3D super-resolved in vitro multiphoton microscopy by saturation of excitation

We demonstrate a significant resolution enhancement beyond the conventional limit in multiphoton microscopy (MPM) using saturated excitation of fluorescence. Our technique achieves super-resolved imaging by temporally modulating the excitation laser-intensity and demodulating the higher harmonics from the saturated fluorescence signal. The improvement of the lateral and axial resolutions is measured on a sample of fluorescent microspheres. While the third harmonic already provides an enhanced resolution, we show that a further improvement can be obtained with an appropriate linear combination of the demodulated harmonics. Finally, we present in vitro imaging of fluorescent microspheres incorporated in HeLa cells to show that this technique performs well in biological samples

Altered neocortical tactile but preserved auditory early change detection responses in Friedreich ataxia

Available online 11 May 2019Objective: To study using magnetoencephalography (MEG) the spatio-temporal dynamics of neocortical responses involved in sensory processing and early change detection in Friedreich ataxia (FRDA). Methods: Tactile (TERs) and auditory (AERs) evoked responses, and early neocortical change detection responses indexed by the mismatch negativity (MMN) were recorded using tactile and auditory oddballs in sixteen FRDA patients and matched healthy subjects. Correlations between the maximal amplitude of each response, genotype and clinical parameters were investigated. Results: Evoked responses were detectable in all FRDA patients but one. In patients, TERs were delayed and reduced in amplitude, while AERs were only delayed. Only tactile MMN responses at the contralateral secondary somatosensory cortex were altered in FRDA patients. Maximal amplitudes of TERs, AERs and tactile MMN correlated with genotype, but did not correlate with clinical parameters. Conclusions: In FRDA, the amplitude of tactile MMN responses at SII cortex are reduced and correlate with the genotype, while auditory MMN responses are not altered. Significance: Somatosensory pathways and tactile early change detection are selectively impaired in FRDAThis study was financially supported by (i) the research grant ‘‘Les Voies du Savoir” from the Fonds Erasme (Brussels, Belgium) and (ii) the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium; research credit: J.0095.16.F). Gilles Naeije was supported by a research grant from the Fonds Erasme (Brussels, Belgium). Mathieu Bourguignon was supported by the program Attract of Innoviris (grant 2015-BB2B-10), by the Spanish Ministry of Economy and Competitiveness (grant PSI2016-77175-P), and by the Marie Skłodowska-Curie Action of the European Commission (grant 743562). Xavier De Tiège is Postdoctorate Clinical Master Specialist at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). The MEG project at the CUB Hôpital Erasme is financially supported by the Fonds Erasme (Research grant ‘‘Les Voies du Savoir”, Brussels, Belgium). The authors would like to thank Brice Marty for his help in MEG data acquisition

Feeding and Stocking Up: Radio-Labelled Food Reveals Exchange Patterns in Ants

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Cortical tracking of lexical speech units in a multi-talker background is immature in school-aged children

Available online 1 December 2022Children have more difficulty perceiving speech in noise than adults. Whether this difficulty relates to an immature processing of prosodic or linguistic elements of the attended speech is still unclear. To address the impact of noise on linguistic processing per se, we assessed how babble noise impacts the cortical tracking of intelligible speech devoid of prosody in school-aged children and adults. Twenty adults and twenty children (7-9 years) listened to synthesized French monosyllabic words presented at 2.5 Hz, either randomly or in 4-word hierarchical structures wherein 2 words formed a phrase at 1.25 Hz, and 2 phrases formed a sentence at 0.625 Hz, with or without babble noise. Neuromagnetic responses to words, phrases and sentences were identified and source-localized. Children and adults displayed significant cortical tracking of words in all conditions, and of phrases and sentences only when words formed meaningful sentences. In children compared with adults, the cortical tracking was lower for all linguistic units in conditions without noise. In the presence of noise, the cortical tracking was similarly reduced for sentence units in both groups, but remained stable for phrase units. Critically, when there was noise, adults increased the cortical tracking of monosyllabic words in the inferior frontal gyri and supratemporal auditory cortices but children did not. This study demonstrates that the difficulties of school-aged children in understanding speech in a multi-talker background might be partly due to an immature tracking of lexical but not supra-lexical linguistic units.Maxime Niesen and Marc Vander Ghinst were supported by the Fonds Erasme (Brussels, Belgium). Mathieu Bourguignon and Julie Ber- tels have been supported by the program Attract of Innoviris (grants 2015-BB2B-10 and 2019-BFB-110). Julie Bertels has been supported by a research grant from the Fonds de Soutien Marguerite-Marie Delacroix (Brussels, Belgium). Xavier De Tiège is Clinical Researcher at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). We warmly thank Mélina Houinsou Hans for her statistical support during the re- view process

Inaccurate cortical tracking of speech in adults with impaired speech perception in noise

Published:10 September 2021Impaired speech perception in noise despite normal peripheral auditory function is a common problem in young adults. Despite a growing body of research, the pathophysiology of this impairment remains unknown. This magnetoencephalography study characterizes the cortical tracking of speech in a multi-talker background in a group of highly selected adult subjects with impaired speech perception in noise without peripheral auditory dysfunction. Magnetoencephalographic signals were recorded from 13 subjects with impaired speech perception in noise (six females, mean age: 30 years) and matched healthy subjects while they were listening to 5 different recordings of stories merged with a multi-talker background at different signal to noise ratios (No Noise, þ10, þ5, 0 and 5dB). The cortical tracking of speech was quantified with coherence between magnetoencephalographic signals and the temporal envelope of (i) the global auditory scene (i.e. the attended speech stream and the multi-talker background noise), (ii) the attended speech stream only and (iii) the multi-talker background noise. Functional connectivity was then estimated between brain areas showing altered cortical tracking of speech in noise in subjects with impaired speech perception in noise and the rest of the brain. All participants demonstrated a selective cortical representation of the attended speech stream in noisy conditions, but subjects with impaired speech perception in noise displayed reduced cortical tracking of speech at the syllable rate (i.e. 4–8Hz) in all noisy conditions. Increased functional connectivity was observed in subjects with impaired speech perception in noise in Noiseless and speech in noise conditions between supratemporal auditory cortices and left-dominant brain areas involved in semantic and attention processes. The difficulty to understand speech in a multi-talker background in subjects with impaired speech perception in noise appears to be related to an inaccurate auditory cortex tracking of speech at the syllable rate. The increased functional connectivity between supratemporal auditory cortices and language/attention-related neocortical areas probably aims at supporting speech perception and subsequent recognition in adverse auditory scenes. Overall, this study argues for a central origin of impaired speech perception in noise in the absence of any peripheral auditory dysfunction.Marc Vander Ghinst, Gilles Naeije and Maxime Niesen were supported by a research grant from the Fonds Erasme (Brussels, Belgium). Mathieu Bourguignon was supported by the Program Attract of Innoviris (grant 2015-BB2B-10), Spanish Ministry of Economy and Competitiveness (grant PSI2016-77175-P) and Marie Skłodowska-Curie Action of the European Commission (grant 743562). Gilles Naeije and Xavier De Tie`ge are Post-doctorate Clinical Master Specialist at the Fonds de la Recherche Scientifique (FRS-FNRS, Brussels, Belgium). This study and the MEG project at the CUB Hoˆpital Erasme were financially supported by the Fonds Erasme (Research Convention ‘Les Voies du Savoir’, Fonds Erasme, Brussels, Belgium)

Synchrony, metastability, dynamic integration, and competition in the spontaneous functional connectivity of the human brain

Available online 3 June 2019.The human brain is functionally organized into large-scale neural networks that are dynamically interconnected. Multiple short-lived states of resting-state functional connectivity (rsFC) identified transiently synchronized networks and cross-network integration. However, little is known about the way brain couplings covary as rsFC states wax and wane. In this magnetoencephalography study, we explore the synchronization structure among the spontaneous interactions of well-known resting-state networks (RSNs). To do so, we extracted modes of dynamic coupling that reflect rsFC synchrony and analyzed their spatio-temporal features. These modes identified transient, sporadic rsFC changes characterized by the widespread integration of RSNs across the brain, most prominently in the β band. This is in line with the metastable rsFC state model of resting-state dynamics, wherein our modes fit as state transition processes. Furthermore, the default-mode network (DMN) stood out as being structured into competitive cross-network couplings with widespread DMN-RSN interactions, especially among the β-band modes. These results substantiate the theory that the DMN is a core network enabling dynamic global brain integration in the β band.This work was supported by the Action de Recherche Concert ee (ARC Consolidation 2015–2019, “Characterization of the electrophysiological bases, the temporal dynamics and the functional relevance of resting state network” attributed to X.D.T.) and by the research convention “Les Voies du Savoir” (Fonds Erasme, Brussels, Belgium). M.B. benefited from the program Attract of Innoviris (grant 2015-BB2B-10), the Spanish Ministry of Economy and Competitiveness (grant PSI2016-77175-P), and theMarie Skłodowska-Curie Action of the European Commission (grant 743562). M.V.G. and G.N.were supported by the Fonds Erasme. N.C. benefited from a research grant from the ARC Consolidation (2014–2017, “Characterization of the electrophysiological bases, the temporal dynamics and the functional relevance of resting state network” attributed to X.D.T.) and from the Fonds Erasme (research convention “Les Voies du Savoir”). X.D.T. is Post-doctorate Clinical Master Specialist at the Fonds de la Recherche Scientifique (F.R.S.-FNRS, Brussels, Belgium). The MEG project at the CUB – H^opital Erasme is financially supported by the Fonds Erasme (research convention “Les Voies du Savoir”)

Current Imaging Techniques for Lymph Node Staging in Prostate Cancer: A Review

Introduction: Lymph node metastases (LNM) represent a proven prognostic factor for biochemical recurrence (BCR)-free survival, metastatic free survival and overall survival in prostate cancer (PCa). Although pelvic node dissection remains the gold standard for the detection of LNM, novel imaging techniques are entering clinical practice, in the effort to improve LNM detection and spare unnecessary surgeries. Aim of the current review is to describe such imaging techniques and explore their advantages and limitations.Evidence Acquisition: The National Library of Medicine Database was searched for relevant articles published between January 2013 and August 2018. A wide search was performed including the combination of following words: “Prostate” and “Cancer” and “staging” and “Lymph Node” and “imaging” and (“MRI” or “PET”). The initial list of selected papers was enriched by individual suggestions of the authors of the present review.Evidence Synthesis: DWI-MRI in detection of lymph node invasion has a sensitivity and specificity of 41 and 94%, respectively. For SPIO MRI using ferumoxtran-10, the sensitivity for detection of LNM with short axis diameter of 5–10 mm is reported at 96.4%, compared to 28.5% with MRI alone. PSMA PET/CT is growing exponentially, both in the initial detection of LNM and for BCR evaluation. Fluciclovine PET could improve detection of subcentimetric pathologic lymph nodes. Sentinel lymph node techniques remain experimental and not validated in the field of PCa.Conclusions: Molecular imaging, particularly PSMA ligand PET imaging, present interesting diagnostic accuracy in LN diagnosis even in subcentimetric LN. DWI-MRI yields good results in LN involvement evaluation and the use of contrast agent such SPIO may improve the detection rate. The SLN technique is limited to experimental protocols and for intermediate or high-risk PCa. Prospective trials are awaited to evaluate the true clinical impact of these imaging techniques on PCa oncologic outcomes

A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells

There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines. At the protein level, DPP6 localizes only in beta and alpha cells within the pancreas. We next generated a high-affinity camelid single-domain antibody (nanobody) targeting human DPP6. The nanobody was radiolabelled and in vivo SPECT/CT imaging and biodistribution studies were performed in immunodeficient mice that were either transplanted with DPP6-expressing Kelly neuroblastoma cells or insulin-producing human EndoC-βH1 cells. The human DPP6-expressing cells were clearly visualized in both models. In conclusion, we have identified a novel beta and alpha cell biomarker and developed a tracer for in vivo imaging of human insulin secreting cells. This provides a useful tool to non-invasively follow up intramuscularly implanted insulin secreting cells

Brief Communication External globus pallidus stimulation modulates brain connectivity in Huntington's disease

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington's disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model