Functional partitioning of sentence processing and emotional prosody in the right perisylvian cortex after perinatal stroke.

In healthy adults different language abilities-sentence processing versus emotional prosody-are supported by the left (LH) versus the right hemisphere (RH), respectively. However, after LH stroke in infancy, RH regions support both abilities with normal outcomes. We investigated how these abilities co-exist in RH regions after LH perinatal stroke by evaluating the overlap in the activation between two fMRI tasks that probed auditory sentence processing and emotional prosody processing. We compared the overlap for these two functions in the RH of individuals with perinatal stroke with the symmetry of these functions in the LH and RH of their healthy siblings. We found less activation overlap in the RH of individuals with LH perinatal stroke than would be expected if both functions retained their typical spatial layout, suggesting that their spatial segregation may be an important feature of a functioning language system.

Rethinking Remapping: Circuit Mechanisms of Recovery after Stroke.

Stroke is one of the most common causes of disability, and there are few treatments that can improve recovery after stroke. Therapeutic development has been hindered because of a lack of understanding of precisely how neural circuits are affected by stroke, and how these circuits change to mediate recovery. Indeed, some of the hypotheses for how the CNS changes to mediate recovery, including remapping, redundancy, and diaschisis, date to more than a century ago. Recent technological advances have enabled the interrogation of neural circuits with ever greater temporal and spatial resolution. These techniques are increasingly being applied across animal models of stroke and to human stroke survivors, and are shedding light on the molecular, structural, and functional changes that neural circuits undergo after stroke. Here we review these studies and highlight important mechanisms that underlie impairment and recovery after stroke. We begin by summarizing knowledge about changes in neural activity that occur in the peri-infarct cortex, specifically considering evidence for the functional remapping hypothesis of recovery. Next, we describe the importance of neural population dynamics, disruptions in these dynamics after stroke, and how allocation of neurons into spared circuits can restore functionality. On a more global scale, we then discuss how effects on long-range pathways, including interhemispheric interactions and corticospinal tract transmission, contribute to post-stroke impairments. Finally, we look forward and consider how a deeper understanding of neural circuit mechanisms of recovery may lead to novel treatments to reduce disability and improve recovery after stroke.

One right can make a left: sentence processing in the right hemisphere after perinatal stroke.

When brain regions that are critical for a cognitive function in adulthood are irreversibly damaged at birth, what patterns of plasticity support the successful development of that function in an alternative location? Here we investigate the consistency of language organization in the right hemisphere (RH) after a left hemisphere (LH) perinatal stroke. We analyzed fMRI data collected during an auditory sentence comprehension task on 14 people with large cortical LH perinatal arterial ischemic strokes (left hemisphere perinatal stroke (LHPS) participants) and 11 healthy sibling controls using a "top voxel" approach that allowed us to compare the same number of active voxels across each participant and in each hemisphere for controls. We found (1) LHPS participants consistently recruited the same RH areas that were a mirror-image of typical LH areas, and (2) the RH areas recruited in LHPS participants aligned better with the strongly activated LH areas of the typically developed brains of control participants (when flipped images were compared) than the weakly activated RH areas. Our findings suggest that the successful development of language processing in the RH after a LH perinatal stroke may in part depend on recruiting an arrangement of frontotemporal areas reflective of the typical dominant LH.

Spoken language processing activates the primary visual cortex.

Primary visual cortex (V1) is generally thought of as a low-level sensory area that primarily processes basic visual features. Although there is evidence for multisensory effects on its activity, these are typically found for the processing of simple sounds and their properties, for example spatially or temporally-congruent simple sounds. However, in congenitally blind individuals, V1 is involved in language processing, with no evidence of major changes in anatomical connectivity that could explain this seemingly drastic functional change. This is at odds with current accounts of neural plasticity, which emphasize the role of connectivity and conserved function in determining a neural tissue's role even after atypical early experiences. To reconcile what appears to be unprecedented functional reorganization with known accounts of plasticity limitations, we tested whether V1's multisensory roles include responses to spoken language in sighted individuals. Using fMRI, we found that V1 in normally sighted individuals was indeed activated by comprehensible spoken sentences as compared to an incomprehensible reversed speech control condition, and more strongly so in the left compared to the right hemisphere. Activation in V1 for language was also significant and comparable for abstract and concrete words, suggesting it was not driven by visual imagery. Last, this activation did not stem from increased attention to the auditory onset of words, nor was it correlated with attentional arousal ratings, making general attention accounts an unlikely explanation. Together these findings suggest that V1 responds to spoken language even in sighted individuals, reflecting the binding of multisensory high-level signals, potentially to predict visual input. This capability might be the basis for the strong V1 language activation observed in people born blind, re-affirming the notion that plasticity is guided by pre-existing connectivity and abilities in the typically developed brain.

Investigating Compensatory Brain Activity in Older Adults with Subjective Cognitive Decline.

BACKGROUND: Preclinical Alzheimer's disease (AD) is one possible cause of subjective cognitive decline (SCD). Normal task performance despite ongoing neurodegeneration is typically considered as neuronal compensation, which is reflected by greater neuronal activity. Compensatory brain activity has been observed in frontal as well as parietal regions in SCD, but data are scarce, especially outside the memory domain. OBJECTIVE: To investigate potential compensatory activity in SCD. Such compensatory activity is particularly expected in participants where blood-based biomarkers indicated amyloid positivity as this implies preclinical AD. METHODS: 52 participants with SCD (mean age: 71.00±5.70) underwent structural and functional neuroimaging (fMRI), targeting episodic memory and spatial abilities, and a neuropsychological assessment. The estimation of amyloid positivity was based on plasma amyloid-ß and phosphorylated tau (pTau181) measures. RESULTS: Our fMRI analyses of the spatial abilities task did not indicate compensation, with only three voxels exceeding an uncorrected threshold at p < 0.001. This finding was not replicated in a subset of 23 biomarker positive individuals. CONCLUSION: Our results do not provide conclusive evidence for compensatory brain activity in SCD. It is possible that neuronal compensation does not manifest at such an early stage as SCD. Alternatively, it is possible that our sample size was too small or that compensatory activity may be too heterogeneous to be detected by group-level statistics. Interventions based on the individual fMRI signal should therefore be explored.

Language and developmental plasticity after perinatal stroke.

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

A Weak Shadow of Early Life Language Processing Persists in the Right Hemisphere of the Mature Brain.

Studies of language organization show a striking change in cerebral dominance for language over development: We begin life with a left hemisphere (LH) bias for language processing, which is weaker than that in adults and which can be overcome if there is a LH injury. Over development this LH bias becomes stronger and can no longer be reversed. Prior work has shown that this change results from a significant reduction in the magnitude of language activation in right hemisphere (RH) regions in adults compared to children. Here we investigate whether the spatial distribution of language activation, albeit weaker in magnitude, still persists in homotopic RH regions of the mature brain. Children aged 4-13 (n = 39) and young adults (n = 14) completed an auditory sentence comprehension fMRI (functional magnetic resonance imaging) task. To equate neural activity across the hemispheres, we applied fixed cutoffs for the number of active voxels that would be included in each hemisphere for each participant. To evaluate homotopicity, we generated left-right flipped versions of each activation map, calculated spatial overlap between the LH and RH activity in frontal and temporal regions, and tested for mean differences in the spatial overlap values between the age groups. We found that, in children as well as in adults, there was indeed a spatially intact shadow of language activity in the right frontal and temporal regions homotopic to the LH language regions. After a LH stroke in adulthood, recovering early-life activation in these regions might assist in enhancing recovery of language abilities.

Emotion recognition impairments and social well-being following right-hemisphere stroke.

Accurately recognizing and responding to the emotions of others is essential for proper social communication and helps bind strong relationships that are particularly important for stroke survivors. Emotion recognition typically engages cortical areas that are predominantly right-lateralized including superior temporal and inferior frontal gyri - regions frequently impacted by right-hemisphere stroke. Since prior work already links right-hemisphere stroke to deficits in emotion recognition, this research aims to extend these findings to determine whether impaired emotion recognition after right-hemisphere stroke is associated with worse social well-being outcomes. Eighteen right-hemisphere stroke patients (≥6 months post-stroke) and 21 neurologically healthy controls completed a multimodal emotion recognition test (Geneva Emotion Recognition Test - Short) and reported engagement in social/non-social activities and levels of social support. Right-hemisphere stroke was associated with worse emotion recognition accuracy, though not all patients exhibited impairment. In line with hypotheses, emotion recognition impairments were associated with greater loss of social activities after stroke, an effect that could not be attributed to stroke severity or loss of non-social activities. Impairments were also linked to reduced patient-reported social support. Results implicate emotion recognition difficulties as a potential antecedent of social withdrawal after stroke and warrant future research to test emotion recognition training post-stroke.

Developmental changes in neural lateralization for visual-spatial function: Evidence from a line-bisection task.

Studies of hemispheric specialization have traditionally cast the left hemisphere as specialized for language and the right hemisphere for spatial function. Much of the supporting evidence for this separation of function comes from studies of healthy adults and those who have sustained lesions to the right or left hemisphere. However, we know little about the developmental origins of lateralization. Recent evidence suggests that the young brain represents language bilaterally, with 4-6-year-olds activating the left-hemisphere regions known to support language in adults as well as homotopic regions in the right hemisphere. This bilateral pattern changes over development, converging on left-hemispheric activation in late childhood. In the present study, we ask whether this same developmental trajectory is observed in a spatial task that is strongly right-lateralized in adults-the line bisection (or "Landmark") task. We examined fMRI activation among children ages 5-11 years as they were asked to judge which end of a bisected vertical line was longer. We found that young children showed bilateral activation, with activation in the same areas of the right hemisphere as has been shown among adults, as well as in the left hemisphere homotopic regions. By age 10, activation was right-lateralized. This strongly resembles the developmental trajectory for language, moving from bilateral to lateralized activation. We discuss potential underlying mechanisms and suggest that understanding the development of lateralization for a range of cognitive functions can play a crucial role in understanding general principles of how and why the brain comes to lateralize certain functions.

Development of bilateral parietal activation for complex visual-spatial function: Evidence from a visual-spatial construction task.

The neural representation of visual-spatial functions has traditionally been ascribed to the right hemisphere, but little is known about these representations in children, including whether and how lateralization of function changes over the course of development. Some studies suggest bilateral activation early in life that develops toward right-lateralization in adulthood, while others find evidence of right-hemispheric dominance in both children and adults. We used a complex visual-spatial construction task to examine the nature of lateralization and its developmental time course in children ages 5-11 years. Participants were shown two puzzle pieces and were asked whether the pieces could fit together to make a square; responses required either mental translation of the pieces (Translation condition) or both mental translation and rotation of the pieces (Rotation condition). Both conditions were compared to a matched Luminance control condition that was similar in terms of visual content and difficulty but required no spatial analysis. Group and single-subject analyses revealed that the Rotation and Translation conditions elicited strongly bilateral activation in the same parietal and occipital locations as have been previously found for adults. These findings show that visual-spatial construction consistently elicits robust bilateral activation from age 5 through adulthood. This challenges the idea that spatial functions are all right-lateralized, either during early development or in adulthood. More generally, these findings provide insights into the developmental course of lateralization across different spatial skills and how this may be influenced by the computational requirements of the particular functions involved.