministration of chloroquine and epinephrine. Chloroquine produced exactly the same local anesthesia as bupivacaine did in a dose-dependent manner. On the ED50 (50 % effective dose) basis, the analgesic potency was chloroquine (4.81 [4.45–5.20] μmol) < bupivacaine (0.46 [0.40‒0.52] μmol) (p < 0.01). At every equipotent dose tested (ED25, ED50 and ED75), chloroquine had a longer duration of cutaneous analgesia than bupivacaine (p < 0.01). Epinephrine enhanced the potency and duration of chloroquine-induced cutaneous analgesia. We found that chloroquine and bupivacaine elicit dose-dependent cutaneous analgesia. Chloroquine is not as potent as bupivacaine, but acts as an infiltrative anesthetic for a longer duration of time and is more potent and effective when used in combination with epinephrine.

Vibration attenuates spasm-like activity in humans with spinal cord injury.

Cutaneous reflexes were tested to examine the neuronal mechanisms contributing to muscle spasms in humans with chronic spinal cord injury (SCI). Specifically, we tested the effect of Achilles and tibialis anterior tendon vibration on the early and late components of the cutaneous reflex and reciprocal Ia inhibition in the soleus and tibialis anterior muscles in humans with chronic SCI. We found that tendon vibration reduced the amplitude of later but not earlier cutaneous reflex in the antagonist but not in the agonist muscle relative to the location of the vibration. In addition, reciprocal Ia inhibition between antagonist ankle muscles increased with tendon vibration and participants with a larger suppression of the later component of the cutaneous reflex had stronger reciprocal Ia inhibition from the antagonistic muscle. Our study is the first to provide evidence that tendon vibration attenuates late cutaneous spasm-like reflex activity, likely via reciprocal inhibitory mechanisms, and may represent a method, when properly targeted, for controlling spasms in humans with SCI. The neuronal mechanisms contributing to the generation of involuntary muscle contractions (spasms) in humans with spinal cord injury (SCI) remain poorly understood. To address this question, we examined the effect of Achilles and tibialis anterior tendon vibration at 20, 40, 80 and 120Hz on the amplitude of the long-polysynaptic (LPR, from reflex onset to 500ms) and long-lasting (LLR, from 500ms to reflex offset) cutaneous reflex evoked by medial plantar nerve stimulation in the soleus and tibialis anterior, and reciprocal Ia inhibition between these muscles, in 25 individuals with chronic SCI. We found that Achilles tendon vibration at 40 and 80Hz, but not other frequencies, reduced the amplitude of the LLR in the tibialis anterior, but not the soleus muscle, without affecting the amplitude of the LPR. Vibratory effects were stronger at 80 than 40Hz. Similar results were found in the soleus muscle when the tibialis anterior tendon was vibrated. Notably, tendon vibration at 80Hz increased reciprocal Ia inhibition between antagonistic ankle muscles and vibratory-induced increases in reciprocal Ia inhibition were correlated with decreases in the LLR, suggesting that participants with a larger suppression of later cutaneous reflex activity had stronger reciprocal Ia inhibition from the antagonistic muscle. Our study is the first to provide evidence that tendon vibration suppresses late spasm-like activity in antagonist but not agonist muscles, likely via reciprocal inhibitory mechanisms, in humans with chronic SCI. We argue that targeted vibration of antagonistic tendons might help to control spasms after SCI.

\u0394-9-Tetrahydrocannabinol treatment during adolescence and alterations in the inhibitory networks of the adult prefrontal cortex in mice subjected to perinatal NMDA receptor antagonist injection and to postweaning social isolation

The prefrontal cortex (PFC) continues its development during adolescence and alterations in its structure and function, particularly of inhibitory networks, have been detected in schizophrenic patients. Since cannabis use during adolescence is a risk factor for this disease, our main objective was to investigate whether THC administration during this period might exacerbate alterations in prefrontocortical inhibitory networks in mice subjected to a perinatal injection of MK801 and postweaning social isolation. This double-hit model (DHM) combines a neurodevelopmental manipulation and the exposure to an aversive experience during early life; previous work has shown that DHM mice have important alterations in the structure and connectivity of PFC interneurons. In the present study we found that DHM had reductions in prepulse inhibition of the startle reflex (PPI), GAD67 expression and cingulate 1 cortex volume. Interestingly, THC by itself induced increases in PPI and decreases in the dendritic complexity of somatostatin expressing interneurons. Both THC and DHM reduced the density of parvalbumin expressing cells surrounded by perineuronal nets and, when combined, they disrupted the ratio between the density of puncta expressing excitatory and inhibitory markers. Our results support previous work showing alterations in parameters involving interneurons in similar animal models and schizophrenic patients. THC treatment does not modify further these parameters, but changes some others related also to interneurons and their plasticity, in some cases in the opposite direction to those induced by the DHM, suggesting a protective effect.

Spatial specificity in attentional modulation of prepulse inhibition of the startle reflex in rats.

Prepulse inhibition (PPI), the suppression of the startle reflex when the startling stimulus is shortly preceded by a weaker non-startling sensory stimulus (prepulse), can be enhanced by selective attention to the prepulse with a marked prepulse-feature specificity. To determine if the attentional modulation of PPI in rats can also be perceptual location specific, this study investigated whether fear-conditioning of a prepulse perceived at a location can enhance PPI only when the conditioned prepulse is perceived at that conditioned location. A continuous narrowband noise (NBN) was delivered by each of the two spatially separated loudspeakers in the frontal azimuth with a silent gap embedded in each NBN. The inter-loudspeaker interval was 1ms (either left or right loudspeaker leading). Due to the precedence effect, both the NBN and gap images were perceived at the leading loudspeaker. The perceptually fused gap was used as the prepulse. To fear-condition one gap prepulse, which was perceived at one loudspeaker, the prepulse was paired with footshock in a temporally precise manner and the other gap (the conditioning-control prepulse) perceived at the other (opposite) loudspeaker was paired with footshock in a random manner. Compared to PPI before conditioning, PPI induced by the fear-conditioned gap perceived at the fear-conditioned loudspeaker, but not that by the conditioning-control gap, was significantly enhanced. Thus, attentional modulation of PPI can be not only prepulse-feature specific, but also perceptual location specific, and involves combined central processes for content and location information.

High-resolution anorectal manometry in children with functional constipation with or without fecal incontinence.

High-resolution anorectal manometry (HR-ARM) is expected to be better than conventional manometry. Our aim was to characterize HR-ARM pressures in children with functional constipation (FC), with or without fecal incontinence (FI). Children with diagnosis of FC, with or without FI, according to Rome-IV criteria, were enrolled. All patients underwent HR-ARM using 24-channel water-perfused catheter. Twenty-nine consecutive children (M/F: 21/8; mean age±SD: 9.5±3.1years; range 4-15), of whom 21 affected by FC without FI (mean age±SD: 9.3±3.23years) and 8 affected by FC with FI (mean age±SD: 10.2±3.08years), were enrolled. No significant differences were found regard to gender and age. The analysis of HR-ARM 3D plots demonstrated asymmetry of the anal canal, with higher pressures in distal halves. Comparing pressures between the two groups, we found lower values in FC with FI than in FC without FI group, with a statistically significance for maximum and mean resting pressures (P=.032 and P=.008, respectively). When evaluating our study population respect to asymptomatic children, we found lower resting pressures, lower maximum squeeze pressure, and higher rectoanal inhibitory reflex (RAIR) values. Our data demonstrate that HR-ARM pressures at rest and during squeezing in FC with FI children are lower than FC without FI subjects, particularly in anteroposterior quadrants. Compared to children without lower gastrointestinal symptoms, children with FC with or without FI show lower pressures and higher values of RAIR.