[Cerebral persistent primitive arteries. Clinical case of combination with intracranial aneurysm and review of the literature]. / Tserebral'nye persistiruyushchie primitivnye arterii. Klinicheskii sluchai sochetaniya s intrakranial'noi anevrizmoi i obzor literatury.

Cerebral persistent primitive arteries are uncommon and associated with cerebrovascular diseases, like cerebral aneurysms. They can cause vertebrobasilar ischemia and neuropathy of the cranial nerves. The authors present a patient with trigeminal artery associated with giant partially thrombosed cavernous internal cerebral artery aneurysm.

Interaction of 5-[4'-(N-Methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(N-methyl-3'-pyridyl)porphyrin Triiodide with SARS-CoV-2 Spike Protein.

The results of experimental studies of the interaction of the S-protein with a monohetaryl-substituted porphyrin containing a benzimidazole residue are presented. It has been revealed that the S-protein forms high-affinity complexes with the specified porphyrin. The porphyrin binding by the SARS-CoV-2 S-protein has proceeded stepwise; at the first stage, the driving force of the complexation is electrostatic interaction between the surface negatively charged regions of the protein and cationic substituents of the porphyrin. At the second stage, the target complex of the S-protein with the porphyrin is formed. It has been established that the introduction of 5-[4'-(N-methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(N-methyl-3'-pyridyl)porphyrin triiodide into a solution of the S-protein complex with the angiotensin-converting enzyme leads to the replacement of the latter with the porphyrin. Displacement of the angiotensin-converting enzyme from the complex with the S-protein under the action of 5-[4'-(N-methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(N-methyl-3'-pyridyl)porphyrin triiodide is the experimental evidence for the porphyrin binding at the receptor-binding domain of the S-protein.

Synthesis of Hetaryl-Substituted Asymmetric Porphyrins and Their Affinity to SARS-CoV-2 Helicase.

Novel porphyrin compounds containing benzothiazole, benzoxazole, and benzimidazole moieties have been prepared and their structures have been confirmed. Molecular docking of non-symmetric hetaryl-substituted porphyrins and chlorin e6 with SARS-CoV-2 helicase has been carried out. The affinity of hetaryl-substituted porphyrins to this protein has been found significantly higher than that of the drugs approved by the FDA and chlorin e6. The structure of the complexes of SARS-CoV-2 helicase with the considered macroheterocyclic compounds has been analyzed. Possible ways to inhibit and photoinactivate SARS-CoV helicase have been suggested basing on the localization of porphyrins and chlorin e6 in the helicase domains.

Place Cell-Like Activity in the Primary Sensorimotor and Premotor Cortex During Monkey Whole-Body Navigation.

Primary motor (M1), primary somatosensory (S1) and dorsal premotor (PMd) cortical areas of rhesus monkeys previously have been associated only with sensorimotor control of limb movements. Here we show that a significant number of neurons in these areas also represent body position and orientation in space. Two rhesus monkeys (K and M) used a wheelchair controlled by a brain-machine interface (BMI) to navigate in a room. During this whole-body navigation, the discharge rates of M1, S1, and PMd neurons correlated with the two-dimensional (2D) room position and the direction of the wheelchair and the monkey head. This place cell-like activity was observed in both monkeys, with 44.6% and 33.3% of neurons encoding room position in monkeys K and M, respectively, and the overlapping populations of 41.0% and 16.0% neurons encoding head direction. These observations suggest that primary sensorimotor and premotor cortical areas in primates are likely involved in allocentrically representing body position in space during whole-body navigation, which is an unexpected finding given the classical hierarchical model of cortical processing that attributes functional specialization for spatial processing to the hippocampal formation.

[Premorbid border-line mental disorders in adolescents and young-aged people].

The aim of the study was to determine the predictive value of some types of premorbid state for the development of border-line mental diseases (neurotic disorders and personality disorders). We examined 579 school students and 523 university students. The study comprised two stages: primary examination and follow-up (2 years). Some forms of premorbid mental disorders and their impact on the development of border-line mental diseases were described. The predictive value of different premorbid disorders was estimated.

[Characteristics of astheniс disorders in adolescents].

A clinical and epidemiological follow-up study of symptoms in asthenic disorders of neurotic level in 56 male adolescents has been conducted. Two clinical variants of asthenic states, including somato-autonomic (32 patients) and affective (24 patients), are defined. The clinical structure of these syndromes and their changes during a one year follow-up and treatment are described. Positive and negative factors that influence the development and prognosis of asthenic states are determined.

[Pre-morbid borderline state in teenagers].

There was effectuated a clinical-epidemiological, follow-up research of frequency, phenomenological peculiarities and dynamics of pre-existing disease borderline disorders among teenagers-schoolers. There were defined several factors, eintraechtigening on forming stable neurotic and personal disorders.

Primate reaching cued by multichannel spatiotemporal cortical microstimulation.

Both humans and animals can discriminate signals delivered to sensory areas of their brains using electrical microstimulation. This opens the possibility of creating an artificial sensory channel that could be implemented in neuroprosthetic devices. Although microstimulation delivered through multiple implanted electrodes could be beneficial for this purpose, appropriate microstimulation protocols have not been developed. Here, we report a series of experiments in which owl monkeys performed reaching movements guided by spatiotemporal patterns of cortical microstimulation delivered to primary somatosensory cortex through chronically implanted multielectrode arrays. The monkeys learned to discriminate microstimulation patterns, and their ability to learn new patterns and new behavioral rules improved during several months of testing. Significantly, information was conveyed to the brain through the interplay of microstimulation patterns delivered to multiple electrodes and the temporal order in which these electrodes were stimulated. This suggests multichannel microstimulation as a viable means of sensorizing neural prostheses.

A comparison of optimal MIMO linear and nonlinear models for brain-machine interfaces.

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

[Substitution of a lengthy defect of the ureter for the vermiform appendix].

The authors share their experiences with the substitution of the ureter for the appendix in three patients. In two of them the lengthy constriction of the pelvic portion of the ureter resulted from postirradiation alterations, in the other--from a gunshot wound of the lumbar area. The sufficient length and diameter of their appendix on a mobile mesentery allowed its being used for the substitution of the ureter. The results of operations were successful and without postoperative complications in all cases.

[Intestinal plastic surgery of the ureter].

Intestinal plastic surgery for ureteral stricture was made in 25 patients (10 unilateral and 15 bilateral strictures). Stricture of the lower third of both ureters was primarily second to operations for colorectal cancer, urinary bladder diverticulesis and scars after radiotherapy. Unilateral strictures resulted from postradiation changes in 9 patients and a shotgun wound of the ureter in 1 patient. Grafts of an isolated segment of the ileum and the vermiform process on the mesentery were transplanted in 22 and 3 patients, respectively. Postoperative intestinal ileus was observed only in one patient who was treated with relaparotomy, intestinal intubation and abdominal drainage. Another patient was reoperated for failure of ureteroappendicoanastomosis. The results of the reoperations were successful. No lethal outcomes were recorded. Upon 0.5-7 year follow-up, all the patients restored normal urodynamics and function of the affected kidney. Thus, use of an isolated segment of the small intestine ensures repair of the defects of one or both the ureters of any location and length. Intestinal repair in extended ureteral lesion is an operation of choice as it reestablishes urine outflow from the kidney, improves its function, relieves symptoms of chronic pyelonephritis and puts away continuous renal and ureteral fistulas.

A novel food-delivery device for neurophysiological and neuropsychological studies in monkeys.

Neurophysiological and neuropsychological studies in monkeys sometimes require an automated food-pellet dispenser. Commercially available dispensers typically sequester the pellet until delivery and, once delivered, the pellet's availability cannot be controlled. The custom-designed dispenser described here overcomes those two limitations. The device is composed of two separate units: a feeder and an electronic controller. The feeder manipulates food pellets with actuators driven by air pressure and delivers them into a serving bowl. The controller's settings determine whether the monkey can retrieve a pellet from the bowl. If the experiment requires that the pellet be visible and within reach, but unavailable for retrieval, the controller enables a trap-door mechanism at the bottom of the bowl. Any motion near the serving bowl, such as that caused by the approach of a monkey's hand, will then trigger the opening of the trap door, which causes the pellet to fall into an enclosed pellet collector. This rapid pellet-removal mechanism can also be triggered by other computer-controlled contingencies. Two of these dispensers have been in operation in an applied laboratory setting for over 2 years.

Prefrontal cortex neurons reflecting reports of a visual illusion.

When a small, focally attended visual stimulus and a larger background frame shift location at the same time, the frame's new location can affect spatial perception. For horizontal displacements on the order of 1--2 degrees, when the frame moves more than the attended stimulus, human subjects may perceive that the attended stimulus has shifted to the right or left when it has not done so. However, that misapprehension does not disable accurate eye movements to the same stimulus. We trained a rhesus monkey to report the direction that an attended stimulus had shifted by making an eye movement to one of the two report targets. Then, using conditions that induce displacement illusions in human subjects, we tested the hypothesis that neuronal activity in the prefrontal cortex (PF) would reflect the displacement directions reported by the monkey, even when they conflicted with the actual displacement, if any, of the attended stimulus. We also predicted that these cells would have directional selectivity for movements used to make those reports, but not for similar eye movements made to fixate the attended stimulus. A population of PF neurons showed the predicted properties, which could not be accounted for on the basis of either eye-movement or frame-shift parameters. This activity, termed report-related, began approximately 150 ms before the onset of the reporting saccade. Another population of PF neurons showed greater directional selectivity for saccadic eye movements made to fixate the attended stimulus than for similar saccades made to report its displacement. In view of the evidence that PF functions to integrate inputs and actions occurring at different times and places, the present findings support the idea that such integration involves movements to acquire response targets, directly, as well as actions guided by less direct response rules, such as perceptual reports.

Tuning for the orientation of spatial attention in dorsal premotor cortex.

We tested whether neuronal activity in the dorsal premotor cortex (PMd) reflected the orientation of selective spatial attention, as opposed to the target of a reaching movement, eye position and saccade direction. These four spatial variables were dissociated in two tasks, which both required that a monkey attend to a robot's location in order to know when to make a movement. However, the target of the reaching movement varied; it was the robot's location in one task, but a different location in the other task. Eye position was recorded, but not explicitly controlled. Of 199 PMd neurons sampled, 19% had activity related to eye position, and an overlapping 11% were related to saccade direction (totaling 24% of the PMd sample). Of the 152 PMd neurons that lacked oculomotor relationships, approximately 20% reflected the orientation of selective spatial attention. Attentional tuning may account, at least in part, for gaze-independent receptive fields and visuospatial, target or goal relationships in tasks involving stimulus-response incompatibility.

Oscillations in the premotor cortex: single-unit activity from awake, behaving monkeys.

We examined single-unit activity in the dorsal premotor cortex for evidence of fast neuronal oscillations. Four rhesus monkeys performed a task in which visuospatial instruction stimuli indicated the direction of forelimb movement to be executed on each trial. After an instructed delay period of 1.5-3 s, movements to either the right or left of a central origin were triggered by a second visuospatial stimulus. From a database of 579 single units, 78 units (13%) contained periodic peaks in their autocorrelation histograms (ACHs), with oscillation frequencies typically 20-30 Hz (mean 27 Hz). An additional 26 units (5%) had oscillatory features that were identified in joint interspike-interval (ISI) plots. Three observations, taken together, suggest entrainment by rhythmic drive extrinsic to these neurons: shuffling ISIs attenuated ACH peaks, indicating a dependency on serial-order effects; oscillation frequency did not change during either increases or decreases in firing rate; and joint ISI plots contained features consistent with a rhythmicity interrupted by intervening discharges. In some cells, oscillations occurred for only one of the two directions of movement. During the delay period, such directional selectivity was observed in 37 units (60% of delay-period oscillators). For at least 17 of these units, we could exclude the possibility that oscillatory directional selectivity resulted from the difficulty in detecting oscillations due to low discharge rates (for one of the two movement directions). Directional selectivity in fast oscillations shows that they can reflect specific aspects of an intended action.

Experience-dependent plasticity of rat barrel cortex: redistribution of activity across barrel-columns.

The redistribution of neuronal activity across rat barrel cortex following an alteration in whisker usage has been investigated. In adult rats, two mystacial vibrissae - D(2) and one neighbor, D(1) or D(3) - were left intact while all other vibrissae on that side of the snout were clipped. Neurons in contralateral barrel cortex were sampled with a microelectrode array 3.5 days later. Stimulation of clipped vibrissae produced a narrow spatial distribution of cortical activity, whereas stimulation of intact vibrissae produced a widened spatial distribution. Simultaneous recordings from multiple cortical barrel-columns suggest that changes in the effective connectivity between barrel-columns may partially account for this redistribution of sensory responses. Evidence is also presented for a second mechanism, a release from inhibition in sensory-deprived cortical areas. A model is therefore proposed where these two mechanisms operate together to regulate the cortical distribution of evoked activity.

Rhythmically firing neostriatal neurons in monkey: activity patterns during reaction-time hand movements.

While previous studies have identified rhythmically firing neurons (RFNs) in monkey neostriatum and these rhythmic firing patterns have been shown to evolve in neostriatal tonically active neurons (TANs) after dopamine input depletion, the activity patterns of RFNs during motor behavior are still far from completely understood. We examined the single-unit activity patterns of neostriatal neurons, recorded in awake behaving monkeys during a wrist movement task, for evidence of rhythmic activity. Monkeys made ballistic wrist flexion and extension movements in response to vibrotactile cues. Animals held a steady wrist position for 0.5 to 2.0 s while awaiting the onset of the go-cues (hold period). Although the majority of neostriatal neurons (274/306) did not fire rhythmically, approximately 10% of the neurons (32/306) fired rhythmically at 10-50 Hz during the hold period. Most RFNs (28/32) showed significant activity changes during the time between go-cue presentation and movement onset (premovement activity). One-half of RFNs exhibited premovement activity that differed as a function of movement direction. Only one RFN may have responded to the delivery of a fruit juice reward. Neuronal firing was analyzed using interspike interval distributions, autocorrelations, and serial correlation techniques. These analyses showed that the activity patterns of most RFNs were consistent with an integrate-and-fire model of neuronal rhythm generation. Changes in RFN activity patterns during the premovement interval and intertrial variations in firing frequency could be explained by changes in the general level of excitatory input. These observations are consistent with the firing properties reported for neostriatal cholinergic interneurons. It has been suggested that tonically active neurons may be cholinergic interneurons and that these neurons show changes in activity related to specific aspects of behavioral paradigms, such as rewards. RFNs may constitute a special class of TANs. The results presented here suggest that RFNs may have a role in movement initiation. We speculate that RFNs may modulate the propagation of cortical oscillations via basal ganglia-thalamic-cortical loops.

[Premorbid states in borderline mental disorders]. / Predboleznennye sostoianiia pri pogranichnykh psikhicheskikh zabolevaniiakh.

Clinico-epidemiological and repeated catamnestic investigations were performed in juveniles and individuals of young age (14-26 year old) in relation to prevalence, structure and dynamics of premorbid neurological disorders and typical personality reactions. Observations were carried out every 4 years. Results of analysis testified the development of borderline mental disorders in one third of teenagers with preneurotic and pronounced characterological reactions. That permitted to consider these deviations as "risk factors" of the appearance of both neuroses and psychopathies.

High-frequency vibratory sensitive neurons in monkey primary somatosensory cortex: entrained and nonentrained responses to vibration during the performance of vibratory-cued hand movements.

The activity of high-frequency vibratory sensitive (HFVS) neurons was recorded in monkey primary somatosensory cortex (SI) while animals performed wrist flexions and extensions in response to 57-Hz or 127-Hz palmar vibration. HFVS neurons were distinguished by their exquisite responsiveness to the higher frequency vibration (127 Hz). These neurons probably received input from Pacinian afferents. Systematic selection of HFVS neurons was made using K-means cluster analysis of neuronal firing rates during stimulating at 127 Hz and 57 Hz. HFVS neurons constituted approximately 4% of all recorded cells and more frequently were found in areas 3b, 1, and 2 (approximately 5% of total in each area) than in area 3a (approximately 1%). Using circular-statistics analyses for nonuniformity of discharges over the vibratory cycle, HFVS neurons were split into two groups of vibration-entrained neurons (E1 and E2 neurons) and one group of nonentrained neurons (NE neurons). E1 neurons were entrained to vibration at both 127 Hz and 57 Hz, whereas E2 neurons were entrained only at one of these vibratory frequencies. Vibration-entrained neurons often exhibited multimodal distributions of interspike intervals (ISIs), with the modes at multiples of the period of vibration. In addition, for these neurons, ISI clusters in joint interval plots commonly had diagonal orientations that were indicative of negative serial correlations of the ISIs, a feature of extrinsically driven rhythmic activity. HFVS neurons located in areas 3a, 3b, and 1 responded to vibration onset at shorter latencies (16.5 +/- 1.6, 19.8 +/- 5.9, and 21.4 +/- 6.4 ms, respectively, during 127-Hz stimulation) than those located in area 2 (35.6 +/- 13.8 ms). These observations are consistent with a scheme in which HFVS area 2 neurons receive their inputs from more anterior areas of SI. Moreover, entrained neurons exhibited shorter response latencies than nonentrained neurons. During 127-Hz stimulation, response latencies were 17.3 +/- 3.0, 17.5 +/- 2.6, and 25.7 +/- 6.4 ms for E1, E2, and NE neurons, respectively, located in areas 3a, 3b, and 1. Thus, entrained and nonentrained HFVS neurons may belong to different hierarchical stages of information processing.

Rhythmically firing (20-50 Hz) neurons in monkey primary somatosensory cortex: activity patterns during initiation of vibratory-cued hand movements.

The activity patterns of rhythmically firing neurons in monkey primary somatosensory cortex (SI) were studied during trained wrist movements that were performed in response to palmar vibration. Of 1,222 neurons extracellularly recorded in SI, 129 cells (approximately 11%) discharged rhythmically (at approximately 30 Hz) during maintained wrist position. During the initiation of vibratory-cued movements, neuronal activity usually decreased at approximately 25 ms after vibration onset followed by an additional decrease in activity at approximately 60 ms prior to movement onset. Rhythmically firing neurons are not likely to be integrate-and-fire neurons because, during activity changes, their rhythmic firing pattern was disrupted rather than modulated. The activity pattern of rhythmically firing neurons was complimentary to that of quickly adapting SI neurons recorded during the performance of this task (Nelson et al., 1991). Moreover, disruptions of rhythmic activity of individual SI neurons were similar to those reported previously for local field potential (LFP) oscillations in sensorimotor cortex during trained movements (Sanes and Donoghue, 1993). However, rhythmic activity of SI neurons did not wax and wane like LFP oscillations (Murthy and Fetz, 1992; Sanes and Donoghue, 1993). It has been suggested that fast (20-50 Hz) cortical oscillations may be initiated by inhibitory interneurons (Cowan and Wilson, 1994; Llinas et al., 1991; Stern and Wilson, 1994). We suggest that rhythmically firing neurons may tonically inhibit quickly adapting neurons and release them from the inhibition at go-cue onsets and prior to voluntary movements. It is possible that rhythmically active neurons may evoke intermittent oscillations in other cortical neurons and thus regulate cortical population oscillations.