Regeneration and Plasticity Induced by Epidural Stimulation in a Rodent Model of Spinal Cord Injury.

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin-eosin) and immunohistochemistry for NeuN, ß-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for ß-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in ß-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury.

Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence.

Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic-tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.

Electrophysiological predictors of hearing deterioration based on AEP monitoring during petroclival meningioma resection.

The objective of this study was to calculate the risk of postsurgical hearing deterioration as a function of changes in the amplitude and latency of the most stable components (waves III and V) of the auditory evoked potential (AEP) during petroclival meningioma resection surgery. We retrospectively analyzed intraoperative AEP monitoring results and pre- and postsurgical hearing status in 40 consecutive patients who were surgically treated for petroclival meningiomas. Statistical analyses were conducted to identify the most sensitive and specific way to predict hearing dysfunction after surgery. Patients' mean age was 59 ± 10 years, and 31 (77.5%) were women. Twelve (30%) patients presented with clinically detectable hearing impairment preoperatively. At the first postoperative assessment, four of those 12 patients reported subjective improvement, and eight reported hearing deterioration. Of those eight, four remained stable and four recovered hearing by the last assessment. Wave III latency reached its highest specificity (100%) and sensitivity (71.43%) at x = 143%. Wave V latency, on the other hand, reached its highest sensitivity (71%) and specificity (93%) at x = 124%. Finally, wave V amplitude reached its highest sensitivity (100%) and specificity (79%) at x = 74%. Intraoperative alterations of wave III latency and wave V amplitude seem to be highly sensitive and specific at predicting the risk of auditory dysfunction in patients undergoing petroclival meningioma resection and should be used to determine maximum resection with preservation of function.

A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration.

The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer's disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions' experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular gyrus and precuneus). Together, this study provides lesion-based evidence for the multidimensional nature of the emotional experiences of envy and Schadenfreude. Our results offer new insights into the mechanisms subsuming complex emotions and moral cognition in neurodegeneration. Moreover, this study presents the exacerbation of envy and Schadenfreude as a new potential hallmark of bvFTD that could impact in diagnosis and progression.

Voxel-Based Lesion Analysis of Ideomotor Apraxia.

Ideomotor apraxia is a cognitive disorder most often resulting from acquired brain lesions (i.e., strokes or tumors). Neuroimaging and lesion studies have implicated several brain regions in praxis and apraxia, but most studies have described (sub)acute patients. This study aimed to extend previous research by analyzing data from 115 left hemisphere chronic stroke patients using the praxis subtest of the Western Aphasia Battery, which is divided into four action types: facial, upper limb, complex, and instrumental. Lesion-symptom mapping was used to identify brain regions most critically associated with difficulties in each of the four subtests. Complex and instrumental action deficits were associated with left precentral, postcentral, and superior parietal gyri (Brodmann areas 2, 3, 4, 5, and 6), while the facial and upper limb action deficits maps were restricted to left inferior, middle, and medial temporal gyri (Brodmann areas 20, 21, 22, and 48). We discuss ideas about neuroplasticity and cortical reorganization in chronic stroke and how different methodologies can reveal different aspects of lesion and recovery networks in apraxia.

Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial.

Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p < 0.001, hazard ratio 0.53, 95%CI 0.36-0.78, p < 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p < 0.05, hazard ratio 0.18, 95%CI 0.05-0.62, p < 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4-78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.

What Does the General Public Know (or Not) About Neuroscience? Effects of Age, Region and Profession in Brazil.

The field of Neuroscience has experienced a growing interest in recent decades, which has led to an exponential growth in the amount of related information made available online as well as the market for Neuroscience-related courses. While this type of knowledge can be greatly beneficial to people working in science, health and education, it can also benefit individuals in other areas. For example, neuroscience knowledge can help people from all fields better understand and critique information about new discoveries or products, and even make better education- and health-related decisions. Online platforms are fertile ground for the creation and spread of fake information, including misrepresentations of scientific knowledge or new discoveries (e.g., neuromyths). These types of false information, once spread, can be difficult to tear down and may have widespread negative effects. For example, even scientists are less likely to access retractions of peer-reviewed articles than the original discredited articles. In this study we surveyed general knowledge about neuroscience and the brain among volunteers in Brazil, Latin America's largest country. We were interested in evaluating the prevalence of neuromyths in this region, and test whether knowledge/neuromyth endorsement differs by age, region, and/or profession. To that end, we created a 30-item survey that was anonymously answered online by 1128 individuals. While younger people (20-29-year-olds) generally responded more accurately than people 60 and older, people in the North responded significantly worse than those in the South and Southeast. Most interestingly, people in the biological sciences consistently responded best, but people in the health sciences responded no better than people in the exact sciences or humanities. Furthermore, years of schooling did not correlate with performance, suggesting that quantity may surpass quality when it comes to extension or graduate-level course offerings. We discuss how our findings can help guide efforts toward improving access to quality information and training in the region.

On the representation of hierarchical structure: Revisiting Darwin's musical protolanguage.

In this article, we address the tenability of Darwin's musical protolanguage, arguing that a more compelling evolutionary scenario is one where a prosodic protolanguage is taken to be the preliminary step to represent the hierarchy involved in linguistic structures within a linear auditory signal. We hypothesize that the establishment of a prosodic protolanguage results from an enhancement of a rhythmic system that transformed linear signals into speech prosody, which in turn can mark syntactic hierarchical relations. To develop this claim, we explore the role of prosodic cues on the parsing of syntactic structures, as well as neuroscientific evidence connecting the evolutionary development of music and linguistic capacities. Finally, we entertain the assumption that the capacity to generate hierarchical structure might have developed as part of tool-making in human prehistory, and hence was established prior to the enhancement of a prosodic protolinguistic system.

Neuroscience Knowledge and Endorsement of Neuromyths among Educators: What Is the Scenario in Brazil?

The field of neuroscience has seen significant growth and interest in recent decades. While neuroscience knowledge can benefit laypeople as well as professionals in many different areas, it may be particularly relevant for educators. With the right information, educators can apply neuroscience-based teaching strategies as well as protect themselves and their students against pseudoscientific ideas and products based on them. Despite rapidly growing sources of available information and courses, studies show that educators in many countries have poor knowledge of brain science and tend to endorse education-related neuromyths. Poor English skills and fewer resources (personal, institutional and governmental) may be additional limitations in Latin America. In order to better understand the scenario in Latin America's largest country, we created an anonymous online survey which was answered by 1634 individuals working in education from all five regions of Brazil. Respondents stated whether they agreed with each statement and reported their level of confidence for each answer. Significant differences in performance were observed across regions, between educators living in capital cities versus the outskirts, between those teaching in private versus public schools, and among educators teaching different levels (pre-school up to college/university). We also observed high endorsement of some key neuromyths, even among groups who performed better overall. To the best of our knowledge, this is the first study to conduct a detailed analysis of the profile of a large group of educators in Brazil. We discuss our findings in terms of efforts to better understand regional and global limitations and develop methods of addressing these most efficiently.

Neuroscience Outside the Box: From the Laboratory to Discussing Drug Abuse at Schools.

One of the effects of the current COVID-19 pandemic is that low-income countries were pushed further into extreme poverty, exacerbating social inequalities and increasing susceptibility to drug use/abuse in people of all ages. The risks of drug abuse may not be fully understood by all members of society, partly because of the taboo nature of the subject, and partly because of the considerable gap between scientific production/understanding and communication of such knowledge to the public at large. Drug use is a major challenge to social development and a leading cause of school dropout rates worldwide. Some public policies adopted in several countries in recent decades failed to prevent drug use, especially because they focused on imposing combative or coercive measures, investing little or nothing in education and prevention. Here we highlight the role of neuroscience education as a valid approach in drug use education and prevention. We propose building a bridge between schools and scientists by promoting information, student engagement and honest dialogue, and show evidence that public policy regulators should be persuaded to support such science-based education programs in their efforts to effect important positive changes in society.

Assessment of Conjunctive Binding in Aging: A Promising Approach for Alzheimer's Disease Detection.

The visual experience of objects lies in the ability to perceive and integrate their constitutive features. Conjunctive binding (CB) is the cognitive function that integrates the features of objects as wholes. This review covers the main findings (over the last 10 years) concerning the role of CB in visual working memory (VWM) and cognitive theory, its neural correlates, as well as perspectives for future work. First, we discuss the theoretical cognitive models of CB and how these relate to other cognitive functions. We then integrate neuroimaging evidence with cognitive theory to identify the neural functional network of CB for encoding and maintenance. Also, we describe the field's transition from experimental to clinical research, which paves the way for work in the area of VWM binding and aging. Finally, we expose the challenges faced by this field of research and analyze its role in the study of dementia and the construction of neuro-cognitive models of conjunctive binding.

Timed action and object naming.

Factors affecting object and action naming were compared in a timed picture-naming paradigm, for drawings of 520 objects and 275 actions, named by adult native speakers of English. Massive differences between object and action naming were observed for all dependent variables, and theoretically relevant differences emerged in the variables that predict retrieval of nouns vs. verbs in this task. Matching object and action items for variables like frequency, age of acquisition, or picture complexity does not result in a match for measures of naming difficulty (name agreement or latency). Conversely, object and action items matched for naming difficulty invariably differ in their other lexical and pictorial properties. A reaction time disadvantage for action naming remains even after controlling for picture properties, target word properties, name agreement itself (reflecting the differential ambiguity of nouns and verbs) as well as a measure of conceptual or psychological complexity based on the number of relevant objects in the scene. Surprisingly, frequency effects run in opposite directions for nouns (higher frequencies yield faster RTs) and verbs (higher frequencies are associated with slower RTs, reflecting a "light verb" strategy that speakers use for difficult items). Implications for method and theory in the study of lexical access are discussed, including relevance to a growing literature on the neurobiology and development of nouns and verbs.

Grey and white matter correlates of picture naming: evidence from a voxel-based lesion analysis of the Boston Naming Test.

A number of recent studies utilizing both functional neuroimaging and lesion analysis techniques in neurologic patients have produced conflicting results with respect to the neural correlates of picture naming. Picture naming involves a number of cognitive processes, from visual perception/recognition to lexical-semantic retrieval to articulation. This middle process, the ability to retrieve a name associated with an object, has been attributed in some cases to posterior portions of the left lateral temporal lobe and in other cases, to anterior temporal cortex. In the current study, we used voxel-based lesion symptom mapping (VLSM) to identify neural correlates of picture naming in a large sample of well-characterized left hemisphere (LH) patients suffering from a range of naming deficits. We tested patients on the Boston Naming Test (BNT), a clinical, standardized measure of picture naming that is widely used in both clinical and research settings. We found that overall performance on the BNT was associated with a network of LH regions that included significant portions of the left anterior to posterior middle temporal gyrus (MTG) and superior temporal gyrus (STG) and underlying white matter, and extended into left inferior parietal cortex. However, when we added covariates to this analysis that controlled for deficits in visual recognition and motor speech in order to isolate brain regions specific to lexical-semantic retrieval, the significant regions that remained were confined almost exclusively to the left mid-posterior MTG and underlying white matter. These findings support the notion that a large network in left peri-Sylvian cortex supports picture naming, but that the left mid-posterior MTG and underlying white matter play a critical role in the core ability to retrieve a name associated with an object or picture.

Action-verb processing in Parkinson's disease: new pathways for motor-language coupling.

Recent studies suggest that action-verb processing is particularly affected in early stage Parkinson's disease (PD), highlighting the potential role of subcortical areas in language processing and in the semantic integration of actions. However, this disorder-related language impairment is frequently unrecognized by clinicians and often remains untreated. Early detection of action-language processing deficits could be critical for diagnosing and developing treatment strategies for PD. In this article, we review how action-verb processing is affected in PD and propose a model in which multiple and parallel frontotemporal circuits between the cortex and the basal ganglia provide the anatomic substrate for supporting action-language processing. We hypothesize that contextual coupling of action-language networks are partially dependent on cortical-subcortical integration, and not only on somatotopic motor cortical organization or in a mirror neuron system. This hypothesis is supported by both experimental and clinical evidence. Then, we identify further research steps that would help to determine the reliability of action-language impairments as an early marker of PD. Finally, theoretical implications for clinical assessment and for models of action-language interaction (action-perception cycle theories, mirror system models of language, and embodied cognition approaches to language) are discussed.

What do brain lesions tell us about theories of embodied semantics and the human mirror neuron system?

Recent work has been mixed with respect to the notion of embodied semantics, which suggests that processing linguistic stimuli referring to motor-related concepts recruits the same sensorimotor regions of cortex involved in the execution and observation of motor acts or the objects associated with those acts. In this study, we asked whether lesions to key sensorimotor regions would preferentially impact the comprehension of stimuli associated with the use of the hand, mouth or foot. Twenty-seven patients with left-hemisphere strokes and 10 age- and education-matched controls were presented with pictures and words representing objects and actions typically associated with the use of the hand, mouth, foot or no body part at all (i.e., neutral). Picture/sound pairs were presented simultaneously, and participants were required to press a space bar only when the item pairs matched (i.e., congruent trials). We conducted two different analyses: 1) we compared task performance of patients with and without lesions in several key areas previously implicated in the putative human mirror neuron system (i.e., Brodmann areas 4/6, 1/2/3, 21 and 44/45), and 2) we conducted Voxel-based Lesion-Symptom Mapping analyses (VLSM; Bates et al., 2003) to identify additional regions associated with the processing of effector-related versus neutral stimuli. Processing of effector-related stimuli was associated with several regions across the left hemisphere, and not solely with premotor/motor or somatosensory regions. We also did not find support for a somatotopically-organized distribution of effector-specific regions. We suggest that, rather than following the strict interpretation of homuncular somatotopy for embodied semantics, these findings support theories proposing the presence of a greater motor-language network which is associated with, but not restricted to, the network responsible for action execution and observation.

Action and object processing in brain-injured speakers of Chinese.

OBJECTIVE: To see whether action and object processing across different tasks and modalities differs in brain-injured speakers of Chinese with varying fluency and lesion locations within the left hemisphere. METHOD: Words and pictures representing actions and objects were presented to a group of 33 participants whose native and/or dominant language was Mandarin Chinese: 23 patients with left-hemisphere lesions due to stroke and 10 language-, age- and education-matched healthy control participants. A set of 120 stimulus items was presented to each participant in three different forms: as black and white line drawings (for picture-naming), as written words (for reading) and as aurally presented words (for word repetition). Patients were divided into groups for two separate analyses: Analysis 1 divided and compared patients based on fluency (Fluent vs. Nonfluent) and Analysis 2 compared patients based on lesion location (Anterior vs. Posterior). RESULTS: Both analyses yielded similar results: Fluent, Nonfluent, Anterior, and Posterior patients all produced significantly more errors when processing action (M = 0.73, SD = 0.45) relative to object (M = 0.79, SD = 0.41) stimuli, and this effect was strongest in the picture-naming task. CONCLUSIONS: As in our previous study with English-speaking participants using the same experimental design (Arévalo et al., 2007, Arévalo, Moineau, Saygin, Ludy, & Bates, 2005), we did not find evidence for a double-dissociation in action and object processing between groups with different lesion and fluency profiles. These combined data bring us closer to a more informed view of action/object processing in the brain in both healthy and brain-injured individuals.

The impact of semantic reference on word class: an fMRI study of action and object naming.

There is a considerable body of neuropsychological and neuroimaging evidence supporting the distinction between the brain correlates of noun and verb processing. It is however still not clear whether the observed differences are imputable to grammatical or semantic factors. Beyond the basic difference that verbs typically refer to actions and nouns typically refer to objects, other semantic distinctions might play a role as organizing principles within and across word classes. One possible candidate is the notion of manipulation and manipulability, which may modulate the word class dissociation. We used functional magnetic resonance imaging (fMRI) to study the impact of semantic reference and word class on brain activity during a picture naming task. Participants named pictures of objects and actions that did or did not involve manipulation. We observed extensive differences in activation associated with the manipulation dimension. In the case of manipulable items, for both nouns and verbs, there were significant activations within a fronto-parietal system subserving hand action representation. However, we found no significant effect of word class when all verbs were compared to all nouns. These results highlight the impact of the biologically crucial sensorimotor dimension of manipulability on the pattern of brain activity associated to picture naming.