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The adult, mature central nervous system (CNS) has limited plasticity. Physical exercising can counteract this limitation by inducing plasticity and fostering processes such as learning, memory consolidation and formation. Little is known about the molecular factors that govern these mechanisms, and how they are connected with exercise. In this study, we used immunohistochemical and behavioral analyses to investigate how running wheel exercise affects expression of the neuronal plasticity-inhibiting protein Nogo-A in the rat cortex, and how it influences motor learning in vivo . Following one week of exercise, rats exhibited a decrease in Nogo-A levels, selectively in motor cortex layer 2/3, but not in layer 5. Nogo-A protein levels returned to baseline after two weeks of running wheel exercise. In a skilled motor task (forelimb-reaching), administration of Nogo-A function-blocking antibodies over the course of the first training week led to improved motor learning. By contrast, Nogo-A antibody application over two weeks of training resulted in impaired learning. Our findings imply a bimodal, time-dependent function of Nogo-A in exercise-induced neuronal plasticity: While an activity-induced suppression of the plasticity-inhibiting protein Nogo-A appears initially beneficial for enhanced motor learning, presumably by allowing greater plasticity in establishing novel synaptic connections, this process is not sustained throughout continued exercise. Instead, upregulation of Nogo-A over the course of the second week of running wheel exercise in rats implies that Nogo-A is required for consolidation of acquired motor skills during the delayed memory consolidation process, possibly by inhibiting ongoing neuronal morphological reorganization to stabilize established synaptic pathways. Our findings suggest that Nogo-A downregulation allows leaning to occur, i.e. opens a ‘learning window’, while its later upregulation stabilizes the learnt engrams. These findings underline the importance of appropriately timing of application of Nogo-A antibodies in future clinical trials that aim to foster memory performance while avoiding adverse effects.

The neurophysiological footprint of brain activity after cardiac arrest and during near-death experience (NDE) is not well understood. Although a hypoactive state of brain activity has been assumed, experimental animal studies have shown increased activity after cardiac arrest, particularly in the gamma-band. No study has yet investigated this matter in humans. Here, we present continuous electroencephalography (EEG) recording from a dying human brain, obtained from an 87-year-old patient undergoing cardiac arrest after traumatic subdural hematoma. An increase of absolute power in gamma activity in the narrow and broad bands and a decrease in theta power is seen after suppression of bilateral hemispheric responses. After cardiac arrest, delta, beta, alpha and gamma power were decreased but a higher percentage of relative gamma power was observed when compared to the interictal interval. Cross-frequency coupling revealed modulation of left-hemispheric gamma activity by alpha and theta rhythms across all windows, even after cessation of cerebral blood flow. The strongest coupling is observed for narrow- and broad-band gamma activity by the alpha waves during left-sided suppression and after cardiac arrest. Albeit the influence of neuronal injury and swelling, our data provide the first evidence from the dying human brain in a non-experimental, real-life acute care clinical setting and advocate that the human brain may possess the capability to generate coordinated activity during the near-death period.

BackgroundMagnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown.MethodsThis multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed.ResultsEngel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year.ConclusionsMRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.

Background and Purpose Clinically, Parkinson's disease (PD) presents with asymmetric motor symptoms. The left nigrostriatal system appears more susceptible to early degeneration than the right, and a left‐lateralized pattern of early neuropathological changes is also described in several neurodegenerative conditions, including Alzheimer's disease, frontotemporal dementia, and Huntington's disease. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well‐characterized cohort of PD patients. Methods Our cohort included 205 PD patients who underwent clinical assessments and T1‐weighted brain MRI's. Patients were classified into Early (n = 109) and Late stage (n = 96) based on disease duration, defined as greater than or less than 10 years of motor symptoms. Cortical thickness was determined using FreeSurfer, and a bootstrapped linear regression model was used to estimate differences in rates of atrophy between Early and Late patients. Results Our results show that patients classified as Early stage exhibit a greater estimated rate of cortical atrophy in left frontal regions, especially the left insula and olfactory sulcus. This pattern was replicated in left‐handed patients, and was not influenced by the degree of motor symptom asymmetry (i.e., left‐sided predominant motor symptoms). Patients classified as Late stage exhibited greater atrophy in the bilateral occipital, and right hemisphere‐predominant cortical areas. Conclusions We show that cortical degeneration in PD differs between cerebral hemispheres, and findings suggest a pattern of early left, and late right hemisphere with posterior cortical atrophy. Further investigation is warranted to elucidate the underlying mechanisms of this asymmetry and pathologic implications. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well‐characterized cohort of PD patients. We describe a pattern of early left‐lateralized cortical atrophy, which holds true regardless of handedness or side of motor severity. Our findings are consistent with previous reports of a left‐lateralized distribution of cortical atrophy in PD and other neurodegenerative disorders. Further investigation is warranted to elucidate the underlying mechanisms of this asymmetry and its implications for pathogenesis in neurodegeneration.

Abstract Robotics applied to cranial surgery is a fast-moving and fascinating field, which is transforming the practice of neurosurgery. With exponential increases in computing power, improvements in connectivity, artificial intelligence, and enhanced precision of accessing target structures, robots are likely to be incorporated into more areas of neurosurgery in the future—making procedures safer and more efficient. Overall, improved efficiency can offset upfront costs and potentially prove cost-effective. In this narrative review, we aim to translate a broad clinical experience into practical information for the incorporation of robotics into neurosurgical practice. We begin with procedures where robotics take the role of a stereotactic frame and guide instruments along a linear trajectory. Next, we discuss robotics in endoscopic surgery, where the robot functions similar to a surgical assistant by holding the endoscope and providing retraction, supplemental lighting, and correlation of the surgical field with navigation. Then, we look at early experience with endovascular robots, where robots carry out tasks of the primary surgeon while the surgeon directs these movements remotely. We briefly discuss a novel microsurgical robot that can perform many of the critical operative steps (with potential for fine motor augmentation) remotely. Finally, we highlight 2 innovative technologies that allow instruments to take nonlinear, predetermined paths to an intracranial destination and allow magnetic control of instruments for real-time adjustment of trajectories. We believe that robots will play an increasingly important role in the future of neurosurgery and aim to cover some of the aspects that this field holds for neurosurgical innovation.

It has been understood, for some time, that modulation of deep brain nuclei within the basal ganglia and thalamus can have a therapeutic effect in patients with movement disorders. Because of its reversibility and adjustability, deep brain stimulation (DBS) has largely come to replace traditional ablation procedures. The clinical effects of DBS vary, depending both on the target being stimulated and on the parameters of stimulation. Both aspects are currently the subject of substantial research and discovery. The most common targets for DBS treatment include the subthalamic nucleus for the treatment of advanced Parkinson’s disease, the ventral intermediate nucleus of the thalamus for the treatment of medically refractory essential tremor, and the globus pallidus interna for the treatment of both cervical and generalized dystonias and Parkinson’s disease. We review the current indications, targets, outcomes, and general procedure of DBS for essential tremor, Parkinson’s disease, and dystonia.

Obsessive-compulsive disorder (OCD) is a common psychiatric disease that is marked by recurring, anxiety-provoking thoughts (obsessions) accompanied by repetitive and time-consuming behaviors (compulsions). Among the controversies in the OCD literature is the issue of the origin of the disease and whether brain changes observed with modern imaging techniques are the causes or results of OCD behaviors and thoughts. These issues remain unresolved; however, significant strides have been made in understanding the illness from both phenomenological and pathophysiological perspectives. The current staple of OCD management remains pharmacological in nature and often occurs in conjunction with cognitive behavioral therapy. Refractory cases, however, are occasionally referred for neurosurgical consultation, and several procedures have been examined. Success in the treatment of Parkinson's disease, the reversibility of the therapy, and a relatively safe side-effect profile have allowed deep brain stimulation (DBS) to be examined as an alternative treatment for some psychiatric conditions. Here we assess the possibility of applying DBS to the treatment of OCD. Morphological, functional metabolic, and volumetric data point to several brain regions that are important to the etiology and maintenance of OCD. Converging evidence from the genetics and neurocircuitry literature suggests that several subcortical structures play prominent roles in the disease. The functional modification of these structures could potentially provide symptom relief. Here, we review the ablative and DBS procedures for refractory OCD, and provide a research-driven hypothesis that highlights the ventromedial head of the caudate nucleus, and structures up- and downstream from it, as potential DBS targets for treatment-resistant disease. We hope that a research-driven approach, premised on converging evidence and previous experience, will lead to a safe and effective DBS procedure that will benefit patients who remain disabled despite presently available therapies.

ObjectiveRefractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive–compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016.DesignHere we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses.ConclusionInterest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Essential tremor (ET) is a movement disorder characterized primarily by action tremor which affects the regulation of movements. Disruptions in cerebello-thalamocortical networks could interfere with cognitive control over actions in ET, for example, the ability to suppress a strong automatic impulse over a more appropriate action (conflict control). The current study investigated whether ET impacts conflict control proficiency. Forty-one ET patients and 29 age-matched healthy controls (HCs) performed a conflict control task (Simon task). Participants were instructed to give a left or right response to a spatially lateralized arrow (direction of the arrow). When the action signaled by the spatial location and direction of the arrow were non-corresponding (induced conflict), the inappropriate action impulse required suppression. Overall, ET patients responded slower and less accurately compared to HCs. ET patients were especially less accurate on non-corresponding conflict (Nc) versus corresponding (Cs) trials. A focused analysis on fast impulsive response rates (based on the accuracy rate at the fastest reaction times on Nc trials) showed that ET patients made more fast errors compared to HCs. Results suggest impaired conflict control in ET compared to HCs. The increased impulsive errors seen in the ET population may be a symptom of deficiencies in the cerebello-thalamocortical networks, or, be caused by indirect effects on the cortico-striatal pathways. Future studies into the functional networks impacted by ET (cortico-striatal and cerebello-thalamocortical pathways) could advance our understanding of inhibitory control in general and the cognitive deficits in ET.