Evidence for a subcortical origin of mirror movements after stroke: A longitudinal study

Following a stroke, mirror movements are unintended movements that appear in the non-paretic hand when the paretic hand voluntarily moves. Mirror movements have previously been linked to overactivation of sensorimotor areas in the non-lesioned hemisphere. In this study, we hypothesized that mirror movements might instead have a subcortical origin, and are the by-product of subcortical motor pathways upregulating their contributions to the paretic hand. To test this idea, we first characterized the time course of mirroring in 53 first-time stroke patients, and compared it to the time course of activities in sensorimotor areas of the lesioned and non-lesioned hemispheres (measured using functional MRI). Mirroring in the non-paretic hand was exaggerated early after stroke (Week 2), but progressively diminished over the year with a time course that parallelled individuation deficits in the paretic hand. We found no evidence of cortical overactivation that could explain the time course changes in behaviour, contrary to the cortical model of mirroring. Consistent with a subcortical origin of mirroring, we predicted that subcortical contributions should broadly recruit fingers in the non-paretic hand, reflecting the limited capacity of subcortical pathways in providing individuated finger control. We therefore characterized finger recruitment patterns in the non-paretic hand during mirroring. During mirroring, non-paretic fingers were broadly recruited, with mirrored forces in homologous fingers being only slightly larger (1.76 times) than those in non-homologous fingers. Throughout recovery, the pattern of finger recruitment during mirroring for patients looked like a scaled version of the corresponding control mirroring pattern, suggesting that the system that is responsible for mirroring in controls is upregulated after stroke. Together, our results suggest that post-stroke mirror movements in the non-paretic hand, like enslaved movements in the paretic hand, are caused by the upregulation of a bilaterally organized subcortical system

Rethinking interhemispheric imbalance as a target for stroke neurorehabilitation

© 2019 American Neurological Association Objective: Patients with chronic stroke have been shown to have failure to release interhemispheric inhibition (IHI) from the intact to the damaged hemisphere before movement execution (premovement IHI). This inhibitory imbalance was found to correlate with poor motor performance in the chronic stage after stroke and has since become a target for therapeutic interventions. The logic of this approach, however, implies that abnormal premovement IHI is causal to poor behavioral outcome and should therefore be present early after stroke when motor impairment is at its worst. To test this idea, in a longitudinal study, we investigated interhemispheric interactions by tracking patients’ premovement IHI for one year following stroke. Methods: We assessed premovement IHI and motor behavior five times over a 1-year period after ischemic stroke in 22 patients and 11 healthy participants. Results: We found that premovement IHI was normal during the acute/subacute period and only became abnormal at the chronic stage; specifically, release of IHI in movement preparation worsened as motor behavior improved. In addition, premovement IHI did not correlate with behavioral measures cross-sectionally, whereas the longitudinal emergence of abnormal premovement IHI from the acute to the chronic stage was inversely correlated with recovery of finger individuation. Interpretation: These results suggest that interhemispheric imbalance is not a cause of poor motor recovery, but instead might be the consequence of underlying recovery processes. These findings call into question the rehabilitation strategy of attempting to rebalance interhemispheric interactions in order to improve motor recovery after stroke. Ann Neurol 2019;85:502–513

Measuring Metal–Metal Communication in a Series of Ketimide-Bridged [Fe2]6+ Complexes

Reaction of Fe(acac)3 with 3 equiv of Li[N═C(R)Ph] (R = Ph, tBu) results in the formation of the [Fe2]6+ complexes, [Fe2(μ-N═C(R)Ph)2(N═C(R)Ph)4] (R = Ph, 1; tBu, 2), in low to moderate yields. Reaction of FeCl2 with 6 equiv of Li(N═C13H8) (HN═C13H8 = 9-fluorenone imine) results in the formation of [Li(THF)2]2[Fe(N═C13H8)4] (3) in good yield. Subsequent oxidation of 3 with ca. 0.8 equiv of I2 generates the [Fe2]6+ complex, [Fe2(μ-N═C13H8)2(N═C13H8)4] (4), along with free fluorenyl ketazine. Complexes 1, 2, and 4 were characterized by 1H NMR spectroscopy, X-ray crystallography, 57Fe Mössbauer spectroscopy, and SQUID magnetometry. The Fe-Fe distances in 1, 2, and 4 range from 2.803(7) to 2.925(1) Å, indicating that no direct Fe-Fe interaction is present in these complexes. The 57Fe Mössbauer spectra for complexes 1, 2, and 4 are all consistent with the presence of symmetry-equivalent high-spin Fe3+ centers. Finally, all three complexes exhibit a similar degree of antiferromagnetic coupling between the metal centers (J = -26 to -30 cm-1), as ascertained by SQUID magnetometry

Metal–Metal-Bonded Fe4 Clusters with Slow Magnetic Relaxation

Reaction of FeBr2 with Li(N═CtBu2) (0.5 equiv) and Zn0 (2 equiv) results in the formation of the formally mixed-valent cluster [Fe4Br2(N═CtBu2)4] (1) in moderate yield. The subsequent reaction of 1 with Na(N═CtBu2) results in formation of [Fe4Br(N═CtBu2)5] (2), also in moderate yield. Both 1 and 2 were characterized by zero-field 57Fe Mössbauer spectroscopy, X-ray crystallography, and superconducting quantum interference device magnetometry. Their tetrahedral [Fe4]6+ cores feature short Fe-Fe interactions (ca. 2.50 Å). Additionally, both 1 and 2 display S = 7 ground states at room temperature and slow magnetic relaxation with zero-field relaxation barriers of Ueff = 14.7(4) and 15.6(7) cm-1, respectively. Moreover, AC magnetic susceptibility measurements were well modeled by assuming an Orbach relaxation process