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Abstract

Photodynamic therapy (PDT) is a clinically approved, non-invasive therapy currently used for several solid tumors, triggering cell death through the generation of reactive oxygen species (ROS). However, the hydrophobic nature of most of the photosensitizers used, such as chlorins, limits the overall effectiveness of PDT. To address this limitation, the use of nanocarriers seems to be a powerful approach. From this perspective, we have recently developed water-soluble and biocompatible, fluorescent, organic nanoparticles (FONPs) functionalized with purpurin-18 and its derivative, chlorin p6 (Cp6), as new PDT agents. In this study, we aimed to investigate the induced cell death mechanism mediated by these functionalized nanoparticles after PDT photoactivation. Our results show strong phototoxic effects of the FONPs[Cp6], mediated by intracellular ROS generation, and subcellular localization in HCT116 and HT-29 human colorectal cancer (CRC) cells. Additionally, we proved that, post-PDT, the FONPs[Cp6] induce apoptosis via the intrinsic mitochondrial pathway, as shown by the significant upregulation of the Bax/Bcl-2 ratio, the activation of caspases 9, 3, and 7, leading poly-ADP-ribose polymerase (PARP-1) cleavage, and DNA fragmentation. Our work demonstrates the photodynamic activity of these nanoparticles, making them promising candidates for the PDT treatment of CRC.

Abstract

Over the past three decades, functional neuroimaging has amassed abundant evidence of the intricate interplay between brain structure and function. However, the potential anatomical and experimental overlap, independence, granularity, and gaps between functions remain poorly understood. Here, we show the latent structure of the current brain-cognition knowledge and its organisation. Our approach utilises the most comprehensive meta-analytic fMRI database (Neurosynth) to compute a three-dimensional embedding space–morphospace capturing the relationship between brain functions as we currently understand them. The space structure enables us to statistically test the relationship between functions expressed as the degree to which the characteristics of each functional map can be anticipated based on its similarities with others–the predictability index. The morphospace can also predict the activation pattern of new, unseen functions and decode thoughts and inner states during movie watching. The framework defined by the morphospace will spur the investigation of novel functions and guide the exploration of the fabric of human cognition.

Abstract

Attention is a heterogeneous function theoretically divided into different systems. While functional magnetic resonance imaging (fMRI) has extensively characterized their functioning, the role of white matter in cognitive function has gained recent interest due to diffusion-weighted imaging advancements. However, most evidence relies on correlations between white matter properties and behavioral or cognitive measures. This study used a new method that combines the signal from distant voxels of fMRI images using the probability of structural connection given by high-resolution normative tractography. We analyzed three fMRI datasets with a visual perceptual task and three attentional manipulations: phasic alerting, spatial orienting, and executive attention. The phasic alerting network engaged temporal areas and their communication with frontal and parietal regions, with left hemisphere dominance. The orienting network involved bilateral fronto-parietal and midline regions communicating by association tracts and interhemispheric fibers. The executive attention network engaged a broad set of brain regions and white matter tracts connecting them, with a particular involvement of frontal areas and their connections with the rest of the brain. These results partially confirm and extend previous knowledge on the neural substrates of the attentional system, offering a more comprehensive understanding through the integration of structure and function.

Abstract

Attention is a heterogeneous function theoretically divided into different systems. While functional magnetic resonance imaging (fMRI) has extensively characterized their functioning, the role of white matter in cognitive function has gained recent interest due to diffusion-weighted imaging advancements. However, most evidence relies on correlations between white matter properties and behavioral or cognitive measures. This study used a new method that combines the signal from distant voxels of fMRI images using the probability of structural connection given by high-resolution normative tractography. We analyzed three fMRI datasets with a visual perceptual task and three attentional manipulations: phasic alerting, spatial orienting, and executive attention. The phasic alerting network engaged temporal areas and their communication with frontal and parietal regions, with left hemisphere dominance. The orienting network involved bilateral fronto-parietal and midline regions communicating by association tracts and interhemispheric fibers. The executive attention network engaged a broad set of brain regions and white matter tracts connecting them, with a particular involvement of frontal areas and their connections with the rest of the brain. These results partially confirm and extend previous knowledge on the neural substrates of the attentional system, offering a more comprehensive understanding through the integration of structure and function.

Abstract

Consciousness, a cornerstone of human cognition, is believed to arise from complex neural interactions. Traditional views have focused on localized fronto-parietal networks or broader inter-regional dynamics. In our study, we leverage advanced fMRI techniques, including the novel Functionnectome framework, to unravel the intricate relationship between brain circuits and functional activity shaping visual consciousness. Our findings underscore the importance of the superior longitudinal fasciculus within the fronto-parietal fibers, linking conscious perception with spatial neglect. Additionally, our data reveal the critical contribution of the temporo-parietal fibers and the splenium of the corpus callosum in connecting visual information with conscious representation and their verbalization. Central to these networks is the thalamus, posited as a conductor in synchronizing these interactive processes. Contrasting traditional fMRI analyses with the Functionnectome approach, our results emphasize the important explanatory power of interactive mechanisms over localized activations for visual consciousness. This research paves the way for a comprehensive understanding of consciousness, highlighting the complex network of neural connections that lead to awareness.

Abstract

Consciousness, a cornerstone of human cognition, is believed to arise from complex neural interactions. Traditional views have focused on localized fronto-parietal networks or broader inter-regional dynamics. In our study, we leverage advanced fMRI techniques, including the novel Functionnectome framework, to unravel the intricate relationship between brain circuits and functional activity shaping visual consciousness. Our findings underscore the importance of the superior longitudinal fasciculus within the fronto-parietal fibers, linking conscious perception with spatial neglect. Additionally, our data reveal the critical contribution of the temporo-parietal fibers and the splenium of the corpus callosum in connecting visual information with conscious representation and their verbalization. Central to these networks is the thalamus, posited as a conductor in synchronizing these interactive processes. Contrasting traditional fMRI analyses with the Functionnectome approach, our results emphasize the important explanatory power of interactive mechanisms over localized activations for visual consciousness. This research paves the way for a comprehensive understanding of consciousness, highlighting the complex network of neural connections that lead to awareness.

Abstract

Limb apraxia is a higher-order motor disorder often occurring post-stroke, which affects skilled actions. It is assessed through tasks involving gesture production or pantomime, recognition, meaningless gesture imitation, complex figure drawing, single and multi-object use. A two-system model for the organisation of actions hypothesizes distinct pathways mediating praxis deficits via conceptual, ‘indirect’, and perceptual ‘direct’ routes to action. Traditional lesion- symptom mapping techniques have failed to identify these distinct routes. We assessed 29 left hemisphere stroke patients to investigate white matter disconnections on deficits of praxis tasks from the Birmingham Cognitive Screening. White matter disconnection maps derived from patients’ structural T1 lesions were created using a diffusion-weighted healthy participant dataset acquired from the human connectome project (HCP). Initial group-level regression analyses revealed significant disconnection between occipital lobes via the splenium of the corpus callosum and involvement of the inferior longitudinal fasciculus in meaningless gesture imitation deficits. There was a trend of left fornix disconnection in gesture production deficits. Further, voxel-wise Bayesian Crawford single-case analyses performed on two patients with the most severe meaningless gesture imitation and meaningful gesture production deficits, respectively, confirmed distinct posterior interhemispheric disconnection, for the former, and disconnections between temporal and frontal areas via the fornix, rostrum of the corpus callosum and anterior cingulum, for the latter. Our results suggest distinct pathways associated with perceptual and conceptual deficits akin to ‘direct’ and ‘indirect’ action routes, with some patients displaying both. Larger studies are needed to validate and elaborate on these findings, advancing our understanding of limb apraxia.

Abstract

Limb apraxia is a higher-order motor disorder often occurring post-stroke, which affects skilled actions. It is assessed through tasks involving gesture production or pantomime, recognition, meaningless gesture imitation, complex figure drawing, single and multi-object use. A two-system model for the organisation of actions hypothesizes distinct pathways mediating praxis deficits via conceptual, ‘indirect’, and perceptual ‘direct’ routes to action. Traditional lesion- symptom mapping techniques have failed to identify these distinct routes. We assessed 29 left hemisphere stroke patients to investigate white matter disconnections on deficits of praxis tasks from the Birmingham Cognitive Screening. White matter disconnection maps derived from patients’ structural T1 lesions were created using a diffusion-weighted healthy participant dataset acquired from the human connectome project (HCP). Initial group-level regression analyses revealed significant disconnection between occipital lobes via the splenium of the corpus callosum and involvement of the inferior longitudinal fasciculus in meaningless gesture imitation deficits. There was a trend of left fornix disconnection in gesture production deficits. Further, voxel-wise Bayesian Crawford single-case analyses performed on two patients with the most severe meaningless gesture imitation and meaningful gesture production deficits, respectively, confirmed distinct posterior interhemispheric disconnection, for the former, and disconnections between temporal and frontal areas via the fornix, rostrum of the corpus callosum and anterior cingulum, for the latter. Our results suggest distinct pathways associated with perceptual and conceptual deficits akin to ‘direct’ and ‘indirect’ action routes, with some patients displaying both. Larger studies are needed to validate and elaborate on these findings, advancing our understanding of limb apraxia.

Abstract

The thalamus has a key role in mediating cortical–subcortical interactions but is often neglected in neuroimaging studies, which mostly focus on changes in cortical structure and activity. One of the main reasons for the thalamus being overlooked is that the delineation of individual thalamic nuclei via neuroimaging remains controversial. Indeed, neuroimaging atlases vary substantially regarding which thalamic nuclei are included and how their delineations were established. Here, we review current and emerging methods for thalamic nuclei segmentation in neuroimaging data and consider the limitations of existing techniques in terms of their research and clinical applicability. We address these challenges by proposing a roadmap to improve thalamic nuclei segmentation in human neuroimaging and, in turn, harmonize research approaches and advance clinical applications. We believe that a collective effort is required to achieve this. We hope that this will ultimately lead to the thalamic nuclei being regarded as key brain regions in their own right and not (as often currently assumed) as simply a gateway between cortical and subcortical regions.