Disengagement of motor cortex from movement control during long-term learning.

Motor learning involves reorganization of the primary motor cortex (M1). However, it remains unclear how the involvement of M1 in movement control changes during long-term learning. To address this, we trained mice in a forelimb-based motor task over months and performed optogenetic inactivation and two-photon calcium imaging in M1 during the long-term training. We found that M1 inactivation impaired the forelimb movements in the early and middle stages, but not in the late stage, indicating that the movements that initially required M1 became independent of M1. As previously shown, M1 population activity became more consistent across trials from the early to middle stage while task performance rapidly improved. However, from the middle to late stage, M1 population activity became again variable despite consistent expert behaviors. This later decline in activity consistency suggests dissociation between M1 and movements. These findings suggest that long-term motor learning can disengage M1 from movement control

Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS(2 ms)), 6 ms (CB→M1 PAS(6 ms)) or 10 ms (CB→M1 PAS(10 ms)) or randomly alternating intervals of 2 and 10 ms (CB→M1 PAS(Control)). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS(2 ms) resulted in MEP potentiation, CB→M1 PAS(6 ms) and CB→M1 PAS(10 ms) in MEP depression, and CB→M1 PAS(Control) in no change. The MEP changes lasted for 30-60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity

Magnetic dipole excitation and its sum rule in nuclei with two valence nucleons

Background: Magnetic dipole (M1) excitation is the leading mode of nuclear excitation by the magnetic field, which couples unnatural-parity states. Since the M1 excitation occurs mainly for open-shell nuclei, the nuclear pairing effect is expected to play a role. As expected from the form of operator, this mode may provide the information on the spin-related properties, including the spin component of dineutron and diproton correlations. In general, the sum rule for M1 transition strength has not been derived yet. Purpose: To investigate the M1 excitation of the systems with two valence nucleons above the closed-shell core, with pairing correlation included, and to establish the M1 sum rule that could be used to validate theoretical and experimental approaches. Possibility to utilize the M1 excitation as a tool to investigate the pairing correlation in medium is also discussed. Method: Three-body model, which consists of a rigid spherical core and two valence nucleons, is employed. Interactions for its two-body subsystems are phenomenologically determined in order to reproduce the two-body and three-body energies. We also derive the M1 sum rule within this three-body picture. Conclusion: The introduced M1 sum rule can be utilized as a benchmark for model calculations of M1 transitions in the systems with two valence nucleons. The total sum of the M1 transition strength is related with the coupled spin of valence nucleons in the open shell, where the pairing correlation is unnegligible. The three-body-model calculations for 18 O, 18 Ne, and 42 Ca nuclei demonstrate a significant effect of the pairing correlations on the low-lying M1 transitions. Therefore, further experimental studies of M1 transitions in those systems are on demand, in order to validate proposed sum rule, provide a suitable probe for the nuclear pairing in medium, as well as to optimize the pairing models.Comment: 10 pages, 3 figures, 4 tables. Revised for re-submission to Phys. Rev.

Reduced contribution of the ipsilateral primary motor cortex to force modulation with short-term motor learning in humans: An NIRS study

How is muscle force modulated during hand exercise? Oxygenation in the contralateral primary motor cortex (M1) has been observed to vary considerably across trials of repetitive handgrip exercise. No linear relationship was observed between the average value of oxygenation determined by a block design study and the force of the handgrip. We found reduced oxygenation in the ipsilateral M1 and unchanged oxygenation in the contralateral M1 during repetitive static handgrip exercises (40% and 60% maximal voluntary contraction; 10 s exercise/75 s rest; 5 sets), which might be due to short-term motor learning. These results support the hypothesis that the ipsilateral M1 might functionally compensate for the contralateral M1 in force modulation during unilateral exercises

Generalized Convexity and Inequalities

Let R+ = (0,infinity) and let M be the family of all mean values of two numbers in R+ (some examples are the arithmetic, geometric, and harmonic means). Given m1, m2 in M, we say that a function f : R+ to R+ is (m1,m2)-convex if f(m1(x,y)) < or = m2(f(x),f(y)) for all x, y in R+ . The usual convexity is the special case when both mean values are arithmetic means. We study the dependence of (m1,m2)-convexity on m1 and m2 and give sufficient conditions for (m1,m2)-convexity of functions defined by Maclaurin series. The criteria involve the Maclaurin coefficients. Our results yield a class of new inequalities for several special functions such as the Gaussian hypergeometric function and a generalized Bessel function.Comment: 17 page

Low-energy enhancement of magnetic dipole radiation

Magnetic dipole strength functions have been deduced from averages of a large number of $M1$ transition strengths calculated within the shell model for the nuclides $^{90}$Zr, $^{94}$Mo, $^{95}$Mo, and $^{96}$Mo. An enhancement of $M1$ strength toward low transition energy has been found for all nuclides considered. Large $M1$ strengths appear for transitions between close-lying states with configurations including proton as well as neutron high-$j$ orbits that re-couple their spins and add up their magnetic moments coherently. The $M1$ strength function deduced from the calculated $M1$ transition strengths is compatible with the low-energy enhancement found in ($^3$He,$^3$He') and $(d,p)$ experiments. The present work presents for the first time an explanation of the experimental findings

Crystal Structures of Influenza A Virus Matrix Protein M1: Variations on a Theme

Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1\u27s multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N1-165-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly different dimer interface that possibly affects dimer stability. More importantly, while one of the monomers is fully defined, the N-terminal half of the second monomer shows considerable disorder that appears inherent in the protein and is potentially physiologically relevant. Such disorder has not been observed in any other previously reported structure at either low or high pH conditions, despite similar crystallization pH conditions. By comparing our novel N1-165-domain structure with other low-pH or neutral-pH M1 structures, it appears that M1 can energetically access different monomer and dimer conformations, as well as oligomeric states, with varying degree of similarities. The study reported here provides further insights into M1 oligomerization that may be essential for viral propagation and infectivity

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches

Effects of the Spin-Orbit and Tensor Interactions on the M1M1 and E2E2 Excitations in Light Nuclei

The effects of varying the spin-orbit and tensor components of a realistic interaction on $M1$ excitation rates and $B(E2)'s$ are studied on nuclei in the $0p$ and $1s-0d$ shells. Not only the total $M1$ but also the spin and orbital parts separately are studied. The single-particle energies are first calculated with the same interaction that is used between the valence nucleons. Later this stringent condition is relaxed somewhat and the $1s$ level is raised relative to $0d$. For nuclei up to $^{28}Si$, much better results i.e stronger $B(M1)$ rates are obtained by increasing the strength of the spin-orbit interaction relative to the free value. This is probably also true for $^{32}S$, but $^{36}Ar$ presents some difficulties. The effects of weakening the tensor interaction are also studied. On a more subtle level, the optimum spin-orbit interaction in the lower half of the $s-d$ shell, as far as $M1$ excitations are concerned, is substantially larger than the difference $E(J=3/2^+)_1-E(J=5/2^+)_1=5.2~MeV$ in $^{17}O$. A larger spin-orbit splitting is also needed to destroy the triaxiality in $^{22}Ne$. Also studied are how much $M1$ orbital and spin strength lies in an observable region and how much is buried in the grass at higher energies. It is noted that for many nuclei the sum $B(M1)_{orbital}+B(M1)_{spin}$ is very close to $B(M1)_{total}$, indicating that the summed cross terms are very small.Comment: 39 pages, revtex 3.