664 research outputs found

    Parcellation of the human substantia nigra based on anatomical connectivity to the striatum

    Get PDF
    Substantia nigra/ventral tegmental area (SN/VTA) subregions, defined by dopaminergic projections to the striatum, are differentially affected by health (e.g. normal aging) and disease (e.g. Parkinson's disease). This may have an impact on reward processing which relies on dopaminergic regions and circuits. We acquired diffusion tensor imaging (DTI) with probabilistic tractography in 30 healthy older adults to determine whether subregions of the SN/VTA could be delineated based on anatomical connectivity to the striatum. We found that a dorsomedial region of the SN/VTA preferentially connected to the ventral striatum whereas a more ventrolateral region connected to the dorsal striatum. These SN/VTA subregions could be characterised by differences in quantitative structural imaging parameters, suggesting different underlying tissue properties. We also observed that these connectivity patterns differentially mapped onto reward dependence personality trait. We show that tractography can be used to parcellate the SN/VTA into anatomically plausible and behaviourally meaningful compartments, an approach that may help future studies to provide a more fine-grained synopsis of pathological changes in the dopaminergic midbrain and their functional impact

    Comprehensive in vivo Mapping of the Human Basal Ganglia and Thalamic Connectome in Individuals Using 7T MRI

    Get PDF
    Basal ganglia circuits are affected in neurological disorders such as Parkinson's disease (PD), essential tremor, dystonia and Tourette syndrome. Understanding the structural and functional connectivity of these circuits is critical for elucidating the mechanisms of the movement and neuropsychiatric disorders, and is vital for developing new therapeutic strategies such as deep brain stimulation (DBS). Knowledge about the connectivity of the human basal ganglia and thalamus has rapidly evolved over recent years through non-invasive imaging techniques, but has remained incomplete because of insufficient resolution and sensitivity of these techniques. Here, we present an imaging and computational protocol designed to generate a comprehensive in vivo and subject-specific, three-dimensional model of the structure and connections of the human basal ganglia. High-resolution structural and functional magnetic resonance images were acquired with a 7-Tesla magnet. Capitalizing on the enhanced signal-to-noise ratio (SNR) and enriched contrast obtained at high-field MRI, detailed structural and connectivity representations of the human basal ganglia and thalamus were achieved. This unique combination of multiple imaging modalities enabled the in-vivo visualization of the individual human basal ganglia and thalamic nuclei, the reconstruction of seven white-matter pathways and their connectivity probability that, to date, have only been reported in animal studies, histologically, or group-averaged MRI population studies. Also described are subject-specific parcellations of the basal ganglia and thalamus into sub-territories based on their distinct connectivity patterns. These anatomical connectivity findings are supported by functional connectivity data derived from resting-state functional MRI (R-fMRI). This work demonstrates new capabilities for studying basal ganglia circuitry, and opens new avenues of investigation into the movement and neuropsychiatric disorders, in individual human subjects

    Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

    Get PDF
    Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction

    Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility.

    Get PDF
    Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum - VS, ventral tegmental area - VTA), motor (supplementary motor areas - SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex - mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex - lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex - dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control.VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. LM is in receipt of an MRC studentship. The BCNI is supported by a WT and MRC grant. ETB is employed part-time by the University of Cambridge and part-time by GSK PLC and is a shareholder of GSK. TWR is a consultant for Cambridge Cognition, Eli Lilly, GSK, Merck, Sharpe and Dohme, Lundbeck, Teva and Shire Pharmaceuticals. He is or has been in receipt of research grants from Lundbeck, Eli Lilly and GSK and is an editor for Springer-Verlag (Psychopharmacology). The remaining authors declare no competing financial interests. The study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.cortex.2015.11.00

    Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging

    Get PDF
    The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery

    In vivo structural connectome of arousal and motor brainstem nuclei by 7 Tesla and 3 Tesla MRI

    Get PDF
    Brainstem nuclei are key participants in the generation and maintenance of arousal, which is a basic function that modulates wakefulness/sleep, autonomic responses, affect, attention, and consciousness. Their mechanism is based on diffuse pathways ascending from the brainstem to the thalamus, hypothalamus, basal forebrain and cortex. Several arousal brainstem nuclei also participate in motor functions that allow humans to respond and interact with the surrounding through a multipathway motor network. Yet, little is known about the structural connectivity of arousal and motor brainstem nuclei in living humans. This is due to the lack of appropriate tools able to accurately visualize brainstem nuclei in conventional imaging. Using a recently developed in vivo probabilistic brainstem nuclei atlas and 7 Tesla diffusion-weighted images (DWI), we built the structural connectome of 18 arousal and motor brainstem nuclei in living humans (n = 19). Furthermore, to investigate the translatability of our findings to standard clinical MRI, we acquired 3 Tesla DWI on the same subjects, and measured the association of the connectome across scanners. For both arousal and motor circuits, our results showed high connectivity within brainstem nuclei, and with expected subcortical and cortical structures based on animal studies. The association between 3 Tesla and 7 Tesla connectivity values was good, especially within the brainstem. The resulting structural connectome might be used as a baseline to better understand arousal and motor functions in health and disease in humans
    corecore