Upper-limb hemiparesis is a prevalent and often refractory sequela of stroke, and conventional rehabilitation approaches often yield limited long-term gains in the chronic phase. Cervical epidural electrical stimulation (EES) has emerged as a promising precision neurorehabilitation strategy to amplify residual corticospinal drive through contact-specific modulation of spinal interneuron excitability. However, the relationship between individual cervical motor recruitment patterns and functional recovery has not been systematically characterized in stroke survivors. Therefore, the present prospective pilot study investigated contact-specific motor mapping and the acute effects of cervical EES on voluntary upper-limb muscle activation in four participants with chronic post-stroke hemiparesis. Four adults with chronic post-stroke hemiparesis (time since stroke 6–28 months; baseline Fugl-Meyer Assessment for Upper Extremity [FMA-UE] scores 6–35) underwent bilateral percutaneous cervical epidural lead implantation spanning C3–T1. Intraoperative contact-specific motor mapping was performed through bipolar stimulation at 2 Hz, yielding individualized cervical recruitment maps that informed subsequent parameter selection. Task-related surface electromyography (EMG) was then recorded under EES-On and EES-Off conditions across six standardized upper-limb movements; EES-On/EES-Off amplitude ratios served as indices of acute stimulation effects. Clinical assessments, including the FMA-UE, Action Research Arm Test (ARAT), and Modified Ashworth Scale (MAS), were administered at baseline and 12–28 days after implantation, with EES active. Intraoperative mapping showed a level-dependent proximal-to-distal pattern of muscle recruitment consistent with cervical somatotopic organization. EES-On was associated with higher voluntary EMG amplitude in most muscles and tasks, with EES-On/EES-Off ratios of up to 11.4 in the wrist flexor during grasping. All four participants had higher FMA-UE scores at the post-implantation assessment (range +4 to +8 points), with changes in three participants falling within or above the published minimal clinically important difference range, and ARAT scores increased in all four participants (+1 to +6 points). Elbow flexor tone increased in two participants, and no serious adverse events occurred. Collectively, these preliminary findings suggest that contact-specific cervical EES, informed by individualized motor mapping, may represent a feasible adjunct intervention for upper-limb rehabilitation following chronic stroke, and provide a neurophysiological rationale for future controlled trials.Clinical trial registrationClinicalTrials.gov, NCT05981989.
IntroductionReproductive experience may affect the antidepressant action of estrogen replacement therapy (ERT). In the most used animal model of menopause, ovariectomized young adult rats, prolame produces estrogenic and antidepressant-like effects, making it a potential alternative to conventional ERT. A previous study indicated that aging cancels out the antidepressant-like effect of estradiol and reduces the window of antidepressant action of prolame, limiting it to only 3 weeks after ovariectomy. However, the aged females (middle-aged) used in that study were retired breeders, a factor that could explain their antidepressant response to both estrogens. Thus, the present study aimed to determine how reproductive experience influences the antidepressant-like effects of estradiol (30 μg/kg) and prolame (60 μg/kg) in middle-aged Wistar rats.MethodsThe antidepressant-like effect of both estrogens was evaluated 3 weeks after ovariectomy in nulliparous and multiparous middle-aged rats using the forced swim test. We also assessed the effect of estrogens on uterine weight.ResultsOur results suggest that reproductive experience confers stress resilience. Prolame, but not estradiol, produced an antidepressant-like effect in middle-aged female rats, both multiparous and nulliparous. Treatment with estradiol and prolame increased uterine weight similarly; however, the uterus of nulliparous rats showed greater sensitivity to estrogens.ConclusionTaken together, the results suggest that prolame might be a viable therapeutic alternative for perimenopausal or postmenopausal women to alleviate depressive symptoms, and a candidate for ERT.
BackgroundMethamphetamine, a potent psychostimulant, is one of the most used substances globally. When administered alone, methamphetamine has powerful rewarding and reinforcing properties and produces numerous health consequences. However, recent national trends reveal that methamphetamine is increasingly being used concurrently with fentanyl. Of particular concern is that many methamphetamine users are unwittingly exposed to fentanyl, due to the increasing rate at which psychostimulants are “laced” with the opioid. While the amplified health risks of the drug combination, such as potential overdoses, are well documented, their shared addictive potential is less clear.MethodsIn this review, we assessed the current literature on the neurobiological mechanisms associated with concurrent methamphetamine and fentanyl use, as well as the behavioral effects of the combined drugs.ResultsAgonism of μ opioid receptors is a critical system involved in modulating the behavioral effects of methamphetamine and fentanyl, including conditioned place preference, cue-reactivity and behavioral sensitization. The existing literature also suggests that methamphetamine and fentanyl may have synergistic interactions that enhance their addictive potential, effects that are likely mediated by μ opioid receptors.ConclusionConcurrent methamphetamine-fentanyl use is a mounting crisis. Unfortunately, the neurobiological and behavioral consequences of this drug combination have not been adequately examined. While the existing literature on concurrent methamphetamine-opioid use indicates that the drugs have synergistic addictive potential, more research specifically examining methamphetamine-fentanyl combinations is needed.
