Cortical topography of intracortical inhibition influences the speed of decision making

The neocortex contains orderly topographic maps; however, their functional role remains controversial. Theoretical studies have suggested a role in minimizing computational costs, whereas empirical studies have focused on spatial localization. Using a tactile multiple-choice reaction time (RT) task before and after the induction of perceptual learning through repetitive sensory stimulation, we extend the framework of cortical topographies by demonstrating that the topographic arrangement of intracortical inhibition contributes to the speed of human perceptual decision-making processes. RTs differ among fingers, displaying an inverted U-shaped function. Simulations using neural fields show the inverted U-shaped RT distribution as an emergent consequence of lateral inhibition. Weakening inhibition through learning shortens RTs, which is modeled through topographically reorganized inhibition. Whereas changes in decision making are often regarded as an outcome of higher cortical areas, our data show that the spatial layout of interaction processes within representational maps contributes to selection and decision-making processes

Sex Differences in Spatial Accuracy Relate to the Neural Activation of Antagonistic Muscles in Young Adults

Sex is an important physiological variable of behavior, but its effect on motor control remains poorly understood. Some evidence suggests that women exhibit greater variability during constant contractions and poorer accuracy during goal-directed tasks. However, it remains unclear whether motor output variability or altered muscle activation impairs accuracy in women. Here, we examine sex differences in endpoint accuracy during ankle goal-directed movements and the activity of the antagonistic muscles. Ten women (23.1 ± 5.1 years) and 10 men (23 ± 3.7 years) aimed to match a target (9° in 180 ms) with ankle dorsiflexion. Participants performed 50 trials and we recorded the endpoint accuracy and the electromyographic (EMG) activity of the primary agonist (Tibialis Anterior; TA) and antagonist (Soleus; SOL) muscles. Women exhibited greater spatial inaccuracy (Position error: t = −2.65, P = 0.016) but not temporal inaccuracy relative to men. The motor output variability was similar for the two sexes (P \u3e 0.2). The spatial inaccuracy in women was related to greater variability in the coordination of the antagonistic muscles (R 2 0.19, P = 0.03). These findings suggest that women are spatially less accurate than men during fast goal-directed movements likely due to an altered activation of the antagonistic muscles

Frontostriatal Maturation Predicts Cognitive Control Failure to Appetitive Cues in Adolescents

Adolescent risk-taking is a public health issue that increases the odds of poor lifetime outcomes. One factor thought to influence adolescents' propensity for risk-taking is an enhanced sensitivity to appetitive cues, relative to an immature capacity to exert sufficient cognitive control. We tested this hypothesis by characterizing interactions among ventral striatal, dorsal striatal, and prefrontal cortical regions with varying appetitive load using fMRI scanning. Child, teen, and adult participants performed a go/no-go task with appetitive (happy faces) and neutral cues (calm faces). Impulse control to neutral cues showed linear improvement with age, whereas teens showed a nonlinear reduction in impulse control to appetitive cues. This performance decrement in teens was paralleled by enhanced activity in the ventral striatum. Prefrontal cortical recruitment correlated with overall accuracy and showed a linear response with age for no-go versus go trials. Connectivity analyses identified a ventral frontostriatal circuit including the inferior frontal gyrus and dorsal striatum during no-go versus go trials. Examining recruitment developmentally showed that teens had greater between-subject ventral-dorsal striatal coactivation relative to children and adults for happy no-go versus go trials. These findings implicate exaggerated ventral striatal representation of appetitive cues in adolescents relative to an intermediary cognitive control response. Connectivity and coactivity data suggest these systems communicate at the level of the dorsal striatum differentially across development. Biased responding in this system is one possible mechanism underlying heightened risk-taking during adolescence

Voluntary Activation and Variability During Maximal Dynamic Contractions with Aging

Whether reduced supraspinal activation contributes to age-related reductions in maximal torque during dynamic contractions is not known. The purpose was to determine whether there are age differences in voluntary activation and its variability when assessed with stimulation at the motor cortex and the muscle during maximal isometric, concentric, and eccentric contractions. Thirty young (23.6 ± 4.1 years) and 31 old (69.0 ± 5.2 years) adults performed maximal isometric, shortening (concentric) and lengthening (eccentric) contractions with the elbow flexor muscles. Maximal isometric contractions were performed at 90° elbow flexion and dynamic contractions at a velocity of 60°/s. Voluntary activation was assessed by superimposing an evoked contraction with transcranial magnetic stimulation (TMS) or with electrical stimulation over the muscle during maximal voluntary contractions (MVCs). Old adults had lower MVC torque during isometric (− 17.9%), concentric (− 19.7%), and eccentric (− 9.9%) contractions than young adults, with less of an age difference for eccentric contractions. Voluntary activation was similar between the three contraction types when assessed with TMS and electrical stimulation, with no age group differences. Old adults, however, were more variable in voluntary activation than young (standard deviation 0.99 ± 0.47% vs. 0.73 ± 0.43%, respectively) to both the motor cortex and muscle, and had greater coactivation of the antagonist muscles during dynamic contractions. Thus, the average voluntary activation to the motor cortex and muscle did not differ with aging; however, supraspinal activation was more variable during maximal dynamic and isometric contractions in the old adults. Lower predictability of voluntary activation may indicate subclinical changes in the central nervous system with advanced aging

Grid Cell Hexagonal Patterns Formed by Fast Self-Organized Learning within Entorhinal Cortex

Grid cells in the dorsal segment of the medial entorhinal cortex (dMEC) show remarkable hexagonal activity patterns, at multiple spatial scales, during spatial navigation. How these hexagonal patterns arise has excited intense interest. It has previously been shown how a selforganizing map can convert firing patterns across entorhinal grid cells into hippocampal place cells that are capable of representing much larger spatial scales. Can grid cell firing fields also arise during navigation through learning within a self-organizing map? A neural model is proposed that converts path integration signals into hexagonal grid cell patterns of multiple scales. This GRID model creates only grid cell patterns with the observed hexagonal structure, predicts how these hexagonal patterns can be learned from experience, and can process biologically plausible neural input and output signals during navigation. These results support a unified computational framework for explaining how entorhinal-hippocampal interactions support spatial navigation.CELEST, a National Science Foundation Science of Learning Center (SBE-0354378); SyNAPSE program of Defense Advanced Research Projects Agency (HR00ll-09-3-0001, HR0011-09-C-0011

On the G-protein-coupled receptor heteromers and their allosteric receptor-receptor interactions in the central nervous system: focus on their role in pain modulation

The modulatory role of allosteric receptor-receptor interactions in the pain pathways of the Central Nervous System and the peripheral nociceptors has become of increasing interest. As integrators of nociceptive and antinociceptive wiring and volume transmission signals, with a major role for the opioid receptor heteromers, they likely have an important role in the pain circuits and may be involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR heteromer. This heteromer contributes to morphine-induced tolerance and dependence, since it becomes abundant and develops a reduced G-protein-coupling with reduced signaling mainly operating via beta-arrestin 2 upon chronic morphine treatment. A DOR antagonist causes a return of the Gi/o binding and coupling to the heteromer and the biological actions of morphine. The gender- and ovarian steroid-dependent recruitment of spinal cord MOR/kappa opioid receptor (KOR) heterodimers enhances antinociceptive functions and if impaired could contribute to chronic pain states in women. MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, mediating morphine induced itch. Other mechanism for the antinociceptive actions of acupuncture along meridians may be that it enhances the cross-desensitization of the TRPA1 (chemical nociceptor)-TRPV1 (capsaicin receptor) heteromeric channel complexes within the nociceptor terminals located along these meridians. Selective ionotropic cannabinoids may also produce cross-desensitization of the TRPA1-TRPV1 heteromeric nociceptor channels by being negative allosteric modulators of these channels leading to antinociception and antihyperalgesia

Initial neuromuscular performance in older women influences response to explosive resistance training

The purpose of the study was to identify both demographic and neuromuscular traits that characterize successful or unsuccessful adaptation to resistance training in older women. Twelve, older women underwent electrically evoked muscle twitches for the knee extensors; and performed maximal, voluntary, isometric knee extensions, followed by eight weeks of resistance training. Prior to training nonresponders had 67% higher twitch peak torque than responders (0.29 ± 0.05 vs. 0.18 ± 0.06 Nm·kg−1 respectively), 64% higher twitch rate of torque development (RTD) (3.96 ± 0.47 vs. 2.42 ± 0.62 Nm·s−1·kg−1), 51% higher voluntary peak torque (1.86 ± 0.40 vs. 1.23 ± 0.33 Nm·kg−1), 101% greater RTD (9.43 ± 1.52 vs. 4.70 ± 2.40 Nm·s−1·kg−1), 86% greater impulse (0.13 ± 0.01 vs. 0.07 ± 0.03 Nm·s·kg−1) and 27% faster motor time (80 ± 13 vs. 109 ± 34 ms), (all P \u3c 0.05). Following training, responders showed an 11% increase in twitch peak torque over baseline (0.18 ± 0.06 to 0.20 ± 0.05 Nm·kg−1), 15% increase in voluntary peak torque (1.23 ± 0.33 to 1.41 ± 0.36 Nm·kg−1), 47% increase in RTD (4.70 ± 2.40 to 6.93 ± 2.02 Nm·s−1·kg−1), 43% increase in impulse (0.07 ± 0.03 to 0.10 ± 0.04 Nm·s·kg−1), and 26% increase in rate of EMG rise (886 ± 214 to 1116 ± 102 % pEMG·s−1) (all P \u3c 0.05). Initially higher muscle mass and contractility, coupled with greater neural drive, likely explains why older women with good muscle performance seem to have a lower capacity for improvement than women with low initial levels of performance

The Organization and Role During Locomotion of the Proximal Musculature of the Cricket Foreleg. II. Electromyographic Activity During Stepping Patterns

A description is made of the patterns of electrical activity in the proximal muscles of the cricket foreleg during restrained locomotion and seeking movements, while the animal is held by the mesonotum, allowing the legs complete freedom of movement. 1. The initiation of the swing phase corresponds to the onset of the abductor muscle activity (Fig. 1). Its duration is matched by that of abduction-promotion and does not depend on the step frequency. Leg position is more variable at the end of the stance than at the end of the swing. 2. The promotor and abductor muscle activities are linked (Fig. 2). At least three units can be distinguished in each and the duration of their bursts is independent of the period (Fig. 3). 3. In the double depressors of the trochanter, muscles 77-lb,c (Fig. 4), one unit per muscle was identified, bursting during the swing phase. The duration of the burst is independent of the period. Some isolated potentials occasionally occur during the stance phase. 4. The overall activity in the lateral and medial remotors is coupled to the period; three main patterns can be described, depending upon the muscle bundle and the velocity of movement (Fig. 5). 5. In the coxal depressors two patterns of activity are described which depend on velocity of stepping (Fig. 6): (i) during regular and fast stepping (at frequencies greater than 2–5 Hz), the activity is coupled to that of the double depressors; (ii) during slow or irregular stepping, the activity is biphasic: an initial burst is followed after a latency correlated to the period by a second one in the second half of the stance phase. Conversely, the latency between the end of the second burst and the onset of the following abductor burst does not depend on the period. In most cases, a fast neurone (large amplitude, short phasic activation) is recruited when a slow one reaches high rates of discharge

The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells

The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, eg, by coactivating the estrogen-related receptor-α (ERRα) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these 2 proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERRα to DNA in a skeletal muscle cell line with elevated PGC-1α and linked the DNA recruitment to global PGC-1α target gene regulation. We found that, surprisingly, ERRα coactivation by PGC-1α is only observed in the minority of all PGC-1α recruitment sites. Nevertheless, a majority of PGC-1α target gene expression is dependent on ERRα. Intriguingly, the interaction between these 2 proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat-binding site configuration for ERRα, and adjacent recruitment of the transcription factor specificity protein 1. These findings thus not only reveal a novel insight into the regulatory network underlying muscle cell plasticity but also strongly link the genomic context of DNA-response elements to control transcription factor-coregulator interactions