Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales

Initial validation of a novel method of presurgical language localization through functional connectivity (fcMRI)

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients (12 left) being evaluated for epilepsy surgery at UCLA (mean age 38.9 [sd 11.4]; 6 female; per Wada 14 left language dominant, 1 right, 1 mixed). Language maps were generated using a recently standardized method relying on a conjunction of language tasks (e.g., visual object naming; auditory naming; reading) to identify known language regions (Broca’s area; inferior and superior Wernicke’s Areas; Angular gyrus; Basal Temporal Language Area; Exner’s Area; and Supplementary Speech Area). With activations defined as network nodes, mean network connectivity was compared via permutation tests with alternate (i) fully random and (ii) proximal random networks. Mean network connectivity was determined in independently-acquired motor fMRI datasets (9 foot, 16 hand, 14 tongue). FINDINGS: 77% (30/39) of clinician-derived language networks exhibited mean connectivity greater than fully random networks (p\u3c0.05). Similarly, 69% (27/39) of clinician-derived language networks exhibited mean connectivity greater than proximal random networks (p\u3c0.05). Further analysis of networks not passing the permutation test suggests that low connectivity of non-valid networks may be driven not by low connectivity across all nodes, but by individual nodes that may not actually possess membership within the network. CONCLUSIONS: This study provides preliminary validity for a novel, clinician-based approach to mapping language cortex pre-surgery. This complements our recent work showing this method is reliable, and supports a proposed study comparing fMRI language maps using this technique with the results of direct stimulation mapping

Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children

AbstractBackgroundPreterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections.MethodsLongitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n=13) compared to T children (n=12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group×age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test—revised (PPVT­R), and Rapid Naming Composite (RDRL_Cmp).ResultsNine regions were generated by the group×age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time.ConclusionsThese findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC

Dense nonrigid motion tracking from a sequence of velocity fields

We have addressed the problem of tracking the non-rigid motion of the heart using a sequence of velocity fields and a sequence of contours. The information from both the contours and the dense velocity fields is integrated into a deforming mesh that is placed over the myocardium at one time frame and then tracked over the entire cardiac cycle. The deformation is guided by a smoothing filter that provides a compro-mise between (i) believing the dense field velocity and the contour data when it is crisp and coherent in a local spatial and temporal sense and (ii) employing a temporally smooth cyclic model of cardiac motion when contour and velocity data are not trustworthy. The method has been carefully evaluated with simu-lated data and phantom data. Experiments with in vivo data have also been conducted.

Functional connectivity and alterations in baseline brain state in humans

This work examines the influence of changes in baseline activity on the intrinsic functional connectivity fMRI (fc-fMRI) in humans. Baseline brain activity was altered by inducing anesthesia (sevoflurane end-tidal concentration 1%) in human volunteers and fc-fMRI maps between the pre-anesthetized and anesthetized conditions were compared across different brain networks. We particularly focused on low-level sensory areas (primary somatosensory, visual, and auditory cortices), the thalamus, and pain (insula), memory (hippocampus) circuits, and the default mode network (DMN), the latter three to examine higher-order brain regions. The results indicate that, while fc-fMRI patterns did not significantly differ (p<0.005; 20-voxel cluster threshold) in sensory cortex and in the DMN between the pre- and anesthetized conditions, fc-fMRI in high-order cognitive regions (i.e. memory and pain circuits) was significantly altered by anesthesia. These findings provide further evidence that fc-fMRI reflects intrinsic brain properties, while also demonstrating that 0.5 MAC sevoflurane anesthesia preferentially modulates higher-order connections