SUMMARY The ability to identify common objects in our environment (forks, pens, mugs) and grasp and manipulate them according to their function in support of behavioral goals is a tacit skill woven into everyday activities. Those abilities are supported by an integrated network of occipital and temporal lobe regions (supporting visual object processing and conceptual knowledge) and parietal and frontal areas (supporting active maintenance of object representations and object-directed actions). This object-processing network can be reliably mapped at the single participant and the group level using functional MRI when participants view images of manipulable objects. The key theoretical gap addressed by this research program concerns how neural representations of objects and actions in one region of the object processing network causally depend on processing in other regions within the network. This program tackles this issue via a new analytic approach, `Voxel-based Lesion Representational Similarity Analyses (VL-RSA). VL-RSA tests how lesions in one part of the brain affect fMRI-measured neural representational spaces in anatomically distant areas. VL-RSA capitalizes on the complementary strengths of neuropsychology (causal inference) and fMRI (high-sensitivity to information decoding). Hypothesis testing across Aims compare representational similarity spaces for a common set of objects and actions in functionally defined ROIs distal to the location of a brain tumor—before and after resective surgery. This approach offers a powerful model to derive causal inferences about processing dependencies across a network of brain regions. Aim 1 studies patients with brain tumors (and surgeries) that spare occipito-temporal cortex (OTC). Aim 1 tests the predictions that lesions to parietal regions of the object processing network will reduce neural responses and within-category multi-voxel pattern similarity specifically for objects (and not for faces, animals, places), and specifically in object-preferring subregions of OTC (as opposed to face/animal preferring regions). Aim 2 studies patients with brain tumors that spare parietal cortex. Aim 2 tests the predictions that occipito- temporal lesions will disrupt representational similarity spaces for object-associated manipulation (praxis) in the supramarginal gyrus, while frontal motor lesions will disrupt grasp representations in aIPS. Clinically oriented Aim 3 tests if representational spaces for objects and actions shift to the right hemisphere regions homologous to the site of the tumor, and the surgery to remove the tumor, and how such reorganization relates behavioral ability. Extensional analyses evaluate the roles of monocular vs binocular cues to depth and `tangibility' of the visual stimuli, and the relation between structural integrity of white matter pathways and core functional outcomes. Fulfilment of the Aims of this program will advance understanding of how brain lesions affect processing d...