Virtual Lesions of the IFG Abolish Response Facilitation for Biological and Non-Biological Cues

Humans are faster to perform a given action following observation of that same action. Converging evidence suggests that the human mirror neuron system (MNS) plays an important role in this phenomenon. However, the specificity of the neural mechanisms governing this effect remain controversial. Specialist theories of imitation suggest that biological cues are maximally capable of eliciting imitative facilitation. Generalist models, on the other hand, posit a broader role for the MNS in linking visual stimuli with appropriate responses. In the present study, we investigated the validity of these two theoretical approaches by disrupting the left and right inferior frontal gyrus (IFG) during the preparation of congruent (imitative) and incongruent (complementary) actions cued by either biological (hand) or non-biological (static dot) stimuli. Delivery of TMS over IFG abolished imitative response facilitation. Critically, this effect was identical whether actions were cued by biological or non-biological stimuli. This finding argues against theories of imitation in which biological stimuli are treated preferentially and stresses the notion of the IFG as a vital center of general perception–action coupling in the human brain

Corticospinal beta-band synchronization entails rhythmic gain modulation

Rhythmic synchronization of neurons in the beta or gamma band occurs almost ubiquitously, and this synchronization has been linked to numerous nervous system functions. Many respective studies make the implicit assumption that neuronal synchronization affects neuronal interactions. Indeed, when neurons synchronize, their output spikes reach postsynaptic neurons together, trigger coincidence detection mechanisms, and therefore have an enhanced impact. There is ample experimental evidence demonstrating this consequence of neuronal synchronization, but beyond this, beta/gamma-band synchronization within a group of neurons might also modulate the impact of synaptic input to that synchronized group. This would constitute a separate mechanism through which synchronization affects neuronal interactions, but direct in vivo evidence for this putative mechanism is lacking. Here, we demonstrate that synchronized beta-band activity of a neuronal group modulates the efficacy of synaptic input to that group in-phase with the beta rhythm. This response modulation was not an addition of rhythmic activity onto the average response but a rhythmic modulation of multiplicative input gain. Our results demonstrate that beta-rhythmic activity of a neuronal target group multiplexes input gain along the rhythm cycle. The actual gain of an input then depends on the precision and the phase of its rhythmic synchronization to this target, providing one mechanistic explanation for why synchronization modulates interactions

Understanding communicative actions:A repetitive TMS study

Previous work has shown that the right posterior superior temporal sulcus (RpSTS) is involved in inferring both instrumental goals and communicative intentions of observed actions (1, 2), using previous knowledge to generate perceptual and/or conceptual inferences (3, 4). Here, we disturb neural activity in RpSTS to test whether this region is necessary for understanding the meaning of novel communicative actions. Thirteen subjects received two 20 min sessions of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS), either over RpSTS (50,-42,14) or over a control region (area MT+, -43,-70,10), before performance of a communicative game and a control task. The game involved controlled non-verbal communicative interactions between pairs of subjects (40 trials). Each pair was asked to jointly create a goal configuration of two geometrical tokens, using the movements of the tokens on a gameboard as the only available communicative channel (5). One participant (a confederate) knew the goal configuration, and she moved her token on the gameboard to inform an addressee (a participant) where and how to position his token. The control task was a visual search paradigm that involved the same stimuli, responses, joint attention, and inter-subjects dependencies, but no communicative necessities. Performance was indexed by Task Efficiency, defined as the number of correct responses per unit of planning time, and by Efficiency Rate, defined as the rate of change (across trials) in Task Efficiency. After rTMS over RpSTS, but not left MT+, the Efficiency Rate of the addresses was reduced in the communicative game, but not in the visual search. In contrast, after rTMS over left MT+, subjects were not able to benefit from experience gained during the previous trials of the visual search task (Task X Site interaction, p<0.05). There were no corresponding interactions between tasks and site of rTMS intervention on the Task Efficiency parameter. These findings qualify how RpSTS contributes to understanding the meaning of non-verbal communicative actions. Repetitive TMS over RpSTS did not disrupt the ability of addressees to interpret novel communicative actions. Rather, this region appears to be necessary for incorporating previous knowledge, accumulated during interactions with a communicative partner, to constrain the inferential process that leads to action understanding

Philips IntelliSpace Cognition digital test battery: equivalence and measurement invariance compared to traditional analog test versions

Objective: To collect evidence of validity for a selection of digital tests on the Philips IntelliSpace Cognition (ISC) platform. Method: A total of 200 healthy participants (age 50-80) completed both the ISC battery and an analog version of the battery during separate visits. The battery included the following screeners and cognitive tests: Mini-Mental State Examination (2nd edition), Clock Drawing Test, Trail-Making Test (TMT), Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure Test (ROCFT), Letter Fluency, Star Cancellation Test, and Digit Span Test. The ISC tests were administered on an iPad Pro and were automatically scored using designated algorithms. The analog tests were administered in line with existing guidelines and scored by trained neuropsychologists. Criterion validity was established through relative agreement coefficients and raw score equivalence tests. In addition,measurement invariance analysis was used to compare the factor structures of both versions. Finally, we explored effects of demographics and experience with digital devices on performance. Results: We found fair to excellent relative agreement between test versions. Absolute equivalence was found for RAVLT, Letter Fluency, Star Cancellation Test, and Digit Span Test. Importantly, we demonstrated equal loadings of the digital and analog test versions on the same set of underlying cognitive domains. Demographic effects were mostly comparable between modalities, and people’s experience with digital devices was found to only influence performance on TMT B. Conclusions: This study provides several sources of evidence for the validity of the ISC test battery, offering an important step in validating ISC for clinical use. Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2021.1974565

Development of On-Line High Performance Liquid Chromatography (HPLC)-Biochemical Detection Methods as Tools in the Identification of Bioactives

Biochemical detection (BCD) methods are commonly used to screen plant extracts for specific biological activities in batch assays. Traditionally, bioactives in the most active extracts were identified through time-consuming bio-assay guided fractionation until single active compounds could be isolated. Not only are isolation procedures often tedious, but they could also lead to artifact formation. On-line coupling of BCD assays to high performance liquid chromatography (HPLC) is gaining ground as a high resolution screening technique to overcome problems associated with pre-isolation by measuring the effects of compounds post-column directly after separation. To date, several on-line HPLC-BCD assays, applied to whole plant extracts and mixtures, have been published. In this review the focus will fall on enzyme-based, receptor-based and antioxidant assays

Prospective, blind study of the triple stimulation technique in the diagnosis of ALS

Abstract Objective: To evaluate the diagnostic yield of magnetic cortical stimulation with the triple stimulation technique (TST) to identify upper motor neuron (UMN) involvement in patients suspected of having ALS. Methods: Fifty-nine patients were recruited to undergo TST in addition to the standard work-up for suspected motor neuron disease. TST combines transcranial magnetic stimulation of the motor cortex with collision studies, which results in a higher sensitivity in detecting UMN involvement. Primary outcome was the number of abnormal TST results in patients with possible ALS. The positivity rate was converted to the number needed to test with TST (NN-TST) for one extra diagnosis of ALS. Results: Fifty patients underwent TST. In the total group (n 059), 18 patients had a motor neuron disorder but did not fulfil criteria for &apos;probable&apos; or &apos;definite&apos; ALS. In four of these patients TST was abnormal (NN-TST, 4.5). One TST was erroneously interpreted as abnormal. TST findings were normal in inclusion body myositis and peripheral nerve disorders. Conclusion: This prospective and blind study confirms open studies of TST in the evaluation of ALS. We suggest that TST can be used to arrive at a diagnosis of &apos;probable&apos; or &apos;definite&apos; ALS in patients lacking UMN signs in the upper extremities

Changes in corticospinal excitability and the direction of evoked movements during motor preparation: A TMS study

BACKGROUND: Preparation of the direction of a forthcoming movement has a particularly strong influence on both reaction times and neuronal activity in the primate motor cortex. Here, we aimed to find direct neurophysiologic evidence for the preparation of movement direction in humans. We used single-pulse transcranial magnetic stimulation (TMS) to evoke isolated thumb-movements, of which the direction can be modulated experimentally, for example by training or by motor tasks. Sixteen healthy subjects performed brisk concentric voluntary thumb movements during a reaction time task in which the required movement direction was precued. We assessed whether preparation for the thumb movement lead to changes in the direction of TMS-evoked movements and to changes in amplitudes of motor-evoked potentials (MEPs) from the hand muscles. RESULTS: When the required movement direction was precued early in the preparatory interval, reaction times were 50 ms faster than when precued at the end of the preparatory interval. Over time, the direction of the TMS-evoked thumb movements became increasingly variable, but it did not turn towards the precued direction. MEPs from the thumb muscle (agonist) were differentially modulated by the direction of the precue, but only in the late phase of the preparatory interval and thereafter. MEPs from the index finger muscle did not depend on the precued direction and progressively decreased during the preparatory interval. CONCLUSION: Our data show that the human corticospinal movement representation undergoes progressive changes during motor preparation. These changes are accompanied by inhibitory changes in corticospinal excitability, which are muscle specific and depend on the prepared movement direction. This inhibition might indicate a corticospinal braking mechanism that counteracts any preparatory motor activation

An overview of the mid-infrared spectro-interferometer MATISSE: science, concept, and current status

MATISSE is the second-generation mid-infrared spectrograph and imager for the Very Large Telescope Interferometer (VLTI) at Paranal. This new interferometric instrument will allow significant advances by opening new avenues in various fundamental research fields: studying the planet-forming region of disks around young stellar objects, understanding the surface structures and mass loss phenomena affecting evolved stars, and probing the environments of black holes in active galactic nuclei. As a first breakthrough, MATISSE will enlarge the spectral domain of current optical interferometers by offering the L and M bands in addition to the N band. This will open a wide wavelength domain, ranging from 2.8 to 13 um, exploring angular scales as small as 3 mas (L band) / 10 mas (N band). As a second breakthrough, MATISSE will allow mid-infrared imaging - closure-phase aperture-synthesis imaging - with up to four Unit Telescopes (UT) or Auxiliary Telescopes (AT) of the VLTI. Moreover, MATISSE will offer a spectral resolution range from R ~ 30 to R ~ 5000. Here, we present one of the main science objectives, the study of protoplanetary disks, that has driven the instrument design and motivated several VLTI upgrades (GRA4MAT and NAOMI). We introduce the physical concept of MATISSE including a description of the signal on the detectors and an evaluation of the expected performances. We also discuss the current status of the MATISSE instrument, which is entering its testing phase, and the foreseen schedule for the next two years that will lead to the first light at Paranal.Comment: SPIE Astronomical Telescopes and Instrumentation conference, June 2016, 11 pages, 6 Figure

The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring. MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness. RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009). CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings