Encoding of speech in convolutional layers and the brain stem based on language experience

Comparing artificial neural networks (ANNs) with outputs of brain imaging techniques has recently seen substantial advances in (computer) vision and text-based language models. Here, we propose a framework to compare biological and artificial neural computations of spoken language representations and propose several new challenges to this paradigm. Using a technique proposed by Begus and Zhou (2021b), we can analyze encoding of any acoustic property in intermediate convolutional layers of an artificial neural network. This allows us to test similarities in speech encoding between the brain and artificial neural networks in a way that is more interpretable than the majority of existing proposals that focus on correlations and supervised models. We introduce fully unsupervised deep generative models (the Generative Adversarial Network architecture) trained on raw speech to the brain-and-ANN-comparison paradigm, which enable testing of both the production and perception principles in human speech. We present a framework that parallels electrophysiological experiments measuring complex Auditory Brainstem Response (cABR) in human brain with intermediate layers in deep convolutional networks. We compared peak latency in cABR relative to the stimulus in the brain stem experiment, and in intermediate convolutional layers relative to the input/output in deep convolutional networks. We also examined and compared the effect of prior language exposure on the peak latency in cABR, and in intermediate convolutional layers of a phonetic property. Specifically, the phonetic property (i.e., VOT =10 ms) is perceived differently by English vs. Spanish speakers as voiced (e.g. [ba]) vs voiceless (e.g. [pa]). Critically, the cABR peak latency to the VOT phonetic property is different between English and Spanish speakers, and peak latency in intermediate convolutional layers is different between English-trained and Spanish-trained computational models. Substantial similarities in peak latency encoding between the human brain and intermediate convolutional networks emerge based on results from eight trained networks (including a replication experiment). The proposed technique can be used to compare encoding between the human brain and intermediate convolutional layers for any acoustic property.

Listeriosis Outbreak in Sheep Raised in Feedlots in the Southern Region of Rio Grande do Sul State, Brazil

Background: A listeriosis outbreak in a sheep fattening feedlot in the Southern Region of Rio Grande do Sul State, Brazil is described. This disease is caused by Listeria monocytogenes and represents a risk to public health since it affects not only ruminants but also humans. This agent is widely spread in the environment, such as in the soil and water. It is also found in decaying vegetable matter and the feces and fluids of domestic animals. The aim of this study was to describe a listeriosis outbreak in sheep raised in feedlots, its epidemiology, and to establish the importance of this disease in this type of sheep management system, evaluate the possible sources of infection, and suggest ways to control it.Cases: Sheep were kept in a 2-sector shed, one with east solar orientation and the other with west solar orientation, the latter with free access to domestic birds. Sheep were fed silage and concentrate. Seven sheep were affected, 5 died and 2 recovered. Clinically, the sheep displayed loss of balance, excessive drooling, and tremors; one exhibited circling, head deviation, apathy, nystagmus, lateral recumbency, paddling, and labored breathing. At necropsy, macroscopic lesions were not found, and histologically several micro-abscesses and perivascular cuffs with lymphocytes, macrophages, and neutrophils were present in the brain stem. Listeria monocytogenes suspected colonies were observed in the microbiological culture, and the bacteria was identified by biochemical analysis. The immunohistochemistry test in brain stem sections was positive for the antibody BD DifcoTM Listeria O Antiserum Poly Serotypes 1 and 4.Discussion: A listeriosis outbreak in a feedlot sheep was confirmed through epidemiological findings, histological lesions, bacterial culture, and immunohistochemistry analysis. This infection is frequent in sheep fed silage of poor quality or other food with improper storage and lack of hygiene. In the present outbreak, the bacteria were isolated from silage. However, it is likely that domestic birds, which were raised in the same place and had free access to the west sector of the feedlot, were the initial source of infection, because the sheep from the opposite sector (east) did not get ill. The disease caused by environmental contamination or through contact with fluids and feces of ducks, chickens, cattle, and pigs has already been described in outbreaks that occurred in the central region of Rio Grande do Sul. Sheep aggregation in feedlot systems is also a favorable factor for the development of the bacteria and the occurrence of outbreaks because the accumulation of feces and urine cause humidity on the stalls. This allows outbreaks to occur in other seasons of the year, such as in the outbreak reported herein. The exchange of silage that served as food for sheep was another control measure, and new cases were not reported 8 months after these procedures were taken. In the outbreak studied, 2 sheep that exhibited clinical signs were treated with oxytetracycline and recovered. Some authors report that treatment for listeriosis is inefficient because neurological lesions are irreversible. Nonetheless, other studies have reported the recovery of some animals when they were treated with oxytetracycline or a combination of oxytetracycline and dexamethasone or ampicillin and gentamicin like in the outbreak described in this paper.Keywords: Listeria monocytogenes, central nervous system, silage, feedlot, ovine.

Complete functional recovery in a child after endovascular treatment of basilar artery occlusion caused by spontaneous dissection: a case report

Stroke caused by dissection of arteries of the vertebrobasilar system in children is still poorly investigated in terms of etiology, means of treatment, course of disease, and prognosis. The aim of this report was to describe the unusual course of a spontaneous dissection of the basilar artery (BA) in a child treated with endovascular techniques and to point out that the plasticity of the brain stem can fully compensate for structural damage caused by stroke. We report the case of a 15-year-old boy who suffered a wake-up stroke with BA occlusion caused by spontaneous dissection. A blood clot was aspirated from the false lumen and the true lumen re-opened, but the patient deteriorated a few hours later, and repeated angiography revealed that the intimal flap was detached, occluding the BA again. The lumen of BA was then reconstructed by a stent. Despite a large pons infarction, the patient was completely recovered 11 months after the onset. The case was analyzed with angiograms and magnetic resonance imaging, macroscopic and microscopic pathological analysis, computed tomographic angiography, magnetic resonance-based angiography, and diffusion tensor imaging. This case illustrates that applied endovascular techniques and intensive care measures can alter the course of potentially fatal brain stem infarction. Our multimodal analysis gives new insight into the anatomical basis for the plasticity mechanism of the brain stem.

Preventive treatment with CGRP monoclonal antibodies restores brain stem habituation deficits and excitability to painful stimuli in migraine: results from a prospective case-control study

Background & Objectives Calcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraine. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and might thus possess disease modifying potential. This study addresses this question by investigating the nociceptive blink reflex (nBR), which is closely tied to central disease activity, before and after treatment with CGRP antibodies. Methods We enrolled 22 patients suffering episodic migraine (21 female, 46.2 ± 13.8 years of age) and 22 age-/gender-matched controls. Patients received assessments of the nBR (R2 component, 10 trials, 6 stimuli/trial) before (V0) and three months (V3) after treatment with CGRP antibodies started, controls were assessed once. The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) of the stimulated/non-stimulated side (_s/_ns) following repeated supraorbital stimulation provide a direct readout of brainstem excitability and habituation as key mechanisms in migraine. Results All patients showed a substantial reduction of headache days/month (V0: 12.4±3.3, V3: 6.6 ± 4.9). R2a_s (Fglobal=5.86, p<0.001; block 1: R2a_s: -28%, p<0.001) and R2a_ns (Fglobal=8.22, p<0.001, block 1: R2a_ns: -22%, p=0.003) were significantly decreased, and R2h_ns was significantly enhanced (Fglobal=3.07, p<0.001; block 6: R2h_ns: r=-1.36, p=0.007) from V0 to V3. The global test for changes of R2h_s was non-significant (Fglobal=1.46, p=0.095). Changes of R2h significantly correlated with improvement of headache frequency (R2h_s, r=0.56, p=0.010; R2h_ns: r=0.45, p=0.045). None of the nBR parameters assessed at baseline predicted treatment response. Discussion We provide evidence that three months of treatment with CGRP antibodies restores brain stem responses to painful stimuli and thus might be considered disease modifying. The nociceptive blink reflex may provide a biomarker to monitor central disease activity. Future studies should evaluate the blink reflex as a clinical biomarker to predict treatment response at baseline and to establish the risk of relapse after treatment discontinuation. Trial registration This trial was prospectively registered at clinicaltrials.gov (ID: NCT04019496, date of registration: July 15, 2019).

Proton therapy for re-irradiation of pediatric diffuse brain stem tumors

Currently, there is no cure for pediatric diffuse brain stem (BS) tumors. Radiotherapy, including proton therapy, is an important component of combination treatment for this cancer, especially in children with a complicated medical history. The article addresses the issues of therapy for pediatric BS tumors and reports the use of proton re-irradiation in a 9-year-old boy with unverified diffuse BS tumor. Proton re-irradiation is an effective treatment option that can sustain and improve the quality of life and prolong survival in children with diffuse BS tumors.

Processing of fMRI-related anxiety and bi-directional information flow between prefrontal cortex and brain stem

Brain–heart synchronization is fundamental for emotional-well-being and brain–heart desynchronization is characteristic for anxiety disorders including specific phobias. Recording BOLD signals with functional magnetic resonance imaging (fMRI) is an important noninvasive diagnostic tool; however, 1–2% of fMRI examinations have to be aborted due to claustrophobia. In the present study, we investigated the information flow between regions of interest (ROI’s) in the cortex and brain stem by using a frequency band close to 0.1 Hz. Causal coupling between signals important in brain–heart interaction (cardiac intervals, respiration, and BOLD signals) was studied by means of Directed Transfer Function based on the Granger causality principle. Compared were initial resting states with elevated anxiety and final resting states with low or no anxiety in a group of fMRI-naïve young subjects. During initial high anxiety the results showed an increased information flow from the middle frontal gyrus (MFG) to the pre-central gyrus (PCG) and to the brainstem. There also was an increased flow from the brainstem to the PCG. While the top-down flow during increased anxiety was predominant, the weaker ascending flow from brainstem structures may characterize a rhythmic pacemaker-like activity that (at least in part) drives respiration. We assume that these changes in information flow reflect successful anxiety processing.