This meta-analysis summarizes evidence from 44 neuroimaging experiments and characterizes the general linguistic network in early deaf individuals. Meta-analytic comparisons with hearing individuals found that a specific set of regions (in particular the left inferior frontal gyrus and posterior middle temporal gyrus) participates in supramodal language processing. In addition to previously described modality-specific differences, the present study showed that the left calcarine gyrus and the right caudate were additionally recruited in deaf compared with hearing individuals. In addition, this study showed that the bilateral posterior superior temporal gyrus is shaped by cross-modal plasticity, whereas the left frontotemporal areas are shaped by early language experience. Although an overall left-lateralized pattern for language processing was observed in the early deaf individuals, regional lateralization was altered in the inferior frontal gyrus and anterior temporal lobe. These findings indicate that the core language network functions in a modality-independent manner, and provide a foundation for determining the contributions of sensory and linguistic experiences in shaping the neural bases of language processing.

Deprivation of one sense can be followed by enhanced development of other senses via cross-modal plasticity mechanisms. To study the effect of whisker tactile deprivation on vision during the early stages of development, we clipped the bilateral whiskers of young mice and found that their vision was impaired but later recovered to normal levels. Our results demonstrate that inhibition of the PI3K/AKT/ERK signaling pathway caused short-term visual impairment during early development, while high expression levels of Crystallin Alpha A (CRYAA) and Gap Junction Protein Alpha 8 (GJA8) in the retina led to the recovery of developmental visual acuity. Interestingly, analysis of single-cell sequencing results from human embryonic retinas at 9-19 gestational weeks (GW) revealed that CRYAA and GJA8 display stage-specific peak expression during human embryonic retinal development, suggesting potential functions in visual development. Our data show that high expression levels of CRYAA and GJA8 in the retina after whisker deprivation rescue impaired visual development, which may provide a foundation for further research on the mechanisms of cross-modal plasticity and in particular, offer new insights into the mechanisms underlying tactile-visual cross-modal development.

Pituitary adenoma (PA) may compress the optic apparatus, resulting in impaired vision. Some patients can experience improved vision rapidly after surgery. During the early period after surgery, however, the change in neurofunction in the extravisual cortex and higher cognitive cortex has yet to be explored.
Our study focused on the changes in the extravisual resting-state networks in patients with PA after vision restoration.
We recruited 14 patients with PA who experienced visual improvement after surgery. The functional connectivity (FC) of 6 seeds [auditory cortex (A1), Broca\'s area, posterior cingulate cortex (PCC) for the default mode network (DMN), right caudal anterior cingulate cortex for the salience network (SN) and left dorsolateral prefrontal cortex for the executive control network (ECN)] were evaluated. A paired t test was conducted to identify the differences between two groups of patients.
Compared with their preoperative counterparts, patients with PA with improved vision exhibited decreased FC with the right A1 in the left insula lobule, right middle temporal gyrus and left postcentral gyrus and increased FC in the right paracentral lobule; decreased FC with the Broca in the left middle temporal gyrus and increased FC in the left insula lobule and right thalamus; decreased FC with the DMN in the right declive and right precuneus; increased FC in right Brodmann area 17, the left cuneus and the right posterior cingulate; decreased FC with the ECN in the right posterior cingulate, right angular and right precuneus; decreased FC with the SN in the right middle temporal gyrus, right hippocampus, and right precuneus; and increased FC in the right fusiform gyrus, the left lingual gyrus and right Brodmann area 19.
Vision restoration may cause a response of cross-modal plasticity and multisensory systems related to A1 and the Broca. The DMN and SN may be involved in top-down control of the subareas within the visual cortex. The precuneus may be involved in the DMN, ECN and SN simultaneously.

The fusiform face area (FFA) is a core cortical region for face information processing. Evidence suggests that its sensitivity to faces is largely innate and tuned by visual experience. However, how experience in different time windows shape the plasticity of the FFA remains unclear. In this study, we investigated the role of visual experience at different time points of an individual\'s early development in the cross-modal face specialization of the FFA. Participants (n = 74) were classified into five groups: congenital blind, early blind, late blind, low vision, and sighted control. Functional magnetic resonance imaging data were acquired when the participants haptically processed carved faces and other objects. Our results showed a robust and highly consistent face-selective activation in the FFA region in the early blind participants, invariant to size and level of abstraction of the face stimuli. The cross-modal face activation in the FFA was much less consistent in other groups. These results suggest that early visual experience primes cross-modal specialization of the FFA, and even after the absence of visual experience for more than 14 years in early blind participants, their FFA can engage in cross-modal processing of face information.

Sensory cortices, classically considered to represent modality-specific sensory information, are also found to engage in multisensory processing. However, how sensory processing in sensory cortices is cross-modally modulated remains an open question. Specifically, we understand little of cross-modal representation in sensory cortices in perceptual tasks and how perceptual learning modifies this process. Here, we recorded neural responses in primary auditory cortex (A1) both while freely moving rats discriminated stimuli in Go/No-Go tasks and when anesthetized. Our data show that cross-modal representation in auditory cortices varies with task contexts. In the task of an audiovisual cue being the target associating with water reward, a significantly higher proportion of auditory neurons showed a visually evoked response. The vast majority of auditory neurons, if processing auditory-visual interactions, exhibit significant multisensory enhancement. However, when the rats performed tasks with unisensory cues being the target, cross-modal inhibition, rather than enhancement, predominated. In addition, multisensory associational learning appeared to leave a trace of plastic change in A1, as a larger proportion of A1 neurons showed multisensory enhancement in anesthesia. These findings indicate that multisensory processing in principle sensory cortices is not static, and having cross-modal interaction in the task requirement can substantially enhance multisensory processing in sensory cortices.

Changes in the electrical activities of visual and auditory thalamic-cortical regions account for the cross-modal enhancement of auditory perception following visual deprivation, but the molecular regulatory factors mediating these changes remain elusive. In this study, we showed that the expression patterns of five glutamate receptor (GluR) subunits which involved in regulating the synaptic plasticity in mouse primary visual (V1) cortex and primary auditory (A1) cortex undergone elaborate modification with layer-specificity after visual deprivation using dark-exposure (DE). The expression levels of NR1 and NR2B were increased, and those of GluR1 and NR2B in the V1 cortex were decreased after DE. In the A1 cortex, the expression levels of NR1, NR2A and NR2B were increased, and the expression levels of GluR1 and GluR2 were decreased after DE. The altered expression levels of GluR subunits selectively happened in the different layers of V1 and A1 cortices. In addition, the expression level of GluR2 in lateral geniculate nucleus (LGN) was decreased. These results provide novel molecular clues for the plastic neural activity in visual and auditory centers in the absence of visual input, and hint the extensive refinement of intracortical circuits and thalamocortical feedback circuits underlying the multisensory cross-modal plasticity.

Sensory experience regulates the structural and functional wiring of sensory cortices. In previous work, we showed that whisker deprivation (WD) from birth not only reduced excitatory synaptic transmission of layer (L) 2/3 pyramidal neurons of the correspondent barrel cortex in mice, but also cross-modally reduced synaptic transmission of L2/3 pyramidal neurons in other sensory cortices. Here, we used in utero electroporation, in combination with optical clearing, to examine the main morphological components regulating neural circuit wiring, namely presynaptic bouton density, spine density, as well as dendrite and axon arbor lengths. We found that WD from P0 to P14 reduced presynaptic bouton density in both L4 and L2/3 inputs to L2/3 pyramidal neurons, as well as spine density across the dendritic tree of L2/3 pyramidal neurons, in the barrel field of the primary somatosensory cortex. The cross-modal effects in the primary auditory cortex were manifested mostly as reduced dendrite and axon arbor size, as well as reduced bouton density of L2/3 inputs. Increasing sensory experience by rearing mice in an enriched environment rescued the effects of WD. Together, these results demonstrate that multiple morphological factors contribute to experience-dependent structural plasticity during early wiring of the sensory cortices.

Cross-modal occipital responses appear to be essential for nonvisual processing in individuals with early blindness. However, it is not clear whether the recruitment of occipital regions depends on functional domain or sensory modality. The current study utilized a coordinate-based meta-analysis to identify the distinct brain regions involved in the functional domains of object, spatial/motion, and language processing and the common brain regions involved in both auditory and tactile modalities in individuals with early blindness. Following the PRISMA guidelines, a total of 55 studies were included in the meta-analysis. The specific analyses revealed the brain regions that are consistently recruited for each function, such as the dorsal fronto-parietal network for spatial function and ventral occipito-temporal network for object function. This is consistent with the literature, suggesting that the two visual streams are preserved in early blind individuals. The contrast analyses found specific activations in the left cuneus and lingual gyrus for language function. This finding is novel and suggests a reverse hierarchical organization of the visual cortex for early blind individuals. The conjunction analyses found common activations in the right middle temporal gyrus, right precuneus and a left parieto-occipital region. Clinically, this work contributes to visual rehabilitation in early blind individuals by revealing the function-dependent and sensory-independent networks during nonvisual processing.

The auditory cortex has been shown to participate in visual processing in individuals with complete auditory deprivation. However, it remains unclear whether partial hearing deprivation like single-sided deafness (SSD) leads to similar cross-modal plasticity. To investigate this, we enrolled individuals with long-term SSD, into functional MRI scans under resting-state and a visuo-spatial working memory task. Contrary to previous findings in bilateral deafness, our study revealed decreased activation in the auditory cortex in both left (LSSD) and right (RSSD) single-sided deafness compared to normal hearing controls, with statistical significance in RSSD. The degree of involvement was correlated with residual hearing ability in RSSD. These observations suggest that SSD can lead to a downward cross-modal plasticity: the more hearing ability lost, the fewer brain resources in the auditory cortex can be applied to visual tasks. In addition, the fronto-parietal cortex was observed to be less activated during the visual task in RSSD while the resting-state fMRI revealed increased functional connectivity between the fronto-parietal cortex and the auditory cortex, suggesting fronto-parietal resources may be recruited less by vision but more by hearing. The LSSD showed a similar alteration trend with RSSD, but without statistical significance. Together these findings may indicate that when hearing is partially deprived in SSD, there may be redistribution for brain resources between hearing and vision, and vision tends to allocate less resources. Our findings in this pilot study of unilateral auditory-deprived individuals enrich the understanding of cross-modal plasticity in the brain.

Loss of vision may enhance the capabilities of auditory perception, but the mechanisms mediating these changes remain elusive. Here, visual deprivation in rats resulted in altered oscillatory activities, which appeared to be the result of a common mechanism underlying neuronal assembly formation in visual and auditory centers. The power of high-frequency β and γ oscillations in V1 (the primary visual cortex) and β oscillations in the LGN (lateral geniculate nucleus) was increased after one week of visual deprivation. Meanwhile, the power of β oscillations in A1 (the primary auditory cortex) and the power of β and γ oscillations in the MGB (medial geniculate body) were also enhanced in the absence of visual input. Furthermore, nerve tracing revealed a bidirectional nerve fiber connection between V1 and A1 cortices, which might be involved in transmitting auditory information to the visual cortex, contributing to enhanced auditory perception after visual deprivation. These results may facilitate the better understanding of multisensory cross-modal plasticity.