Brain Sciences — Open Access Journal

Prosodic cues in speech are indispensable for comprehending a speaker’s message, recognizing emphasis and emotion, parsing segmental units, and disambiguating syntactic structures. While it is commonly accepted that prosody provides a fundamental service to higher-level features of speech, the neural underpinnings of prosody processing are not clearly defined in the cognitive neuroscience literature. Many recent electrophysiological studies have examined speech comprehension by measuring neural entrainment to the speech amplitude envelope, using a variety of methods including phase-locking algorithms and stimulus reconstruction. Here we review recent evidence for neural tracking of the speech envelope and demonstrate the importance of prosodic contributions to the neural tracking of speech. Prosodic cues may offer a foundation for supporting neural synchronization to the speech envelope, which scaffolds linguistic processing. We argue that prosody has an inherent role in speech perception, and future research should fill the gap in our knowledge of how prosody contributes to speech envelope entrainment. Full article

The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. M1 is identified by C3 and C4 of the 10/20 EEG system yet the reliability of 10/20 EEG measurements by novice research raters is unknown. We investigated the reliability of the 10/20 EEG measurements for C3 and C4 in 25 adult participants. Two novice raters were assessed for inter-rater reliability. Both raters received two hours of instruction from a registered neurodiagnostic technician. One of the raters completed the measurements across two testing days for intra-rater reliability. Relative reliability was determined using the intraclass coefficient (ICC) and absolute reliability. We observed a low to fair inter and intra-rater ICC for motor cortex measurements. The absolute reliability was <1.0 cm by different novice raters and on different days. Although a low error was observed, consideration of the integrity of the targeted region of the brain is critical when designing tDCS interventions in clinical populations who may have compromised brain structure, due to a lesion or altered anatomy. Full article

Abnormal sensory-based behaviors are a defining feature of autism spectrum disorders (ASD). Dr. A. Jean Ayres was the first occupational therapist to conceptualize Sensory Integration (SI) theories and therapies to address these deficits. Her work was based on neurological knowledge of the 1970’s. Since then, advancements in neuroimaging techniques make it possible to better understand the brain areas that may underlie sensory processing deficits in ASD. In this article, we explore the postulates proposed by Ayres (i.e., registration, modulation, motivation) through current neuroimaging literature. To this end, we review the neural underpinnings of sensory processing and integration in ASD by examining the literature on neurophysiological responses to sensory stimuli in individuals with ASD as well as structural and network organization using a variety of neuroimaging techniques. Many aspects of Ayres’ hypotheses about the nature of the disorder were found to be highly consistent with current literature on sensory processing in children with ASD but there are some discrepancies across various methodological techniques and ASD development. With additional characterization, neurophysiological profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions, such as SI therapy. Full article

Uncovering brain-behavior mechanisms is the ultimate goal of neuroscience. A formidable amount of discoveries has been made in the past 50 years, but the very essence of brain-behavior mechanisms still escapes us. The recent exploitation of machine learning (ML) tools in neuroscience opens new avenues for illuminating these mechanisms. A key advantage of ML is to enable the treatment of large data, combing highly complex processes. This essay provides a glimpse of how ML tools could test a heuristic neural systems model of motivated behavior, the triadic neural systems model, which was designed to understand behavioral transitions in adolescence. This essay previews analytic strategies, using fictitious examples, to demonstrate the potential power of ML to decrypt the neural networks of motivated behavior, generically and across development. Of note, our intent is not to provide a tutorial for these analyses nor a pipeline. The ultimate objective is to relate, as simply as possible, how complex neuroscience constructs can benefit from ML methods for validation and further discovery. By extension, the present work provides a guide that can serve to query the mechanisms underlying the contributions of prefrontal circuits to emotion regulation. The target audience concerns mainly clinical neuroscientists. As a caveat, this broad approach leaves gaps, for which references to comprehensive publications are provided. Full article

The pattern of gait after hip arthroplasty strongly affects regeneration and quality of life. Acoustic feedback could be a supportive method for patients to improve their walking ability and to regain a symmetric and steady gait. In this study, a new gait sonification method with two different modes—real-time feedback (RTF) and instructive model sequences (IMS)—is presented. The impact of the method on gait symmetry and steadiness of 20 hip arthroplasty patients was investigated. Patients were either assigned to a sonification group (SG) (n = 10) or a control group (CG) (n = 10). All of them performed 10 gait training sessions (TS) lasting 20 min, in which kinematic data were measured using an inertial sensor system. Results demonstrate converging step lengths of the affected and unaffected leg over time in SG compared with a nearly parallel development of both legs in CG. Within the SG, a higher variability of stride length and stride time was found during the RTF training mode in comparison to the IMS mode. Therefore, the presented dual mode method provides the potential to support gait rehabilitation as well as home-based gait training of orthopedic patients with various restrictions. Full article

Anxiety disorders that develop in adolescence represent a significant burden and are particularly challenging to treat, due in no small part to the high occurrence of relapse in this age group following exposure therapy. This pattern of persistent fear is preserved across species; relative to those younger and older, adolescents consistently show poorer extinction, a key process underpinning exposure therapy. This suggests that the neural processes underlying fear extinction are temporarily but profoundly compromised during adolescence. The formation, retrieval, and modification of fear- and extinction-associated memories are regulated by a forebrain network consisting of the prefrontal cortex (PFC), the amygdala, and the hippocampus. These regions undergo robust maturational changes in early life, with unique alterations in structure and function occurring throughout adolescence. In this review, we focus primarily on two of these regions—the PFC and the amygdala—and discuss how changes in plasticity, synaptic transmission, inhibition/excitation, and connectivity (including modulation by hippocampal afferents to the PFC) may contribute to transient deficits in extinction retention. We end with a brief consideration of how exposure to stress during this adolescent window of vulnerability can permanently disrupt neurodevelopment, leading to lasting impairments in pathways of emotional regulation. Full article

Our discovery of low-threshold stimulation-induced locomotion in the pedunculopontine nucleus (PPN) led to the clinical use of deep brain stimulation (DBS) for the treatment of disorders such as Parkinson’s disease (PD) that manifest gait and postural disorders. Three additional major discoveries on the properties of PPN neurons have opened new areas of research for the treatment of motor and arousal disorders. The description of (a) electrical coupling, (b) intrinsic gamma oscillations, and (c) gene regulation in the PPN has identified a number of novel therapeutic targets and methods for the treatment of a number of neurological and psychiatric disorders. We first delve into the circuit, cellular, intracellular, and molecular organization of the PPN, and then consider the clinical results to date on PPN DBS. This comprehensive review will provide valuable information to explain the network effects of PPN DBS, point to new directions for treatment, and highlight a number of issues related to PPN DBS. Full article

Prior work showed differential alterations in early somatosensory evoked potentials (SEPs) and improved motor learning while in acute tonic pain. The aim of the current study was to determine the interactive effect of acute tonic pain and early motor learning on corticospinal excitability as measured by transcranial magnetic stimulation (TMS). Two groups of twelve participants (n = 24) were randomly assigned to a control (inert lotion) or capsaicin (capsaicin cream) group. TMS input–output (IO) curves were performed at baseline, post-application, and following motor learning acquisition. Following the application of the creams, participants in both groups completed a motor tracing task (pre-test and an acquisition test) followed by a retention test (completed without capsaicin) within 24–48 h. Following an acquisition phase, there was a significant increase in the slope of the TMS IO curves for the control group (p < 0.05), and no significant change for the capsaicin group (p = 0.57). Both groups improved in accuracy following an acquisition phase (p < 0.001). The capsaicin group outperformed the control group at pre-test (p < 0.005), following an acquisition phase (p < 0.005), and following a retention test (p < 0.005). When data was normalized to the pre-test values, the learning effects were similar for both groups post-acquisition and at retention (p < 0.005), with no interactive effect of group. The acute tonic pain in this study was shown to negate the increase in IO slope observed for the control group despite the fact that motor performance improved similarly to the control group following acquisition and retention. This study highlights the need to better understand the implications of neural changes accompanying early motor learning, particularly while in pain. Full article

Chronic smoking has been shown to have deleterious effects on brain function and is an important risk factor for ischemic stroke. Reduced cortical excitability has been shown among chronic smokers compared with non-smokers to have a long-term effect and so far no study has assessed the effect of smoking on short-term motor learning. Paired associative stimulation (PAS) is a commonly used method for inducing changes in excitability of the motor cortex (M1) in a way that simulates short-term motor learning. This study employed PAS to investigate the effect of chronic cigarette smoking on plasticity of M1. Stimulator output required to elicit a motor-evoked potential (MEP) of approximately 1 mV was similar between the groups prior to PAS. MEP response to single pulse stimuli increased in the control group and remained above baseline level for at least 30 min after the intervention, but not in the smokers who showed no significant increase in MEP size. The silent period was similar between groups at all time points of the experiment. This study suggests that chronic smoking may have a negative effect on the response to PAS and infers that chronic smoking may have a deleterious effect on the adaptability of M1. Full article

In a recent opinion article, we explained why we think that defining developmental dyslexia as a neurodevelopmental disorder and neuroimaging studies on dyslexia are useful. A recent response has made some claims of generalized misinterpretation and misconception in the field. Since that was a direct reply to our article, we would like to clarify our opinion on some of those claims. Full article

Objective: The aim of this paper is to describe the progressive changes of chronic cluster headaches (CHs) in a patient who is being treated by a multimodal approach, using pharmacology, neurostimulation and physiotherapy. Subject: A male patient, 42 years of age was diagnosed with left-sided refractory chronic CH by a neurologist in November 2009. In June 2014, the patient underwent a surgical intervention in which a bilateral occipital nerve neurostimulator was implanted as a treatment for headache. Methods: Case report. Results: Primary findings included a decreased frequency of CH which lasted up to 2 months and sometimes even without pain. Besides this, there were decreased levels of anxiety, helplessness (PCS subscale) and a decreased impact of headache (HIT-6 scale). Bilateral pressure pain thresholds (PPTs) were improved along with an increase in strength and motor control of the neck muscles. These improvements were present at the conclusion of the treatment and maintained up to 4 months after the treatment. Conclusions: A multimodal approach, including pharmacology, neurostimulation and physiotherapy may be beneficial for patients with chronic CHs. Further studies such as case series and clinical trials are needed to confirm these results. Full article

The most conserved molecular phenotype of Fragile X Syndrome (FXS) is aberrant protein synthesis. This has been validated in a variety of experimental model systems from zebrafish to rats, patient-derived lymphoblasts and fibroblasts. With the advent of personalized medicine paradigms, patient-derived cells and their derivatives are gaining more translational importance, not only to model disease in a dish, but also for biomarker discovery. Here we review past and current practices of measuring protein synthesis in FXS, studies in patient derived cells and the inherent challenges in measuring protein synthesis in them to offer usable avenues of modeling this important metabolic metric for further biomarker development. Full article

In this study we explored metaphor and idiom competencies in two clinical populations, children with autistic spectrum disorder (ASD) and children with Klinefelter syndrome (KS), (age range: 9–12), compared to typically developing (TD) children of the same age. These three groups were tested with two multiple-choice tests assessing idiom comprehension through iconic and verbal alternatives and a metaphor comprehension test composed of novel, physical-psychological metaphors, requesting verbal explanations. To these instruments, another test was added, assessing basic sentence comprehension. Performances on the different linguistic tasks were examined by means of discriminant analysis which showed that idiom comprehension had a very small weight in distinguishing children with ASD from TD controls, whereas metaphor explanation did distinguish them. This study suggests that figurative language comprehension is not a “core deficit” per se in individuals with ASD. Only when the task requires to explicitly construct and explain a semantic mapping between the two terms of a metaphor does the performance of children with ASD significantly deviate from the typical population. These results are interpreted in terms of a difficulty in children with ASD and KS with complex cognitive and linguistic processes and also in relation with clinical assessment. Full article

Type 2 diabetes is associated with diabetic cognopathy. Anti-hyperglycemic sodium glucose transporter 2 (SGLT2) inhibitors have shown promise in reducing cognitive impairment in mice with type 2 diabetes mellitus. We recently described marked ultrastructural (US) remodeling of the neurovascular unit (NVU) in type 2 diabetic db/db female mice. Herein, we tested whether the SGLT-2 inhibitor, empagliflozin (EMPA), protects the NVU from abnormal remodeling in cortical gray and subcortical white matter. Ten-week-old female wild-type and db/db mice were divided into lean controls (CKC, n = 3), untreated db/db (DBC, n = 3), and EMPA-treated db/db (DBE, n = 3). Empagliflozin was added to mouse chow to deliver 10 mg kg⁻¹ day⁻¹ and fed for ten weeks, initiated at 10 weeks of age. Brains from 20-week-old mice were immediately immersion fixed for transmission electron microscopic study. Compared to CKC, DBC exhibited US abnormalities characterized by mural endothelial cell tight and adherens junction attenuation and/or loss, pericyte attenuation and/or loss, basement membrane thickening, glia astrocyte activation with detachment and retraction from mural cells, microglia cell activation with aberrant mitochondria, and oligodendrocyte–myelin splitting, disarray, and axonal collapse. We conclude that these abnormalities in the NVU were prevented in DBE. Empagliflozin may provide neuroprotection in the diabetic brain. Full article

Alcohol use disorder is a devastating disease with a complex etiology. Recent preclinical studies have revealed that paternal preconception chronic intermittent ethanol (EtOH) exposure via vaporized EtOH altered drinking behaviors and sensitivity to EtOH selectively in male offspring. In the current study, we used a voluntary oral route of paternal preconception EtOH exposure, i.e., intermittent every-other-day two-bottle choice drinking, and tested offspring for behavioral alterations. Fifteen EtOH drinking sires and 10 control sires were mated to EtOH naïve females to produce EtOH-sired and control-sired offspring. These offspring were tested using the elevated plus maze, open field, drinking in the dark, and unlimited access two-bottle choice assays. We found that paternal preconception every-other-day two-bottle choice drinking resulted in reduced EtOH consumption selectively in male offspring in the drinking in the dark assay compared to control-sired offspring. No differences were detected in either sex in the unlimited access two-bottle choice and elevated plus maze assays. Open field analysis revealed complex changes in basal behavior and EtOH-induced behaviors that were sex specific. We concluded that paternal preconception voluntary EtOH consumption has persistent effects that impact the next generation. This study adds to a growing appreciation that one’s behavioral response to EtOH and EtOH drinking behavior are impacted by EtOH exposure of the prior generation. Full article

A 48-year-old male, who suffered from a stroke resulting in cerebellum damage and occlusion of the left vertebral artery, underwent stromal vascular fraction therapy. The clinical status of the patient was monitored by a modified Stroke Specific Quality of Life Scale before therapy and at 3, 9, 12, 18, 24, and 32 months after therapy. Three months after therapy, the patient felt a reduction in pain, vertigo, and fatigue. After 9 months, he was able to walk safely on his own. After 24 months, he was able to ride a bicycle. After 32 months, he felt completely healthy without any limitations or handicaps. Therefore, intravenous application of stromal vascular fraction cells represents a promising strategy for the treatment of patients after a stroke. Full article

Massage therapy is widely used as a complementary therapy in the elderly. Here, we investigate the effect of hand and foot massage therapy on psychological factors and electroencephalographic (EEG) activity in elderly people requiring long-term care. We included 12 elderly people requiring long-term care, who were randomly divided into two groups (A and B). Group A received hand massage and group B received foot massage, both for 15 min each. After 1 week, group A received foot massage and group B received hand massage, both for 15 min each. We assessed emotions and mood states with a Likert scale after each massage and resting-state EEG activity was measured before and after each massage. Our results showed that both hand and foot massage led to a high degree of pleasant, relaxed, and refreshed feelings. Moreover, resting-state alpha activity significantly increased in the left insular cortex after hand massage (p < 0.05), and in the right and left posterior cingulate cortex after foot massage (p < 0.05). This study suggests that hand and foot massage therapy modulate psychological factors and EEG activity in elderly people requiring long-term care. Full article

This paper explores the importance of preconceptual meaning in speech and music, stressing the role of affective vocalizations as a common ancestral instrument in communicative interactions. Speech and music are sensory rich stimuli, both at the level of production and perception, which involve different body channels, mainly the face and the voice. However, this bimodal approach has been challenged as being too restrictive. A broader conception argues for an action-oriented embodied approach that stresses the reciprocity between multisensory processing and articulatory-motor routines. There is, however, a distinction between language and music, with the latter being largely unable to function referentially. Contrary to the centrifugal tendency of language to direct the attention of the receiver away from the text or speech proper, music is centripetal in directing the listener’s attention to the auditory material itself. Sound, therefore, can be considered as the meeting point between speech and music and the question can be raised as to the shared components between the interpretation of sound in the domain of speech and music. In order to answer these questions, this paper elaborates on the following topics: (i) The relationship between speech and music with a special focus on early vocalizations in humans and non-human primates; (ii) the transition from sound to meaning in speech and music; (iii) the role of emotion and affect in early sound processing; (iv) vocalizations and nonverbal affect burst in communicative sound comprehension; and (v) the acoustic features of affective sound with a special emphasis on temporal and spectrographic cues as parts of speech prosody and musical expressiveness. Full article

The fragile X-related disorders (FXDs) are a group of clinical conditions that result primarily from an unusual mutation, the expansion of a CGG-repeat tract in exon 1 of the FMR1 gene. Mouse models are proving useful for understanding many aspects of disease pathology in these disorders. There is also reason to think that such models may be useful for understanding the molecular basis of the unusual mutation responsible for these disorders. This review will discuss what has been learnt to date about mechanisms of repeat instability from a knock-in FXD mouse model and what the implications of these findings may be for humans carrying expansion-prone FMR1 alleles. Full article