The oculomotor nerve (OCN) is the main motor nerve innervating eye muscles and can be involved in multiple flammatory, compressive, or pathologies. The diffusion magnetic resonance imaging (dMRI) tractography is now widely used to describe the trajectory of the OCN. However, the complex cranial structure leads to difficulties in fiber orientation distribution (FOD) modeling, fiber tracking, and region of interest (ROI) selection. Currently, the identification of OCN relies on expert manual operation, resulting in challenges, such as the carries high clinical, time-consuming, and labor costs. Thus, we propose a method that can automatically identify OCN from dMRI tractography. First, we choose the multi-shell multi-tissue constraint spherical deconvolution (MSMT-CSD) FOD estimation model and deterministic tractography to describe the 3D trajectory of the OCN. Then, we rely on the well-established computational pipeline and anatomical expertise to create a data-driven OCN tractography atlas from 40 HCP data. We identify six clusters belonging to the OCN from the atlas, including the structures of three kinds of positional relationships (pass between, pass through, and go around) with the red nuclei and two kinds of positional relationships with medial longitudinal fasciculus. Finally, we apply the proposed OCN atlas to identify the OCN automatically from 40 new HCP subjects and two patients with brainstem cavernous malformation. In terms of spatial overlap and visualization, experiment results show that the automatically and manually identified OCN fibers are consistent. Our proposed OCN atlas provides an effective tool for identifying OCN by avoiding the traditional selection strategy of ROIs.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Magnetic resonance imaging (MRI) has been one of the primary instruments to measure the properties of the human brain non-invasively in vivo. MRI data generally needs to go through a series of processing steps (i.e., a pipeline) before statistical analysis. Currently, the processing pipelines for multi-modal MRI data are still rare, in contrast to single-modal pipelines. Furthermore, the reliability and validity of the output of the pipelines are critical for the MRI studies. However, the reliability and validity measures are not available or adequate for almost all pipelines. Here, we present PhiPipe, a multi-modal MRI processing pipeline. PhiPipe could process T1-weighted, resting-state BOLD, and diffusion-weighted MRI data and generate commonly used brain features in neuroimaging. We evaluated the test-retest reliability of PhiPipe's brain features by computing intra-class correlations (ICC) in four public datasets with repeated scans. We further evaluated the predictive validity by computing the correlation of brain features with chronological age in three public adult lifespan datasets. The multivariate reliability and predictive validity of the PhiPipe results were also evaluated. The results of PhiPipe were consistent with previous studies, showing comparable or better reliability and validity when compared with two popular single-modality pipelines, namely DPARSF and PANDA. The publicly available PhiPipe provides a simple-to-use solution to multi-modal MRI data processing. The accompanied reliability and validity assessments could help researchers make informed choices in experimental design and statistical analysis. Furthermore, this study provides a framework for evaluating the reliability and validity of image processing pipelines.

Previous neuroimaging studies demonstrated that ventromedial prefrontal cortex (vmPFC) activity reflects how much an individual positively views each person (impression). Here, we investigated whether the degree to which individuals think others positively view them (reflected impression) is similarly tracked by activity in the vmPFC by using fMRI and speed-dating events. We also examined whether activity of the vmPFC in response to the faces of others would predict the impression formed through direct interactions with them. The task consisted of three sessions: pre-speed-dating fMRI, speed-dating events, and post-speed-dating fMRI (not reported here). During the pre-speed-dating fMRI, each participant passively viewed the faces of others whom they would meet in the subsequent speed-dating events. After the fMRI, they rated the impression and reflected impression of each face. During the speed-dating events, the participants had 3-min conversations with partners whose faces were presented during the fMRI task, and they were asked to choose the partners whom they preferred at the end of the events. The results revealed that the value of both the impression and reflected impression were automatically represented in the vmPFC. However, the impression fully mediated the link between the reflected impression and vmPFC activity. These results highlight a close link between reflected appraisal and impression formation and provide important insights into neural and psychological models of how the reflected impression is formed in the human brain.

To solve spatial tasks, the human brain asks for support from the visual cortices. Nonetheless, representing spatial information is not fixed but depends on the reference frames in which the spatial inputs are involved. The present study investigates how the kind of spatial representations influences the recruitment of visual areas during multisensory spatial tasks. Our study tested participants in an electroencephalography experiment involving two audio-visual (AV) spatial tasks: a spatial bisection, in which participants estimated the relative position in space of an AV stimulus in relation to the position of two other stimuli, and a spatial localization, in which participants localized one AV stimulus in relation to themselves. Results revealed that spatial tasks specifically modulated the occipital event-related potentials (ERPs) after the onset of the stimuli. We observed a greater contralateral early occipital component (50-90 ms) when participants solved the spatial bisection, and a more robust later occipital response (110-160 ms) when they processed the spatial localization. This observation suggests that different spatial representations elicited by multisensory stimuli are sustained by separate neurophysiological mechanisms.

Volumetric assessments of the hippocampus and other brain structures during childhood provide useful indices of brain development and correlates of cognitive functioning in typically and atypically developing children. Automated methods such as FreeSurfer promise efficient and replicable segmentation, but may include errors which are avoided by trained manual tracers. A recently devised automated correction tool that uses a machine learning algorithm to remove systematic errors, the Automatic Segmentation Adapter Tool (ASAT), was capable of substantially improving the accuracy of FreeSurfer segmentations in an adult sample [Wang et al., 2011], but the utility of ASAT has not been examined in pediatric samples. In Study 1, the validity of FreeSurfer and ASAT corrected hippocampal segmentations were examined in 20 typically developing children and 20 children with autism spectrum disorder aged 2 and 3 years. We showed that while neither FreeSurfer nor ASAT accuracy differed by disorder or age, the accuracy of ASAT corrected segmentations were substantially better than FreeSurfer segmentations in every case, using as few as 10 training examples. In Study 2, we applied ASAT to 89 typically developing children aged 2 to 4 years to examine relations between hippocampal volume, age, sex, and expressive language. Girls had smaller hippocampi overall, and in left hippocampus this difference was larger in older than younger girls. Expressive language ability was greater in older children, and this difference was larger in those with larger hippocampi, bilaterally. Overall, this research shows that ASAT is highly reliable and useful to examinations relating behavior to hippocampal structure.

People preferentially imitate others who are similar to them or have high social status. Such imitative biases are thought to have evolved because they increase the efficiency of cultural acquisition. Here we focused on distinguishing between self-similarity and social status as two candidate mechanisms underlying neural responses to a person's race during imitation. We used fMRI to measure neural responses when 20 African American (AA) and 20 European American (EA) young adults imitated AA, EA and Chinese American (CA) models and also passively observed their gestures and faces. We found that both AA and EA participants exhibited more activity in lateral frontoparietal and visual regions when imitating AAs compared with EAs or CAs. These results suggest that racial self-similarity is not likely to modulate neural responses to race during imitation, in contrast with findings from previous neuroimaging studies of face perception and action observation. Furthermore, AA and EA participants associated AAs with lower social status than EAs or CAs, suggesting that the social status associated with different racial groups may instead modulate neural activity during imitation of individuals from those groups. Taken together, these findings suggest that neural responses to race during imitation are driven by socially learned associations rather than self-similarity. This may reflect the adaptive role of imitation in social learning, where learning from higher status models can be more beneficial. This study provides neural evidence consistent with evolutionary theories of cultural acquisition.

The homeostatic regulation of feeding behavior requires an organism to be able to integrate information from its internal environment, including peripheral visceral signals about the body's current energy needs, with information from its external environment, such as the palatability of energy-rich food stimuli. The insula, which serves as the brain's primary sensory cortex for representing both visceral signals from the body and taste signals from the mouth and tongue, is a likely candidate region in which this integration might occur. However, to date it has been unclear whether information from these two homeostatically critical faculties is merely co-represented in the human insula, or actually integrated there. Recent functional neuroimaging evidence of a common substrate for visceral interoception and taste perception within the human dorsal mid-insula suggests a model whereby a single population of neurons may integrate viscerosensory and gustatory signals. To test this model, we used fMRI-Adaptation to identify whether insula regions that exhibit repetition suppression following repeated interoception trials would then also exhibit adapted responses to subsequent gustatory stimuli. Multiple mid and anterior regions of the insula exhibited adaptation to interoceptive trials specifically, but only the dorsal mid-insula regions exhibited an adapted gustatory response following interoception. The discovery of this gustatory-interoceptive convergence within the neurons of the human insula supports the existence of a heretofore-undocumented neural pathway by which visceral signals from the periphery modulate the activity of brain regions involved in feeding behavior. Hum Brain Mapp 38:2150-2164, 2017. © 2017 Wiley Periodicals, Inc.

Neuroscience literature increasingly suggests a conceptual self composed of interacting neural regions, rather than independent local activations, yet such claims have yet to be investigated. We, thus, combined task-dependent meta-analytic connectivity modeling (MACM) with task-independent resting-state (RS) connectivity analysis to delineate the neural network of the self, across both states. Given psychological evidence implicating the self's interdependence on social information, we also delineated the neural network underlying conceptual other-processing. To elucidate the relation between the self-/other-networks and their function, we mined the MACM metadata to generate a cognitive-behavioral profile for an empirically identified region specific to conceptual self, the pregenual anterior cingulate (pACC), and conceptual other, posterior cingulate/precuneus (PCC/PC). Mining of 7,200 published, task-dependent, neuroimaging studies, using healthy human subjects, yielded 193 studies activating the self-related seed and were conjoined with RS connectivity analysis to delineate a differentiated self-network composed of the pACC (seed) and anterior insula, relative to other functional connectivity. Additionally, 106 studies activating the other-related seed were conjoined with RS connectivity analysis to delineate a differentiated other-network of PCC/PC (seed) and angular gyrus/temporoparietal junction, relative to self-functional connectivity. The self-network seed related to emotional conflict resolution and motivational processing, whereas the other-network seed related to socially oriented processing and contextual information integration. Notably, our findings revealed shared RS connectivity between ensuing self-/other-networks within the ventromedial prefrontal cortex and medial orbitofrontal cortex, suggesting self-updating via integration of self-relevant social information. We, therefore, present initial neurobiological evidence corroborating the increasing claims of an intricate self-network, the architecture of which may promote social value processing.

Language comprehension depends on tight functional interactions between distributed brain regions. While these interactions are established for semantic and syntactic processes, the functional network of speech intonation - the linguistic variation of pitch - has been scarcely defined. Particularly little is known about intonation in tonal languages, in which pitch not only serves intonation but also expresses meaning via lexical tones. The present study used psychophysiological interaction analyses of functional magnetic resonance imaging data to characterise the neural networks underlying intonation and tone processing in native Mandarin Chinese speakers. Participants categorised either intonation or tone of monosyllabic Mandarin words that gradually varied between statement and question and between Tone 2 and Tone 4. Intonation processing induced bilateral fronto-temporal activity and increased functional connectivity between left inferior frontal gyrus and bilateral temporal regions, likely linking auditory perception and labelling of intonation categories in a phonological network. Tone processing induced bilateral temporal activity, associated with the auditory representation of tonal (phonemic) categories. Together, the present data demonstrate the breadth of the functional intonation network in a tonal language including higher-level phonological processes in addition to auditory representations common to both intonation and tone.

Recurrent anticipation of ominous events is central to obsessions, the core symptom of obsessive-compulsive disorder (OCD), yet the neural basis of intrinsic anticipatory processing in OCD is unknown. We studied nonmedicated adults with OCD and case matched healthy controls in a visual-spatial working memory task with distractor. Magnetoencephalography was used to examine the medial cortex activity during anticipation of to-be-inhibited distractors and to-be-facilitated retrieval stimuli. In OCD anticipatory activation to distractors was abnormally reduced within the posterior cingulate and fusiform gyrus compared to prominent activation in controls. Conversely, OCD subjects displayed significantly increased activation to retrieval stimuli within the anterior cingulate and supplementary motor cortex. This previously unreported discordant pattern of medial anticipatory activation in OCD was accompanied by normal performance accuracy. While increased anterior cortex activation in OCD is commonly viewed as failure of inhibition, the current pattern of data implicates the operation of an anterior compensatory mechanism amending the posterior medial self-regulatory networks disrupted in OCD.

White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD), which contributes to about 50% of dementias worldwide. Microstructural alterations in deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In 141 CSVD patients, processing speed was assessed using Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (volume on T2-FLAIR) and diffusion MRI measures. SWM imaging measures had a large contribution to processing speed, despite a relatively low SWM WMH burden. Across all imaging measures, SWM free water (FW) had the strongest association with processing speed, followed by SWM mean diffusivity (MD). SWM FW was the only marker to significantly increase between two subgroups with the lowest WMH burdens. When comparing two subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Mediation analysis revealed that SWM FW fully mediated the association between WMH volume and processing speed, while no mediation effect of MD or DWM FW was observed. Overall, results suggest that the SWM has an important contribution to processing speed, while SWM FW is a sensitive imaging marker associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes.

Current neuroimaging acquisition and processing approaches tend to be optimised for quality rather than speed. However, rapid acquisition and processing of neuroimaging data can lead to novel neuroimaging paradigms, such as adaptive acquisition, where rapidly processed data is used to inform subsequent image acquisition steps. Here we first evaluate the impact of several processing steps on the processing time and quality of registration of manually labelled T1 -weighted MRI scans. Subsequently, we apply the selected rapid processing pipeline both to rapidly acquired multicontrast EPImix scans of 95 participants (which include T1 -FLAIR, T2 , T2 *, T2 -FLAIR, DWI and ADC contrasts, acquired in ~1 min), as well as to slower, more standard single-contrast T1 -weighted scans of a subset of 66 participants. We quantify the correspondence between EPImix T1 -FLAIR and single-contrast T1 -weighted scans, using correlations between voxels and regions of interest across participants, measures of within- and between-participant identifiability as well as regional structural covariance networks. Furthermore, we explore the use of EPImix for the rapid construction of morphometric similarity networks. Finally, we quantify the reliability of EPImix-derived data using test-retest scans of 10 participants. Our results demonstrate that quantitative information can be derived from a neuroimaging scan acquired and processed within minutes, which could further be used to implement adaptive multimodal imaging and tailor neuroimaging examinations to individual patients.

Auditory sentence comprehension involves processing content (semantics), grammar (syntax), and intonation (prosody). The left inferior frontal gyrus (IFG) is involved in sentence comprehension guided by these different cues, with neuroimaging studies preferentially locating syntactic and semantic processing in separate IFG subregions. However, this regional specialisation has not been confirmed with a neurostimulation method. Consequently, the causal role of such a specialisation remains unclear. This study probed the role of the posterior IFG (pIFG) for syntactic processing and the anterior IFG (aIFG) for semantic processing with repetitive transcranial magnetic stimulation (rTMS) in a task that required the interpretation of the sentence's prosodic realisation. Healthy participants performed a sentence completion task with syntactic and semantic decisions, while receiving 10 Hz rTMS over either left aIFG, pIFG, or vertex (control). Initial behavioural analyses showed an inhibitory effect on accuracy without task-specificity. However, electric field simulations revealed differential effects for both subregions. In the aIFG, stronger stimulation led to slower semantic processing, with no effect of pIFG stimulation. In contrast, we found a facilitatory effect on syntactic processing in both aIFG and pIFG, where higher stimulation strength was related to faster responses. Our results provide first evidence for the functional relevance of left aIFG in semantic processing guided by intonation. The stimulation effect on syntactic responses emphasises the importance of the IFG for syntax processing, without supporting the hypothesis of a pIFG-specific involvement. Together, the results support the notion of functionally specialised IFG subregions for diverse but fundamental cues for language processing.

Natural language processing unfolds information overtime as spatially separated, multimodal, and interconnected neural processes. Existing noninvasive subtraction-based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed rapid phase-encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging data, as well as overcoming scanner noise and head-motion challenges during overt language tasks. We captured real-time information flows as coherent hemodynamic waves traveling over the cortical surface during listening, reading aloud, reciting, and oral cross-language interpreting tasks. We were able to observe the timing, location, direction, and surge of traveling waves in all language tasks, which were visualized as "brainstorms" on brain "weather" maps. The paths of hemodynamic traveling waves provide direct evidence for dual-stream models of the visual and auditory systems as well as logistics models for crossmodal and cross-language processing. Specifically, we have tracked down the step-by-step processing of written or spoken sentences first being received and processed by the visual or auditory streams, carried across language and domain-general cognitive regions, and finally delivered as overt speeches monitored through the auditory cortex, which gives a complete picture of information flows across the brain during natural language functioning. PRACTITIONER POINTS: Phase-encoded fMRI enables simultaneous imaging of high spatial and temporal resolution, capturing continuous spatiotemporal dynamics of the entire brain during real-time overt natural language tasks. Spatiotemporal traveling wave patterns provide direct evidence for constructing comprehensive and explicit models of human information processing. This study unlocks the potential of applying rapid phase-encoded fMRI to indirectly track the underlying neural information flows of sequential sensory, motor, and high-order cognitive processes.

Certain kinds of stimuli can be processed on multiple levels. While the neural correlates of different levels of processing (LOPs) have been investigated to some extent, most of the studies involve skills and/or knowledge already present when performing the task. In this study we specifically sought to identify neural correlates of an evolving skill that allows the transition from perceptual to a lexico-semantic stimulus analysis. Eighteen participants were trained to decode 12 letters of Morse code that were presented acoustically inside and outside of the scanner environment. Morse code was presented in trains of three letters while brain activity was assessed with fMRI. Participants either attended to the stimulus length (perceptual analysis), or evaluated its meaning distinguishing words from nonwords (lexico-semantic analysis). Perceptual and lexico-semantic analyses shared a mutual network comprising the left premotor cortex, the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Perceptual analysis was associated with a strong brain activation in the SMA and the superior temporal gyrus bilaterally (STG), which remained unaltered from pre and post training. In the lexico-semantic analysis post learning, study participants showed additional activation in the left inferior frontal cortex (IFC) and in the left occipitotemporal cortex (OTC), regions known to be critically involved in lexical processing. Our data provide evidence for cortical plasticity evolving with a learning process enabling the transition from perceptual to lexico-semantic stimulus analysis. Importantly, the activation pattern remains task-related LOP and is thus the result of a decision process as to which LOP to engage in.

Thermoreception is an important cutaneous sense, which plays a role in the maintenance of our body temperature and in the detection of potential noxious heat stimulation. In this study, we investigated event-related fields (ERFs) and neural oscillatory activities, which were modulated by warmth stimulation. We developed a warmth stimulator that could elicit a warmth sensation, without pain or tactile sensation, by using a deep-penetrating 980-nm diode laser. The index finger of each participant (n = 24) was irradiated with the laser warmth stimulus, and the cortical responses were measured using magnetoencephalography (MEG). The ERFs and oscillatory responses had late latencies (∼1.3 s and 1.0-1.5 s for ERFs and oscillatory responses, respectively), which could be explained by a slow conduction velocity of warmth-specific C-fibers. Cortical sources of warmth-related ERFs were seen in the bilateral primary and secondary somatosensory cortices (SI and SII), posterior part of the anterior cingulate cortex (pACC), ipsilateral primary motor, and premotor cortex. Thus, we suggested that SI, SII, and pACC play a role in processing the warmth sensation. Time-frequency analysis demonstrated the suppression of the alpha (8-13 Hz) and beta (18-23 Hz) band power in the bilateral sensorimotor cortex. We proposed that the suppressions in alpha and beta band power are involved in the automatic response to the input of warmth stimulation and sensorimotor interactions. The delta band power (1-4 Hz) increased in the frontal, temporal, and cingulate cortices. The power changes in delta band might be related with the attentional processes during the warmth stimulation.

Everyday communication is accompanied by visual information from several sources, including co-speech gestures, which provide semantic information listeners use to help disambiguate the speaker's message. Using fMRI, we examined how gestures influence neural activity in brain regions associated with processing semantic information. The BOLD response was recorded while participants listened to stories under three audiovisual conditions and one auditory-only (speech alone) condition. In the first audiovisual condition, the storyteller produced gestures that naturally accompany speech. In the second, the storyteller made semantically unrelated hand movements. In the third, the storyteller kept her hands still. In addition to inferior parietal and posterior superior and middle temporal regions, bilateral posterior superior temporal sulcus and left anterior inferior frontal gyrus responded more strongly to speech when it was further accompanied by gesture, regardless of the semantic relation to speech. However, the right inferior frontal gyrus was sensitive to the semantic import of the hand movements, demonstrating more activity when hand movements were semantically unrelated to the accompanying speech. These findings show that perceiving hand movements during speech modulates the distributed pattern of neural activation involved in both biological motion perception and discourse comprehension, suggesting listeners attempt to find meaning, not only in the words speakers produce, but also in the hand movements that accompany speech.

Autism spectrum disorder (ASD) is characterized by social deficits and atypical facial processing of emotional expressions. The underlying neuropathology of these abnormalities is still unclear. Recent studies implicate cerebellum in emotional processing; other studies show cerebellar abnormalities in ASD. Here, we elucidate the spatiotemporal activation of cerebellar lobules in ASD during emotional processing of happy and angry faces in adolescents with ASD and typically developing (TD) controls. Using magnetoencephalography, we calculated dynamic statistical parametric maps across a period of 500 ms after emotional stimuli onset and determined differences between group activity to happy and angry emotions. Following happy face presentation, adolescents with ASD exhibited only left-hemispheric cerebellar activation in a cluster extending from lobule VI to lobule V (compared to TD controls). Following angry face presentation, adolescents with ASD exhibited only midline cerebellar activation (posterior IX vermis). Our findings indicate an early (125-175 ms) overactivation in cerebellar activity only for happy faces and a later overactivation for both happy (250-450 ms) and angry (250-350 ms) faces in adolescents with ASD. The prioritized hemispheric activity (happy faces) could reflect the promotion of a more flexible and adaptive social behavior, while the latter midline activity (angry faces) may guide conforming behavior.

Although multiple sclerosis (MS) is frequently accompanied by visuo-cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were shown target stimuli followed by a mask presented 8-150 ms later and had to compare the target to a reference stimulus. Retinal integrity (via optical coherence tomography), optic tract integrity (visual evoked potential; VEP) and whole brain structural connectivity (probabilistic tractography) were assessed as complementary structural brain integrity markers. On a psychophysical level, pwMS reached conscious access later than HC (50 vs. 16 ms, p < .001). The delay increased with disease duration (p < .001, β = .37) and disability (p < .001, β = .24), but did not correlate with conscious information processing speed (Symbol digit modality test, β = .07, p = .817). No association was found for VEP and retinal integrity markers. Moreover, pwMS were characterized by decreased brain activation during unconscious processing compared with HC. No group differences were found during conscious processing. Finally, a complementary structural brain integrity analysis showed that a reduced fractional anisotropy in corpus callosum and an impaired connection between right insula and primary visual areas was related to delayed conscious access in pwMS. Our study revealed slowed conscious access to visual stimulus material in MS and a complex pattern of functional and structural alterations coupled to unconscious processing of/delayed conscious access to visual stimulus material in MS.