Center of pressure and center of mass behavior during gait initiation on inclined surfaces: A statistical parametric mapping analysis

This study analyzed gait initiation (GI) on inclined surfaces with 68 young adult subjects of both sexes. Ground reaction forces and moments were collected using two AMTI force platforms, of which one was in a horizontal position and the other was inclined by 8% in relation to the horizontal plane. Departing from a standing position, each participant executed three trials in the following conditions: horizontal position (HOR), inclined position at ankle dorsi-flexion (UP), and inclined position at ankle plantar-flexion (DOWN). Statistical parametric mapping analysis was performed over the entire center of pressure (COP) and center of mass (COM) time series. COP excursion did not show significant differences in the medial-lateral (ML) direction in both inclined conditions, but it was greater in the anterior-posterior (AP) direction for both inclined conditions. COP velocities are smaller in discrete portions of GI for the UP and DOWN conditions. COM displacement was greater in the ML direction during anticipatory postural adjustments (APA) in the UP condition, and COM moves faster in the ML direction during APA in the UP condition but slower at the end of GI for both the UP and the DOWN conditions. The COP-COM vector showed a greater angle in the DOWN condition. We observed changes for COP and COM in GI in both the UP and the DOWN conditions, with the latter showing changes for a great extent of the task. Both the UP and the DOWN conditions showed increased COM displacement and velocity. The predominant characteristic during GI on inclined surfaces, including APA, appears to be the displacement of the COM.     

Bow Your Head in Shame,or, Hold Your Head Up with Pride: Semantic Processing of Self-Esteem Concepts Orients Attention Vertically

Embodied cognition holds that abstract concepts are grounded in perceptual-motor simulations. If a given embodied metaphor maps onto a spatial representation, then thinking of that concept should bias the allocation of attention. In this study, we used positive and negative self-esteem words to examine two properties of conceptual cueing. First, we tested the orientation-specificity hypothesis, which predicts that conceptual cues should selectively activate certain spatial axes (in this case, valenced self-esteem concepts should activate vertical space), instead of any spatial continuum. Second, we tested whether conceptual cueing requires semantic processing, or if it can be achieved with shallow visual processing of the cue words. Participants viewed centrally presented words consisting of high or low self-esteem traits (e.g., brave, timid) before detecting a target above or below the cue in the vertical condition, or on the left or right of the word in the horizontal condition. Participants were faster to detect targets when their location was compatible with the valence of the word cues, but only in the vertical condition. Moreover, this effect was observed when participants processed the semantics of the word, but not when processing its orthography. The results show that conceptual cueing by spatial metaphors is orientation-specific, and that an explicit consideration of the word cues’ semantics is required for conceptual cueing to occur.     

UP States Protect Ongoing Cortical Activity from Thalamic Inputs

Cortical neurons in vitro and in vivo fluctuate spontaneously between two stable membrane potentials: a depolarized UP state and a hyperpolarized DOWN state. UP states temporally correspond with multineuronal firing sequences which may be important for information processing. To examine how thalamic inputs interact with ongoing cortical UP state activity, we used calcium imaging and targeted whole-cell recordings of activated neurons in thalamocortical slices of mouse somatosensory cortex. Whereas thalamic stimulation during DOWN states generated multineuronal, synchronized UP states, identical stimulation during UP states had no effect on the subthreshold membrane dynamics of the vast majority of cells or on ongoing multineuronal temporal patterns. Both thalamocortical and corticocortical PSPs were significantly reduced and neuronal input resistance was significantly decreased during cortical UP states – mechanistically consistent with UP state insensitivity. Our results demonstrate that cortical dynamics during UP states are insensitive to thalamic inputs.     

Methods for predicting cortical UP and DOWN states from the phase of deep layer local field potentials

During anesthesia, slow-wave sleep and quiet wakefulness, neuronal membrane potentials collectively switch between de- and hyperpolarized levels, the cortical UP and DOWN states. Previous studies have shown that these cortical UP/DOWN states affect the excitability of individual neurons in response to sensory stimuli, indicating that a significant amount of the trial-to-trial variability in neuronal responses can be attributed to ongoing fluctuations in network activity. However, as intracellular recordings are frequently not available, it is important to be able to estimate their occurrence purely from extracellular data. Here, we combine in vivo whole cell recordings from single neurons with multi-site extracellular microelectrode recordings, to quantify the performance of various approaches to predicting UP/DOWN states from the deep-layer local field potential (LFP). We find that UP/DOWN states in deep cortical layers of rat primary auditory cortex (A1) are predictable from the phase of LFP at low frequencies (< 4 Hz), and that the likelihood of a given state varies sinusoidally with the phase of LFP at these frequencies. We introduce a novel method of detecting cortical state by combining information concerning the phase of the LFP and ongoing multi-unit activity.     

Sleepy dialogues between cortex and hippocampus: who talks to whom?

During NREM sleep, neocortical neurons undergo near-synchronous transitions, every second or so, between UP states, during which they are depolarized and fire actively, and DOWN states, during which they are hyperpolarized and completely silent. In this issue of Neuron, Isomura et al. report that slow oscillations of membrane potential occur near-synchronously not only in neocortex but also in entorhinal cortex and subiculum. Within the hippocampus proper, pyramidal neurons lack the bistability of UP and DOWN states, but their firing is strongly modulated by cortical activity during the UP state. Intriguingly, many hippocampal neurons fire during the cortical DOWN state. Thus, during sleep UP states, the cortex can talk to the hippocampus, but it is unclear whether the hippocampus talks back.     

Integration and segregation of activity in entorhinal-hippocampal subregions by neocortical slow oscillations

Brain systems communicate by means of neuronal oscillations at multiple temporal and spatial scales. In anesthetized rats, we find that neocortical "slow" oscillation engages neurons in prefrontal, somatosensory, entorhinal, and subicular cortices into synchronous transitions between UP and DOWN states, with a corresponding bimodal distribution of their membrane potential. The membrane potential of hippocampal granule cells and CA3 and CA1 pyramidal cells lacked bimodality, yet it was influenced by the slow oscillation in a region-specific manner. Furthermore, in both anesthetized and naturally sleeping rats, the cortical UP states resulted in increased activity of dentate and most CA1 neurons, as well as the highest probability of ripple events. Yet, the CA3-CA1 network could self-organize into gamma bursts and occasional ripples during the DOWN state. Thus, neo/paleocortical and hippocampal networks periodically reset, self-organize, and temporally coordinate their cell assemblies via the slow oscillation.     

Pyrrolidine ring puckering in cis and trans-proline residues in proteins and polypeptides. Different puckers are favoured in certain situations.

In a set of proteins studied at high resolution by X-ray crystallography over a half of all cis and trans-proline residues could be unambiguously assigned to one of the two forms of pyrrolidine ring puckering, called UP and DOWN. Of these, 89% of the cis-proline residues exhibit the DOWN pucker, while the trans-proline residues, on average, are about evenly distributed between the two forms. Of trans-proline residues found in alpha-helices, 79% have the UP ring pucker. trans-proline residues occurring in other situations are more equally distributed between the two forms of pucker, although further generalizations may be possible. Proline residues in a set of crystal structures of short polypeptides were also examined. As in the protein sample, a tendency for the cis-proline residues to have the DOWN pucker was observed, but the effect was less pronounced.     

Gait stability,variability and complexity on inclined surfaces

This study evaluated the gait stability, variability, and complexity of healthy young adults on inclined surfaces. A total of 49 individuals walked on a treadmill at their preferred speed for 4 min at inclinations of 6%, 8%, and 10% in upward (UP) and downward (DOWN) conditions, and in horizontal (0%) condition. Gait variability was assessed using average standard deviation trunk acceleration between strides (VAR), gait stability was assessed using margin of stability (MoS) and maximum Lyapunov exponent (λs), and gait complexity was assessed using sample entropy (SEn). Trunk variability (VAR) increased in the medial-lateral (ML), anterior-posterior, and vertical directions for all inclined conditions. The SEn values indicated that movement complexity decreased almost linearly from DOWN to UP conditions, reflecting changes in gait pattern with longer and slower steps as inclination increased. The DOWN conditions were associated with the highest variability and lowest stability in the MoS ML, but not in λs. Stability was lower in UP conditions, which exhibited the largest λs values. The overall results support the hypothesis that inclined surfaces decrease gait stability and alter gait variability, particularly in UP conditions.     

Structure of spontaneous UP and DOWN transitions self-organizing in a cortical network model

Synaptic plasticity is considered to play a crucial role in the experience-dependent self-organization of local cortical networks. In the absence of sensory stimuli, cerebral cortex exhibits spontaneous membrane potential transitions between an UP and a DOWN state. To reveal how cortical networks develop spontaneous activity, or conversely, how spontaneous activity structures cortical networks, we analyze the self-organization of a recurrent network model of excitatory and inhibitory neurons, which is realistic enough to replicate UP–DOWN states, with spike-timing-dependent plasticity (STDP). The individual neurons in the self-organized network exhibit a variety of temporal patterns in the two-state transitions. In addition, the model develops a feed-forward network-like structure that produces a diverse repertoire of precise sequences of the UP state. Our model shows that the self-organized activity well resembles the spontaneous activity of cortical networks if STDP is accompanied by the pruning of weak synapses. These results suggest that the two-state membrane potential transitions play an active role in structuring local cortical circuits.     

Risk for Eating Disorders Modulates Startle-Responses to Body Words

Body image disturbances are core symptoms of eating disorders (EDs). Recent evidence suggests that changes in body image may occur prior to ED onset and are not restricted to in-vivo exposure (e.g. mirror image), but also evident during presentation of abstract cues such as body shape and weight-related words. In the present study startle modulation, heart rate and subjective evaluations were examined during reading of body words and neutral words in 41 student female volunteers screened for risk of EDs. The aim was to determine if responses to body words are attributable to a general negativity bias regardless of ED risk or if activated, ED relevant negative body schemas facilitate priming of defensive responses. Heart rate and word ratings differed between body words and neutral words in the whole female sample, supporting a general processing bias for body weight and shape-related concepts in young women regardless of ED risk. Startle modulation was specifically related to eating disorder symptoms, as was indicated by significant positive correlations with self-reported body dissatisfaction. These results emphasize the relevance of examining body schema representations as a function of ED risk across different levels of responding. Peripheral-physiological measures such as the startle reflex could possibly be used as predictors of females’ risk for developing EDs in the future.     

Effect of sensory-motor latencies and active muscular stiffness on stability for an ankle-hip model of balance on a balance board

To achieve human upright posture (UP) and avoid falls, the central nervous system processes visual, vestibular, and proprioceptive information to activate the appropriate muscles to accelerate or decelerate the body’s center of mass. In this process, sensory-motor (SM) latencies and muscular deficits, even in healthy older adults, may cause falls. This condition is worse for people with chronic neuromuscular deficits (stroke survivors, patients with multiple sclerosis or Parkinson’s disease). One therapeutic approach is to recover or improve quiet UP by utilizing a balance board (BB) (a rotating surface with a tunable stiffness and time delay), where a patient attempts to maintain UP while task difficulty is manipulated. While BBs are commonly used, it is unclear how UP is maintained or how changes in system parameters such as SM latencies and BB time delay affect UP stability. To understand these questions, it is important that mathematical models be developed with enough degrees-of-freedom to capture the many responses evoked during the maintenance of UP on a BB. This paper presents an ankle-hip model of balance on a BB, which is used to study the combined effect of SM latencies and active muscular stiffness of the ankle and hip joints, and the BB stiffness and time delay on UP stability. The analysis predicts that people with proprioceptive, visual, vestibular loss, or increased SM latencies may show either leaning postures or larger body-sway. The results show that the BB time delay and the visual and vestibular feedback have the largest impact on UP stability.     

Facultative heterochromatin: is there a distinctive molecular signature?

The Latin word "facultas" literally means "opportunity." Facultative heterochromatin (fHC) then designates genomic regions in the nucleus of a eukaryotic cell that have the opportunity to adopt open or compact conformations within temporal and spatial contexts. This review focuses on the molecular and functional aspects of fHC that distinguish it from constitutive heterochromatin (cHC) and euchromatin (EC) and discusses various concepts regarding the regulation of fHC structure. We begin by revisiting the historical developments that gave rise to our current appreciation of fHC.     

Metastable states, phase transitions, and persistent neural activity

A new mathematical model to describe the spiking rate of a neural population is derived, which considers both the mean and the variance of the activity. Bifurcation analysis identifies a critical interval of parameter values in which the standard bistability regime coexists with an additional third attractor corresponding to the metastable state of bounded mean activity and high variance. To understand the structure of spatio-temporal activity in the metastable state, we study a simple discrete-time model of binary elements with random noise locally coupled on the grid, which produces rich dynamics including metastability. A critical value of the noise amplitude is identified; in the vicinity of this value the system is flexible and can easily generate transitions between UP and DOWN metastable states, either autonomously or in response to a control process. These metastable states and phase transitions provide a proper basis for the modelling of persistent neural activity reported in many experimental studies.     

"Good Is Up” Is Not Always Better: A Memory Advantage for Words in Metaphor-Incompatible Locations

Four experiments examined whether memory for positive and negative words depended on word location and vertical hand movements. Cognitive processing is known to be facilitated when valenced stimuli are presented in locations that are congruent with the GOOD is UP conceptual metaphor, relative to when they are presented in incongruent locations. In both free recall and recognition tasks, we find a memory advantage for words that had been studied in metaphor incongruent locations (positive down, negative up). This incongruity advantage depends on the location of words during encoding, but no evidence was found to suggest that other spatial associations, such as the vertical position of the hand at encoding or word location during retrieval, affect memory. The results indicate that metaphors, like schemas, categories, and stereotypes, can influence cognition in complex ways, producing variable outcomes across different tasks.     

Direct evidence from parietal extinction of enhancement of visual attention near a visible hand

Brain areas exist that appear to be specialized for the coding of visual space surrounding the body (peripersonal space). In marked contrast to neurons in earlier visual areas, cells have been reported in parietal and frontal lobes that effectively respond only when visual stimuli are located in spatial proximity to a particular body part (for example, face, arm or hand) [1-4]. Despite several single-cell studies, the representation of near visual space has scarcely been investigated in humans. Here we focus on the neuropsychological phenomenon of visual extinction following unilateral brain damage. Patients with this disorder may respond well to a single stimulus in either visual field; however, when two stimuli are presented concurrently, the contralesional stimulus is disregarded or poorly identified. Extinction is commonly thought to reflect a pathological bias in selective vision favoring the ipsilesional side under competitive conditions, as a result of the unilateral brain lesion [5-7]. We examined a parietally damaged patient (D.P.) to determine whether visual extinction is modulated by the position of the hands in peripersonal space. We measured the severity of visual extinction in a task which held constant visual and spatial information about stimuli, while varying the distance between hands and stimuli. We found that selection in the affected visual field was remarkably more efficient when visual events were presented in the space near the contralesional finger than far from it. However, the amelioration of extinction dissolved when hands were covered from view, implying that the effect of hand position was not mediated purely through proprioception. These findings illustrate the importance of the spatial relationship between hand position and object location for the internal construction of visual peripersonal space in humans.     

Spatial genome organization during T-cell differentiation

The spatial organization of genomes within the mammalian cell nucleus is non-random. The functional relevance of spatial genome organization might be in influencing gene expression programs as cells undergo changes during development and differentiation. To gain insight into the plasticity of genomes in space and time and to correlate the activity of specific genes with their nuclear position, we systematically analyzed the spatial genome organization in differentiating mouse T-cells. We find significant global reorganization of centromeres, chromosomes and gene loci during the differentiation process. Centromeres were repositioned from a preferentially internal distribution in undifferentiated cells to a preferentially peripheral position in differentiated CD4+ and CD8+ cells. Chromosome 6, containing the differentially expressed T-cell markers CD4 and CD8, underwent differential changes in position depending on whether cells differentiated into CD4+ or CD8+ thymocytes. Similarly, the two marker loci CD4 and CD8 showed distinct behavior in their position relative to the chromosome 6 centromere at various stages of differentiation. Our results demonstrate that significant spatial genome reorganization occurs during differentiation and indicate that the relationship between dynamic genome topology and single gene regulation is highly complex.     

STDP in a bistable synapse model based on CaMKII and associated signaling pathways

The calcium/calmodulin-dependent protein kinase II (CaMKII) plays a key role in the induction of long-term postsynaptic modifications following calcium entry. Experiments suggest that these long-term synaptic changes are all-or-none switch-like events between discrete states. The biochemical network involving CaMKII and its regulating protein signaling cascade has been hypothesized to durably maintain the evoked synaptic state in the form of a bistable switch. However, it is still unclear whether experimental LTP/LTD protocols lead to corresponding transitions between the two states in realistic models of such a network. We present a detailed biochemical model of the CaMKII autophosphorylation and the protein signaling cascade governing the CaMKII dephosphorylation. As previously shown, two stable states of the CaMKII phosphorylation level exist at resting intracellular calcium concentration, and high calcium transients can switch the system from the weakly phosphorylated (DOWN) to the highly phosphorylated (UP) state of the CaMKII (similar to a LTP event). We show here that increased CaMKII dephosphorylation activity at intermediate Ca²⁺ concentrations can lead to switching from the UP to the DOWN state (similar to a LTD event). This can be achieved if protein phosphatase activity promoting CaMKII dephosphorylation activates at lower Ca²⁺ levels than kinase activity. Finally, it is shown that the CaMKII system can qualitatively reproduce results of plasticity outcomes in response to spike-timing dependent plasticity (STDP) and presynaptic stimulation protocols. This shows that the CaMKII protein network can account for both induction, through LTP/LTD-like transitions, and storage, due to its bistability, of synaptic changes.     

Neuregulin 4: A “Hotline” Between Brown Fat and Liver

The discovery that functional brown adipose tissue (BAT) in adult humans is inversely related to body fat mass and may reflect metabolic health has stimulated adipose tissue research to explore activation of BAT as a potential target for antiobesity treatments. In addition to the capacity of BAT to increase energy expenditure and glucose and lipid uptake, BAT secretes factors that may contribute to the regulation of whole‐body metabolism. Among signals released from BAT, neuregulin 4 (NRG4) has been recently identified as an endocrine factor that may link the activation of BAT to protection against diet‐induced obesity, insulin resistance, and hepatic steatosis. NRG4 was shown to directly reduce lipogenesis in hepatocytes, and it could indirectly activate BAT via sympathetic neurons or via inducing brown adipocyte–like signatures in white adipocytes in a paracrine manner. However, the potential relevance of NRG4 as a diagnostic tool or target for the treatment of obesity‐related diseases remains to be explored.     

Cortical functional connectivity during the retention of affective pictures in working memory: EEG-source theta coherence analysis

The pattern of cortical functional connectivity in the source space was studied in a group of righthanded adult participants (N = 44:17 women, 27 men, aged M = 29.61 ± 6.45 years). Participants retained the traces of realistic pictures of positive, neutral, and negative emotional valences in their working memory (WM) while performing the same-different task. Within the framework of this task, participants had to compare the initial picture against a target picture that followed after a specified delay. The coherence (COH) between the pairs of cortical sources chosen in advance according to fMRI data was estimated in the theta frequency range for the period preceding the initial stimulus, during the retention of the initial stimulus in WM, and during the rest interval between successive trials. Two distinct sets of functional links were found. The links of the first type that presumably reflected the involvement of sustained attention were between the dorsal anterior cingulate cortex, the prefrontal areas, and temporal areas of the right hemispheres. When compared to the rest period, the links of this type showed strengthening not only during the retention period but also during the period preceding the initial picture. The links of the second type presumably reflected a progressive neocortex-to-hippocampus functional integration with increasing memory load and strengthened exclusively during the retention period. These links were between the parietal, temporal and prefrontal cortices in the lateral surface of both hemispheres with the additional inclusion of the posterior cingulate cortex and the medial parietal cortex in the left hemisphere. The impact of emotional valence on the strength and topography of the functional links of the second type was found. In the left hemisphere, the increase of strength of cortical interaction was more pronounced for the pictures of positive valence than for the pictures of either neutral or negative valences. When compared to the pictures of neutral valence, the retention of pictorial information of both positive and negative valence showed some extraneous integration of the cortical areas for the theta rhythm. This finding might be related to the additional load exerted by emotionally colored pictures onto the mechanisms of short-time retention of visual information.     

The flexibility in the proline ring couples to the protein backbone

In proteins, the proline ring exists predominantly in two discrete states. However, there is also a small but significant amount of flexibility in the proline ring of high-resolution protein structures. We have found that this side-chain flexibility is coupled to the backbone conformation. To study this coupling, we have developed a model that is simply based on geometric and steric factors and not on energetics. We show that the coupling between phi and chi1 torsions in the proline ring can be described by an analytic equation that was developed by Bricard in 1897, and we describe a computer algorithm that implements the equation. The model predicts the observed coupling very well. The strain in the C(gamma)-C(delta)-N angle appears to be the principal barrier between the UP and DOWN pucker. This strain is relaxed to allow the proline ring to flatten in the rare PLANAR conformation.