The influence of hand posture on tactile processing: Evidence from a 7T functional magnetic resonance imaging study.

Although behavioral evidence has shown that postural changes influence the ability to localize or detect tactile stimuli, little is known regarding the brain areas that modulate these effects. This 7T functional magnetic resonance imaging (fMRI) study explores the effects of touch of the hand as a function of hand location (right or left side of the body) and hand configuration (open or closed). We predicted that changes in hand configuration would be represented in contralateral primary somatosensory cortex (S1) and the anterior intraparietal area (aIPS), whereas change in position of the hand would be associated with alterations in activation in the superior parietal lobule. Multivoxel pattern analysis and a region of interest approach partially supported our predictions. Decoding accuracy for hand location was above chance level in superior parietal lobule (SPL) and in the anterior intraparietal (aIPS) area; above chance classification of hand configuration was observed in SPL and S1. This evidence confirmed the role of the parietal cortex in postural effects on touch and the possible role of S1 in coding the body form representation of the hand.

Mechanisms and neuroanatomy of response selection in tool and non-tool action tasks: Evidence from left-hemisphere stroke.

The ability to select between potential actions is central to the complex process of tool use. After left hemisphere stroke, individuals with limb apraxia make more hand action errors when gesturing the use of tools with conflicting hand actions for grasping-to-move and use (e.g., screwdriver) relative to tools that are grasped-to-move and used with the same hand action (e.g., hammer). Prior research indicates that this grasp-use interference effect is driven by abnormalities in the competitive action selection process. The goal of this project was to determine whether common mechanisms and neural substrates support the competitive selection of task-appropriate responses in both tool and non-tool domains. If so, the grasp-use interference effect in a tool use gesturing task should be correlated with response interference effects in the classic Eriksen flanker and Simon tasks, and at least partly overlapping neural regions should subserve the 3 tasks. Sixty-four left hemisphere stroke survivors (33 with apraxia) participated in the tool- and non-tool interference tasks and underwent T1 anatomical MRI. There were robust grasp-use interference effects (grasp-use conflict test) and response interference effects (Eriksen flanker and Simon tasks), but these effects were not correlated. Lesion-symptom mapping analyses showed that lesions to the left inferior parietal lobule, ventral premotor cortex, and insula were associated with grasp-use interference. Lesions to the left inferior parietal lobule, postcentral gyrus, insula, caudate, and putamen were associated with response interference in the Eriksen flanker task. Lesions to the left caudate and putamen were also associated with response interference in the Simon task. Our results suggest that the selection of hand posture for tool use is mediated by distinct cognitive mechanisms and partly distinct neuroanatomic substrates from those mapping a stimulus to an appropriate motor response in non-tool domains.

Single-case disconnectome lesion-symptom mapping: Identifying two subtypes of limb apraxia.

Influential theories of skilled action posit that distinct cognitive mechanisms and neuroanatomic substrates support meaningless gesture imitation and tool use pantomiming, and poor performance on these tasks are hallmarks of limb apraxia. Yet prior research has primarily investigated brain-behavior relations at the group level; thus, it is unclear whether we can identify individuals with isolated impairments in meaningless gesture imitation or tool use pantomiming whose performance is associated with a distinct neuroanatomic lesion profile. The goal of this study was to test the hypothesis that individuals with disproportionately worse performance in meaningless gesture imitation would exhibit cortical damage and white matter disconnection in left fronto-parietal brain regions, whereas individuals with disproportionately worse performance in tool use pantomiming would exhibit cortical damage and white matter disconnection in left temporo-parietal brain regions. Fifty-eight participants who experienced a left cerebrovascular accident took part in a meaningless gesture imitation task, a tool use pantomiming task, and a T1 structural MRI. Two participants were identified who had relatively small lesions and disproportionate impairments on one task relative to the other, as well as below-control-level performance on one task and not the other. Using these criteria, one participant was disproportionately impaired at meaningless gesture imitation, and the other participant was disproportionately impaired at pantomiming tool use. Graph theoretic analysis of each participant's structural disconnectome demonstrated that disproportionately worse meaningless gesture imitation performance was associated with disconnection among the left inferior parietal lobule, the left superior parietal lobule, and the left middle and superior frontal gyri, whereas disproportionately worse tool use pantomiming performance was associated with disconnection between left temporal and parietal regions. Our results demonstrate that relatively focal lesions to specific portions of the Tool Use Network can be associated with distinct limb apraxia subtypes.

Scene context shapes category representational geometry during processing of tools.

Tools are ubiquitous in human environments and to think about them we use concepts. Increasingly, conceptual representation is thought to be dynamic and sensitive to the goals of the observer. Indeed, observer goals can reshape representational geometry within cortical networks supporting concepts. In the present study, we investigated the novel hypothesis that task-irrelevant scene context may implicitly alter the representational geometry of regions within the tool network. Participants performed conceptual judgments on images of tools embedded in scenes that either suggested their use (i.e., a kitchen timer sitting on a kitchen counter with vegetables in a frying pan) or that they would simply be moved (i.e., a kitchen timer sitting in an open drawer with other miscellaneous kitchen items around). We investigated whether representations in the tool network reflect category, grip, and shape information using a representational similarity analysis (RSA). We show that a) a number of regions of the tool network reflect category information about tools and b) category information predicts patterns in supramarginal gyrus more strongly in use contexts than in move contexts. Together, these results show that information about tool category is distributed across different regions of the tool network and that scene context helps shape the representational geometry of the tool network.

Structural Disconnection of the Tool Use Network after Left Hemisphere Stroke Predicts Limb Apraxia Severity.

Producing a tool use gesture is a complex process drawing upon the integration of stored knowledge of tools and their associated actions with sensory-motor mechanisms supporting the planning and control of hand and arm actions. Understanding how sensory-motor systems in parietal cortex interface with semantic representations of actions and objects in the temporal lobe remains a critical issue and is hypothesized to be a key determinant of the severity of limb apraxia, a deficit in producing skilled action after left hemisphere stroke. We used voxel-based and connectome-based lesion-symptom mapping with data from 57 left hemisphere stroke participants to assess the lesion sites and structural disconnection patterns associated with poor tool use gesturing. We found that structural disconnection among the left inferior parietal lobule, lateral and ventral temporal cortices, and middle and superior frontal gyri predicted the severity of tool use gesturing performance. Control analyses demonstrated that reductions in right-hand grip strength were associated with motor system disconnection, largely bypassing regions supporting tool use gesturing. Our findings provide evidence that limb apraxia may arise, in part, from a disconnection between conceptual representations in the temporal lobe and mechanisms enabling skilled action production in the inferior parietal lobule.

Reorganized language network connectivity after left arcuate fasciculus resection: A case study.

Understanding the neural mechanisms that support spontaneous recovery of cognitive abilities can place important constraints on mechanistic theories of brain organization and function, and holds potential to inform clinical interventions. Connectivity-based MRI measures have emerged as a way to study how recovery from brain injury is modulated by changes in intra- and inter-hemispheric connectivity. Here we report a detailed and multi-modal case study of a 26 year-old male who presented with a left inferior parietal glioma infiltrating the left arcuate fasciculus. The patient underwent pre- and post-operative functional MRI and Diffusion Tensor Imaging, as well as behavioral assessments of language, motor, vision and praxis. The surgery for removal of the tumor was carried out with the patient awake, and direct electrical stimulation mapping was used to evaluate cortical language centers. The patient developed a specific difficulty with repeating sentences toward the end of the surgery, after resection of the tumor and partial transection of the arcuate fasciculus. The patient recovered from the sentence repetition impairments over several months after the operation. Coincident with the patient's cognitive recovery, we document a pattern whereby intra-hemispheric functional connectivity was reduced in the left hemisphere, while inter-hemispheric connectivity increased between classic left hemisphere language regions and their right hemisphere homologues. These findings suggest that increased synchrony between the two hemispheres, in the setting of focal transection of the left arcuate fasciculus, can facilitate functional recovery.

A common neural signature of brain injury in concussion and subconcussion.

The midbrain is biomechanically susceptible to force loading from repetitive subconcussive head impacts (RSHI), is a site of tauopathy in chronic traumatic encephalopathy (CTE), and regulates functions (e.g., eye movements) often disrupted in concussion. In a prospective longitudinal design, we demonstrate there are reductions in midbrain white matter integrity due to a single season of collegiate football, and that the amount of reduction in midbrain white matter integrity is related to the amount of rotational acceleration to which players' brains are exposed. We then replicate the observation of reduced midbrain white matter integrity in a retrospective cohort of individuals with frank concussion, and further show that variance in white matter integrity is correlated with levels of serum-based tau, a marker of blood-brain barrier disruption. These findings mean that noninvasive structural MRI of the midbrain is a succinct index of both clinically silent white matter injury as well as frank concussion.

Translational Brain Mapping at the University of Rochester Medical Center: Preserving the Mind Through Personalized Brain Mapping.

The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, neuroanesthesia, and neurosurgery. Patients who have tumors or epileptogenic tissue in eloquent brain areas are studied preoperatively with functional and structural MRI, and intraoperatively with direct electrical stimulation mapping. Post-operative neural and cognitive outcome measures fuel basic science studies about the factors that mediate good versus poor outcome after surgery, and how brain mapping can be further optimized to ensure the best outcome for future patients. In this article, we describe the interdisciplinary workflow that allows our team to meet the synergistic goals of optimizing patient outcome and advancing scientific understanding of the human brain.

Reduced competition between tool action neighbors in left hemisphere stroke.

When pantomiming the use of tools, patients with limb apraxia after left hemisphere stroke (LCVA) produce more spatiotemporal hand action errors with tools associated with conflicting actions for use versus grasp-to-pick-up (e.g., corkscrew) than tools having a single action for both use and grasp (e.g., hammer). There are two possible accounts for this pattern of results. Reduced performance with 'conflict' tools may simply reflect weakened automaticity of use action activation, which is evident only when the use and grasp actions are not redundant. Alternatively, poor use performance may reflect a reduced ability of appropriate tool use actions to compete with task-inappropriate action representations. To address this issue, we developed a Stroop-like experiment in which 21 LCVA and 8 neurotypical participants performed pantomime actions in blocks containing two tools that were similar ("neighbors") in terms of hand action or function, or were unrelated on either dimension. In a congruent condition, they pantomimed the use action associated with the visually presented tool, whereas in an incongruent condition, they pantomimed the use action for the other tool in the block. Relative to controls and other task conditions, LCVA participants showed reductions in hand action errors in incongruent relative to congruent action trials; furthermore, the degree of reduction in this incongruence effect was related to the participants' susceptibility to grasp-on-use conflict in a separate test of pantomime to the sight of tools. Support vector regression lesion-symptom mapping analyses identified the left inferior frontal gyrus, supramarginal gyrus, and superior longitudinal fasciculus as core neuroanatomical sites associated with abnormal performance. Collectively, the results indicate that weakened activation of tool use actions in limb apraxia gives rise to reduced ability of these actions to compete for task-appropriate selection when competition arises within single tools (grasp-on-use conflict) as well as between two tools (reduced neighborhood effects).

Gesturing tool use and tool transport actions modulates inferior parietal functional connectivity with the dorsal and ventral object processing pathways.

Interacting with manipulable objects (tools) requires the integration of diverse computations supported by anatomically remote regions. Previous functional neuroimaging research has demonstrated the left supramarginal (SMG) exhibits functional connectivity to both ventral and dorsal pathways, supporting the integration of ventrally-mediated tool properties and conceptual knowledge with dorsally-computed volumetric and structural representations of tools. This architecture affords us the opportunity to test whether interactions between the left SMG, ventral visual pathway, and dorsal visual pathway are differentially modulated when participants plan and generate tool-directed gestures emphasizing functional manipulation (tool use gesturing) or structure-based grasping (tool transport gesturing). We found that functional connectivity between the left SMG, ventral temporal cortex (bilateral fusiform gyri), and dorsal visual pathway (left superior parietal lobule/posterior intraparietal sulcus) was maximal for tool transport planning and gesturing, whereas functional connectivity between the left SMG, left ventral anterior temporal lobe, and left frontal operculum was maximal for tool use planning and gesturing. These results demonstrate that functional connectivity to the left SMG is differentially modulated by tool use and tool transport gesturing, suggesting that distinct tool features computed by the two object processing pathways are integrated in the parietal lobe in the service of tool-directed action.

Decoding intransitive actions in primary motor cortex using fMRI: toward a componential theory of 'action primitives' in motor cortex.

Multivoxel pattern analysis (MVPA) over functional MRI data can distinguish neural representational states that do not differ in their overall amplitude of BOLD contrast. Here we used MVPA to test whether simple intransitive actions can be distinguished in primary motor cortex. Participants rotated and flexed each of their extremities (hands and feet) during fMRI scanning. The primary motor cortex for the hand/wrist was functionally defined in each hemisphere in each subject. Within those subject-specific ROIs, we found that the average amplitude of BOLD contrast for two different movements of the contralateral hand (rotation, flexion) were higher than for the ipsilateral hand, as well as movements by both feet; however, there was no difference in amplitude between the two different types of movements for the contralateral hand. Using multivoxel pattern analysis (linear correlation), we were able to distinguish the two movements for the contralateral hand. These findings demonstrate that simple intransitive actions can be distinguished in primary motor areas using multivoxel pattern analysis.

Domain-Specific Diaschisis: Lesions to Parietal Action Areas Modulate Neural Responses to Tools in the Ventral Stream.

Neural responses to small manipulable objects ("tools") in high-level visual areas in ventral temporal cortex (VTC) provide an opportunity to test how anatomically remote regions modulate ventral stream processing in a domain-specific manner. Prior patient studies indicate that grasp-relevant information can be computed about objects by dorsal stream structures independently of processing in VTC. Prior functional neuroimaging studies indicate privileged functional connectivity between regions of VTC exhibiting tool preferences and regions of parietal cortex supporting object-directed action. Here we test whether lesions to parietal cortex modulate tool preferences within ventral and lateral temporal cortex. We found that lesions to the left anterior intraparietal sulcus, a region that supports hand-shaping during object grasping and manipulation, modulate tool preferences in left VTC and in the left posterior middle temporal gyrus. Control analyses demonstrated that neural responses to "place" stimuli in left VTC were unaffected by lesions to parietal cortex, indicating domain-specific consequences for ventral stream neural responses in the setting of parietal lesions. These findings provide causal evidence that neural specificity for "tools" in ventral and lateral temporal lobe areas may arise, in part, from online inputs to VTC from parietal areas that receive inputs via the dorsal visual pathway.

Visual and visuomotor processing of hands and tools as a case study of cross talk between the dorsal and ventral streams.

A major principle of organization of the visual system is between a dorsal stream that processes visuomotor information and a ventral stream that supports object recognition. Most research has focused on dissociating processing across these two streams. Here we focus on how the two streams interact. We tested neurologically-intact and impaired participants in an object categorization task over two classes of objects that depend on processing within both streams-hands and tools. We measured how unconscious processing of images from one of these categories (e.g., tools) affects the recognition of images from the other category (i.e., hands). Our findings with neurologically-intact participants demonstrated that processing an image of a hand hampers the subsequent processing of an image of a tool, and vice versa. These results were not present in apraxic patients (N = 3). These findings suggest local and global inhibitory processes working in tandem to co-register information across the two streams.

Task- and domain-specific modulation of functional connectivity in the ventral and dorsal object-processing pathways.

A whole-brain network of regions collectively supports the ability to recognize and use objects-the Tool Processing Network. Little is known about how functional interactions within the Tool Processing Network are modulated in a task-dependent manner. We designed an fMRI experiment in which participants were required to either generate object pantomimes or to carry out a picture matching task over the same images of tools, while holding all aspects of stimulus presentation constant across the tasks. The Tool Processing Network was defined with an independent functional localizer, and functional connectivity within the network was measured during the pantomime and picture matching tasks. Relative to tool picture matching, tool pantomiming led to an increase in functional connectivity between ventral stream regions and left parietal and frontal-motor areas; in contrast, the matching task was associated with an increase in functional connectivity among regions in ventral temporo-occipital cortex, and between ventral temporal regions and the left inferior parietal lobule. Graph-theory analyses over the functional connectivity data indicated that the left premotor cortex and left lateral occipital complex were hub-like (exhibited high betweenness centrality) during tool pantomiming, while ventral stream regions (left medial fusiform gyrus and left posterior middle temporal gyrus) were hub-like during the picture matching task. These results demonstrate task-specific modulation of functional interactions among a common set of regions, and indicate dynamic coupling of anatomically remote regions in task-dependent manner.

A Role for the Frontal Aslant Tract in Speech Planning: A Neurosurgical Case Study.

Frontal and temporal white matter pathways play key roles in language processing, but the specific computations supported by different tracts remain a matter of study. A role in speech planning has been proposed for a recently described pathway, the frontal aslant tract (FAT), which connects the posterior inferior frontal gyrus to the pre-SMA. Here, we use longitudinal functional and structural MRI and behavioral testing to evaluate the behavioral consequences of a lesion to the left FAT that was incurred during surgical resection of a frontal glioma in a 60-year-old woman, Patient AF. The pattern of performance in AF is compared, using the same measures, with that in a 37-year-old individual who underwent a left anterior temporal resection and hippocampectomy (Patient AG). AF and AG were both cognitively intact preoperatively but exhibited specific and doubly dissociable behavioral deficits postoperatively: AF had dysfluent speech but no word finding difficulty, whereas AG had word finding difficulty but otherwise fluent speech. Probabilistic tractography showed that the left FAT was lesioned postoperatively in AF (but not AG) whereas the inferior longitudinal fasciculus was lesioned in AG (but not AF). Those structural changes were supported by corresponding changes in functional connectivity to the posterior inferior frontal gyrus: decreased functional connectivity postoperatively between the posterior inferior frontal gyrus and pre-SMA in AF (but not AG) and decreased functional connectivity between the posterior inferior frontal gyrus and the middle temporal gyrus in AG (but not AF). We suggest from these findings that the left FAT serves as a key communicative link between sentence planning and lexical access processes.

Abstract Representations of Object-Directed Action in the Left Inferior Parietal Lobule.

Prior neuroimaging and neuropsychological research indicates that the left inferior parietal lobule in the human brain is a critical substrate for representing object manipulation knowledge. In the present functional MRI study we used multivoxel pattern analyses to test whether action similarity among objects can be decoded in the inferior parietal lobule independent of the task applied to objects (identification or pantomime) and stimulus format in which stimuli are presented (pictures or printed words). Participants pantomimed the use of objects, cued by printed words, or identified pictures of objects. Classifiers were trained and tested across task (e.g., training data: pantomime; testing data: identification), stimulus format (e.g., training data: word format; testing format: picture) and specific objects (e.g., training data: scissors vs. corkscrew; testing data: pliers vs. screwdriver). The only brain region in which action relations among objects could be decoded across task, stimulus format and objects was the inferior parietal lobule. By contrast, medial aspects of the ventral surface of the left temporal lobe represented object function, albeit not at the same level of abstractness as actions in the inferior parietal lobule. These results suggest compulsory access to abstract action information in the inferior parietal lobe even when simply identifying objects.

Direct Electrical Stimulation in the Human Brain Disrupts Melody Processing.

Prior research using functional magnetic resonance imaging (fMRI) [1-4] and behavioral studies of patients with acquired or congenital amusia [5-8] suggest that the right posterior superior temporal gyrus (STG) in the human brain is specialized for aspects of music processing (for review, see [9-12]). Intracranial electrical brain stimulation in awake neurosurgery patients is a powerful means to determine the computations supported by specific brain regions and networks [13-21] because it provides reversible causal evidence with high spatial resolution (for review, see [22, 23]). Prior intracranial stimulation or cortical cooling studies have investigated musical abilities related to reading music scores [13, 14] and singing familiar songs [24, 25]. However, individuals with amusia (congenitally, or from a brain injury) have difficulty humming melodies but can be spared for singing familiar songs with familiar lyrics [26]. Here we report a detailed study of a musician with a low-grade tumor in the right temporal lobe. Functional MRI was used pre-operatively to localize music processing to the right STG, and the patient subsequently underwent awake intraoperative mapping using direct electrical stimulation during a melody repetition task. Stimulation of the right STG induced "music arrest" and errors in pitch but did not affect language processing. These findings provide causal evidence for the functional segregation of music and language processing in the human brain and confirm a specific role of the right STG in melody processing. VIDEO ABSTRACT.

Connectivity-based constraints on category-specificity in the ventral object processing pathway.

Recent efforts to characterize visual object representations in the ventral object processing pathway in the human brain have led to contrasting proposals about the causes of neural specificity for different categories. Here we use multivariate techniques in a novel way to relate patterns of functional connectivity to patterns of stimulus preferences. Stimulus preferences were measured throughout the ventral stream to tools, animals, faces and places; separately, we measured the strength of functional connectivity of each voxel in the ventral stream to category-preferring regions outside the ventral stream. Multivariate analyses were then performed over ventral stream voxels, relating 'category-preferences' to 'functional connectivity preferences'. We show that the relation of those two measures doubly dissociates 'tools' and 'places', within what is ostensibly 'place' selective cortex (parahippocampal gyrus). Specifically, in the parahippocampal gyrus, functional connectivity to the left inferior parietal lobule is selectively related to stimulus preferences for tools (and not places), while functional connectivity to retrosplenial cortex is selectively related to place preferences (and not tools preferences). These findings indicate that functional connectivity can be used to index representational content rather than just provide an understanding of 'which regions are talking to which regions'. We suggest that the connectivity of the brain is what drives category-specificity in the ventral stream, and that if this is correct, then understanding the connectivity of the ventral stream will be key to understanding the causes and function of category-specific neural organization.

Resilience to the contralateral visual field bias as a window into object representations.

Viewing images of manipulable objects elicits differential blood oxygen level-dependent (BOLD) contrast across parietal and dorsal occipital areas of the human brain that support object-directed reaching, grasping, and complex object manipulation. However, it is unknown which object-selective regions of parietal cortex receive their principal inputs from the ventral object-processing pathway and which receive their inputs from the dorsal object-processing pathway. Parietal areas that receive their inputs from the ventral visual pathway, rather than from the dorsal stream, will have inputs that are already filtered through object categorization and identification processes. This predicts that parietal regions that receive inputs from the ventral visual pathway should exhibit object-selective responses that are resilient to contralateral visual field biases. To test this hypothesis, adult participants viewed images of tools and animals that were presented to the left or right visual fields during functional magnetic resonance imaging (fMRI). We found that the left inferior parietal lobule showed robust tool preferences independently of the visual field in which tool stimuli were presented. In contrast, a region in posterior parietal/dorsal occipital cortex in the right hemisphere exhibited an interaction between visual field and category: tool-preferences were strongest contralateral to the stimulus. These findings suggest that action knowledge accessed in the left inferior parietal lobule operates over inputs that are abstracted from the visual input and is contingent on analysis by the ventral visual pathway, consistent with its putative role in supporting object manipulation knowledge.