Search

Purpose: The purpose of this systematic review and meta‐analysis was to analyze the clinical and radiographic outcomes of patients rehabilitated using a single implant supporting a crown with a cantilever extension or two implants supporting two single crowns. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) 2020 guidelines, a systematic review of relevant literature published from 2000 was conducted in the Cochrane Library, Scopus, and MEDLINE databases. Moreover, a manual search was performed. A meta‐analysis of the resulting data was carried out. Peri‐implant marginal bone level, probing pocket depth, prevalence of technical and mechanical complications, implant survival rate, and prosthesis survival rate were assessed. Results: The meta‐analysis showed a non‐statistically significant change in the peri‐implant marginal bone level and probing pocket depth in the cantilever group and revealed a non‐significant prevalence of technical complications, showing a 27% rate in the cantilever group. The analysis of the prosthesis survival rate in the cantilever group showed a mean survival rate of 99% while the comparison of the implant survival between the two groups revealed an odds ratio of 0.50. Conclusions: The use of a single implant supporting a crown with a cantilever extension does not result in lower implant survival rate if compared with two implants supporting two single crowns. Moreover, a high prosthesis survival rate was observed in the cantilever group even if the high prevalence of complications should be carefully considered by the clinician. [ABSTRACT FROM AUTHOR]

The orbitofrontal cortex (OFC) is crucial for tracking various aspects of expected outcomes, thereby helping to guide choices and support learning. Our previous study showed that the effects of reward timing and size on the activity of single units in OFC were dissociable when these attributes were manipulated independently (Roesch et al., 2006). However, in real-life decision-making scenarios, outcome features often change simultaneously, so here we investigated how OFC neurons in male rats integrate information about the timing and identity (flavor) of reward and respond to changes in these features, according to whether they were changed simultaneously or separately. We found that a substantial number of OFC neurons fired differentially to immediate versus delayed reward and to the different reward flavors. However, contrary to the previous study, selectivity for timing was strongly correlated with selectivity for identity. Taken together with the previous research, these results suggest that when reward features are correlated, OFC tends to “pack” them into unitary constructs, whereas when they are independent, OFC tends to “crack” them into separate constructs. Furthermore, we found that when both reward timing and flavor were changed, reward-responsive OFC neurons showed unique activity patterns preceding and during the omission of an expected reward. Interestingly, this OFC activity is similar and slightly preceded the ventral tegmental area dopamine (VTA DA) activity observed in a previous study (Takahashi et al., 2023), consistent with the role of OFC in providing predictive information to VTA DA neurons. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the survival and marginal bone loss of single-unit short implants (≤ 8 mm in length) in the premolar-molar area. It also compared cemented with screw-retained restorations. Materials and Methods: In this clinical retrospective study, short implants supporting a single crown in the premolarmolar region were selected. Demographic-, surgical-, implant-, and prosthesis-related data were obtained. The predictor variable was the type of prosthesis retention. The principal variables were survival rate and marginal bone loss. The secondary variables were prosthesis survival and technical and biologic complications. Results: A total of 113 patients (56 ± 11 years of age) with 128 short implants were assessed. The mean follow-up time from implant insertion was 25.47 ± 14.95 months. Fifty-one crowns were cemented and 77 were screw-retained. No failure events were recorded for the implants and the prostheses. The distal marginal bone loss was significantly lower in the screw-retained crowns than in the cemented crowns. Marginal bone loss ≥ 2 mm as a biologic complication was more frequent in the cemented crowns. Two screw-loosening events were observed in the screw-retained restorations. These events were resolved by screw retightening. Conclusion: Short implants could be an effective option to support a single-unit prosthesis in the premolar-molar areas of the maxillae. [ABSTRACT FROM AUTHOR]

We are able to temporally organize multiple movements in a purposeful manner in everyday life. Both the dorsal premotor (PMd) area and pre-supplementary motor area (pre-SMA) are known to be involved in the performance of motor sequences. However, it is unclear how each area differentially contributes to controlling multiple motor sequences. To address this issue, we recorded singleunit activity in both areas while monkeys (one male, one female) performed sixteen motor sequences. Each sequence comprised either a series of two identical movements (repetition) or two different movements (nonrepetition). The sequence was initially instructed with visual signals but had to be remembered thereafter. Here, we showed that the activity of single neurons in both areas transitioned from reactive-to predictive encoding while motor sequences were memorized. In the memory-guided trials, in particular, the activity of PMd cells preferentially represented the second movement (2M) in the sequence leading to a reward generally regardless of the first movement (1M). Such activity frequently began even before the 1M in a prospective manner, and was enhanced in nonrepetition sequences. Behaviorally, a lack of the activity enhancement often resulted in premature execution of the 2M. In contrast, cells in pre-SMA instantiated particular sequences of actions by coordinating switching or nonswitching movements in sequence. Our findings suggest that PMd and pre-SMA play complementary roles within behavioral contexts: PMd preferentially controls the movement that leads to a reward rather than the sequence per se, whereas pre-SMA coordinates all elements in a sequence by integrating temporal orders of multiple movements. [ABSTRACT FROM AUTHOR]

Background and Objectives: Single-unit transfusions continue to be a widespread transfusion practice. Single-unit red blood cell (RBC) transfusions were treated with substantial denunciation in the past but recently have been reviewed as to whether it is acceptable or could be acceptable. This study was undertaken to observe the overall profile of the patients receiving the single-unit transfusion and analyze the possible rationale of such transfusion. Methods: This was a retrospective record-based study conducted in multispecialty tertiary level care teaching hospital over a period of 1 year from January to December 2017. Variables included were age, gender, diagnosis, indication for transfusion, pre- and post-hemoglobin, additional modality of treatment received including other blood components and length of hospital stay. Qualitative variables were described as number and percentages, and quantitative variables as number, mean, and standard deviation. Results: During the study, 50,880 blood components were issued out of which, packed RBCs (PRBCs) accounted to 19760. Twenty-four percent (4742 units) of the total blood units were transfused as single unit of PRBC. 52.1% of these single-unit transfusions were carried out by the surgical specialties. Conclusion: Single-unit transfusions are more common in medical specialties probably due to the chronic nature of the diseases. However, even in surgical specialties, especially those striving toward reducing blood usage and the ones operating in more of an elective setting, single-unit transfusions were higher. [ABSTRACT FROM AUTHOR]

The Kölliker-Fuse (KF) nucleus is a part of the parabrachial complex, located in the dorsolateral pons. It is involved in the chemoreflex-evoked cardiovascular and respiratory changes, but the role of GABA and glutamate in cardiovascular chemoreflex has not been shown yet. This study was performed to determine the role of GABA, glutamate, and their interaction in the KF, in cardiovascular chemoreflex in anesthetized rat. The antagonists were microinjected into the KF, and arterial pressure, heart rate, and single-unit responses were recorded simultaneously. The chemoreflex was evoked by i.v. injection of KCN, consisted of a short pressor followed by long bradycardia responses. Both responses were significantly attenuated by injection of a synaptic blocker (CoCl2) into the KF, confirming involvement of the KF in generating the reflex. Microinjection of AP5, an NMDA receptor antagonist, into the KF significantly attenuated the pressor and bradycardia responses, while blocking the AMPA receptors by CNQX had no significant effect. Blockade of GABAA receptors by bicuculline methiodide (BMI) potentiated both responses. Co-injection of BMI and CNQX potentiated the responses too. Co-injection of BMI and AP5 had no significant effect on the pressor response but significantly attenuated the bradycardia response. In conclusion, the KF plays a role in generating cardiovascular chemoreflex via its glutamate NMDA but not AMPA receptors. GABA inhibits both components of this reflex through GABAA receptors. There is an interaction between GABAA and NMDA receptors in regulating the bradycardia response of the reflex. Single-unit results were also presented which were correlated with and supported the homodynamic findings. [ABSTRACT FROM AUTHOR]

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices. [ABSTRACT FROM AUTHOR]

A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (~ 10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (>40 ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms. [ABSTRACT FROM AUTHOR]

Natural sounds such as vocalizations often have covarying acoustic attributes, resulting in redundancy in neural coding. The efficient coding hypothesis proposes that sensory systems are able to detect such covariation and adapt to reduce redundancy, leading to more efficient neural coding. Recent psychoacoustic studies have shown the auditory system can rapidly adapt to efficiently encode two covarying dimensions as a single dimension, following passive exposure to sounds in which temporal and spectral attributes covaried in a correlated fashion. However, these studies observed a cost to this adaptation, which was a loss of sensitivity to the orthogonal dimension. Here we explore the neural basis of this psychophysical phenomenon by recording single-unit responses from the primary auditory cortex in awake ferrets exposed passively to stimuli with two correlated attributes, similar in stimulus design to the psychoacoustic experiments in humans. We found: (1) the signal-to-noise ratio of spike-rate coding of cortical responses driven by sounds with correlated attributes remained unchanged along the exposure dimension, but was reduced along the orthogonal dimension; (2) performance of a decoder trained with spike data to discriminate stimuli along the orthogonal dimension was equally reduced; (3) correlations between neurons tuned to the two covarying attributes decreased after exposure; and (4) these exposure effects still occurred if sounds were correlated along two acoustic dimensions, but varied randomly along a third dimension. These neurophysiological results are consistent with the efficient coding hypothesis and may help deepen our understanding of how the auditory system encodes and represents acoustic regularities and covariance. [ABSTRACT FROM AUTHOR]

It has long been known from microneurographic recordings in human subjects that the activity of postganglionic sympathetic axons occurs as spontaneous bursts, with muscle sympathetic nerve activity (MSNA) exhibiting strong cardiac rhythmicity via the baroreflex and skin sympathetic nerve activity showing much weaker cardiac modulation. Here we review the firing properties of single sympathetic neurons, obtained using highly selective microelectrodes. Individual vasoconstrictor neurons supplying muscle or skin, or sudomotor neurons supplying sweat glands, always discharge with a low firing probability (~30%) and at very low frequencies (~0.5 Hz). Moreover, they usually fire only once per cardiac interval but can fire greater than four times within a burst. Modeling has shown that this pattern can best be explained by individual neurons being driven by, on average, two preganglionic inputs. Unitary recordings of muscle vasoconstrictor neurons have been made in several pathophysiological states, including heart failure, hypertension, obstructive sleep apnea, bronchiectasis, chronic obstructive pulmonary disease, depression, and panic disorder. The augmented MSNA in each of these diseases features an increase in firing probability and discharge frequency of individual muscle vasoconstrictor neurons above that seen in healthy subjects, yet firing rates rarely exceed 1 Hz. However, unlike patients with heart failure, all patients with respiratory disease or panic disorder, and patients with hyperhidrosis, exhibited an increase in multiple within-burst firing, which emphasizes the different modes by which the sympathetic nervous system grades its output in pathophysiological states of high sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

Background: Double-unit cord blood transplantation (CBT) can be used to overcome the limitation of single-unit CBT with low cell content for adults and larger adolescents. However, whether double-unit CBT is superior to single-unit CBT remains controversial. Methods: We reviewed the medical records of 228 consecutive hematological malignancies who received CBT between November 2005 and December 2013. Ninety-seven eligible patients met the criteria (age ≥14 years and body weight ≥50kg) and were enrolled in this study. Results: The incidence of myeloid engraftment in the double-unit CBT group was significantly lower that in the single-unit CBT group (89.2 vs. 96.7%) (p= 0.026), and the incidence of platelet engraftment in the double-unit CBT group was slightly lower (70.3 vs. 86.7%) (p= 0.057). The 5-year transplant-related mortality rate was significantly higher in the double-unit CBT group when compared with that of the single-unit CBT group [54.1 vs. 33.3%,p= 0.026]. The 5-year probabilities of overall survival, disease-free survival and graft-versus-host disease (GVHD) -free/relapse-free survival in the double-unit CBT group were significantly lower than that of the single-unit CBT group (37.8 vs. 56.7%,p= 0.037; 32.4 vs. 55.0%,p= 0.017; 24.3 vs. 50.0%,p= 0.006). The incidences of GVHD and relapse were similar. Conclusions: For adolescent and adult hematological malignancies with heavier body weight (≥50kg), double-unit CBT has an inferior clinical outcome when compared with single-unit CBT having a sufficient cell dose. Double-unit CBT should only reserve for patients who need an urgent transplant but lacking of a related or unrelated donor and without an adequately dosed single CB. [ABSTRACT FROM AUTHOR]

Reciprocal connections between the orbitofrontal cortex (OFC) and the basolateral nucleus of the amygdala (BLA) provide a critical circuit for guiding normal behavior when information about expected outcomes is required. Recently, we reported that outcome signaling by OFC neurons is also necessary for learning in the face of unexpected outcomes during a Pavlovian over-expectation task. Key to learning in this task is the ability to build on prior learning to infer or estimate an amount of reward never previously received. OFC was critical to this process. Notably, in parallel work, we found that BLA was not necessary for learning in this setting. This suggested a dissociation in which the BLA might be critical for acquiring information about the outcomes but not for subsequently using it to make novel predictions. Here we evaluated this hypothesis by recording single-unit activity from BLA in rats during the same Pavlovian over-expectation task used previously.Wefound that spiking activity recorded in BLA in control rats did reflect novel outcome estimates derived from the integration of prior learning, however consistent with a model in which this process occurs in the OFC, these correlates were entirely abolished by ipsilateral OFC lesions. These data indicate that this information about these novel predictions is represented in the BLA, supported via direct or indirect input from the OFC, even though it does not appear to be necessary for learning. [ABSTRACT FROM AUTHOR]

As drug use becomes chronic, aberrant striatal processing contributes to the development of perseverative drug-taking behaviors. Two particular portions of the striatum, the nucleus accumbens ( NAc) and the dorsolateral striatum ( DLS), are known to undergo neurobiological changes from acute to chronic drug use. However, little is known about the exact progression of changes in functional striatal processing as drug intake persists. We sampled single-unit activity in the NAc and DLS throughout 24 daily sessions of chronic long-access cocaine self-administration, and longitudinally tracked firing rates ( FR) specifically during the operant response, an upward vertical head movement. A total of 103 neurons were held longitudinally and immunohistochemically localised to either NAc Medial Shell ( n = 29), NAc Core ( n = 30), or DLS ( n = 54). We modeled changes representative of each category as a whole. Results demonstrated that FRs of DLS Head Movement neurons were significantly increased relative to baseline during all sessions, while FRs of DLS Uncategorised neurons were significantly reduced relative to baseline during all sessions. NAc Shell neurons' FRs were also significantly decreased relative to baseline during all sessions while FRs of NAc Core neurons were reduced relative to baseline only during training days 1-18 but were not significantly reduced on the remaining sessions (19-24). The data suggest that all striatal subregions show changes in FR during the operant response relative to baseline, but longitudinal changes in response firing patterns were observed only in the NAc Core, suggesting that this region is particularly susceptible to plastic changes induced by abused drugs. [ABSTRACT FROM AUTHOR]

Speech reception depends critically on temporal modulations in the amplitude envelope of the speech signal. Reverberation encountered in everyday environments can substantially attenuate these modulations. To assess the effect of reverberation on the neural coding of amplitude envelope, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbit using sinusoidally amplitude modulated (AM) broadband noise stimuli presented in simulated anechoic and reverberant environments. Although reverberation degraded both rate and temporal coding of AM in IC neurons, in most neurons, the degradation in temporal coding was smaller than the AM attenuation in the stimulus. This compensation could largely be accounted for by the compressive shape of the modulation input-output function (MIOF), which describes the nonlinear transformation of modulation depth from acoustic stimuli into neural responses. Additionally, in a subset of neurons, the temporal coding of AM was better for reverberant stimuli than for anechoic stimuli having the same modulation depth at the ear. Using hybrid anechoic stimuli that selectively possess certain properties of reverberant sounds, we show that this reverberant advantage is not caused by envelope distortion, static interaural decorrelation, or spectral coloration. Overall, our results suggest that the auditory system may possess dual mechanisms that make the coding of amplitude envelope relatively robust in reverberation: one general mechanism operating for all stimuli with small modulation depths, and another mechanism dependent on very specific properties of reverberant stimuli, possibly the periodic fluctuations in interaural correlation at the modulation frequency. [ABSTRACT FROM AUTHOR]

Auditory neurophysiology has demonstrated how basic acoustic features are mapped in the brain, but it is still not clear how multiple sound components are integrated over time and recognized as an object. We investigated the role of statistical learning in encoding the sequential features of complex sounds by recording neuronal responses bilaterally in the auditory forebrain of awake songbirds that were passively exposed to long sound streams. These streams contained sequential regularities, and were similar to streams used in human infants to demonstrate statistical learning for speech sounds. For stimulus patterns with contiguous transitions and with nonadjacent elements, single and multiunit responses reflected neuronal discrimination of the familiar patterns from novel patterns. In addition, discrimination of nonadjacent patterns was stronger in the right hemisphere than in the left, and may reflect an effect of top-down modulation that is lateralized. Responses to recurring patterns showed stimulus-specific adaptation, a sparsening of neural activity that may contribute to encoding invariants in the sound stream and that appears to increase coding efficiency for the familiar stimuli across the population of neurons recorded. As auditory information about the world must be received serially over time, recognition of complex auditory objects may depend on this type of mnemonic process to create and differentiate representations of recently heard sounds. [ABSTRACT FROM AUTHOR]

Many speech sounds and animal vocalizations contain components, referred to as complex tones, that consist of a fundamental frequency (F0) and higher harmonics. In this study we examined single-unit activity recorded in the core (A1) and lateral belt (LB) areas of auditory cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted conspecific vocalizations ("coos"). The latter consisted of complex-tone segments in which F0 was matched to a corresponding pure-tone stimulus. In both animals, neuronal latencies to pure-tone stimuli at the best frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might be expected, since LB is considered to be at a hierarchically higher level than A1. On the other hand, the latency of LB responses to coos was ~10 to 20 ms shorter than to the corresponding pure-tone BF, suggesting facilitation in LB by the harmonics. This latency reduction by coos was not observed in A1, resulting in similar coo latencies in A1 and LB. Multi-peaked neurons were present in both A1 and LB; however, harmonically-related peaks were observed in LB for both early and late response components, whereas in A1 they were observed only for late components. Our results suggest that harmonic features, such as relationships between specific frequency intervals of communication calls, are processed at relatively early stages of the auditory cortical pathway, but preferentially in LB. [ABSTRACT FROM AUTHOR]

Many speech sounds and animal vocalizations contain components, referred to as complex tones, that consist of a fundamental frequency (F0) and higher harmonics. In this study we examined single-unit activity recorded in the core (A1) and lateral belt (LB) areas of auditory cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted conspecific vocalizations ('coos'). The latter consisted of complex-tone segments in which F0 was matched to a corresponding pure-tone stimulus. In both animals, neuronal latencies to pure-tone stimuli at the best frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might be expected, since LB is considered to be at a hierarchically higher level than A1. On the other hand, the latency of LB responses to coos was ~10 to 20 ms shorter than to the corresponding pure-tone BF, suggesting facilitation in LB by the harmonics. This latency reduction by coos was not observed in A1, resulting in similar coo latencies in A1 and LB. Multi-peaked neurons were present in both A1 and LB; however, harmonically-related peaks were observed in LB for both early and late response components, whereas in A1 they were observed only for late components. Our results suggest that harmonic features, such as relationships between specific frequency intervals of communication calls, are processed at relatively early stages of the auditory cortical pathway, but preferentially in LB. [ABSTRACT FROM AUTHOR]

Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects. [ABSTRACT FROM AUTHOR]

Because the cardiovascular system and respiration are so intimately coupled, disturbances in respiratory control often lead to disturbances in cardiovascular control. Obstructive Sleep Apnea (OSA), Chronic Obstructive Pulmonary Disease (COPD), and Bronchiectasis (BE) are all associated with a greatly elevated muscle vasoconstrictor drive (muscle sympathetic nerve activity, MSNA). Indeed, the increase in MSNA is comparable to that seen in congestive heart failure (CHF), in which the increase in MSNA compensates for the reduced cardiac output and thereby assists in maintaining blood pressure. However, in OSA - but not COPD or BE - the increase in MSNA can lead to hypertension. Here, the features of the sympathoexcitation in OSA, COPD, and BE are reviewed in terms of the firing properties of post-ganglionic muscle vasoconstrictor neurons. Compared to healthy subjects with low levels of resting MSNA, single-unit recordings revealed that the augmented MSNA seen in OSA, BE, COPD, and CHF were each associated with an increase in firing probability and mean firing rates of individual neurons. However, unlike patients with heart failure, all patients with respiratory disease exhibited an increase in multiple within-burst firing which, it is argued, reflects an increase in central sympathetic drive. Similar patterns to those seen in OSA, COPD, and BE were seen in healthy subjects during an acute increase in muscle vasoconstrictor drive. These observations emphasize the differences by which the sympathetic nervous system grades its output in health and disease, with an increase in firing probability of active neurons and recruitment of additional neurons being the dominant mechanisms. [ABSTRACT FROM AUTHOR]

ntagonising the NMDA ( N-methyl- d-aspartate) receptor complex is a widely hypothesised therapeutic approach in several neurodegenerative conditions, such as Alzheimer's disease. Memantine, a moderate affinity uncompetitive NMDA receptor antagonist, has been in clinical use for several years and numerous experimental data support its NMDA receptor blocking effects. It has recently been reported in transfected HEK293T cells that physiological concentrations of Mg may impart partial NMDA receptor subtype selectivity and weaken the overall inhibitory actions of memantine in NMDA receptor-mediated cellular events. In the present study, we set out to investigate the effect of intravenously applied memantine on iontophoresed NMDA-evoked firing of hippocampal CA1 neurons using in vivo conditions. Cumulative doses of memantine in the rat (4, 8 and 16 mg/kg i.v.) caused the firing rate to decrease in a dose-dependent manner to 77 ± 7, 58 ± 8 and 34 ± 12% of control, respectively, while saline application had no significant effect. We show that therapeutic doses of memantine are able to antagonize NMDA receptor-mediated activity in the principal cells of the hippocampus in vivo, i.e. in the presence of physiological concentrations of Mg. [ABSTRACT FROM AUTHOR]

The aggregated form of amyloid-β (Aβ)_{1-42} has been shown to increase N-methyl-D-aspartic acid (NMDA) evoked neuronal activity in vivo. Here we further characterized this phenomenon by investigating the role of integrin activation and downstream Src kinase activity using in vivo electrophysiology and in vitro intracellular Ca^{2+} measurements. Pretreatment of differentiated SH-SY5Y cells with fibrillar Aβ _{1-42} markedly enhanced the intracellular calcium increases caused by NMDA receptor (NMDA-R) stimulation. Function blocking antibody against β1 integrin depressed the facilitatory effects of Aβ _{1-42}. Similarly, Aβ_{1-42} facilitated NMDA-R driven firing of hippocampal neurons in vivo, and this effect was reduced by neutralizing antibody against β1 integrins. The positive action of Aβ _{1-42} on NMDA-R dependent responses was also depressed by an inhibitor known to block Src kinase. These results support the hypothesis that aggregated Aβ _{1-42} is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation. [ABSTRACT FROM AUTHOR]

The aim of this article is to examine what factors underlie the choice of organisational form when franchisors add new franchised units to their networks. Franchisors may grant new units to existing franchisees (multi-unit franchising (MUF)) or to new franchisees (single-unit franchising). We find that this choice depends on the existence of contractual problems (namely adverse selection and moral hazard) and several network characteristics influence the magnitude of these problems. In particular, we found a positive relationship between the intensity of the use of MUF and network size, geographical concentration of the units of the network, and industries where customers tend to be non-repetitive. [ABSTRACT FROM AUTHOR]

The article presents a study which examines a combined auction-bargaining model in a procurement setting, where a buyer procures an indivisible good from one of many competing sellers. The model consists of two phases, the auction phase and the bargaining phase. It found the symmetric equilibrium bidding strategy as easy to understand, thus, the combined auction-bargaining model generates much profit to the buyer compared to the standard auction.

The underlying cause of Alzheimer's disease (AD) is thought to be the accumulation and aggregation of a misfolded protein, amyloid-β (Aβ). A promising strategy against AD is the application of protective, peptide-based neuroprotective agents that selectively bind to Aβ. We recently described a pentapeptide, LPYFDa, which recognizes Aβ_{1-42} and protects neurons against the toxic effects of aggregated Aβ_{1-42} both in vitro and in vivo. Our previous work indicated that the in vivo ejection of fibrillar Aβ_{1-42} into the hippocampal CA1 region resulted in a massive increase in the NMDA-evoked neuronal firing rate. Our current aim was to study whether intraperitoneally administered LPYFDa is capable of protecting against the synaptotoxic action of fibrillar Aβ_{1-42} administered by iontophoresis. Our investigations of the in vivo biodistribution of tritium-labelled LPYFDa and single-unit electrophysiology revealed that LPYFDa readily crosses the blood-brain barrier, and protects the synapses against the excitatory action of fibrillar A&beta_{1-42} in a relatively wide temporal window in rat. This pentapeptide may serve as a lead compound for the design of novel drug candidates for the prevention of AD. [ABSTRACT FROM AUTHOR]

Idiopathic palmar-plantar hyperhidrosis is characterized by excessive sweating of the palms and feet, and is commonly treated by transthoracic regional sympathicotomy. As the condition is believed to be due to a high sudomotor drive, we wanted to assess the firing properties of individual sudomotor neurones in this state of sympathoexcitation, extending our recent work on other pathologies associated with high sympathetic nerve activity. Single-unit recordings were made from eight sudomotor neurones supplying the fingers via tungsten microelectrodes inserted percutaneously into the median nerve at the wrist or upper arm. Typical of sudomotor, muscle vasoconstrictor and cutaneous vasoconstrictor neurones recorded in healthy individuals in states of high sympathetic drive, all units had low firing probabilities (active in only 30.0 ± 6.7 (SE) % of cardiac intervals) and primarily fired only once per heart beat. The percentage of cardiac intervals in which the neurones generated 1, 2, 3 or 4 spikes was 60.4 ± 6.3, 22.9 ± 3.9, 9.7 ± 2.1 and 3.4 ± 1.3%, respectively. For comparison, these values were 77.6 ± 7.7, 15.0 ± 4.1, 4.6 ± 2.3 and 1.8 ± 1.3% for eight sudomotor neurones innervating the hairy skin of the foot during thermally-induced sweating in normal subjects. We conclude that the firing properties of spontaneously active sudomotor neurones in subjects with hyperhidrosis are similar to those of sudomotor neurones active during thermal sweating, reflecting an increase in central sympathetic drive to the sweat glands in hyperhidrosis. [ABSTRACT FROM AUTHOR]

Emotional learning requires the coordinated action of neural populations in limbic and cortical networks. Here, we performed simultaneous extracellular recordings from gustatory cortical (GC) and basolateral amygdalar (BLA) neural ensembles as awake, behaving rats learned to dislike the taste of saccharin [via conditioned taste aversion (CTA)]. Learning-related changes in single-neuron sensory responses were observed in both regions, but the nature of the changes was region specific. In GC, most changes were restricted to relatively late aspects of the response (starting ~ 1.0 s after stimulus administration), supporting our hypothesis that in this paradigm palatability-related information resides exclusively in later cortical responses. In contrast, and consistent with data suggesting the amygdala's primary role in judging stimulus palatability, CTA altered all components of BLA taste responses, including the earliest. Finally, learning caused dramatic increases in the functional connectivity (measured in terms of cross-correlation peak heights) between pairs of simultaneously recorded BLA and GC neurons, increases that were evident only during taste processing. Our simultaneous assays of the activity of single neurons in multiple relevant brain regions across learning suggest that the transmission of taste information through amygdala-- cortical circuits plays a vital role in CTA memory formation. [ABSTRACT FROM AUTHOR]

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory. [ABSTRACT FROM AUTHOR]

The article discusses a study which proposed a technique to record the firing patterns of gonadotropin-releasing hormone (GnRH) neurons in brain slices continuously for several hours. The study used mice that were transgenically engineered to express green fluorescent protein (GFP) in GnRH neurons using the murine GnRH promoter. GnRH neurons were viewed with an Olympus BX50WI upright fluorescent microscope equipped with infrared differential interference contrast.

A variety of studies have shown that motor cortical areas can be activated by observation of familiar actions. Here, we describe single-neuron responses in monkey primary motor (MI) and dorsal premotor (PMd) cortices during passive observation and execution of a familiar task. We show that the spiking modulation, preferred directions, and encoded information of cells in MI and PMd remain consistent during both observation and movement. Furthermore, we find that the presence of a visual target is necessary to elicit this congruent neural activity during observation. These findings along with results from our analysis of the oscillatory power in the beta frequency of the local field potential are consistent with previous imaging and EEG studies that have suggested that congruence between observation and action is a general feature of the motor system, even outside of canonical "mirror" areas. Such congruent activity has proposed relevance to motor learning, mimicry, and communication and has practical applications for the development of motorcortical neuroprostheses in paralyzed patients. [ABSTRACT FROM AUTHOR]

The effects of attention on neuronal responses in visual cortex have been likened to a change in stimulus contrast. Attention and stimulus contrast both modulate the magnitude of neuronal responses. However, changes in stimulus contrast also affect the latency of visual responses. Although many neurophysiological studies have examined how attention affects the strength of neuronal responses, few have considered whether attention affects neuronal latencies. To compare directly the effects of stimulus contrast and attention, we recorded responses from individual neurons in area V4 of macaque monkeys while they performed a task that independently controlled spatial attention and stimulus contrast. As expected, changes in stimulus contrast affected both the magnitude and latency of neuronal responses. Although attention had the expected effects on the magnitudes of neuronal responses, we did not detect statistically reliable changes in neuronal latency. A direct comparison of the effects of contrast and attention revealed a reliable difference. When a shift in spatial attention decreased response magnitude, response latency increased much less than when the same magnitude change was caused by reducing stimulus contrast. Thus, attention is distinct from contrast in the way it affects the relationship between neuronal response magnitude and latency. [ABSTRACT FROM AUTHOR]

The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc), which has long been implicated in goal-directed behavior, plays a critical role in this circuit, the prefrontal cortex (PFC) appears to process the events that directly trigger relapse: exposure to acute stress, cues previously associated with the drug, and the drug itself. In this paper, we review animal models of relapse and what they have revealed about the mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking behavior. We also present electrophysiological data from PFC illustrating how the hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed at the neuronal level. Our preliminary findings suggest a role for PFC in processing information related to cocaine seeking but not the hedonic effects of the drug. Further use of this recording technology can help dissect the functions of PFC and other components of the neural circuitry underlying relapse. [ABSTRACT FROM AUTHOR]

Single and multi-unit floating matrices of risedronate sodium were prepared using Gelucire® 43/01 by melt solidification and melt granulation technique, respectively. The controlled release floating matrices were evaluated for in vitro and in vivo floating ability and in vitro drug release. Effect of aging on Gelucire® 43/01 was evaluated by hot stage microscopy (HSM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Multi-unit system obtained has shown initial burst release, which was suppressed in single unit system. Both single- as well as multi-unit systems showed increase in rate of drug release on aging due to changes in the properties of the Gelucire® 43/01. Multi-unit matrices obtained by melt granulation were relatively easier for scale up and advantageous if the initial burst release does not cause any significant clinical adversity. [ABSTRACT FROM AUTHOR]

Purpose:The present study examined the effect of electrical kindling on the interictal temporal response properties of single units recorded from primary auditory cortex (AI) of the adult cat.Methods:Cats were permanently implanted with electrodes in AI, kindled twice daily for 40 sessions, and the contralateral AI was subsequently mapped. Kindling stimulation consisted of 1-s trains of biphasic square-wave pulses applied at a frequency of 60 Hz, 100μA above the afterdischarge (AD) threshold. The EEG activity was recorded during each kindling session, and the behavioral manifestation was scored. Subsequent to kindling, multiple single-unit responses were recorded under ketamine anesthesia in response to 1-s-long periodic click trains, with click rates between 2 and 64 Hz. Neuronal responses were characterized according to their ability to respond in time-locked fashion to the clicks.Results:Kindling stimulation resulted in progression of the AD characteristics and seizure behavior, with six of 10 kindled cats reaching a fully generalized state. In the fully kindled cats, the best modulation frequencies and limiting following rates for the single-unit responses were significantly lower compared with those of naive and sham controls.Conclusions:Repeated epileptiform activity interferes with temporal processing in cat auditory cortex in the interictal state. This may have implications for people with epileptic foci in auditory-related areas. [ABSTRACT FROM AUTHOR]

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while hh viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero–order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process. [ABSTRACT FROM AUTHOR]

This study compared the release behavior of single-unit (tablets, capsules) and multiple-unit (minitablets in capsules) controlled-release systems of furosemide. The swelling and erosion behaviors of these systems, which contained the swellable hydrophilic polymers sodium alginate (high viscosity) and Carbopol 974P, were compared. Swelling and erosion experiments showed a high degree of swelling and limited erosion for the Carbopol preparations, whereas less swelling but greater erosion was observed for the sodium alginate preparations. The sodium alginate preparations were eroded in 6 hours, while Carbopol preparations exhibited limited erosion within this period of time. These results appear to be attributed to the physicochemical characteristics of the polymers used in this study. Polymer characteristics greatly influenced the release of furosemide (model drug) from the formulations prepared and tested. Sodium alginate had a less pronounced sustained release effect compared with Carbopol (ie, in 8 hours all 3 sodium alginate dosage forms displayed complete release of furosemide, while only 30% of the drug was released from Carbopol dosage forms). Finally, all 3 Carbopol dosage forms (single- and multiple-unit) displayed similar release behavior while sodium alginate dosage forms displayed a different and more distinctive behavior. Minitablets and tablets showed a greater sustained release effect compared with capsules. Evaluation of the release data indicates that the release mechanism for sodium alginate formulations may be attributed to erosion/dissolution, while for Carbopol it may be attributed mainly to polymer relaxation and diffusion of the drug from the polymer surface. [ABSTRACT FROM AUTHOR]

A technique is described for in vivo localization of microelectrodes during single-unit recording in the alert monkey. Four hollow glass spheres filled with copper sulfate and iohexol were affixed to the surface of the animal's skull prior to the acquisition of a series of coronal magnetic resonance (MR) images. These reference beads were visible in both X-ray and MR images. Cranial recording chambers were then implanted bilaterally over the amygdaloid complex. A microelectrode was advanced to various depths in the subject's brain. At each selected microelectrode site, five radiographs were obtained and a small electrolytic lesion was made. Based on the data from the radiographs, we computed the position of the microelectrode tip at each site relative to the reference beads. With a precision of 625 μm, this method was used to predict the neuroanatomical location of ten microlesions placed in both subcortical and cortical structures. Postmortem histological analysis revealed that the actual location of the lesions closely matched predictions arrived at using the X-ray/MRI localization technique. This technique thus provides an accurate, reliable and noninvasive method for in vivo localization of microelectrode recording sites. [ABSTRACT FROM AUTHOR]

The parabrachial nucleus in mammals is intimately connected with other vocalization controlling brainstem structures. It, along with ventromedially adjacent structures, also has been identified as the pneumotaxic center, and as such shows strong respiratory related activity in the anesthetized cat. The current study examines the neuronal activity in cat parabrachial regions during production of instrumentally conditioned vocalizations. Most of the units in our sample show considerable activity during periods between vocalizations. For many units, firing rate fluctuates during the respiratory cycle, although apparently not as strongly as reported in the decerebrate cat. Also, there is often strong phasic activity during periods where animals are licking to ingest their food rewards. During the peri-vocalization period, various neural activity patterns can be recorded. Most common is an activity increase during the vocalization itself. Moreover, in some units, this activity increase has an auditory component. A smaller number of units show other activity patterns, including a suppression of activity during vocalization and activity increases preceding the vocalization. Overall, our results suggest that the parabrachial region's involvement in vocal control is quite complex, involving convergence of respiratory, acoustic, vocalization-related, and perhaps somatosensory influences. [ABSTRACT FROM AUTHOR]

Neuromodulation as a non‐drug alternative for managing visceral pain in irritable bowel syndrome (IBS) may target sensitized afferents of distal colon and rectum (colorectum), especially their somata in the dorsal root ganglion (DRG). Developing selective DRG stimulation to manage visceral pain requires knowledge of the topological distribution of colorectal afferent somata which are sparsely distributed in the DRG. Here, we implemented GCaMP6f to conduct high‐throughput optical recordings of colorectal afferent activities in lumbosacral DRG, that is, optical electrophysiology. Using a mouse ex vivo preparation with distal colorectum and L5‐S1 DRG in continuity, we recorded 791 colorectal afferents' responses to graded colorectal distension (15, 30, 40, and 60 mmHg) and/or luminal shear flow (20–30 mL/min), then functionally classified them into four mechanosensitive classes, and determined the topological distribution of their somata in the DRG. Of the 791 colorectal afferents, 90.8% were in the L6 DRG, 8.3% in the S1 DRG, and only 0.9% in the L5 DRG. L6 afferents had all four classes: 29% mucosal, 18.4% muscular‐mucosal, 34% low‐threshold (LT) muscular, and 18.2% high‐threshold (HT) muscular afferents. S1 afferents only had three classes: 19.7% mucosal, 34.8% LT muscular, and 45.5% HT muscular afferents. All seven L5 afferents were HT muscular. In L6 DRG, somata of HT muscular afferents were clustered in the caudal region whereas somata of the other classes did not cluster in specific regions. Outcomes of this study can directly inform the design and improvement of next‐generation neuromodulation devices that target the DRG to alleviate visceral pain in IBS patients. [ABSTRACT FROM AUTHOR]