Naturalistic stimuli reveal a sensitive period in cross modal responses of visual cortex: Evidence from adult-onset blindness.

How do life experiences impact cortical function? In people who are born blind, the "visual" cortices are recruited during nonvisual tasks, such as Braille reading and sound localization. Do visual cortices have a latent capacity to respond to nonvisual information throughout the lifespan? Alternatively, is there a sensitive period of heightened plasticity that makes visual cortex repurposing especially possible during childhood? To gain insight into these questions, we leveraged meaningful naturalistic auditory stimuli to simultaneously engage a broad range of cognitive domains and quantify cross-modal responses across congenitally blind (n = 22), adult-onset blind (vision loss >18 years-of-age, n = 14) and sighted (n = 22) individuals. During fMRI scanning, participants listened to two types of meaningful naturalistic auditory stimuli: excerpts from movies and a spoken narrative. As controls, participants heard the same narrative with the sentences shuffled and the narrative played backwards (i.e., meaningless sounds). We correlated the voxel-wise timecourses of different participants within condition and group. For all groups, all stimulus conditions induced synchrony in auditory cortex while only the narrative stimuli synchronized responses in higher-cognitive fronto-parietal and temporal regions. As previously reported, inter-subject synchrony in visual cortices was higher in congenitally blind than sighted blindfolded participants and this between-group difference was particularly pronounced for meaningful stimuli (movies and narrative). Critically, visual cortex synchrony was no higher in adult-onset blind than sighted blindfolded participants and did not increase with blindness duration. Sensitive period plasticity enables cross-modal repurposing in visual cortices.

Naturalistic Audio-Movies reveal common spatial organization across "visual" cortices of different blind individuals.

Occipital cortices of different sighted people contain analogous maps of visual information (e.g. foveal vs. peripheral). In congenital blindness, "visual" cortices respond to nonvisual stimuli. Do visual cortices of different blind people represent common informational maps? We leverage naturalistic stimuli and inter-subject pattern similarity analysis to address this question. Blindfolded sighted (n = 22) and congenitally blind (n = 22) participants listened to 6 sound clips (5-7 min each): 3 auditory excerpts from movies; a naturalistic spoken narrative; and matched degraded auditory stimuli (Backwards Speech, scrambled sentences), during functional magnetic resonance imaging scanning. We compared the spatial activity patterns evoked by each unique 10-s segment of the different auditory excerpts across blind and sighted people. Segments of meaningful naturalistic stimuli produced distinctive activity patterns in frontotemporal networks that were shared across blind and across sighted individuals. In the blind group only, segment-specific, cross-subject patterns emerged in visual cortex, but only for meaningful naturalistic stimuli and not Backwards Speech. Spatial patterns of activity within visual cortices are sensitive to time-varying information in meaningful naturalistic auditory stimuli in a broadly similar manner across blind individuals.

Superior verbal but not nonverbal memory in congenital blindness.

Previous studies suggest that people who are congenitally blind outperform sighted people on some memory tasks. Whether blindness-associated memory advantages are specific to verbal materials or are also observed with nonverbal sounds has not been determined. Congenitally blind individuals (n = 20) and age and education matched blindfolded sighted controls (n = 22) performed a series of auditory memory tasks. These included: verbal forward and backward letter spans, a complex letter span with intervening equations, as well as two matched recognition tasks: one with verbal stimuli (i.e., letters) and one with nonverbal complex meaningless sounds. Replicating previously observed findings, blind participants outperformed sighted people on forward and backward letter span tasks. Blind participants also recalled more letters on the complex letter span task despite the interference of intervening equations. Critically, the same blind participants showed larger advantages on the verbal as compared to the nonverbal recognition task. These results suggest that blindness selectively enhances memory for verbal material. Possible explanations for blindness-related verbal memory advantages include blindness-induced memory practice and 'visual' cortex recruitment for verbal processing.

'Visual' cortices of congenitally blind adults are sensitive to response selection demands in a go/no-go task.

Studies of occipital cortex plasticity in blindness provide insight into how intrinsic constraints interact with experience to determine cortical specialization. We tested the cognitive nature and anatomical origins of occipital responses during non-verbal, non-spatial auditory tasks. In a go/no-go task, congenitally blind (N=23) and sighted (N=24) individuals heard rapidly occurring (<1/s) non-verbal sounds and made one of two button presses (frequent-go 50%, infrequent-go 25%) or withheld a response (no-go, 25%). Rapid and frequent button presses heighten response selection/inhibition demands on the no-go trials: In sighted and blind adults a right-lateralized prefrontal (PFC) network responded most to no-go trials, followed by infrequent-go and finally frequent-go trials. In the blind group only, a right-lateralized occipital network showed the same response profile and the laterality of occipital and PFC responses was correlated across blind individuals. A second experiment with spoken sentences and equations (N=16) found that no-go responses in occipital cortex are distinct from previously identified occipital responses to spoken language. Finally, in resting-state data (N=30 blind, N=31 blindfolded sighted), no-go responsive 'visual' cortex of blind relative to sighted participants was more synchronized with PFC and less synchronized with primary auditory and sensory-motor cortices. No-go responsive occipital cortex showed higher resting-state correlations with no-go responsive PFC than language responsive inferior frontal cortex. We conclude that in blindness, a right-lateralized occipital network responds to non-verbal executive processes, including response selection. These results suggest that connectivity with fronto-parietal executive networks is a key mechanism for plasticity in blindness.

When Not Choosing Leads to Not Liking: Choice-Induced Preference in Infancy.

The question of how people's preferences are shaped by their choices has generated decades of research. In a classic example, work on cognitive dissonance has found that observers who must choose between two equally attractive options subsequently avoid the unchosen option, suggesting that not choosing the item led them to like it less. However, almost all of the research on such choice-induced preference focuses on adults, leaving open the question of how much experience is necessary for its emergence. Here, we examined the developmental roots of this phenomenon in preverbal infants (N = 189). In a series of seven experiments using a free-choice paradigm, we found that infants experienced choice-induced preference change similar to adults'. Infants' choice patterns reflected genuine preference change and not attraction to novelty or inherent attitudes toward the options. Hence, choice shapes preferences-even without extensive experience making decisions and without a well-developed self-concept.

Enhanced performance on a sentence comprehension task in congenitally blind adults.

People born blind habitually experience linguistic utterances in the absence of visual cues and activate "visual" cortices during sentence comprehension. Do blind individuals show superior performance on sentence processing tasks? Congenitally blind (n=25) and age and education matched sighted (n=52) participants answered yes/no who-did-what-to-whom questions for auditorily-presented sentences, some of which contained a grammatical complexity manipulation (long-distance movement dependency or garden path). Short-term memory was measured with a forward and backward letter-spans. A battery of control tasks included two speeded math tasks and vocabulary and reading tasks from Woodcock Johnson III. The blind group outperformed the sighted on the sentence comprehension task, particularly for garden-path sentences, and on short-term memory span tasks, but performed similar to the sighted on control tasks. Sentence comprehension performance was not correlated with span performance, suggesting independent enhancements.

Naturalistic Audio-Movies and Narrative Synchronize "Visual" Cortices across Congenitally Blind But Not Sighted Individuals.

How does developmental experience, as opposed to intrinsic physiology, shape cortical function? Naturalistic stimuli were used to elicit neural synchrony in individuals blind from birth (n = 18) and those who grew up with sight (n = 18). Blind and blindfolded sighted participants passively listened to three audio-movie clips, an auditory narrative, a sentence shuffled version of the narrative (maintaining language but lacking a plotline), and a version of the narrative backward (lacking both language and plot). For both groups, early auditory cortices were synchronized to a similar degree across stimulus types, whereas higher-cognitive temporoparietal and prefrontal areas were more synchronized by meaningful, temporally extended stimuli (i.e., audio movies and narrative). "Visual" cortices were more synchronized across blind than sighted individuals, but only for audio-movies and narrative. In the blind group, visual cortex synchrony was low for backward speech and intermediate for sentence shuffle. Meaningful auditory stimuli synchronize visual cortices of people born blind.SIGNIFICANCE STATEMENT Naturalistic stimuli engage cognitive processing at many levels. Here, we harnessed this richness to investigate the effect of experience on cortical function. We find that listening to naturalistic audio movies and narrative drives synchronized activity across "visual" cortices of blind, more so than sighted, individuals. Visual cortex synchronization varies with meaningfulness and cognitive complexity. Higher synchrony is observed for temporally extended meaningful stimuli (e.g., movies/narrative), intermediate for shuffled sentences, lowest for time varying complex noise. By contrast, auditory cortex was synchronized equally by meaningful and meaningless stimuli. In congenitally blind individuals most of visual cortex is engaged by meaningful naturalistic stimuli.

A signal detection theory analysis of behavioral pattern separation paradigms.

Behavioral pattern separation (BPS) paradigms ask participants to discriminate previously encoded (old) stimuli from highly similar (lure) and categorically distinct (novel) stimuli. The lure-old discrimination, thought to uniquely reflect pattern separation in the hippocampal formation, is typically pitted against the traditional novel-old discrimination. However, BPS paradigms have measured lure-old discrimination neither consistently across studies nor in such a way that allows for accurate comparison to novel-old discrimination. Therefore, we advocate for signal detection theory (SDT) as a unified framework. Moreover, we compare SDT with previously used measures of lure-old discrimination, indicating how other formulas' inaccuracies can lead to erroneous conclusions.

Functional connectivity of the frontoparietal network predicts cognitive modulation of pain.

The experience of pain can be significantly influenced by expectancy (predictive cues). This ability to modulate pain has the potential to affect therapeutic analgesia substantially and constitutes a foundation for nonpharmacological pain relief. In this study, we investigated (1) brain regions involved in visual cue modulation of pain during anticipation of pain, pain administration, and pain rating; and (2) the association between pretest resting state functional connectivity and the magnitude of cue effects on pain ratings. We found that after cue conditioning, visual cues can significantly modulate subjective pain ratings. Functional magnetic resonance imaging results suggested that brain regions pertaining to the frontoparietal network (prefrontal and parietal cortex) and a pain/emotion modulatory region (rostral anterior cingulate cortex) are involved in cue modulation during both pain anticipation and administration stage. Most interestingly, we found that pretest resting state functional connectivity between the frontoparietal network (as identified by independent component analysis) and the rostral anterior cingulate cortex/medial prefrontal cortex was positively associated with cue effects on pain rating changes. We believe that these findings will shed new light on our understanding of variable cue/expectancy effects across individuals and how the intrinsic connectivity of the brain may influence expectancy-induced modulation of pain.

Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment.

BACKGROUND: Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. RESULTS: Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels. CONCLUSIONS: Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.