Neural Topography Research Articles

Temporal hierarchy of observed goal-directed actions

During social interactions, we continuously integrate current and previous information over varying timescales to infer other people's action intentions. Motor cognition theories argue for a hierarchical organization of goal-directed actions based on temporal scales. Accordingly, transient motor primitives are represented at lower levels of the hierarchy, a combination of primitives building motor sequences at subordinate levels, and more stable overarching action goals at superordinate levels. A neural topography of hierarchal timescales for information accumulation was previously shown in the visual and auditory domains. However, whether such a temporal hierarchy can also account for observed goal-directed action representations in motor pathways remains to be determined. Thus, the current study examined the neural architecture underlying the processing of observed goal-directed actions using inter-subject correlation (ISC) of fMRI activity. Observers (n = 24) viewed sequential hand movements presented in their intact order or piecewise scrambled at three timescales pertaining to goal-directed action evolution (Primitives: ± 1.5 s, Sub-Goals: ± 4 s, and High-Goals: ± 10 s). The results revealed differential intrinsic temporal capacities for integrating goal-directed action information across brain areas engaged in action observation. Longer timescales (> ± 10 s) were found in the posterior parietal and dorsal premotor compared to the ventral premotor (± 4 s) and anterior parietal (± 1.5 s) cortex. Moreover, our results revealed a hemispheric bias with more extended timescales in the right MT+, primary somatosensory, and early visual cortices compared to their homotopic regions in the left hemisphere. Our findings corroborate a hierarchical neural mapping of observed actions based on temporal scales of goals and provide further support for a ubiquitous time-dependent neural organization of information processing across multiple modalities.

Spatiotemporal Psychopathology – An integrated brain-mind approach and catatonia

Catatonia is featured by complex symptoms combining motor, affective and behavioral phenomena as well as by its syndrome character with trans-diagnostic occurrence. It paradigmatically shows the limits of current forms of psychopathology like affective and cognitive approaches with respect to both clinical symptoms and brain mechanisms. We therefore suggest Spatiotemporal Psychopathology (STPP) which, as recently introduced, is here developed further following the latest findings in both clinical psychiatry and neuroscience. STPP is characterized by two core features: (i) an experience-based approach that accounts for symptoms primarily in terms of first-person experience of time-space as distinct from third-person observation of specific functions and related behavior; (ii) an integrated brain-mind approach where the brain's neural topography and dynamic, e.g., inner time and space, are shared by the mind's mental topography and dynamic, e.g., time-space experience, as their “common currency”. We demonstrate how these two features can well account for both symptom complexity and trans-diagnostic nature of catatonia. In conclusion, catatonia can serve as paradigmatic example for the need to develop a more comprehensive psychopathological approach in psychiatry. This is provided by STPP that allows integrating subjective experience, clinical symptoms and the brain's neural activity in terms of their inner space-time, e.g., topography and dynamic.

Intrinsic dynamics and topography of sensory input systems.

The brain is continuously bombarded by external stimuli, which are processed in different input systems. The intrinsic features of these sensory input systems remain yet unclear. Investigating topography and dynamics of input systems is the goal of our study in order to better understand the intrinsic features that shape their neural processing. Using a functional magnetic resonance imaging dataset, we measured neural topography and dynamics of the input systems during rest and task states. Neural dynamics were probed by scale-free activity, measured with the power-law exponent (PLE), as well as by order/disorder as measured with sample entropy (SampEn). Our main findings during both rest and task states are: 1) differences in neural dynamics (PLE, SampEn) between regions within each of the three sensory input systems 2) differences in topography and dynamics among the three input systems; 3) PLE and SampEn correlate and, as demonstrated in simulation, show non-linear relationship in the critical range of PLE; 4) scale-free activity during rest mediates the transition of SampEn from rest to task as probed in a mediation model. We conclude that the sensory input systems are characterized by their intrinsic topographic and dynamic organization which, through scale-free activity, modulates their input processing.

Bayesian Model for Covid-19 to Achieve Immunity by Parsimony of Exponential Functions Minimizing the Inoculum

A ribonucleoside analog MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets and might be able to diminish transmission until vaccineinduced or naturally acquired protective herd immunity is reached [1]. As skinner pointed out, behavioral problems have to be solved through behavioral engineering [2]. Cybernetics has full application in the present condition. As in alcohol consumption, smoking, drugs, gun crimes, wars, and sexually acquired diseases, the teleological Aristotelian causes are not tobacco, drugs, and any other issue, but the aberrant behavior. The situation is not trivial and involves non-classic logic and other mathematical logics [3,4]. The neural topography corresponds to the nucleus accumbens. The latter is the battlefield, and the subject’s obsession is the rise of the neurotransmitter dopamine [3,4]. In general, people are very demanding from their governments; nevertheless, at the same time, they are deeply tolerant with their aberrant behavior promoting the dissemination of the SARSCoV-2 [4,5]. This paper examines how to deal with this problem from a scientific perspective, considering probability methods and classical and doxastic logic, using the Parsimony Principle aiming to reach immunity by minimizing the inoculum.

Resection rectopexy—laparoscopic neuromapping reveals neurogenic pathways to the lower segment of the rectum: preliminary results

Nerve sparing in functional pelvic floor surgery is strongly recommended as intraoperative damage to the autonomic nerves may predispose to persistent or worsened anorectal and urogenital function. The aim of this study was to investigate the intraoperative neural topography above the pelvic floor in patients undergoing laparoscopic resection rectopexy in combination with electrophysiologic neuromapping. Ten consecutive female patients underwent laparoscopic resection rectopexy for rectal prolapse. Intraoperative identification of pelvic autonomic nerves was carried out with a novel intraoperative neuromonitoring system based on electric stimulation under simultaneous electromyography of the internal anal sphincter and manometry of the bladder. Neuromonitoring results were compared to patients' preoperative anorectal and urogenital function and their functional results at the 3-month follow-up. Laparoscopy in combination with electrophysiologic neuromapping revealed neurogenic pathways to the lower segment of the rectum during surgical mobilization. In all procedures, intraoperative neuromonitoring finally confirmed functional nerve integrity to the internal anal sphincter and the bladder. Patients with preoperatively diagnosed fecal incontinence were continent at the 3-month follow-up. The Wexner score improved in median from preoperative 4 (range 1-18) to 1 (range 0-3) at follow-up (p = 0.012). Cleveland Clinical Constipation Score improved in median from 10 (range 5-17) to 3 (range 1-7; p = 0.005). In none of the investigated patients a new onset of urinary dysfunction did occur. No change in sexual function was observed. Laparoscopy in combination with electrophysiologic neuromapping during nerve-sparing resection rectopexy identified and preserved neurogenic pathways heading to the lower segment of the rectum above the level of the pelvic floor.

Comment to: Pre-operative determination of anatomic variations of the small saphenous vein for varicose vein surgery by three-dimensional computed tomography venography, by Kim SY, Park EA, Shin YC, et al. Phlebology 2012;27:235-41.

Short saphenous vein (SSV) surgery is more challenging due to higher recurrence and complication rates than great saphenous vein (GSV) surgery. The main reason for that is the presence of many anatomic variations in SSV anatomy and the close proximity of the vein with adjacent nerves in the somewhat crowded popliteal fossa. Accurate anatomic knowledge about the varicose veins (VV) and neural topography is necessary to prevent nerve damage during surgery. Duplex ultrasound (DUS) imaging is the gold standard investigation for VV, but has limitations such as operator-dependent variable results, a time-consuming procedure, possible omission of perforators in unusual locations and a difficulty in the evaluation of pelvic vessels. Three-dimensional computed tomography venography (3D-CTV) cannot replace DUS, but can provide additional powerful 3D images. The exact anatomy of the individual patient can be evaluated before surgery, so that the surgery can be performed with full knowledge of the patient specific anatomy and hemodynamic. This may contribute to minimizing complications and recurrence after VV surgery with SSV reflux. From January 2005 until December 2007 a total of 120 limbs in 103 patients with SSV insufficiency confirmed by duplex underwent conventional operations of high ligation, segmental stripping and varicosectomy....

An Enhanced Hypercube-Based Encoding for Evolving the Placement, Density, and Connectivity of Neurons

Intelligence in nature is the product of living brains, which are themselves the product of natural evolution. Although researchers in the field of neuroevolution (NE) attempt to recapitulate this process, artificial neural networks (ANNs) so far evolved through NE algorithms do not match the distinctive capabilities of biological brains. The recently introduced hypercube-based neuroevolution of augmenting topologies (HyperNEAT) approach narrowed this gap by demonstrating that the pattern of weights across the connectivity of an ANN can be generated as a function of its geometry, thereby allowing large ANNs to be evolved for high-dimensional problems. Yet the positions and number of the neurons connected through this approach must be decided a priori by the user and, unlike in living brains, cannot change during evolution. Evolvable-substrate HyperNEAT (ES-HyperNEAT), introduced in this article, addresses this limitation by automatically deducing the node geometry from implicit information in the pattern of weights encoded by HyperNEAT, thereby avoiding the need to evolve explicit placement. This approach not only can evolve the location of every neuron in the network, but also can represent regions of varying density, which means resolution can increase holistically over evolution. ES-HyperNEAT is demonstrated through multi-task, maze navigation, and modular retina domains, revealing that the ANNs generated by this new approach assume natural properties such as neural topography and geometric regularity. Also importantly, ES-HyperNEAT's compact indirect encoding can be seeded to begin with a bias toward a desired class of ANN topographies, which facilitates the evolutionary search. The main conclusion is that ES-HyperNEAT significantly expands the scope of neural structures that evolution can discover.

Glioma Cell Migration on Three-dimensional Nanofiber Scaffolds Is Regulated by Substrate Topography and Abolished by Inhibition of STAT3 Signaling

A hallmark of malignant gliomas is their ability to disperse through neural tissue, leading to long-term failure of all known therapies. Identifying new antimigratory targets could reduce glioma recurrence and improve therapeutic efficacy, but screens based on conventional migration assays are hampered by the limited ability of these assays to reproduce native cell motility. Here, we have analyzed the motility, gene expression, and sensitivity to migration inhibitors of glioma cells cultured on scaffolds formed by submicron-sized fibers (nanofibers) mimicking the neural topography. Glioma cells cultured on aligned nanofiber scaffolds reproduced the elongated morphology of cells migrating in white matter tissue and were highly sensitive to myosin II inhibition but only moderately affected by stress fiber disruption. In contrast, the same cells displayed a flat morphology and opposite sensitivity to myosin II and actin inhibition when cultured on conventional tissue culture polystyrene. Gene expression analysis indicated a correlation between migration on aligned nanofibers and increased STAT3 signaling, a known driver of glioma progression. Accordingly, cell migration out of glioblastoma-derived neurospheres and tumor explants was reduced by STAT3 inhibitors at subtoxic concentrations. Remarkably, these inhibitors were ineffective when tested at the same concentrations in a conventional two-dimensional migration assay. We conclude that migration of glioma cells is regulated by topographical cues that affect cell adhesion and gene expression. Cell migration analysis using nanofiber scaffolds could be used to reproduce native mechanisms of migration and to identify antimigratory strategies not disclosed by other in vitro models.

Neuronal Control of Drosophila Courtship Song

The courtship song of the Drosophila male serves as a genetically tractable model for the investigation of the neural mechanisms of decision-making, action selection, and motor pattern generation. Singing has been causally linked to the activity of the set of neurons that express the sex-specific fru transcripts, but the specific neurons involved have not been identified. Here we identify five distinct classes of fru neuron that trigger or compose the song. Our data suggest that P1 and pIP10 neurons in the brain mediate the decision to sing, and to act upon this decision, while the thoracic neurons dPR1, vPR6, and vMS11 are components of a central pattern generator that times and shapes the song's pulses. These neurons are potentially connected in a functional circuit, with the descending pIP10 neuron linking the brain and thoracic song centers. Sexual dimorphisms in each of these neurons may explain why only males sing.

The anatomy of the small saphenous vein: Fascial and neural relations, saphenofemoral junction, and valves

Varicose veins are a frequent burden, also in the small saphenous system. Yet its basic anatomy is not described consistently. We therefore investigated the fascial and neural relationships of the small saphenous vein (SSV) as well as the frequency and position of valves and the different junctional patterns, also considering the thigh extension. We dissected the legs of 51 cadavers during the regular dissection course held in winter 2007 at Innsbruck Medical University, with a total of 86 SSVs investigable proximally and 94 SSVs distally. A distinct saphenous fascia is present in 93 of 94 cases. It starts with a mean distance of 5.1 cm (SD 1.2 cm) proximal to the calcaneal tuber, where the tributaries to the SSV join to form a common trunk. The neural topography at the level of the gastrocnemius muscle's origins shows the medial sural cutaneous nerve in 88% medially and in 12% laterally to the SSV, the tibial nerve in 64% medially and in 36% laterally, and the common fibular nerve in 98% medially and in 2% laterally to the vein. The saphenopopliteal junction (SPJ) resembled in about 37% type A (UIP-classification), 15% type B, and 24% type C. A total of 17% of specimens showed a venous web or star at the popliteal fossa and 6% had a doubled junction. A thigh extension could be demonstrated in about 84%. A most proximal valve was present in only 94% at a mean distance of 1.2 cm (SD 1.4 cm) to the SSVs orifice. A consecutive distal valve was only present in 65% with a mean distance of 5.1 cm (SD 2.3 cm). Two fascial points or regions can be described in the SSVs' course and its own saphenous fascia is demonstrated macroscopically in almost all cases. The neural topography is highly individual. The SPJ is highly individual where we found hitherto unclassified patterns in a remarkable number of veins. Venous valves are not as frequent as we supposed them to be. Furthermore, not all most proximal valves seem to be terminal valves.

The Sex-Determination Genes fruitless and doublesex Specify a Neural Substrate Required for Courtship Song

SummaryCourtship song is a critical component of male courtship behavior in Drosophila, making the female more receptive to copulation and communicating species-specific information [1–6]. Sex mosaic studies have shown that the sex of certain regions of the central nervous system (CNS) is critical to song production [7]. Our examination of one of these regions, the mesothoracic ganglion (Msg), revealed the coexpression of two sex-determination genes, fruitless (fru) and doublesex (dsx). Because both genes are involved in creating a sexually dimorphic CNS [8, 9] and are necessary for song production [10–13], we investigated the individual contributions of fru and dsx to the specification of a male CNS and song production. We show a novel requirement for dsx in specifying a sexually dimorphic population of fru-expressing neurons in the Msg. Moreover, by using females constitutively expressing the male-specific isoforms of fru (FruM), we show a critical requirement for the male isoform of dsx (DsxM), alongside FruM, in the specification of courtship song. Therefore, although FruM expression is sufficient for the performance of many male-specific behaviors [14], we have shown that without DsxM, the determination of a male-specific CNS and thus a full complement of male behaviors are not realized.

Neural Topography and Content of Movement Representations

We have used implicit motor imagery to investigate the neural correlates of motor planning independently from actual movements. Subjects were presented with drawings of left or right hands and asked to judge the hand laterality, regardless of the stimulus rotation from its upright orientation. We paired this task with a visual imagery control task, in which subjects were presented with typographical characters and asked to report whether they saw a canonical letter or its mirror image, regardless of its rotation. We measured neurovascular activity with fast event-related fMRI, distinguishing responses parametrically related to motor imagery from responses evoked by visual imagery and other task-related phenomena. By quantifying behavioral and neurovascular correlates of imagery on a trial-by-trial basis, we could discriminate between stimulus-related, mental rotation-related, and response-related neural activity. We found that specific portions of the posterior parietal and precentral cortex increased their activity as a function of mental rotation only during the motor imagery task. Within these regions, the parietal cortex was visually responsive, whereas the dorsal precentral cortex was not. Response- but not rotation-related activity was found around the left central sulcus (putative primary motor cortex) during both imagery tasks. Our study provides novel evidence on the topography and content of movement representations in the human brain. During intended action, the posterior parietal cortex combines somatosensory and visuomotor information, whereas the dorsal premotor cortex generates the actual motor plan, and the primary motor cortex deals with movement execution. We discuss the relevance of these results in the context of current models of action planning.

Learning cortical topography from spatiotemporal stimuli

Stimulus representation is a functional interpretation of early sensory cortices. Early sensory cortices are subject to stimulus-induced modifications. Common models for stimulus-induced learning within topographic representations are based on the stimuli's spatial structure and probability distribution. Furthermore, we argue that average temporal stimulus distances reflect the stimuli's relatedness. As topographic representations reflect the stimuli's relatedness, the temporal structure of incoming stimuli is important for the learning in cortical maps. Motivated by recent neurobiological findings, we present an approach of cortical self-organization that additionally takes temporal stimulus aspects into account. The proposed model transforms average interstimulus intervals into representational distances. Thereby, neural topography is related to stimulus dynamics. This offers a new time-based interpretation of cortical maps. Our approach is based on a wave-like spread of cortical activity. Interactions between dynamics and feedforward activations lead to shifts of neural activity. The psychophysical saltation phenomenon may represent an analogue to the shifts proposed here. With regard to cortical plasticity, we offer an explanation for neurobiological findings that other models cannot explain. Moreover, we predict cortical reorganizations under new experimental, spatiotemporal conditions. With regard to psychophysics, we relate the saltation phenomenon to dynamics and interaction in early sensory cortices and predict further effects in the perception of spatiotemporal stimuli.

Neural Topography and Chronology of Memory Consolidation: A Review of Functional Inactivation Findings

Findings on the role of subcortical and cortical structures in mnemonic processes, obtained by means of the reversible functional inactivation technique, are reviewed. The main advantage of this method (subcortical or cortical administration of local anesthetics or tetrodotoxin) is that it provides information not only on “where” but also “when” and for “how long” these processes take place, thus adding to the topographical dimension the chronological one. The review covers several types of memory (e.g., passive avoidance and spatial memory) studies examining the neural substrates of memory consolidation on the basis of the functional inactivation of the nucleus of the solitary tract, parabrachial nuclei, substantia nigra, hippocampus (dorsal and ventral), nucleus basalis magnocellularis, amygdala, medial septal area, striatum, olfactory bulb, and neocortex. The data are discussed in relation to earlier research and with respect to the anatomical and functional connectivity of the examined centers.

Respiratory and cardiac rhythms as windows to central and autonomic biobehavioral regulation: Selection of window frames, keeping the panes clean and viewing the neural topography

Respiratory and cardiovascular processes figure importantly in biobehavioral regulation. Various cardiac and respiratory measures may, furthermore, index the activity of relatively distinct central and autonomic mechanisms. In this regard, I consider ventilatory indices of central drive and timing of respiration, and rhythmic cardiac-interval fluctuations as reflections of parasympathetic and sympathetic cardiac influences. Particular emphasis is placed upon the phenomenon of respiratory sinus arrhythmia (RSA). A number of conceptual and methodological questions are addressed concerning quantification and inference. Among others, these include the following issues: (1) What is the evidence that the three cardiac periodicities slower than heart rate reflect distinct autonomic mechanisms? (2) Does RSA reflect tonic or phasic parasympathetic regulation of heart rate? (3) Do specific quantification procedures for measuring these rhythms provide superior estimates? (4) What are some potential pitfalls for quantification and inference

Sparing of the flexor carpi ulnaris in ulnar neuropathy at the elbow

A common misconception attributes sparing of the flexor carpi ulnaris (FCU) in ulnar neuropathy at the elbow (UNE) to its innervating branch arising "at or above the elbow." We examined the relationship of FCU branches to the medial epicondyle (ME) and humeroulnar aponeurotic arcade (HUA) in 30 cadaver elbows. In only three did the first FCU branch arise at or proximal to the ME. In 36 UNE cases with fibrillations in the first dorsal interosseous, the FCU was normal in 10, mildly abnormal in 11, and severely abnormal in 15. FCU involvement correlated with the severity of the neuropathy and with whether compression was retroepicondylar or at the HUA. We conclude that sparing of the FCU in UNE is unrelated to the level of origin of its innervating branch, but rather is related to the internal neural topography and to the severity and level of compression.

Neural topography of courtship song in sex mosaics ofDrosophila melanogaster

The control of courtship song inDrosophila melanogaster was mapped to the central nervous system using sex mosaics. Some male-female mosaics follow females and extend their wings at them. This behavior is associated with male brain tissue. Only about two-thirds of the courting mosaics have a normal pulse song when courting; the rest produces abnormal sonic output when extending and vibrating their wings, or no sound at all. Normal pulse song is most closely associated with male genotype in the ventral thoracic ganglia. The substructure in these ganglia closest to the tentative focus is the ventral mesothoracic neuromere. This focus for pulse song is domineering, in that male tissue in either the left or right ganglion is sufficient for normal singing by both the left and right wing. Sine song was produced by only some of the mosaics with normal pulse song. Mapping of the sine song did not lead to a definitive focus, but the genotype of particular regions of the brain and thoracic ganglia tend to be associated with production of sine song.

Neural steroid hormone receptors

(1) Cell nuclear and cytoplasmic receptors for estrogens, androgens, and glucocorticoids have been identified in brains and pituitary glands of vertebrates. With respect to topography, estradiol (E 2) receptors are localized primarily in the hypophysiotrophic area and amygdala; 5-α-dihydrotestosterone (DHT) receptors are found in hypothalamus and limbic regions in smaller amounts and more uniformly distributed than those for estradiol; and corticosterone receptors are found in the hippocampal formation, septum, entorhinal cortex and amygdala. (2) Where information is available, mainly for estrogen receptors, their neural topography shows a remarkable constancy among vertebrates. The neural topography of estrogen and glucocorticoid receptors of rat and rhesus monkey will be compared. (3) A complicating factor in the study of androgens interacting with the brain is the conversion of testosterone (T) in neural tissue to both estrogenic and androgenic metabolites. Two of the products, E 2 and DHT, are recovered attached to cell nuclear receptors in the rat brain, whereas only DHT and T itself are found in pituitary cell nuclei. Evidence from other laboratories suggests that interactions of E 2 and DHT or T with intracellular receptors each subserve different behavioral and neuroendocrine functions in the rat. (4) The topography of estrogen receptors in the rat brain provides an excellent opportunity for studying estrogen action on brain chemistry. Estrogen effects on monoamine oxidase, choline acetylase, and glucose-6-phosphate dehydrogenase activity will be described. The overall importance of the action of steroid hormones on gene expression will be briefly discussed.