Humanbecoming leading-following: the meaning of holding up the mirror

In this column, readers are invited to reflect upon leadership and the meaning of leading-following from the perspective of Parse's humanbecoming school of thought, using the metaphor of holding up the mirror.     

The anthropomorphic brain: the mirror neuron system responds to human and robotic actions

In humans and monkeys the mirror neuron system transforms seen actions into our inner representation of these actions. Here we asked if this system responds also if we see an industrial robot perform similar actions. We localised the motor areas involved in the execution of hand actions, presented the same subjects blocks of movies of humans or robots perform a variety of actions. The mirror system was activated strongly by the sight of both human and robotic actions, with no significant differences between these two agents. Finally we observed that seeing a robot perform a single action repeatedly within a block failed to activate the mirror system. This latter finding suggests that previous studies may have failed to find mirror activations to robotic actions because of the repetitiveness of the presented actions. Our findings suggest that the mirror neuron system could contribute to the understanding of a wider range of actions than previously assumed, and that the goal of an action might be more important for mirror activations than the way in which the action is performed.     

Sound frequency representation in cat auditory cortex

Using the intrinsic signal optical recording technique, we reconstructed the two-dimensional pattern of stimulus-evoked neuronal activities in the auditory cortex of anesthetized and paralyzed cats. The average magnitude of intrinsic signal in response to a pure tone stimulus increased steadily as the sound pressure level increased. A detailed analysis demonstrated that the evoked signals at early frames were scaled by the sound pressure level, which in turn indicated the presence of a minimum level of sound pressure beyond which stimulus-related intrinsic signal can be generated. Intrinsic signals evoked significantly by pure tone stimuli of different frequencies were localized and arranged in an orderly manner in the middle ectosylvian gyrus, which indicates that the primary auditory field (AI) is tonotopically organized. The arrangement of optimal frequencies obtained from optical recordings of the same auditory cortex, which were conducted on different days, was highly reproducible. Furthermore, other auditory fields surrounding AI in the recorded area were allocated based on the observed tonotopicity. We also conducted unit recordings on the cats used for optical recording with the same set of acoustic stimuli. The gross feature of the arrangement of optimal frequencies determined by unit recordings agreed with the tonotopic arrangement determined by the optical recording, although the precise agreement was not obtained.     

The role of actions in auditory object discrimination

Action representations can interact with object recognition processes. For example, so-called mirror neurons respond both when performing an action and when seeing or hearing such actions. Investigations of auditory object processing have largely focused on categorical discrimination, which begins within the initial 100 ms post-stimulus onset and subsequently engages distinct cortical networks. Whether action representations themselves contribute to auditory object recognition and the precise kinds of actions recruiting the auditory–visual mirror neuron system remain poorly understood. We applied electrical neuroimaging analyses to auditory evoked potentials (AEPs) in response to sounds of man-made objects that were further subdivided between sounds conveying a socio-functional context and typically cuing a responsive action by the listener (e.g. a ringing telephone) and those that are not linked to such a context and do not typically elicit responsive actions (e.g. notes on a piano). This distinction was validated psychophysically by a separate cohort of listeners. Beginning ~ 300 ms, responses to such context-related sounds significantly differed from context-free sounds both in the strength and topography of the electric field. This latency is > 200 ms subsequent to general categorical discrimination. Additionally, such topographic differences indicate that sounds of different action sub-types engage distinct configurations of intracranial generators. Statistical analysis of source estimations identified differential activity within premotor and inferior (pre)frontal regions (Brodmann's areas (BA) 6, BA8, and BA45/46/47) in response to sounds of actions typically cuing a responsive action. We discuss our results in terms of a spatio-temporal model of auditory object processing and the interplay between semantic and action representations.     

Cortical representation of release from auditory masking

The aim of the present study was to find a functional MRI correlate in human auditory cortex of the psychoacoustical effect of release from masking, using amplitude-modulated noise stimuli. A sinusoidal target signal was embedded in a bandlimited white noise, which was either unmodulated or (co)modulated. Psychoacoustical thresholds were measured for the target signals in both types of masking noise, using an adaptive procedure. The mean threshold difference between the unmodulated and the comodulated condition, i.e., the release from masking, was 15 dB. The same listeners then participated in an fMRI experiment, recording activation of auditory cortex in response to tones in the presence of modulated and unmodulated noise maskers at five different signal-to-noise ratios. In general, a spatial dissociation of changes of overall level and signal-to-noise ratio in auditory cortex was found, replicating a previous fMRI study on pure-tone masking. The comparison of the fMRI activation maps for a signal presented in modulated and in unmodulated noise reveals that those regions in the antero-lateral part of Heschl's gyrus previously shown to represent the audibility of a tonal target (rather than overall level) exhibit a stronger activation for the modulated than for the unmodulated conditions. This result is interpreted as a physiological correlate of the psychoacoustical effect of comodulation masking release at the level of the auditory cortex.     

Neural representation of observed actions in the parietal and premotor cortex

We investigated the neural representation of observed actions in the human parietal and premotor cortex, which comprise the action observation network or the mirror neuron system for action recognition. Participants observed object-directed hand actions, in which action as well as other properties were independently manipulated: action (grasp or touch), object (cup or bottle), perspective (1st or 3rd person), hand (right or left), and image size (large or small). We then used multi-voxel pattern analysis to determine whether each feature could be correctly decoded from regional activities. The early visual area showed significant above-chance classification accuracy, particularly high in perspective, hand, and size, consistent with pixel-wise dissimilarity of stimuli. In contrast, the highest decoding accuracy for action was observed in the anterior intraparietal sulcus (aIPS) and the ventral premotor cortex (PMv). Moreover, the decoder for action could be correctly generalized for images with high dissimilarity in the parietal and premotor region, but not in the visual area. Our study indicates that the parietal and premotor regions encode observed actions independent of retinal variations, which may subserve our capacity for invariant action recognition of others.     

Neuromagnetic representation of musical register information in human auditory cortex

Pulse-resonance sounds like vowels or instrumental tones contain acoustic information about the physical size of the sound source (pulse rate) and body resonators (resonance scale). Previous research has revealed correlates of these variables in humans using functional neuroimaging. Here, we report two experiments that use magnetoencephalography to study the neuromagnetic representations of pulse rate and resonance scale in human auditory cortex. In Experiment 1, auditory evoked fields were recorded from nineteen subjects presented with French horn tones, the pulse rate and resonance scale of which had been manipulated independently using a mucoder. In Experiment 2, fifteen subjects listened to French horn tones which differed in resonance scale but which lacked pulse rate cues. The resulting cortical activity was evaluated by spatio-temporal source analysis. Changes in pulse rate elicited a well-defined N1m component with cortical generators located at the border between Heschl's gyrus and planum temporale. Changes in resonance scale elicited a second, independent, N1m component located in planum temporale. Our results demonstrate that resonance scale can be distinguished in its neuromagnetic representation from cortical activity related to the sound's pulse rate. Moreover, the existence of two separate components in the N1m sensitive to register information highlights the importance of this time window for the processing of frequency information in human auditory cortex.     

Intrarenal actions of the new adenosine agonist CGS 21680A, selective for the A2 receptor

The purpose of this study was to define the direct intrarenal actions of the new adenosine agonist CGS 21680A (hydrochloride "A" salt of (2-[p-2-carboxyethyl)phenethylamino]5'-N-ethyl-carboxamido adenosine), which is selective for the A2 receptor. CGS 21680A was infused into the left renal artery, while simultaneously measuring blood pressure (BP) and parameters of renal function from both the left and right kidneys. At doses higher than 0.05 micrograms/kg/min, CGS 21680A appeared to leak from the circulation of the infused kidney in pharmacologically significant quantities, inasmuch as BP fell and renal blood flow was increased and renal vascular resistance decreased in the noninfused contralateral kidney. At doses of 0.025 to 0.05 micrograms/kg/min, CGS 21680A appeared localized to the renal circulation, because neither BP nor any measured parameter of contralateral renal function was altered. Intrarenal infusion of 0.025 to 0.05 micrograms/kg/min of CGS 21680A increased renal blood flow but not glomerular filtration rate leading to a fall in the filtration fraction. Urine volume and urinary sodium excretion were unaffected by selective intrarenal infusion of CGS 21680A. Plasma renin activity and renin secretion rate were also not altered significantly by intrarenal infusion of 0.05 micrograms/kg/min of CGS 21680A. In contrast plasma renin activity increased significantly in response to the intrarenal infusion of 0.075 micrograms/kg/min of CGS 21680A, a dose which leaked from the kidney and lowered BP. The results presented suggest that the new adenosine agonist CGS 21680A exerts a direct intrarenal effect on renal hemodynamics, but does not affect urine volume or sodium excretion or directly influence renin release.     

Renal actions of a new adenosine agonist, CGS 21680A selective for the A2 receptor

This study compares the renal actions of the A2 selective adenosine agonist, CGS 21680A, with the A1 selective adenosine agonist, N6-cyclopentyladenosine (CPA), and the nonselective agonist, 5'-N-ethylcarboxamide adenosine (NECA), in the anesthetized dog. Initial receptor binding studies in dog brain demonstrated that CPA and CGS 21680A were selective for the A1 and A2 adenosine receptor, respectively, whereas NECA displayed slightly greater affinity for A1 than A2 adenosine receptors in the canine brain. Intravenous infusion of CGS 21680A (0.25 and 2.5 micrograms/kg/min) decreased blood pressure (BP) and increased heart rate (HR). CGS 21680A transiently increased renal blood flow (RBF) and either did not change or, at the highest dose infused, decreased glomerular filtration rate (GFR). Both urine volume (UV) and urinary sodium excretion (UNaV) also were decreased by CGS 21680A. At the lowest infusion rate (0.025 micrograms/kg/min) CGS 21680A produced a slowly developing increase in RBF, no change in GFR and a significant decrease in sodium excretion. Intravenous infusion of CPA (15 micrograms/kg/min) lowered BP and HR RBF and GFR. UNaV, UV and renin release also were inhibited by CPA. At a lower infusion rate (2.5 micrograms/kg/min), CPA markedly inhibited UNaV in the absence of a significant change in either BP or renal hemodynamic parameters. Infusion of NECA (0.01 and 0.1 micrograms/kg/min) lowered BP but did not change HR. Furthermore, RBF was increased by NECA, whereas UV and UNaV were inhibited in the absence of a change in GFR. These results may be explained by the relative selectivity of each analog for A1 or A2 adenosine receptors.     

双镜结合选择性术中胆道造影治疗胆囊炎急性发作65例临床分析

目的评价双镜结合选择性术中胆道造影治疗胆囊炎急性发作的疗效。方法回顾性分析本院2007年1月～2010年12月65例按腹腔镜联合胆道镜结合选择性术中胆道造影方法治疗胆囊炎急性发作的临床资料。结果 43例行腹腔镜下胆囊切除术,6例中转开腹行胆囊切除术,16例发现或证实胆总管内有结石,其中3例中转开腹行胆囊切除+胆总管切开取石,13例腔镜手术成功,其中1例胆道镜经胆囊管切开取石术,胆总管未放置T管;12例行腔镜下胆囊切除+胆总管切开胆道镜取石术,胆总管内放置T管,术后6～8周行纤维胆道镜检查,1例发现残余结石,拔除T管后经窦道取净,11例未发现胆总管残余结石,再次行胆道造影后未发现结石,拔除T管,术中出血30～130 mL,手术时间90～220 min,术后住院4～8 d,所有病例均无发生并发症。结论腹腔镜联合胆道镜结合选择性术中胆道造影治疗胆囊炎急性发作并胆总管结石,患者创伤小,康复快,胆管结石残留少,安全有效,减少不必要的阴性胆总管切开探查。术中不能取净胆总管结石者,术后可通过T管窦道行纤维胆道镜取石。     

Acting together in and beyond the mirror neuron system

Moving a set dinner table often takes two people, and doing so without spilling the glasses requires the close coordination of the two agents' actions. It has been argued that the mirror neuron system may be the key neural locus of such coordination. Instead, here we show that such coordination recruits two separable sets of areas: one that could translate between motor and visual codes and one that could integrate these information to achieve common goals. The former includes regions of the putative mirror neuron system, the latter, regions of the prefrontal, posterior parietal and temporal lobe adjacent to the putative mirror neuron system. Both networks were more active while participants cooperated with a human agent, responding to their actions, compared to a computer that did not, evidencing their social dimension. This finding shows that although the putative mirror neuron system can play a critical role in joint actions by translating both agents' actions into a common code, the flexible remapping of our own actions with those of others required during joint actions seems to be performed outside of the putative mirror neuron system.     

Pharmacological actions of SQ 29,548, a novel selective thromboxane antagonist

SQ 29,548, [1S-[1 alpha,2 beta (5Z),3 beta,4 alpha]-7-[3-[[2-[(phenylamino) carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1] hept-2-yl]-5-heptenoic acid, and the racemic modification, +/- SQ 29,548, were identified as active inhibitors of human platelet aggregation induced by arachidonic acid, collagen, epinephrine (2 degrees phase) and the thromboxane A2 mimics, 9,11-azo prostaglandin (PG) H2 and 11,9-epoxymethano PGH2. SQ 29,548 did not inhibit aggregation induced by ADP, and it did not prevent PGD2 from inhibiting ADP-induced platelet aggregation. Inhibition of platelet function by +/- SQ 29,548 was not associated with inhibition of cyclooxygenase or thromboxane synthetase or with changes in platelet cyclic AMP. In guinea-pig trachea and rat aorta, +/- SQ 29,548 competitively antagonized the activity of 9,11-azo PGH2 with pA2 values of 7.8 and 8.4, respectively. The chiral compound, SQ 29,548 competitively antagonized contractions of guinea-pig tracheal spirals caused by 11,9-epoxymethano PGH2 with a pA2 value of 9.1. The +/- SQ 29,548 competitively antagonized tracheal responses to 11,9-epoxymethano PGH2 and PGD2 with pA2 values of 8.2 and 8.3, respectively, indicating that PGD2 and the thromboxane A2 mimic probably act at the same receptor in guinea-pig tracheal smooth muscle. Contractions of guinea-pig tracheal spirals induced by PGE2 were not antagonized, and those caused by PGF2 alpha were only partially antagonized by +/- SQ 29,548. The +/- SQ 29,548 also significantly inhibited the aorta contracting activity of 11,9-epoxymethano PGH2 (pA2 = 9.1) and thromboxane A2 released from perfused guinea-pig lungs upon arachidonic acid challenge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cellular and molecular actions of Methylene Blue in the nervous system

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide‐induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 93–117, 2010     

Diuretic actions in man of a selective kappa opioid agonist: U-62,066E

The effect of a selective kappa opioid agonist, U-62,066E, on urine formation in human volunteers was assessed. Volunteers received single intramuscular injections of either placebo or 2, 3, 4, 5 or 6 micrograms/kg of U-62,066E in a randomized, double-blind study. U-62,066E caused dose-dependent maximal increases in urine volume of 2.6 times control in the first 4 hr after administration. A corresponding decrease in urine osmolality to 20% of base-line values occurred. No changes in total urinary Na, K or Cl excretion were identified. Kappa agonists produce a water-only diuresis at low doses in humans. The mechanism of this effect was not examined in this study but probably relates to alterations in antidiuretic hormone activity.     

Regional hemodynamic actions of selective corticotropin-releasing factor type 2 receptor ligands in conscious rats

In conscious male Sprague-Dawley rats, we compared regional hemodynamic actions of the selective corticotropin-releasing factor type 2 (CRF(2)) receptor ligands human and mouse urocortin 2 (hUCN2 and mUCN2, respectively) with those of CRF. Bolus i.v. doses of 3 and 30 pmol kg(-1) hUCN2, mUCN2, or CRF had no significant hemodynamic actions, but at doses of 300 and 3000 pmol kg(-1), all three peptides caused dose-dependent tachycardia and hypotension, with rapid-onset, short-duration, mesenteric vasodilatation and slower-onset, more prolonged hindquarters vasodilatation but little or no change in renal vascular conductance. Pretreatment with the nonselective CRF receptor antagonist astressin or the selective CRF(2) receptor antagonist antisauvagine 30 abolished all the cardiovascular actions of all three peptides. Indomethacin had no effect on responses to hUCN2, and there was no evidence for any involvement of nitric oxide (NO) in the vasodilator actions of hUCN2. There was no evidence that recruitment of angiotensin- and endothelin-mediated vasoconstrictor mechanisms counteracted the vascular actions of hUCN2. The results indicate that the hemodynamic effects of i.v. hUCN2, mUCN2, and CRF depend on activation of CRF(2) receptors and do not involve NO or prostanoids.