Age-related differences in finger interdependence during complex hand movements.

The well-known decrease in finger dexterity during healthy aging leads to a significant reduction in quality of life. Still, the exact patterns of altered finger kinematics of older adults in daily life are fairly unexplored. Finger interdependence is the unintentional co-movement of fingers that are not intended to move, and it is known to vary across the lifespan. Nevertheless, the magnitude and direction of age-related differences in finger interdependence are ambiguous across studies and tasks and have not been explored in the context of daily life finger movements. We investigated five different free and daily-life-inspired finger movements of the right, dominant hand as well as a sequential finger tapping task of the thumb against the other fingers, in 17 younger (22 to 37 years) and 17 older (62 to 80 years) adults using an exoskeleton data glove for data recording. Using inferential statistics, we found that the unintentional co-movement of fingers generally decreases with age in all performed daily-life-inspired movements. Finger tapping, however, showed a trend towards higher finger interdependence for older compared to younger adults. Using machine learning, we predicted the age group of a person from finger interdependence features of single movement trials significantly better than chance level for the daily-life-inspired movements, but not for finger tapping. Taken together, we show that for specific tasks, decreased finger interdependence (i.e., less co-movement) could potentially act as a marker of human aging that specifically characterizes older adults' complex finger movements in daily life.

Tactile memory impairments in younger and older adults.

Human tactile memory allows us to remember and retrieve the multitude of somatosensory experiences we undergo in everyday life. An unsolved question is how tactile memory mechanisms change with increasing age. We here use the ability to remember fine-grained tactile patterns passively presented to the fingertip to investigate age-related changes in tactile memory performance. In experiment 1, we varied the degree of similarity between one learned and several new tactile patterns to test on age-related changes in the "uniqueness" of a stored tactile memory trace. In experiment 2, we varied the degree of stimulus completeness of both known and new tactile patterns to test on age-related changes in the weighting between known and novel tactile information. Results reveal that older adults show only weak impairments in both precision and bias of tactile memories, however, they show specific deficits in reaching peak performance > 85% in both experiments. In addition, both younger and older adults show a pattern completion bias for touch, indicating a higher weighting of known compared to new information. These results allow us to develop new models on how younger and older adults store and recall tactile experiences of the past, and how this influences their everyday behavior.

How the inner repetition of a desired perception changes actual tactile perception.

Autosuggestion is a cognitive process where the inner repetition of a thought actively influences one's own perceptual state. In spite of its potential benefits for medical interventions, this technique has gained little scientific attention so far. Here, we took advantage of the known link between intensity and frequency perception in touch ('Békésy effect'). In three separate experiments, participants were asked to modulate the perceived intensity of vibrotactile stimuli at the fingertip through the inner reiteration of the thought that this perception feels very strong (Experiment 1, n = 19) or very weak (Experiments 2, n = 38, and 3, n = 20), while they were asked to report the perceived frequency. We show that the task to change the perceived intensity of a tactile stimulus via the inner reiteration of a thought modulates tactile frequency perception. This constitutes the first experimental demonstration that an experimental design that triggers autosuggestion alters participants' tactile perception using a response orthogonal to the suggested variable. We discuss whether this cognitive process could be used to influence the perception of pain in a clinical context.

Multimodal layer modelling reveals in vivo pathology in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterized by the loss of motor control. Current understanding of ALS pathology is largely based on post-mortem investigations at advanced disease stages. A systematic in vivo description of the microstructural changes that characterize early stage ALS, and their subsequent development, is so far lacking. Recent advances in ultra-high field (7 T) MRI data modelling allow us to investigate cortical layers in vivo. Given the layer-specific and topographic signature of ALS pathology, we combined submillimetre structural 7 T MRI data (qT1, QSM), functional localizers of body parts (upper limb, lower limb, face) and layer modelling to systematically describe pathology in the primary motor cortex (M1), in 12 living ALS patients with reference to 12 matched controls. Longitudinal sampling was performed for a subset of patients. We calculated multimodal pathology maps for each layer (superficial layer, layer 5a, layer 5b, layer 6) of M1 to identify hot spots of demyelination, iron and calcium accumulation in different cortical fields. We show preserved mean cortical thickness and layer architecture of M1, despite significantly increased iron in layer 6 and significantly increased calcium in layer 5a and superficial layer, in patients compared to controls. The behaviourally first-affected cortical field shows significantly increased iron in L6 compared to other fields, while calcium accumulation is atopographic and significantly increased in the low myelin borders between cortical fields compared to the fields themselves. A subset of patients with longitudinal data shows that the low myelin borders are particularly disrupted and that calcium hot spots, but to a lesser extent iron hot spots, precede demyelination. Finally, we highlight that a very slow progressing patient (Patient P4) shows a distinct pathology profile compared to the other patients. Our data show that layer-specific markers of in vivo pathology can be identified in ALS patients with a single 7 T MRI measurement after first diagnosis, and that such data provide critical insights into the individual disease state. Our data highlight the non-topographic architecture of ALS disease spread and the role of calcium, rather than iron accumulation, in predicting future demyelination. We also highlight a potentially important role of low myelin borders, that are known to connect to multiple areas within the M1 architecture, in disease spread. Finally, the distinct pathology profile of a very-slow progressing patient (Patient P4) highlights a distinction between disease duration and progression. Our findings demonstrate the importance of in vivo histology imaging for the diagnosis and prognosis of neurodegenerative diseases such as ALS.

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.

Layer-specific vulnerability is a mechanism of topographic map aging.

Topographic maps form a critical feature of cortical organization, yet are poorly described with respect to their microstructure in the living aging brain. We acquired quantitative structural and functional 7T-MRI data from younger and older adults to characterize layer-wise topographic maps of the primary motor cortex (M1). Using parcellation-inspired techniques, we show that quantitative T1 and Quantitative Susceptibility Maps values of the hand, face, and foot areas differ significantly, revealing microstructurally distinct cortical fields in M1. We show that these fields are distinct in older adults and that myelin borders between them do not degenerate. We further show that the output layer 5 of M1 shows a particular vulnerability to age-related increased iron, while layer 5 and the superficial layer show increased diamagnetic substance, likely reflecting calcifications. Taken together, we provide a novel 3D model of M1 microstructure, where body parts form distinct structural units, but layers show specific vulnerability toward increased iron and calcium in older adults. Our findings have implications for understanding sensorimotor organization and aging, in addition to topographic disease spread.

The 3D Structural Architecture of the Human Hand Area Is Nontopographic.

The functional topography of the human primary somatosensory cortex hand area is a widely studied model system to understand sensory organization and plasticity. It is so far unclear whether the underlying 3D structural architecture also shows a topographic organization. We used 7 Tesla (7T) magnetic resonance imaging (MRI) data to quantify layer-specific myelin, iron, and mineralization in relation to population receptive field maps of individual finger representations in Brodman area 3b (BA 3b) of human S1 in female and male younger adults. This 3D description allowed us to identify a characteristic profile of layer-specific myelin and iron deposition in the BA 3b hand area, but revealed an absence of structural differences, an absence of low-myelin borders, and high similarity of 3D microstructure profiles between individual fingers. However, structural differences and borders were detected between the hand and face areas. We conclude that the 3D structural architecture of the human hand area is nontopographic, unlike in some monkey species, which suggests a high degree of flexibility for functional finger organization and a new perspective on human topographic plasticity.SIGNIFICANCE STATEMENT Using ultra-high-field MRI, we provide the first comprehensive in vivo description of the 3D structural architecture of the human BA 3b hand area in relation to functional population receptive field maps. High similarity of precise finger-specific 3D profiles, together with an absence of structural differences and an absence of low-myelin borders between individual fingers, reveals the 3D structural architecture of the human hand area to be nontopographic. This suggests reduced structural limitations to cortical plasticity and reorganization and allows for shared representational features across fingers.

Discriminating Free Hand Movements Using Support Vector Machine and Recurrent Neural Network Algorithms.

Decoding natural hand movements is of interest for human-computer interaction and may constitute a helpful tool in the diagnosis of motor diseases and rehabilitation monitoring. However, the accurate measurement of complex hand movements and the decoding of dynamic movement data remains challenging. Here, we introduce two algorithms, one based on support vector machine (SVM) classification combined with dynamic time warping, and the other based on a long short-term memory (LSTM) neural network, which were designed to discriminate small differences in defined sequences of hand movements. We recorded hand movement data from 17 younger and 17 older adults using an exoskeletal data glove while they were performing six different movement tasks. Accuracy rates in decoding the different movement types were similarly high for SVM and LSTM in across-subject classification, but, for within-subject classification, SVM outperformed LSTM. The SVM-based approach, therefore, appears particularly promising for the development of movement decoding tools, in particular if the goal is to generalize across age groups, for example for detecting specific motor disorders or tracking their progress over time.

Cross-dimensional interference between time and distance during spatial navigation is mediated by speed representations in intraparietal sulcus and area hMT.

When navigating a straight path, perceived travel time and perceived traveled distance are linked via movement speed. Behavioral studies have revealed systematic interferences between the perception of travel time and distance, but the role of neuronal representations of movement speed for these effects has not been addressed to date. Using a combined fMRI-behavioral paradigm, we investigate the neuronal representations that underlie cross-dimensional interferences between travel time and traveled distance. Participants underwent fMRI while experiencing visual forward movements for either a short or a long duration, and covering either a short or a long distance. At the behavioral level, we found bi-directional interference effects between time and distance perception, which was correlated with greater representational similarity in speed-sensitive brain regions. The strength of the distance-on-time effect scaled with representational similarity in the left human middle temporal complex (hMT+), and the strength of the time-on-distance effect scaled with representational similarity in the right intraparietal sulcus (IPS). In accordance with the idea that the interference is mediated by the perception of speed, distance-on-time and time-on-distance effects were of opposing directions. Increases in traveled distance led to increases in perceived travel time, while increases in travel time led to decreases in perceived traveled distance. Together, these findings support the view that cross-dimensional interference effects between travel time and traveled distance are mediated by neuronal representations of movement speed.

Clinical Manifestations of Body Memories: The Impact of Past Bodily Experiences on Mental Health.

Bodily experiences such as the feeling of touch, pain or inner signals of the body are deeply emotional and activate brain networks that mediate their perception and higher-order processing. While the ad hoc perception of bodily signals and their influence on behavior is empirically well studied, there is a knowledge gap on how we store and retrieve bodily experiences that we perceived in the past, and how this influences our everyday life. Here, we explore the hypothesis that negative body memories, that is, negative bodily experiences of the past that are stored in memory and influence behavior, contribute to the development of somatic manifestations of mental health problems including somatic symptoms, traumatic re-experiences or dissociative symptoms. By combining knowledge from the areas of cognitive neuroscience and clinical neuroscience with insights from psychotherapy, we identify Clinical Body Memory (CBM) mechanisms that specify how mental health problems could be driven by corporeal experiences stored in memory. The major argument is that the investigation of the neuronal mechanisms that underlie the storage and retrieval of body memories provides us with empirical access to reduce the negative impact of body memories on mental health.

An Automated Tongue Tracker for Quantifying Bulbar Function in ALS.

Introduction: Bulbar symptoms, including difficulty swallowing and speaking, are common in amyotrophic lateral sclerosis (ALS) and other neurological disorders, such as stroke. The presence of bulbar symptoms provides important information regarding clinical outcomes, such as survival time after diagnosis. Nevertheless, there are currently no easily accessible, quantitative methods to measure bulbar function in patients. Methods: We developed an open-source tool called Tongue Tracker (TT) to quantify bulbar function by training a neural network to track kinematic tongue features of short video clips of lateral tongue movements. We tested 16 healthy controls and ten patients with ALS, of whom two patients were clinically diagnosed with bulbar-onset type and eight patients were clinically diagnosed with limb-onset type. Of the limb-onset patients, five patients also showed symptoms of bulbar impairment. Results: We validated TT by comparing the results with manual delineation of tongue movements in the clips. We demonstrate an early-stage bulbar-onset patient who showed fewer and slower tongue sweeps compared to healthy controls and limb-onset patients and we show that five bulbar-impaired limb-onset patients have a different tongue kinematic profile compared to healthy controls. Discussion: TT may serve to detect quantitative markers of bulbar dysfunction in ALS and other motor disorders, such as stroke, by identifying signatures of spasticity or muscle weakness that affects tongue movement speed and/or tongue movement topography.

Autosuggestion: a cognitive process that empowers your brain?

Autosuggestion is a cognitive process that is believed to enable control over one's own cognitive and physiological states. Despite its potential importance for basic science and clinical applications, such as in rehabilitation, stress reduction, or pain therapy, the neurocognitive mechanisms and psychological concepts that underlie autosuggestion are poorly defined. Here, by reviewing empirical data on autosuggestion and related phenomena such as mental imagery, mental simulation, and suggestion, we offer a neurocognitive concept of autosuggestion. We argue that autosuggestion is characterized by three major factors: reinstantiation, reiteration, and volitional, active control over one's own physiological states. We also propose that autosuggestion might involve the 'overwriting' of existing predictions or brain states that expect the most common (but not desired) outcome. We discuss potential experimental paradigms that could be used to study autosuggestion in the future, and discuss the strengths and weaknesses of current evidence. This review provides a first overview on how to define, experimentally induce, and study autosuggestion, which may facilitate its use in basic science and clinical practice.

Impaired remapping of social relationships in older adults.

Social relationships are a central aspect of our everyday life, yet our ability to change established social relationships is an under-investigated topic. Here, we use the concept of cognitive mapping to investigate the plasticity of social relationships in younger and older adults. We describe social relationships within a 'social space', defined as a two-dimensional grid composed of the axis 'power' and 'affiliation', and investigate it using a 3D virtual environment with interacting avatars. We show that participants remap dimensions in 'social space' when avatars show conflicting behavior compared to consistent behavior and that, while older adults show similar updating behavior than younger adults, they show a distinct reduction in remapping social space. Our data provide first evidence that older adults show more rigid social behavior when avatars change their behavior in the dimensions of power and affiliation, which may explain age-related social behavior differences in everyday life.

The organizational principles of de-differentiated topographic maps in somatosensory cortex.

Topographic maps are a fundamental feature of cortex architecture in the mammalian brain. One common theory is that the de-differentiation of topographic maps links to impairments in everyday behavior due to less precise functional map readouts. Here, we tested this theory by characterizing de-differentiated topographic maps in primary somatosensory cortex (SI) of younger and older adults by means of ultra-high resolution functional magnetic resonance imaging together with perceptual finger individuation and hand motor performance. Older adults' SI maps showed similar amplitude and size to younger adults' maps, but presented with less representational similarity between distant fingers. Larger population receptive field sizes in older adults' maps did not correlate with behavior, whereas reduced cortical distances between D2 and D3 related to worse finger individuation but better motor performance. Our data uncover the drawbacks of a simple de-differentiation model of topographic map function, and motivate the introduction of feature-based models of cortical reorganization.

Encoding schemes in somatosensation: From micro- to meta-topography.

Encoding schemes are systematic large-scale arrangements that convert incoming sensory information into a format required for further information processing. The increased spatial resolution of brain images obtained with ultra-high field magnetic resonance imaging at 7 T (7T-MRI) and above increases the granularity and precision of processing units that mediate the link between neuronal encoding and functional readouts. Here, these new developments are reviewed with a focus on human tactile encoding schemes derived from small-scale processing units (in the order of 0.5-5 mm) that are relevant for theoretical and practical concepts of somatosensory encoding and cortical plasticity. Precisely, we review recent approaches to characterize meso-scale maps, layer units, and cortical fields in the sensorimotor cortex of the living human brain and discuss their impact on theories of perception, motor control, topographic encoding, and cortical plasticity. Finally, we discuss concepts on the integration of small-scale processing units into functional networks that span multiple topographic maps and multiple cortical areas. Novel research areas are highlighted that may help to bridge the gap between cortical microstructure and meta-topographic models on brain anatomy and function.

A Mechanical Stimulation Glove to Induce Hebbian Plasticity at the Fingertip.

Repetitive sensory stimulation of the fingertip induces Hebbian plasticity in the sensorimotor cortex that benefits the tactile and motor behavior of the hand in healthy younger adults, older adults, and patients. To use this method outside the laboratory, robust and portable stimulation systems are needed that allow prolonged stimulation phases over several hours without compromising on signal intensity or personal mobility. Here, we introduce two stimulation gloves that apply finger- and frequency-specific mechanical stimulation to individual fingertips over prolonged periods. The stimulators are built into commercially available cotton gloves and apply stimulation either via loudspeaker membranes or via linear resonant actuators (LRAs). We tested the efficiency of both gloves to induce Hebbian plasticity in younger adults by using two established measures of tactile performance, the grating orientation task (GOT), and the two-point discrimination task (2PDT). Both tests were performed before and after 3 h of sensory finger stimulation using one of either glove system. As a control condition, a non-stimulated finger was tested in both tasks before and after stimulation. The results show no significant effect of sensory stimulation on GOT thresholds, but a significant decrease in the 2PDT thresholds after compared to before the training at the stimulated finger only. The loudspeaker membrane improved performance in the 2PDT in 10/16 participants, whereas the LRA improved performance in the 2PDT in 13/16 participants. Stimulation gloves with built-in modules may be used in future larger-scale cohort studies on sensorimotor plasticity, rehabilitation, and learning.

Preserved multisensory body representations in advanced age.

The internal representation of the body emerges via the integration of multisensory body cues. Sensory signal transfer and the ability to integrate multisensory information deteriorate significantly with increasing age. However, there is little empirical evidence on age-related changes in body representations based on multisensory integration. Here, we used a standard paradigm for evaluating body representations based on multisensory integration, the rubber hand illusion, and compared the amount of proprioceptive drift and changes in perceived body ownership triggered by the integration of visual, tactile, and proprioceptive cues between younger and older adults. To account for potential age-related differences in the temporal stability of the illusion, proprioceptive drift was measured at five different time points. Our results show that older adults used synchronous visuo-tactile cues similarly to younger adults to update both the position of their own hand, and their feeling of ownership over the artificial hand. Independent of visuo-tactile synchrony, older adults perceived their hand as closer to their body than younger adults did, and showed a less stable representation of this in-depth hand position. This proprioceptive bias towards the body did not correlate with the strength of the illusion. Our results indicate that the integration of visual and tactile cues is largely preserved in advanced age when used to update limb position, whereas proprioception worsens with age. This may be linked to two different pathways that underlie changes in body representations over the life span.

LISA improves statistical analysis for fMRI.

One of the principal goals in functional magnetic resonance imaging (fMRI) is the detection of local activation in the human brain. However, lack of statistical power and inflated false positive rates have recently been identified as major problems in this regard. Here, we propose a non-parametric and threshold-free framework called LISA to address this demand. It uses a non-linear filter for incorporating spatial context without sacrificing spatial precision. Multiple comparison correction is achieved by controlling the false discovery rate in the filtered maps. Compared to widely used other methods, it shows a boost in statistical power and allows to find small activation areas that have previously evaded detection. The spatial sensitivity of LISA makes it especially suitable for the analysis of high-resolution fMRI data acquired at ultrahigh field (≥7 Tesla).

Modelling the Human Cortex in Three Dimensions.

In cognitive neuroscience, brain-behaviour relationships are usually mapped onto a 2D cortical sheet. Cortical layers are a critical but often ignored third dimension of human cortical function. Improved resolution has put us on the threshold of beginning to image human cognition in three dimensions.