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At least 19 recordsLinked to original sources

Learning neural dynamics through instructive signals.

Rapid learning is essential for flexible behavior, but its basis in the brain remains unknown. Here we introduce the PRISM plasticity rule, a unifying mechanistic model of three well-established, fast-acting synaptic plasticity rules-in hippocampus, cerebellum and mushroom body-which relies exclusively on pre-synaptic activity and an "instructive signal" from another brain area. Using a multi-region network model we show that guiding PRISM plasticity with instructive signals enables the network to quickly learn extremely flexible nonlinear dynamics underlying behaviorally relevant computations, as well as to emulate unknown external system dynamics from real-time error signals, which we demonstrate with comprehensive simulations supported by exact mathematical theory. Thus, PRISM plasticity guided by instructive signals is well-suited to rapidly learn general-purpose neural computations-in contrast to canonical Hebbian rules. Finally, we show how including this plasticity rule in artificial learning algorithms can solve long-range temporal credit assignment, a long-standing challenge in machine learning.

cerebellum

Glycolytic activity instructs germ layer proportions through regulation of Nodal and Wnt signaling.

Metabolic pathways can influence cell fate decisions, yet their regulative role during embryonic development remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in regulating signaling pathways involved in mesoderm and endoderm specification. Using a mouse embryonic stem cell (mESC)-based in vitro model for gastrulation, we found that glycolysis inhibition increases ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. We further show that glycolysis acts as an upstream regulator of Nodal and Wnt signaling and that its influence on cell fate specification can be decoupled from its effects on growth. Finally, we confirm the generality of our findings using a human gastrulation model. Our work underscores the dependence of signaling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision-making.

Glycolysis

[Spatial distribution of correlative associations in the electrical activity of schizophrenic patients].

The paper deals with the space distribution of correlational contacts of electric activity in 5 areas of the cortical brain in producing non-signal photo stimula and in conditional trace reflexes with a preliminary verbal instruction. Such studies were convened in schizophrenic patients and in normals. The author assessed the general and regional coefficient of cross-correlations in certain time periods prior to and following production of photo signals. More distinct differences between normals and schizophrenic patients (especially with juvenile malignant schizophrenia) were seen after an instruction and conditional signals. In patients the signal activity was not accompanied by a formation of a system of functional contacts which may be seen in normals, and which possibly may be the basis in the functioning of a conditional reflex.

Cerebral Cortex

Control of stiffness by the medium latency electromyographic response to limb perturbation.

It is hypothesized that the medium latency electromyographic (EMG) response (ML) to limb perturbation functions to preset limb stiffness to a constant initial level. Three predictions are derived from this hypothesis: Firstly, in the presence of an instruction calling for opposition to limb perturbation, a control signal, ML, will be observed and will lead to the establishment of a constant level of limb stiffness. Secondly, in the absence of an instruction to oppose, no control signal will be observed and correspondingly a constant stiffness will not be generated. Thirdly, the latency of onset of stiffness control will covary with the latency of onset of ML. These predictions were tested in experiments involving perturbation of the human forearm about the elbow joint, with surface EMG measurements and computation of the limb stiffness function. The results are in accord with these predictions, and support the hypothesis that ML functions in the feedforward control of limb stiffness.

Adult

A study of exercise performance and heart rate: the response to exercise of a small group of manual workers before and after retirement.

Measurements of walking pattern, exercise performance, heart rate response to exercise and body composition have been made in 13 male manual workers at retirement and again one and two years later. The exercise consisted of walking, in accordance with standard instructions; heart rate and footfall signals were recorded on magnetic tape during the test using body-borne tape recorders. After the first year highly significant reductions in walking speed were found but no significant changes in walking pattern, heart rate response or body composition. When the measurements made at the end of one year of retirement were compared with those made at the end of two years no significant changes were found.

Aged

Smooth pursuit eye movements and attention in psychiatric patients.

The effects of two putative attention-engaging maneuvers on tracking performance were studied in three groups of subjects: inpatients (n = 19), outpatients (n = 19), and controls (n = 20). One method involved realerting subjects during tracking by repeating instructions to track carefully. The second method, a signal detection task incorporated into the tracking stimulus, required that subjects signal their perception of brief interruptions of the tracking light by pressing a hand-held button. The tracking performance of inpatients was significantly inferior to that of both outpatients and controls, whereas tracking performance of these two latter groups did not differ. Verbal realerting did not significantly improve tracking performance in any group; moreover, during the administration of these instructions there was an increase in tracking errors in inpatients. Inpatients also made more tracking errors than comparison groups during signal detection trials. Other subject factors of possible relevance to tracking performance, e.g., age, gender, and level of arousal, were found not to covary with tracking accuracy in a manner which would explain the observed group differences. It is unlikely that voluntary inattention is the basis for the observed impaired tracking in hospitalized psychiatric patients; the data are more consistent with an interpretation based on heightened distractibility or information overload in these patients.

Adolescent

[Multielectronic computerized EMG: technical notes on the recording and parallel off-line elaboration].

A Multielectrodic EMG analysis program is developing. The purpose is to get as short as possible the main EMG parameters (amplitude, duration, frequency) of most motor units, and to reach an estimation of the anatomical extent of single units. According to the muscle extent a variable number of electrodes are inserted crosswise the fibers. EMG signals are simultaneously recorded on a multichannel AMPEX FR1300 and then off-line processed by a 21MX HP minicomputer connected with a 5Mbytes disc drive. Some technical problems had to be solved:channel amplification adjustment to avoid any difference among preamplifiers calibration and filtering, severe hum filtering of main power that is specially strong in nultielectrodic recording systems, the need of sampling at the same Nyquist time the signals of different channels. The computer is instructed to identify the "sinchronous" units i.e. the motor units recorded from more than one channel. These motor units are detected, counted and deleted from all the channels, except the one where they show the maximum amplitude. The percentage of these sinchronous units depends upon the interelectrodic distance and their anatomical area, thus it can support an evaluation of motor unit anatomical spread.

Computers

Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article

[The semiautomatic speech audiometry (author's transl)].

In co-operation with the Viennatone Company we developed an apparatus to perform a "semiautomatic speech audiometry (SAS)". The patient is instructed to repeat the understood words into a cassette recorder when a signal lamp is on. The sequence of the test including the attenuation of intensities and a programmed change of the ear to be tested is automatically controlled. The evaluation of the patient's answers can be carried out by the assistent at any time that is suitable. The advantages of the SAS are a gain in time and the fact that during the test performance the assistent is free to pursue other activities. With the means of the SAS the possibility is now available to perform speech audiometry in very well frequented surgeries of specialists. In a surgery the apparatus was tested in 700 patients with success.

Audiometry

[Inhibition of a conditioned reflex evoked emotional response as an "instrument" of avoidance].

A method has been elaborated of training the human subjects to avoid electric shocks by overcoming the "fear" caused by a warning signal. A previously elaborated differentiated conditioned skin-galvanic response (SGR) to a sound stimulus served as a criterion of the emotional reaction. The SGR was projected on an oscilloscope screen. The electric shock was automatically delivered at the moment when the amplitude of the conditioned SGR exceeded the level marked on the screen. The subject was instructed, by overcoming the "fear", to retain the SGR amplitude below the level. If the subject succeeded in overcoming the conditioned SGR to the signal, the shock was not delivered. Since, the suppression of the conditioned SGR served as a "instrument" of avoidance and became consolidated as a habit based on a positive reinforcement. The subjects developed a stable attraction to repetition of training sessions in which they learned to suppress the "anxiety" caused by a signal of "threat".

Avoidance Learning

Central nervous system physiology of electroreception, a review.

There are several reasons why one can expect that the study of electric fish may prove instructive about general mechanisms of sensory processing and neuronal integration. These reasons include the following: the simplicity of the electrical signals which are the normal input and output; the availability of a variety of stereotyped behaviors to characterize the system as a whole; the case with which individual receptors or primary afferents can be activated; the demonstrated presence of corollary discharge and reafference mechanisms for motor control over sensory input; the presence of highly specialized CNS structures which have evolved to meet the unusual demands of the electrosensory system. Work relating to these and other aspects of the electrosensory systems is discussed with an emphasis on the potential which these systems offer.

Afferent Pathways

Proprioceptive influences on directional hearing: dependence on the movement type.

Proprioceptive effects (PE) on directional hearing, i.e., sound image shifts relatively to the sound source, produced by changes in head position, were studied in their dependence on head movement type in two groups of listeners. The first group included subjects in whom horizontal head deviation to the right or to the left, performed on instruction before the presentation of clicks, caused sound image displacement of 10-15 degrees. When the same sounds were made signals of movement direction, i.e., of pointing with the head at the sound source, PE became fully inhibited in all subjects. The second group included listeners in whom PE was either absent or only very small; substitution of passive head deviations for active turns resulted (in 63 percent of cases) in PEs which presumably had been previously inhibited. Thus identical muscle activities play different roles in auditory spatial perception depending on the type of movement and on the significance of the acoustic signal for the motor act.

Auditory Perception

Discrimination of infants' cry-signals.

A technique for clustering infants' cry-signals on the basis of perceptually discriminable acoustic characteristics is reported. A cry-sequence containing all pairwise combinations of 24 signals was constructed. These signals have been used previously in cry-recognition studies (e.g., Wasz-Hockert, et al., 1968) and consist of six each of pain, hunger, pleasure, and birth. 20 musically competent subjects were tested individually and instructed to compare each cry with the one immediately preceding it in the sequence. Forced-choice "similarity" scores were summed for every pair of cries. These "similarity scores" were data for both a manual and a computerized clustering method. There was absolute agreement between these two methods, and the clusters of cry-signals correspond very closely to the four original cry groups. This seems a valid technique for examining the acoustic similarity of infants' cry-signals.

Adolescent

Tonic stretch reflexes in lip, tongue and jaw muscles.

Despite considerable speculation it remains unclear as to whether stretch reflexes perform a functional role in speech articulator muscles. Recent research, however, has shown that long loop stretch reflex mechanisms are brought into play during voluntary contraction of limb muscles and a functional role in oscillatory damping has been suggested. It was decided, therefore, to use a method and a technique of analysis similar to that used in limb muscles to search for tonic stretch reflex (TSR) responses in lip, tongue and jaw muscles during sustained voluntary contraction. The term 'action TSR' is used to differentiate stretch reflex responses measured from voluntary activity from those measured at rest. Simultaneous electromyogram (EMG) recordings were taken from the lip, tongue and jaw musculature in normal, stutterer and cerebral spastic subjects. Subjects were instructed to hold the appropriate articulator in a fixed position while the experiment applied an irregular, continuously changing, stretching force. The stretch and EMG signals were analyzed using a cross correlation and spectral analysis technique. This provided a sensitive means of detecting any EMG fluctuations which covaried with applied stretch and might therefore be classified as reflex. No suggestion of such action TSR responses could be found in lip or tongue muscles of any of the subjects tested, including the cerebral spastic subjects with dysarthric speech. It is therefore concluded that action TSR mechanisms are not operative in control of lip and tongue muscles in man. Furthermore, dysarthric speech in cerebral spasticity cannot be attributed to exaggerated tone of lip and tongue muscles resulting from hypersensitivity of TSR mechanisms. In contrast, clear action TSR responses were demonstrable in jaw closing muscles while in jaw opening muscles, small amplitude responses were detected but were not substantial in comparison with background activity. Since the action TSR is present in jaw and limb muscles, but absent in lip and tongue muscles, the suggestion of a functional role of this reflex in damping mechanical oscillations associated with inertial loads is further supported.

Adult

Contingency contrast effects in discrimination conditioning.

Three experiments observed differential electrodermal responding to signal stimuli (CSs) by contrasting positive, random, and negative contingencies between the signals and strong stimuli (UCSs). Experimentation began as a test of the proposition that electrodermal response to a random signal (or CSR) would lie between the response to a reinforced or excitatory stimulus (CS+) and that to a nonreinforced or inhibitory stimulus (CS- or CSI). A clear intermediate position for CSR did not result. Instead it appeared that CSR was operating as a mildly excitatory signal. This led to a second experiment where response to pairs of stimuli with different contingent relations could be compared in independent samples. The pairs were CS+ and CS-, CS+ and CSR, and CSR and CS-. Differential responding was observed in all pairs and response to CSR was significantly larger in the group receiving CSR with CS- than it was in the group receiving CSR with CS+. A contingency contrast effect was suggested. A third experiment explored the implications of a contingency contrast effect by varying overall UCS density, the duration of "safety intervals," and the presence or absence of instructions about contingencies. The UCS density and instruction variables influenced the differential performance to CSR and CS-, a result that was interpreted as further evidence for a perceptual contingency-contrast effect. Some theoretical implications of such a contrast phenomenon are examined, as they apply to autonomic learning. The CS is interpreted as a signal supplying contingency information that is dependent upon a complex of factors in the stimulation environment.

Association Learning

Cortical evoked potentials elicited by real speech words and human sounds.

Averaged evoked potentials were recorded from PZ and left and right temporo-parietal electodes to real speech words and human sounds in 8 right-handed subjects. Stimuli were presented in a "no task" condition where the subject was instructed to listen attentively, and a vigilance condition where the subject responded to a particular word or sound during a run of such stimuli. The vigilance condition produced two classes of stimuli:signals and non-signals. Evoked potentials to physically identical words or sounds were examined when they were "no task", non-signal and signal stimuli. P300 amplitude increased significantly as a function of increasing task demands going from "no task" to non-signal to signal. When a strict statistical criterion for multiple comparisons (Bonferroni test) was applied in looking for asymmetries between hemispheres, only 2 isolated left greater than right differences turned out to be significant. Review of the literature concerning evoked potential correlates of differential hemispheric processing pointed up flaws in design, statistical technique, and inconsistencies in reported findings which suggested that while evoked potentials may sometimes reflect differences in hemispheric functioning, this effect is marginal at best.

Adult

Signal functions of infant facial expression and gaze direction during mother-infant face-to-face play.

Recent studies of adult-infant interaction suggest that adults modify their behavior in order to change or maintain an infant's state of arousal. We pursued this question by asking whether mothers modify their actions in response to infant facial expression or gaze direction. Subjects were 7 mother-infant (4--8 month old) pairs in which mothers were instructed to bet their babies to smile. From these filmed interactions the infant's mouth, gaze, and head direction were coded, and the mother's movements were coded as single acts or bouts. Results of an exploratory analysis indicate that, when trying to get a baby to smile using tactile and kinesthetic stimulation, mothers tend to respond to negative changes of affect and attention by changing the content of their actions, taking a long pause, or decreasing the number of acts in a bout.

Arousal

A data analysis microcomputer package (DAMP) for biomedical signals.

The advent of cheap, powerful microcomputer systems makes the analysis of data via sophisticated techniques available to the personnel who are non-specialists in computing systems. The DAMP package described here is intended for use on personal computers and has therefore been written in BASIC for portability. The analysis techniques are powerful, comprising algorithms to perform sample-data generation, plotting displays, digital data filtering, auto-correlation functions, fast Fourier transforms and autoregressive modelling. The last technique contains a number of options including the display of z-plane plots, frequency response of the model, residual plotting and auto-correlation of the residuals. Illustrative results are shown from psychological mood data and rat locomotor activity. The package is designed both to instruct a user in the techniques of spectral analysis, and also to provide a range of methods for investigating time and frequency behaviour of biomedical data.

Biomedical Engineering