Biology subjects

Kahn, I.

Publications and source records attributed to Kahn, I..

3 recordsLinked to original sources

bioRxiv2019

Structural integrity following focused ultrasound thalamotomy and its correlation with tremor relief

BackgroundMagnetic-resonance-guided focused ultrasound ablation of ventral intermediate nucleus of the thalamus is a new treatment for tremor disorders.\n\nObjectivesWe sought to evaluate the white matter integrity prior to and following focused ultrasound ablation and its correlation with clinical outcome.\n\nMethods22 patients with essential tremor and 17 patients with Parkinsons disease underwent tremor and quality-of-life assessments prior to and at one and six months following focused ultrasound ablation. All patients underwent MRI including T1, T2-FLAIR and diffusion weighted imaging before treatment and at one day, 7-10 days, 1-3 months, and 6 months or more following it. Diffusivity parameters were calculated and fiber tractography measures were extracted. Change in diffusivity parameters were assessed inside the ablated core, in the motor thalamus and throughout the dentato-rubro-thalamo-cortical tract.\n\nResultsWe found short-term changes in the motor thalamus and in the tract between the thalamus and regions within the dentato-rubro-thalamo-cortical tract. Long term damage was found in the ablated core and in the tract connecting the thalamus and red-nucleus. Inverse correlation was found between fractional anisotropy in the motor thalamus one day following ablation and tremor improvement in both patient groups, with lower values before treatment associated with better outcome (tremor relief) in essential tremor patients.\n\nConclusionsShort-and long-term changes in white matter integrity are present following focused ultrasound thalamotomy. Regions demonstrating long-term white matter changes may be responsible for the tremor relief seen in patients, implicating these regions in the disorders pathogenesis.

neuroscience↗

bioRxiv2019

Loss of function in the autism and learning disabilities associated gene Nf1 disrupts corticocortical and corticostriatal functional connectivity in human and mouse

Children with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/-). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/- mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/- mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.

neuroscience↗

bioRxiv2019

Individual structural features constrain the functional connectome

Whole brain dynamics intuitively depends upon the internal wiring of the brain; but to which extent the individual structural connectome constrains the corresponding functional connectome is unknown, even though its importance is uncontested. After acquiring structural data from individual mice, we virtualized their brain networks and simulated in silico functional MRI data. Theoretical results were validated against empirical awake functional MRI data obtained from the same mice. We demonstrate that individual structural connectomes predict the functional organization of individual brains. Using a virtual mouse brain derived from the Allen Mouse Brain Connectivity Atlas, we further show that the dominant predictors of individual structure-function relations are the asymmetry and the weights of the structural links. Model predictions were validated experimentally using tracer injections, identifying which missing connections (not measurable with diffusion MRI) are important for whole brain dynamics in the mouse. Individual variations thus define a specific structural fingerprint with direct impact upon the functional organization of individual brains, a key feature for personalized medicine.\n\nSIGNIFICANCE STATEMENTThe structural connectome is a key determinant of brain function and dysfunction. The connectome-based model approach aims to understand the functional organization of the brain by modeling the brain as a dynamical system and then studying how the functional architecture rises from the underlying structural skeleton. Here, taking advantage of mice studies, we systematically investigated the informative content of different structural features in explaining the emergence of the functional ones. We demonstrate that individual variations define a specific structural fingerprint with a direct impact upon the functional organization of individual brains stressing the importance of using individualized models to understand brain function. We show how limitations of connectome reconstruction with the diffusion-MRI method restrict our comprehension of the structural-functional relation.

neuroscience↗