Brain Sci., Volume 7, Issue 5 (May 2017) – 10 articles

Neuronal migration is one of the pivotal steps to form a functional brain, and disorganization of this process is believed to underlie the pathology of psychiatric disorders including schizophrenia, autism spectrum disorders (ASD) and epilepsy. However, it is not clear how abnormal neuronal migration causes mental dysfunction. Recently, a key gene for various psychiatric diseases, the Autism susceptibility candidate 2 (AUTS2), has been shown to regulate neuronal migration, which gives new insight into understanding this question. Interestingly, the AUTS2 protein has dual functions: Cytoplasmic AUTS2 regulates actin cytoskeleton to control neuronal migration and neurite extension, while nuclear AUTS2 controls transcription of various genes as a component of the polycomb complex 1 (PRC1). In this review, we discuss AUTS2 from the viewpoint of human genetics, molecular function, brain development, and behavior in animal models, focusing on its role in neuronal migration. Full article

The migration of neuronal cells in the developing cerebral cortex is essential for proper development of the brain and brain networks. Disturbances in this process, due to genetic abnormalities or exogenous factors, leads to aberrant brain formation, brain network formation, and brain function. In the last decade, there has been extensive research in the field of neuronal migration. In this review, we describe different methods and approaches to assess and study neuronal migration in the developing cerebral cortex. First, we discuss several genetic methods, techniques and genetic models that have been used to study neuronal migration in the developing cortex. Second, we describe several molecular approaches to study aberrant neuronal migration in the cortex which can be used to elucidate the underlying mechanisms of neuronal migration. Finally, we describe model systems to investigate and assess the potential toxicity effect of prenatal exposure to environmental chemicals on proper brain formation and neuronal migration. Full article

In embodied theories on language, it is widely accepted that experience in acting generates an expectation of this action when hearing the word for it. However, how this expectation emerges during language acquisition is still not well understood. Assuming that the intermodal presentation of information facilitates perception, prior research had suggested that early in infancy, mothers perform their actions in temporal synchrony with language. Further research revealed that this synchrony is a form of multimodal responsive behavior related to the child’s later language development. Expanding on these findings, this article explores the relationship between action–language synchrony and the acquisition of verbs. Using qualitative and quantitative methods, we analyzed the coordination of verbs and action in mothers’ input to six-month-old infants and related these maternal strategies to the infants’ later production of verbs. We found that the verbs used by mothers in these early interactions were tightly coordinated with the ongoing action and very frequently responsive to infant actions. It is concluded that use of these multimodal strategies could significantly predict the number of spoken verbs in infants’ vocabulary at 24 months. Full article

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer’s disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration. Full article

Alzheimer’s disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a control group of 29 healthy elderly (HE) people. They all underwent a CT and AC in a counterbalanced order following a crossover design. Resting-state functional MRI and neuropsychological testing were acquired before and after each period. We tested post-CT and post-AC changes of cognitive abilities, of the functional connectivity of the DMN, and of topological network properties derived from graph theory and network-based statistics. Only CT produced functional changes, increasing the functional connectivity of the posterior DMN in all three groups. mAD also showed functional changes in the medial temporal lobe and topological changes in the anterior cingulum, whereas aMCI showed more widespread topological changes involving the frontal lobes, the cerebellum and the thalamus. Our results suggest specific functional connectivity changes after CT for aMCI and mAD. Full article

The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified. Full article

Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration. Full article

Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS). We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols. Our patient was a 22-year-old male suffering from severe and complex TS. Treatment with nabiximols was commenced at a dose of 1 puff/day (= 100 μL containing 2.7 mg THC and 2.5 mg cannabidiol (CBD)) and slowly increased up to a dosage of 3 × 3 puffs/day (= 24.3 mg THC and 22.5 mg CBD). Several clinical measures for tics, premonitory urges, and global impairment were acquired before and after two weeks of treatment. Treatment with nabiximols resulted in major improvements of both tics and premonitory urges, but also global impairment and health-related quality of life according to all used measurements without causing relevant adverse effects. Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS. Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting. Full article

Traumatic brain injury outcomes can be classified as acute or chronic. Acute outcomes refer to injuries that occur immediately at the time of the injury and subsequent short-term consequences. Chronic outcomes refer to adverse outcomes that are more long-term. In mild traumatic brain injury, recovery from acute outcomes typically occurs very rapidly, i.e., within 2 weeks, with full recovery expected by 90 days. However, some 10%–15% individuals can remain symptomatic for much longer with an outcome termed post-concussive syndrome. This outcome is difficult to predict since there are very few rigorous, prospective studies of this syndrome. Full article

Background: Social anxiety is highly prevalent among people with psychosis and linked with significant social disability and poorer prognosis. Although cognitive-behavioural therapy (CBT) has shown to be effective for the treatment of social anxiety in non-psychotic populations, there is a lack of evidence on the clinical effectiveness of CBT for the treatment of social anxiety when this is co-morbid in psychosis. Methods: A systematic review to summarise and critically appraise the literature on the effectiveness of CBT interventions for the treatment of social anxiety in psychosis. Results: Two studies were included in the review assessing the effectiveness of group CBT for social anxiety in schizophrenia, both of poor methodological quality. Preliminary findings suggest that group-based CBT is effective in treating symptoms of social anxiety, depression and associated distress in people with schizophrenia. Conclusion: The evidence-base is not robust enough to provide clear implications for practice about the effectiveness of CBT for the treatment of social anxiety in psychosis. Future research should focus on methodologically rigorous randomised controlled trials with embedded process evaluation to assess the effectiveness of CBT interventions in targeting symptoms of social anxiety in psychosis and identify mechanisms of change. Full article