Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume. Male Wistar rats were divided into 2 groups: HI and control. The HI procedure consisted of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O₂ and 92% N₂) on the 7th postnatal day. Two months later, animals were evaluated in the open field test during a single 5-min session, and in the 5-choice serial reaction time task (5-CSRTT), over 25 weeks. Our results demonstrated that animals submitted to HI manifest cognitive impairments in task acquisition, deficits in sustained attention, and increases in impulsivity and compulsivity in response to task manipulation in the 5-CSRTT. Locomotor activity observed in open field did not differ between groups. Moreover, brain volume loss in the total hemisphere, cerebral cortex, white matter, hippocampus, and striatum were observed in HI animals, especially on the side ipsilateral to the lesion. From these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD that are associated with general brain atrophy.
A coordinated pattern of multi-muscle activation is essential to produce efficient reaching trajectories. Disruption of these coordinated activation patterns, termed synergies, is evident following stroke and results in reaching deficits; however, preclinical investigation of this phenomenon has been largely ignored. Furthermore, traditional outcome measures of post-stroke performance seldom distinguish between impairment restitution and compensatory movement strategies. We sought to address this by using kinematic analysis to characterize reaching movements and kinematic synergies of rats performing the Montoya staircase task, before and after ischemic stroke. Synergy was defined as the simultaneous movement of the wrist and other proximal forelimb joints (i.e. shoulder, elbow) during reaching. Following stroke, rats exhibited less individuation between joints, moving the affected limb more as a unit. Moreover, abnormal flexor synergy characterized by concurrent elbow flexion, shoulder adduction, and external rotation was evident. These abnormalities ultimately led to inefficient and unstable reaching trajectories, and decreased reaching performance (pellets retrieved). The observed reaching abnormalities in this preclinical stroke model are similar to those classically observed in humans. This highlights the potential of kinematic analysis to better align preclinical and clinical outcome measures, which is essential for developing future rehabilitation strategies following stroke.
5 September 2019 in Journal of NeuroEngineering and Rehabilitation
Impairments of functional mobility may affect locomotion and quality of life in subjects with Parkinson’s disease (PD). Movement smoothness measurements, such as the spectral arc length (SPARC), are novel approaches to quantify movement quality. Previous studies analyzed SPARC in simple walking conditions. However, SPARC outcomes during functional mobility tasks in subjects with PD and freezing of gait (FOG) were never investigated. This study aimed to analyze SPARC during the Timed Up and Go (TUG) test in individuals with PD and FOG. Thirty-one participants with PD and FOG and six healthy controls were included. SPARC during TUG test was calculated for linear and angular accelerations using an inertial measurement unit system. SPARC data were correlated with clinical parameters: motor section of the Unified Parkinson’s Disease Rating Scale, Hoehn & Yahr scale, Freezing of Gait Questionnaire, and TUG test. We reported lower SPARC values (reduced smoothness) during the entire TUG test, turn and stand to sit in subjects with PD and FOG, compared to healthy controls. Unlike healthy controls, individuals with PD and FOG displayed a broad spectral range that encompassed several dominant frequencies. SPARC metrics also correlated with all the above-mentioned clinical parameters. SPARC values provide valid and relevant clinical data about movement quality (e.g., smoothness) of subjects with PD and FOG during a functional mobility test.
Von Monakow’s theory of diaschisis states the functional ‘standstill’ of intact brain regions that are remote from a damaged area, often implied in recovery of function. Accordingly, neural plasticity and activity patterns related to recovery are also occurring at the same regions. Recovery relies on plasticity in the periinfarct and homotopic contralesional regions and involves relearning to perform movements. Seeking evidence for a relearning mechanism following stroke, we found that rodents display many features that resemble classical learning and memory mechanisms. Compensatory relearning is likely to be accompanied by gradual shaping of these regions and pathways, with participating neurons progressively adapting cortico-striato-thalamic activity and synaptic strengths at different cortico-thalamic loops – adapting function relayed by the striatum. Motor cortex functional maps are progressively reinforced and shaped by these loops as the striatum searches for different functional actions. Several cortical and striatal cellular mechanisms that influence motor learning may also influence post-stroke compensatory relearning. Future research should focus on how different neuromodulatory systems could act before, during or after rehabilitation to improve stroke recovery.
Systems biology postulates the balance between energy production and conservation in optimizing locomotion. Here, we analyzed how mechanical energy production and conservation influenced metabolic energy expenditure in stroke survivors during treadmill walking at different speeds. We used the body center of mass (BCoM) and segmental center of mass to calculate mechanical energy production: external and each segment's mechanical work (Wseg). We also estimated energy conservation by applying the pendular transduction framework (i.e. energy transduction within the step; Rint). Energy conservation was likely optimized by the paretic lower-limb acting as a rigid shaft while the non-paretic limb pushed the BCoM forward at the slower walking speed. Wseg production was characterized by greater movements between the limbs and body, a compensatory strategy used mainly by the non-paretic limbs. Overall, Wseg production following a stroke was characterized by non-paretic upper-limb compensation, but also by an exaggerated lift of the paretic leg. This study also highlights how post-stroke subjects may perform a more economic gait while walking on a treadmill at preferred walking speeds. Complex neural adaptations optimize energy production and conservation at the systems level, and may fundament new insights onto post-stroke neurorehabilitation. This article has and associated First Person interview with the first author of the paper.