Inferior olivary inactivation abolishes conditioned eyeblinks: Extinction or cerebellar malfunction?

The inferior olive (IO) is a required component of neural circuits controlling the classical conditioning of eyeblink responses. Previous reports indicated that lesioning or inactivating the IO abolishes conditioned eyeblinks (CRs), but there was disagreement regarding the timing of the CR performance deficit. As a result, it was not clear whether IO inactivation produces unlearning of CRs or a non-specific dysfunction of cerebellar circuits. Since most of these studies used methods that could block unrelated axons passing through the IO region, additional experiments are required to further elucidate IO function, using inactivating agents that act selectively on cell bodies. In the present study, the IO was inactivated using the glutamate receptor antagonist DGG and the GABA-A receptor agonist muscimol in rabbits performing well-learned CRs. Effects of inactivating the IO on CR expression and on neuronal activity in the anterior cerebellar interposed nucleus (IN) were examined. We found that either blocking excitatory glutamate inputs or activating inhibitory GABA inputs to the IO abolished CRs. This effect occurred with variable delay following drug injections. Additional experiments, in which post-injection testing was delayed to allow for drug diffusion, revealed invariably immediate suppression of CRs. This demonstrated that suppressing IO activity using DGG or muscimol does not induce unlearning of CRs. Single-unit recording during DGG injections revealed that CR suppression was paralleled by a dramatic suppression of IN neuronal activity. We concluded that inactivating the rostral parts of the IO complex abolishes CRs by producing a tonic malfunction of cerebellar eyeblink conditioning circuits.     

Acute brain MRI–DWI patterns and stroke recurrence after mild-moderate stroke

Brain ischemic lesions identified by diffusion-weighted imaging (DWI) have been shown to predict high risk of early future ischemic events in patients with transient ischemic attacks and minor stroke. The aim of this study is to analyze different brain MRI–DWI patterns in patients with mild-moderate stroke to define acute patterns related with a higher risk of stroke recurrence in long-term follow-up (from 6 to 36 months). Retrospective review of case series from a prospective stroke record including 253 patients with mild-moderate stroke (NIHSS from 1 to 7) and acute MRI–DWI lesions. MRI–DWI lesions were analyzed to determine clinically relevant lesions, based on the number, location, age and affected arterial territories. We defined three patterns: (1) multiple versus single lesions; (2) single deep versus single cortical lesions; and (3) single lesions versus multiple lesions affecting different arterial territories and/or of different age. The impact of these patterns on recurrence was analyzed by Cox regression analysis. 38 patients (15.0%) suffered a recurrence. Univariate analysis showed the risk of recurrence for each pattern. Pattern 1: patients with multiple lesions had greater risk of recurrence than those with single lesions (28.2 vs. 9.9%; OR: 3.75 (95% CI: 1.76–7.27), p < 0.0001). Pattern 2: patients with single cortical lesions had higher risk than those with deep lesions (14.3 vs. 6.7% OR: 2.33 (95% CI: 0.86–6.33), p < 0.089). Pattern 3: patients with multiple DWI in different territories or different age had the highest recurrence rate (30.6%), OR: 4.01 (95% CI: 1.70–9.47), p < 0.001, compared to patients with single lesions. Cox regression analysis adjusted by possible confounders, showed that for pattern 1 the OR for recurrence was 2.49 (95% CI: 1.27–4.89), p = 0.008; for pattern 2, OR:1.99 (95% CI: 0.74–5.37), p = 0.17; for pattern 3, OR: 2.85 (95% CI: 1.31–6.15), p = 0.008. Brain MRI–DWI patterns assessed in the acute phase of mild-moderate stroke are useful to identify those patients at high risk of recurrence.     

Changes in brain activation in stroke patients after mental practice and physical exercise： a functional MRI study

Mental practice is a new rehabilitation method that reters to the mental rehearsal ot motor imagery content with the goal of improving motor performance. However, the relationship between activated regions and motor recovery after mental practice training is not well understood. In this study, 15 patients who suffered a firstever subcortical stroke with neurological deficits affecting the right hand, but no significant cognitive impairment were recruited. 10 patients underwent mental practice combined with physical practice training, and 5 patients only underwent physical practice training. We observed brain activation regions after 4 weeks of training, and explored the correlation of activation changes with functional recovery of the affected hands. The results showed that, after 4 weeks of mental practice combined with physical training, the Fugl-Meyer assessment score for the affected right hand was significantly increased than that after 4 weeks of practice training alone. Functional MRI showed enhanced activation in the left primary somatosensory cortex, attenuated activation intensity in the right primary motor cortex, and enhanced right cerebellar activation observed during the motor imagery task using the affected right hand after mental practice training. The changes in brain cortical activity were related to functional recovery of the hand. Experimental findings indicate that cortical and cerebellar functional reorganization following mental practice contributed to the improvement of hand function.     

Review: Could neurotransmitters influence neurogenesis and neurorepair after stroke?

Brain ischaemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells is redirected towards the peri‐infarct region. The success of new neurorestorative treatments for damaged brain implies the need to describe with greater accuracy the mechanisms in charge of regulating adult neurogenesis, under both physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone (SVZ), thus being part of the complex signal network that exerts a remarkable influence on the production of new neurones. Neurotransmitters provide a link between brain activity and SVZ neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may prove a valuable tool to be utilized as a neurorestorative therapy in this pathology.