Separation of bimodal fMRI responses in mouse somatosensory areas into V1 and non-V1 contributions.

Multisensory integration is necessary for the animal to survive in the real world. While conventional methods have been extensively used to investigate the multisensory integration process in various brain areas, its long-range interactions remain less explored. In this study, our goal was to investigate interactions between visual and somatosensory networks on a whole-brain scale using 15.2-T BOLD fMRI. We compared unimodal to bimodal BOLD fMRI responses and dissected potential cross-modal pathways with silencing of primary visual cortex (V1) by optogenetic stimulation of local GABAergic neurons. Our data showed that the influence of visual stimulus on whisker activity is higher than the influence of whisker stimulus on visual activity. Optogenetic silencing of V1 revealed that visual information is conveyed to whisker processing via both V1 and non-V1 pathways. The first-order ventral posteromedial thalamic nucleus (VPM) was functionally affected by non-V1 sources, while the higher-order posterior medial thalamic nucleus (POm) was predominantly modulated by V1 but not non-V1 inputs. The primary somatosensory barrel field (S1BF) was influenced by both V1 and non-V1 inputs. These observations provide valuable insights for into the integration of whisker and visual sensory information.

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.

fMRI, LFP, and anatomical evidence for hierarchical nociceptive routing pathway between somatosensory and insular cortices.

The directional organization of multiple nociceptive regions, particularly within obscure operculoinsular areas, underlying multidimensional pain processing remains elusive. This study aims to establish the fundamental organization between somatosensory and insular cortices in routing nociceptive information. By employing an integrated multimodal approach of high-field fMRI, intracranial electrophysiology, and transsynaptic viral tracing in rats, we observed a hierarchically organized connection of S1/S2 → posterior insula → anterior insula in routing nociceptive information. The directional nociceptive pathway determined by early fMRI responses was consistent with that examined by early evoked LFP, intrinsic effective connectivity, and anatomical projection, suggesting fMRI could provide a valuable facility to discern directional neural circuits in animals and humans non-invasively. Moreover, our knowledge of the nociceptive hierarchical organization of somatosensory and insular cortices and the interface role of the posterior insula may have implications for the development of targeted pain therapies.

Stimulus awareness is associated with secondary somatosensory cortex activation in an inattentional numbness paradigm.

While inattentional blindness and deafness studies have revealed neural correlates of consciousness (NCC) without the confound of task relevance in the visual and auditory modality, comparable studies for the somatosensory modality are lacking. Here, we investigated NCC using functional magnetic resonance imaging (fMRI) in an inattentional numbness paradigm. Participants (N = 44) received weak electrical stimulation on the left hand while solving a demanding visual task. Half of the participants were informed that task-irrelevant weak tactile stimuli above the detection threshold would be applied during the experiment, while the other half expected stimuli below the detection threshold. Unexpected awareness assessments after the experiment revealed that altogether 10 participants did not consciously perceive the somatosensory stimuli during the visual task. Awareness was not significantly modulated by prior information. The fMRI data show that awareness of stimuli led to increased activation in the contralateral secondary somatosensory cortex. We found no significant effects of stimulus awareness in the primary somatosensory cortex or frontoparietal areas. Thus, our results support the hypothesis that somatosensory stimulus awareness is mainly based on activation in higher areas of the somatosensory cortex and does not require strong activation in extended anterior or posterior networks, which is usually seen when perceived stimuli are task-relevant.

Brain Mapping Using a Graphene Electrode Array.

Cortical maps represent the spatial organization of location-dependent neural responses to sensorimotor stimuli in the cerebral cortex, enabling the prediction of physiologically relevant behaviors. Various methods, such as penetrating electrodes, electroencephalography, positron emission tomography, magnetoencephalography, and functional magnetic resonance imaging, have been used to obtain cortical maps. However, these methods are limited by poor spatiotemporal resolution, low signal-to-noise ratio (SNR), high costs, and non-biocompatibility or cause physical damage to the brain. This study proposes a graphene array-based somatosensory mapping method as a feature of electrocorticography that offers superior biocompatibility, high spatiotemporal resolution, desirable SNR, and minimized tissue damage, overcoming the drawbacks of previous methods. This study demonstrated the feasibility of a graphene electrode array for somatosensory mapping in rats. The presented protocol can be applied not only to the somatosensory cortex but also to other cortices such as the auditory, visual, and motor cortex, providing advanced technology for clinical implementation.

Reduced dimension stimulus decoding and column-based modeling reveal architectural differences of primary somatosensory finger maps between younger and older adults.

The primary somatosensory cortex (SI) contains fine-grained tactile representations of the body, arranged in an orderly fashion. The use of ultra-high resolution fMRI data to detect group differences, for example between younger and older adults' SI maps, is challenging, because group alignment often does not preserve the high spatial detail of the data. Here, we use robust-shared response modeling (rSRM) that allows group analyses by mapping individual stimulus-driven responses to a lower dimensional shared feature space, to detect age-related differences in tactile representations between younger and older adults using 7T-fMRI data. Using this method, we show that finger representations are more precise in Brodmann-Area (BA) 3b and BA1 compared to BA2 and motor areas, and that this hierarchical processing is preserved across age groups. By combining rSRM with column-based decoding (C-SRM), we further show that the number of columns that optimally describes finger maps in SI is higher in younger compared to older adults in BA1, indicating a greater columnar size in older adults' SI. Taken together, we conclude that rSRM is suitable for finding fine-grained group differences in ultra-high resolution fMRI data, and we provide first evidence that the columnar architecture in SI changes with increasing age.

Rapid Processing of Observed Touch through Social Perceptual Brain Regions: An EEG-fMRI Fusion Study.

Seeing social touch triggers a strong social-affective response that involves multiple brain networks, including visual, social perceptual, and somatosensory systems. Previous studies have identified the specific functional role of each system, but little is known about the speed and directionality of the information flow. Is this information extracted via the social perceptual system or from simulation from somatosensory cortex? To address this, we examined the spatiotemporal neural processing of observed touch. Twenty-one human participants (seven males) watched 500-ms video clips showing social and nonsocial touch during electroencephalogram (EEG) recording. Visual and social-affective features were rapidly extracted in the brain, beginning at 90 and 150 ms after video onset, respectively. Combining the EEG data with functional magnetic resonance imaging (fMRI) data from our prior study with the same stimuli reveals that neural information first arises in early visual cortex (EVC), then in the temporoparietal junction and posterior superior temporal sulcus (TPJ/pSTS), and finally in the somatosensory cortex. EVC and TPJ/pSTS uniquely explain EEG neural patterns, while somatosensory cortex does not contribute to EEG patterns alone, suggesting that social-affective information may flow from TPJ/pSTS to somatosensory cortex. Together, these findings show that social touch is processed quickly, within the timeframe of feedforward visual processes, and that the social-affective meaning of touch is first extracted by a social perceptual pathway. Such rapid processing of social touch may be vital to its effective use during social interaction.SIGNIFICANCE STATEMENT Seeing physical contact between people evokes a strong social-emotional response. Previous research has identified the brain systems responsible for this response, but little is known about how quickly and in what direction the information flows. We demonstrated that the brain processes the social-emotional meaning of observed touch quickly, starting as early as 150 ms after the stimulus onset. By combining electroencephalogram (EEG) data with functional magnetic resonance imaging (fMRI) data, we show for the first time that the social-affective meaning of touch is first extracted by a social perceptual pathway and followed by the later involvement of somatosensory simulation. This rapid processing of touch through the social perceptual route may play a pivotal role in effective usage of touch in social communication and interaction.

Two-Dimensional Population Receptive Field Mapping of Human Primary Somatosensory Cortex.

Functional magnetic resonance imaging can provide detailed maps of how sensory space is mapped in the human brain. Here, we use a novel 16 stimulator setup (a 4 × 4 grid) to measure two-dimensional sensory maps of between and within-digit (D2-D4) space using high spatial-resolution (1.25 mm isotropic) imaging at 7 Tesla together with population receptive field (pRF) mapping in 10 participants. Using a 2D Gaussian pRF model, we capture maps of the coverage of digits D2-D5 across Brodmann areas and estimate pRF size and shape. In addition, we compare results to previous studies that used fewer stimulators by constraining pRF models to a 1D Gaussian Between Digit or 1D Gaussian Within Digit model. We show that pRFs across somatosensory areas tend to have a strong preference to cover the within-digit axis. We show an increase in pRF size moving from D2-D5. We quantify pRF shapes in Brodmann area (BA) 3b, 3a, 1, 2 and show differences in pRF size in Brodmann areas 3a-2, with larger estimates for BA2. Generally, the 2D Gaussian pRF model better represents pRF coverage maps generated by our data, which itself is produced from a 2D stimulation grid.

Pneumatic tactile stimulus delivery system for studying brain responses evoked by active finger touch with fMRI.

BACKGROUND: Primates use their hands to actively touch objects and collect information. To study tactile information processing, it is important for participants to experience tactile stimuli through active touch while monitoring brain activities. NEW METHOD: Here, we developed a pneumatic tactile stimulus delivery system (pTDS) that delivers various tactile stimuli on a programmed schedule and allows voluntary finger touches during MRI scanning. The pTDS uses a pneumatic actuator to move tactile stimuli and place them in a finger hole. A photosensor detects the time when an index finger touches a tactile stimulus, enabling the analysis of the touch-elicited brain responses. RESULTS: We examined brain responses while the participants actively touched braille objects presented by the pTDS. BOLD responses during tactile perception were significantly stronger in a finger touch area of the contralateral somatosensory cortex compared with that of visual perception. CONCLUSION: The pTDS enables MR studies of brain mechanisms for tactile processes through natural finger touch.

Fine-grained topographic organization within somatosensory cortex during resting-state and emotional face-matching task and its association with ASD traits.

Sensory atypicalities are particularly common in autism spectrum disorders (ASD). Nevertheless, our knowledge about the divergent functioning of the underlying somatosensory region and its association with ASD phenotype features is limited. We applied a data-driven approach to map the fine-grained variations in functional connectivity of the primary somatosensory cortex (S1) to the rest of the brain in 240 autistic and 164 neurotypical individuals from the EU-AIMS LEAP dataset, aged between 7 and 30. We estimated the S1 connection topography ('connectopy') at rest and during the emotional face-matching (Hariri) task, an established measure of emotion reactivity, and accessed its association with a set of clinical and behavioral variables. We first demonstrated that the S1 connectopy is organized along a dorsoventral axis, mapping onto the S1 somatotopic organization. We then found that its spatial characteristics were linked to the individuals' adaptive functioning skills, as measured by the Vineland Adaptive Behavior Scales, across the whole sample. Higher functional differentiation characterized the S1 connectopies of individuals with higher daily life adaptive skills. Notably, we detected significant differences between rest and the Hariri task in the S1 connectopies, as well as their projection maps onto the rest of the brain suggesting a task-modulating effect on S1 due to emotion processing. All in all, variation of adaptive skills appears to be reflected in the brain's mesoscale neural circuitry, as shown by the S1 connectivity profile, which is also differentially modulated during rest and emotional processing.

Artificial gravity during a spaceflight analog alters brain sensory connectivity.

Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre- to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.

Transcranial focused ultrasound stimulation of cortical and thalamic somatosensory areas in human.

The effects of transcranial focused ultrasound (FUS) stimulation of the primary somatosensory cortex and its thalamic projection (i.e., ventral posterolateral nucleus) on the generation of electroencephalographic (EEG) responses were evaluated in healthy human volunteers. Stimulation of the unilateral somatosensory circuits corresponding to the non-dominant hand generated EEG evoked potentials across all participants; however, not all perceived stimulation-mediated tactile sensations of the hand. These FUS-evoked EEG potentials (FEP) were observed from both brain hemispheres and shared similarities with somatosensory evoked potentials (SSEP) from median nerve stimulation. Use of a 0.5 ms pulse duration (PD) sonication given at 70% duty cycle, compared to the use of 1 and 2 ms PD, elicited more distinctive FEP peak features from the hemisphere ipsilateral to sonication. Although several participants reported hearing tones associated with FUS stimulation, the observed FEP were not likely to be confounded by the auditory sensation based on a separate measurement of auditory evoked potentials (AEP) to tonal stimulation (mimicking the same repetition frequency as the FUS stimulation). Off-line changes in resting-state functional connectivity (FC) associated with thalamic stimulation revealed that the FUS stimulation enhanced connectivity in a network of sensorimotor and sensory integration areas, which lasted for at least more than an hour. Clinical neurological evaluations, EEG, and neuroanatomical MRI did not reveal any adverse or unintended effects of sonication, attesting its safety. These results suggest that FUS stimulation may induce long-term neuroplasticity in humans, indicating its neurotherapeutic potential for various neurological and neuropsychiatric conditions.

Similar somatotopy for active and passive digit representation in primary somatosensory cortex.

Scientists traditionally use passive stimulation to examine the organisation of primary somatosensory cortex (SI). However, given the close, bidirectional relationship between the somatosensory and motor systems, active paradigms involving free movement may uncover alternative SI representational motifs. Here, we used 7 Tesla functional magnetic resonance imaging to compare hallmark features of SI digit representation between active and passive tasks which were unmatched on task or stimulus properties. The spatial location of digit maps, somatotopic organisation, and inter-digit representational structure were largely consistent between tasks, indicating representational consistency. We also observed some task differences. The active task produced higher univariate activity and multivariate representational information content (inter-digit distances). The passive task showed a trend towards greater selectivity for digits versus their neighbours. Our findings highlight that, while the gross features of SI functional organisation are task invariant, it is important to also consider motor contributions to digit representation.

Talking with hands and feet: Selective somatosensory attention and fMRI enable robust and convenient brain-based communication.

In brain-based communication, voluntarily modulated brain signals (instead of motor output) are utilized to interact with the outside world. The possibility to circumvent the motor system constitutes an important alternative option for severely paralyzed. Most communication brain-computer interface (BCI) paradigms require intact visual capabilities and impose a high cognitive load, but for some patients, these requirements are not given. In these situations, a better-suited, less cognitively demanding information-encoding approach may exploit auditorily-cued selective somatosensory attention to vibrotactile stimulation. Here, we propose, validate and optimize a novel communication-BCI paradigm using differential fMRI activation patterns evoked by selective somatosensory attention to tactile stimulation of the right hand or left foot. Using cytoarchitectonic probability maps and multi-voxel pattern analysis (MVPA), we show that the locus of selective somatosensory attention can be decoded from fMRI-signal patterns in (especially primary) somatosensory cortex with high accuracy and reliability, with the highest classification accuracy (85.93%) achieved when using Brodmann area 2 (SI-BA2) at a probability level of 0.2. Based on this outcome, we developed and validated a novel somatosensory attention-based yes/no communication procedure and demonstrated its high effectiveness even when using only a limited amount of (MVPA) training data. For the BCI user, the paradigm is straightforward, eye-independent, and requires only limited cognitive functioning. In addition, it is BCI-operator friendly given its objective and expertise-independent procedure. For these reasons, our novel communication paradigm has high potential for clinical applications.

Content Representation of Tactile Mental Imagery in Primary Somatosensory Cortex.

The imagination of tactile stimulation has been shown to activate primary somatosensory cortex (S1) with a somatotopic specificity akin to that seen during the perception of tactile stimuli. Using fMRI and multivariate pattern analysis, we investigate whether this recruitment of sensory regions also reflects content-specific activation (i.e., whether the activation in S1 is specific to the mental content participants imagined). To this end, healthy volunteers (n = 21) either perceived or imagined three types of vibrotactile stimuli (mental content) while fMRI data were acquired. Independent of the content, during tactile mental imagery we found activation of frontoparietal regions, supplemented with activation in the contralateral BA2 subregion of S1, replicating previous reports. While the imagery of the three different stimuli did not reveal univariate activation differences, using multivariate pattern classification, we were able to decode the imagined stimulus type from BA2. Moreover, cross-classification revealed that tactile imagery elicits activation patterns similar to those evoked by the perception of the respective stimuli. These findings promote the idea that mental tactile imagery involves the recruitment of content-specific activation patterns in sensory cortices, namely in S1.

Identifying the distinct spectral dynamics of laminar-specific interhemispheric connectivity with bilateral line-scanning fMRI.

Despite extensive efforts to identify interhemispheric functional connectivity (FC) with resting-state (rs-) fMRI, correlated low-frequency rs-fMRI signal fluctuation across homotopic cortices originates from multiple sources. It remains challenging to differentiate circuit-specific FC from global regulation. Here, we developed a bilateral line-scanning fMRI method to detect laminar-specific rs-fMRI signals from homologous forepaw somatosensory cortices with high spatial and temporal resolution in rat brains. Based on spectral coherence analysis, two distinct bilateral fluctuation spectral features were identified: ultra-slow fluctuation (<0.04 Hz) across all cortical laminae versus Layer (L) 2/3-specific evoked BOLD at 0.05 Hz based on 4 s on/16 s off block design and resting-state fluctuations at 0.08-0.1 Hz. Based on the measurements of evoked BOLD signal at corpus callosum (CC), this L2/3-specific 0.05 Hz signal is likely associated with neuronal circuit-specific activity driven by the callosal projection, which dampened ultra-slow oscillation less than 0.04 Hz. Also, the rs-fMRI power variability clustering analysis showed that the appearance of L2/3-specific 0.08-0.1 Hz signal fluctuation is independent of the ultra-slow oscillation across different trials. Thus, distinct laminar-specific bilateral FC patterns at different frequency ranges can be identified by the bilateral line-scanning fMRI method.

Aftereffects of alpha transcranial alternating current stimulation over the primary sensorimotor cortex on cortical processing of pain.

ABSTRACT: Transcranial alternating current stimulation (tACS) is believed to modulate brain oscillations in a frequency-specific manner. Given the correlation between sensorimotor α-oscillations and pain perception, tACS that targets sensorimotor α-oscillations has the potential to reduce pain. Therefore, this study sought to determine the aftereffects of α-tACS over unilateral primary sensorimotor cortex (SM1) on the perceptual and neural responses to noxious painful stimulation of the contralateral hand. Using a double-blinded and sham-controlled design, 60 healthy participants were recruited to receive either α-tACS or sham stimulation of unilateral SM1 through an electrode montage in a 4 × 1 ring configuration. Neural responses to laser nociceptive stimuli were assessed using functional magnetic resonance imaging immediately before and after α-tACS intervention. Perceptual reports were recorded simultaneously. Compared with sham stimulation, α-tACS attenuated bilateral SM1 responses to painful stimuli delivered to the contralateral hand. Although α-tACS did not exert direct effect on subjective pain perception, it can indirectly decrease ratings of pain perception by reducing brain activity within the targeted SM1. Moreover, α-tACS decreased the functional connectivity between the targeted SM1 and a network of regions that are crucially involved in pain processing, including the middle cingulate cortex, contralateral somatosensory cortex, and dorsolateral prefrontal cortex. These results demonstrated that after α-tACS applied over the unilateral SM1 does attenuate subsequent neural processing of pain within bilateral sensorimotor regions as well as sensorimotor functional connectivity. The findings provide evidence that sensorimotor α-oscillations directly affect pain processing and support the application of sensorimotor α-tACS for inducing pain analgesia.

Decoding sounds depicting hand-object interactions in primary somatosensory cortex.

Neurons, even in the earliest sensory regions of cortex, are subject to a great deal of contextual influences from both within and across modality connections. Recent work has shown that primary sensory areas can respond to and, in some cases, discriminate stimuli that are not of their target modality: for example, primary somatosensory cortex (SI) discriminates visual images of graspable objects. In the present work, we investigated whether SI would discriminate sounds depicting hand-object interactions (e.g. bouncing a ball). In a rapid event-related functional magnetic resonance imaging experiment, participants listened attentively to sounds from 3 categories: hand-object interactions, and control categories of pure tones and animal vocalizations, while performing a one-back repetition detection task. Multivoxel pattern analysis revealed significant decoding of hand-object interaction sounds within SI, but not for either control category. Crucially, in the hand-sensitive voxels defined from an independent tactile localizer, decoding accuracies were significantly higher for hand-object interactions compared to pure tones in left SI. Our findings indicate that simply hearing sounds depicting familiar hand-object interactions elicit different patterns of activity in SI, despite the complete absence of tactile stimulation. These results highlight the rich contextual information that can be transmitted across sensory modalities even to primary sensory areas.

Intact finger representation within primary sensorimotor cortex of musician's dystonia.

Musician's dystonia presents with a persistent deterioration of motor control during musical performance. A predominant hypothesis has been that this is underpinned by maladaptive neural changes to the somatotopic organization of finger representations within primary somatosensory cortex. Here, we tested this hypothesis by investigating the finger-specific activity patterns in the primary somatosensory and motor cortex using functional MRI and multivariate pattern analysis in nine musicians with dystonia and nine healthy musicians. A purpose-built keyboard device allowed characterization of activity patterns elicited during passive extension and active finger presses of individual fingers. We analysed the data using both traditional spatial analysis and state-of-the art multivariate analyses. Our analysis reveals that digit representations in musicians were poorly captured by spatial analyses. An optimized spatial metric found clear somatotopy but no difference in the spatial geometry between fingers with dystonia. Representational similarity analysis was confirmed as a more reliable technique than all spatial metrics evaluated. Significantly, the dissimilarity architecture was equivalent for musicians with and without dystonia. No expansion or spatial shift of digit representation maps were found in the symptomatic group. Our results therefore indicate that the neural representation of generic finger maps in primary sensorimotor cortex is intact in musician's dystonia. These results speak against the idea that task-specific dystonia is associated with a distorted hand somatotopy and lend weight to an alternative hypothesis that task-specific dystonia is due to a higher-order disruption of skill encoding. Such a formulation can better explain the task-specific deficit and offers alternative inroads for therapeutic interventions.

Alterations in Functional Connectivity of Thalamus and Primary Somatosensory Cortex in Painful and Painless Diabetic Peripheral Neuropathy.

OBJECTIVE: In this study we aimed to investigate the functional connectivity of brain regions involved in sensory processing in diabetes with and without painful and painless diabetic peripheral neuropathy (DPN) and the association with peripheral nerve function and pain intensity. RESEARCH DESIGN AND METHODS: In this cross-sectional study we used resting-state functional MRI (fMRI) to investigate functional brain connectivity of 19 individuals with type 1 diabetes and painful DPN, 19 with type 1 diabetes and painless DPN, 18 with type 1 diabetes without DPN, and 20 healthy control subjects. Seed-based connectivity analyses were performed for thalamus, postcentral gyrus, and insula, and the connectivity z scores were correlated with peripheral nerve function measurements and pain scores. RESULTS: Overall, compared with those with painful DPN and healthy control subjects, subjects with type 1 diabetes without DPN showed hyperconnectivity between thalamus and motor areas and between postcentral gyrus and motor areas (all P ≤ 0.029). Poorer peripheral nerve functions and higher pain scores were associated with lower connectivity of the thalamus and postcentral gyrus (all P ≤ 0.043). No connectivity differences were found in insula (all P ≥ 0.071). CONCLUSIONS: Higher functional connectivity of thalamus and postcentral gyrus appeared only in diabetes without neuropathic complications. Thalamic/postcentral gyral connectivity measures demonstrated an association with peripheral nerve functions. Based on thalamic connectivity, it was possible to group the phenotypes of type 1 diabetes with painful/painless DPN and type 1 diabetes without DPN. The results of the current study support that fMRI can be used for phenotyping, and with validation, it may contribute to early detection and prevention of neuropathic complications.