Axial motion estimation and correction for simultaneous multi-plane two-photon calcium imaging

Two-photon imaging in behaving animals is typically accompanied by brain motion. For functional imaging experiments, for example with genetically encoded calcium indicators, such brain motion induces changes in fluorescence intensity. These motion related intensity changes or motion artifacts cannot easily be separated from neural activity induced signals. While lateral motion within the focal plane can be corrected by computationally aligning images, axial motion, out of the focal plane, cannot easily be corrected. Here, we develop an algorithm for axial motion correction for non-ratiometric calcium indicators taking advantage of simultaneous multi-plane imaging. Using at least two simultaneously recorded focal planes, the algorithm separates motion related and neural activity induced changes in fluorescence intensity. The developed motion correction approach allows axial motion estimation and correction at high frame rates for isolated structures in the imaging volume in vivo, such as sparse expression patterns in the fruit fly brain.

A strain-based investigation of the accuracy of embedded markers used in tracking cadaveric brain motion

Measurements of intracranial brain displacement in cadaveric specimens have been instrumental to the validation finite element (FE) models of brain injury. These data collections have used radiographic and sonomicrometric techniques, requiring the use of tissue-embedded tracking markers; however, marker accuracy has never been adequately characterized. Marker tracking precision has been previously conflated with measurement accuracy, not accounting for changes in the natural responseof surrounding tissues due to marker presence. Non-negligible inertia, high stiffness, and the aspect ratio of markers all contribute to this interference. This work investigated the dynamic coupling between published marker designs (NDTs, Sonomicrometry Crystals, and Tin) and a new elastomeric marker, and a block of tissue simulant subjected to a drop impact. The measured strains were compared to the baseline response of the simulant containing massless markers. The results found notable evidence of interference in simulant strain amplitudes as well as considerable directional bias in the response of some markers. The elastomeric marker was found to have minimal interference in the deformation field. FutureFE model validation will need to account for the considerable interference and directional biases to the natural response of brain tissue in existing cadaveric datasets to maintain confidence in strain predictions.

“Mickey Mousing” in the Brain: Motion-Sound Synesthesia and the Subcortical Substrate of Audio-Visual Integration

Motion-sound synesthesia is characterized by illusory auditory sensations linked to the pattern and rhythms of motion (dubbed “Mickey Mousing” as in cinema) of visually experienced but soundless object, like an optical flow array, a ball bouncing or a horse galloping. In an MRI study with a group of three synesthetes and a group of eighteen control participants, we found structural changes in the brains of synesthetes in the subcortical multisensory areas of the superior and inferior colliculi. In addition, functional magnetic resonance imaging data showed activity in motion-sensitive regions, as well as temporal and occipital areas, and the cerebellum. However, the synesthetes had a higher activation within the left and right cuneus, with stronger activations when viewing optical flow stimuli. There was also a general difference in connectivity of the colliculi with the above mentioned regions between the two groups. These findings implicate low-level mechanisms within the human neuroaxis as a substrate for local connectivity and cross activity between perceptual processes that are “distant” in terms of cortical topography. The present findings underline the importance of considering the role of subcortical systems and their connectivity to multimodal regions of the cortex and they strengthen a parsimonious account of synesthesia, at the least of the visual-auditory type.

The relationship between directional components of dynamic response and maximum principal strain for impacts to an American football helmet

Impact parameters used to design the American football helmet and the parameters associated with mechanisms of concussive injury are not consistent. Head impacts resulting in concussive injury in football are characterized as events creating rotational motion of the head that generate brain tissue strain. The extent of tissue strain influences the resulting severity of injury. Helmet technology aimed to decrease brain tissue strain by reducing the extent of brain motion could help reduce injury risk. Current helmet performance and evaluation measures, such as peak resultant of linear and rotational acceleration, do not fully define directional brain motion and therefore cannot provide sufficient information for this type of improvement. This study was conducted to determine whether coordinate components (X, Y, and Z) of linear and rotational acceleration would correlate with maximum principal strain, a common measure of brain injury risk. Coordinate components define directional motion of the head and offer a specific design parameter more easily reduced using engineered structures than peak resultant acceleration. In addition to coordinate components, this study introduces the dominant component, defined as the coordinate component with the highest contribution to the resultant acceleration, for additional evaluation. The results show that the relationship between the X, Y, and Z coordinate components of acceleration and maximum principal strain is location- and direction-dependent. The study indicates a strong relationship between the peak resultant and dominant components of acceleration to maximum principal strain. Because the dominant component of acceleration accounts for direction and location, identifying the relationship between dominant acceleration and maximum principal strain demonstrates the potential use of this metric to improve future helmet innovation aimed at reducing tissue strain.