Biology subjects

Mazzetti, C.

Publications and source records attributed to Mazzetti, C..

5 recordsLinked to original sources

bioRxiv2023

Modulation of alpha oscillations by attention is predicted by hemispheric asymmetries of subcortical regions.

Evidence suggests that subcortical structures play a role in high-level cognitive functions such as the allocation of spatial attention. While there is abundant evidence in humans for posterior alpha band oscillations being modulated by spatial attention, little is known about how subcortical regions contribute to these oscillatory modulations, particularly under varying conditions of cognitive challenge. In this study, we combined MEG and structural MRI data to investigate the role of subcortical structures in controlling the allocation of attentional resources by employing a cued spatial attention paradigm with varying levels of perceptual load. We asked whether hemispheric lateralization of volumetric measures of the thalamus and basal ganglia predicted the hemispheric modulation of alpha-band power. Lateral asymmetry of the globus pallidus, caudate nucleus, and thalamus predicted attention-related modulations of posterior alpha oscillations. When the perceptual load was applied to the target and the distractor was salient caudate nucleus asymmetry predicted alpha-band modulations. Globus Pallidus was predictive of alpha-band modulations when either the target had a high load, or the distractor was salient, but not both. Finally, the asymmetry of the thalamus predicted alpha band modulation when neither component of the task was perceptually demanding. In addition to delivering new insight into the subcortical circuity controlling alpha oscillations with spatial attention, our finding might also have clinical applications. We provide a framework that could be followed for detecting how structural changes in subcortical regions that are associated with neurological disorders can be reflected in the modulation of oscillatory brain activity.

neuroscience↗

bioRxiv2020

Dorsal to ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate's effect on beta oscillations in ADHD

BackgroundWhile pharmacological treatment with Methylphenidate (MPH) is a first line intervention for ADHD, its mechanisms of action have yet to be elucidated. In a previous MEG study, we demonstrated that MPH in ADHD normalizes beta depression in preparation to motor responses (1). We here seek to identify the white matter tracts that mediate MPHs effect on beta oscillations. MethodsWe implemented a double-blind placebo-controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off MPH. Results were compared with an age/IQ-matched typically developing (TD) group performing the same task. Estimates of white matter tracts were obtained through diffusion tensor imaging (DTI). Based on aprioristic selection model criteria, we sought to determine the fiber tracts associated with electrophysiological, behavioral and clinical features of attentional functions. ResultsWe identified three main tracts: the anterior thalamic radiation (ATR), the Superior Longitudinal Fasciculus ( parietal endings) (SLFp) and Superior Longitudinal Fasciculus ( temporal endings) (SLFt). ADHD symptoms severity was associated with lower fractional anisotropy (FA) within the ATR. In addition, individuals with relatively higher FA in SLFp compared to SLFt showed faster and more accurate behavioral responses to MPH. Furthermore, the same parieto-temporal FA gradient explained the effects of MPH on beta modulation: subjects with ADHD exhibiting higher FA in SLFp compared to SLFt also displayed greater effects of MPH on beta power during response preparation. ConclusionsBased on MPHs modulatory effects on striatal dopamine levels, our data suggest that the behavioral deficits and aberrant oscillatory modulations observed in ADHD depend on a structural connectivity imbalance within the SLF, caused by a diffusivity gradient in favor of temporal rather than parietal, fiber tracts.

neuroscience↗

bioRxiv2020

Methylphenidate normalizes aberrant beta oscillations and reduces alpha power during retention in children with ADHD

Attention Deficit-Hyperactivity Disorder (ADHD) has been intensively studied in neurodevelopmental research, with the aim to identify the neural substrates of the disorder. Prior studies have established that brain oscillations in specific frequency ranges associated with attention and motor tasks are altered in ADHD patients as compared to typically developing (TD) peers. We hypothesized that the behavioral improvement following medication in ADHD patients should be accompanied by a normalization in the modulation of such oscillations. We hence implemented a double-blind placebo-controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off stimulant medication (methylphenidate, MPH). Results were compared with an age/IQ-matched TD group performing the same task, to assess the effect of MPH on oscillatory activity in the alpha (7 - 13Hz) and beta (15 - 30Hz) bands. We observed that depression of beta band oscillation over motor cortex in preparation to the response in ADHD boys on placebo were significantly lower as compared to the TD group. Importantly MPH resulted in a normalization of the beta depression, which then reached the same levels as in the control subjects. Furthermore, alpha power increased during the preparation interval in the ADHD control group, supposedly reflecting working memory maintenance of the cue information. This increase was significantly reduced in the ADHD group on MPH, reflecting a reduced impact on working memory load. This is the first MEG study showing task related changes in brain oscillations with MPH in children with ADHD. Significance statementBrain oscillations in the alpha (7-13Hz) and beta (15-30Hz) frequency bands are thought to underly different aspects of attentional processing and their aberrant modulation has been reported in ADHD. Here, we used a child-friendly adaptation of a Posner cueing paradigm to investigate such oscillations in children with and without a diagnosis of ADHD, and further examined the effects of methylphenidate (MPH) in the latter group. We showed that MPH restores aberrant patterns of beta desynchronization and reduces alpha power during retention in the ADHD group, concomitant to an improvement in behavioural performance.

neuroscience↗

bioRxiv2018

Hemispheric Asymmetry of Globus Pallidus Explains Reward-related Posterior Alpha Modulation in Humans

While subcortical structures like the basal ganglia have been widely explored in relation to motor control, recent evidence suggests that their mechanisms extend to the domain of attentional switching. We here investigated the subcortical involvement in reward related top-down control of visual alpha-band oscillations (8 - 13 Hz), which have been consistently linked to mechanisms supporting the allocation of visuo-spatial attention. Given that items associated with contextual saliency (e.g. monetary reward or loss) attract attention, it is not surprising that the acquired salience of visual items further modulates. The executive networks controlling such reward-dependent modulations of oscillatory brain activity have yet to be fully elucidated. Although such networks have been explored in terms of cortico-cortical interactions, subcortical regions are likely to be involved. To uncover this, we combined MRI and MEG data from 17 male and 11 female participants, investigating whether derived measures of subcortical structural asymmetries predict interhemispheric modulation of alpha power during a spatial attention task. We show that volumetric hemispheric lateralization of globus pallidus (GP) and thalamus (Th) explains individual hemispheric biases in the ability to modulate posterior alpha power. Importantly, for the GP, this effect became stronger when the value-saliency parings in the task increased. Our findings suggest that the GP and Th in humans are part of a subcortical executive control network, differentially involved in modulating posterior alpha activity in the presence of saliency. Further investigation aimed at uncovering the interaction between subcortical and neocortical attentional networks would provide useful insight in future studies.\n\nSignificance statementWhile the involvement of subcortical regions into higher level cognitive processing, such as attention and reward attribution, has been already indicated in previous studies, little is known about its relationship with the functional oscillatory underpinnings of said processes. In particular, interhemispheric modulation of alpha band (8-13Hz) oscillations, as recorded with magnetoencephalography (MEG), has been previously shown to vary as a function of salience (i.e. monetary reward/loss) in a spatial attention task. We here provide novel insights into the link between subcortical and cortical control of visual attention. Using the same reward-related spatial attention paradigm, we show that the volumetric lateralization of subcortical structures (specifically Globus Pallidus and Thalamus) explains individual biases in the modulation of visual alpha activity.

neuroscience↗

bioRxiv2017

Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase: pseudouridimycin

There is an urgent need for new antibacterial drugs effective against bacterial pathogens resistant to current drugs1-2. Nucleoside-analog inhibitors (NAIs) of viral nucleotide polymerases have had transformative impact in treatment of HIV3 and HCV4. NAIs of bacterial RNA polymerase (RNAP) potentially could have major impact on treatment of bacterial infection, particularly because functional constraints on substitution of RNAP nucleoside triphosphate (NTP) binding sites4-5 could limit resistance emergence4-5. Here we report the discovery, from microbial extract screening, of an NAI that inhibits bacterial RNAP and exhibits antibacterial activity against a broad spectrum of drug-sensitive and drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a novel microbial natural product consisting of a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6'-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, potently and selectively inhibits bacterial growth in culture, and potently clears infection in a mouse model of Streptococcus pyogenes peritonitis. PUM inhibits RNAP through a binding site on RNAP (the \"i+1\" NTP binding site) and mechanism (competition with UTP for occupancy of the \"i+1\" NTP binding site) that differ from those of the RNAP inhibitor and current antibacterial drug rifampin (Rif). PUM exhibits additive antibacterial activity when co-administered with Rif, exhibits no cross-resistance with Rif, and exhibits a spontaneous resistance rate an order-of-magnitude lower than that of Rif. The results provide the first example of a selective NAI of bacterial RNAP, provide an advanced lead compound for antibacterial drug development, and provide structural information and synthetic routes that enable lead optimization for antibacterial drug development.

molecular biology↗