Olov Oscarsson (1931-1996) of Lund University, a Pioneer in Cerebellar Neurobiology.

The present Cerebellar Classic highlights the experimental work of the Swedish neurophysiologist Olov Oscarsson (1931-1996) on the afferent innervation of the cerebellum by axons emanating from neurons in the spinal cord and the inferior olive. Historically, the schemes of cerebellar division had been principally based on the external morphology of lobules and fissures. However, the macroscopic anatomical division of the cerebellum does not coincide with its pattern of functional organization. By defining a system of longitudinal somatotopy, Oscarsson contributed to the much needed plan of cerebellar division that correlates experimental information on axonal connections with physiology. His contribution has ultimately led to the currently accepted microzonal modular scheme of cerebellar corticonuclear microcomplexes.

The evidence against somatotopic organization of function in the primate corticospinal tract.

We review the spatial organization of corticospinal outputs from different cortical areas and how this reflects the varied functions mediated by the corticospinal tract. A long-standing question is whether the primate corticospinal tract shows somatotopical organization. Although this has been clearly demonstrated for corticofugal outputs passing through the internal capsule and cerebral peduncle, there is accumulating evidence against somatotopy in the pyramidal tract in the lower brainstem and in the spinal course of the corticospinal tract. Answering the question on somatotopy has important consequences for understanding the effects of incomplete spinal cord injury. Our recent study in the macaque monkey, using high-resolution dextran tracers, demonstrated a great deal of intermingling of fibres originating from primary motor cortex arm/hand, shoulder and leg areas. We quantified the distribution of fibres belonging to these different projections and found no significant difference in their distribution across different subsectors of the pyramidal tract or lateral corticospinal tract, arguing against somatotopy. We further demonstrated intermingling with corticospinal outputs derived from premotor and supplementary motor arm areas. We present new evidence against somatotopy for corticospinal projections from rostral and caudal cingulate motor areas and from somatosensory areas of the parietal cortex. In the pyramidal tract and lateral corticospinal tract, fibres from the cingulate motor areas overlap with each other. Fibres from the primary somatosensory cortex arm area completely overlap those from the leg area. There is also substantial overlap of both these outputs with those from posterior parietal sensorimotor areas. We argue that the extensive intermingling of corticospinal outputs from so many different cortical regions must represent an organizational principle, closely related to its mediation of many different functions and its large range of fibre diameters. The motor sequelae of incomplete spinal injury, such as central cord syndrome and 'cruciate paralysis', include much greater deficits in upper than in lower limb movement. Current teaching and text book explanations of these symptoms are still based on a supposed corticospinal somatotopy or 'lamination', with greater vulnerability of arm and hand versus leg fibres. We suggest that such explanations should now be finally abandoned. Instead, the clinical and neurobiological implications of the complex organization of the corticospinal tract need now to be taken into consideration. This leads us to consider the evidence for a greater relative influence of the corticospinal tract on upper versus lower limb movements, the former best characterized by skilled hand and digit movements.

Detailed organisation of the human midbrain periaqueductal grey revealed using ultra-high field magnetic resonance imaging.

The midbrain periaqueductal grey (PAG) is a critical region for the mediation of pain-related behavioural responses. Neuronal tract tracing techniques in experimental animal studies have demonstrated that the lateral column of the PAG (lPAG) displays a crude somatotopy, which is thought to be critical for the selection of contextually appropriate behavioural responses, without the need for higher brain input. In addition to the different behavioural responses to cutaneous and muscle pain - active withdrawal versus passive coping - there is evidence that cutaneous pain is processed in the region of the lPAG and muscle pain in the adjacent ventrolateral PAG (vlPAG). Given the fundamental nature of these behavioural responses to cutaneous and muscle pain, these PAG circuits are assumed to have been preserved, though yet to be definitively documented in humans. Using ultra-high field (7-Tesla) functional magnetic resonance imaging we determined the locations of signal intensity changes in the PAG during noxious cutaneous heat stimuli and muscle pain in healthy control participants. Images were processed and blood oxygen level dependant (BOLD) signal changes within the PAG determined. It was observed that noxious cutaneous stimulation of the lip, cheek, and ear evoked maximal increases in BOLD activation in the rostral contralateral PAG, whereas noxious cutaneous stimulation of the thumb and toe evoked increases in the caudal contralateral PAG. Analysis of individual participants demonstrated that these activations were located in the lPAG. Furthermore, we found that deep muscular pain evoked the greatest increases in signal intensity in the vlPAG. These data suggest that the crude somatotopic organization of the PAG may be phyletically preserved between experimental animals and humans, with a body-face delineation capable of producing an appropriate behavioural response based on the location and tissue origin of a noxious stimulus.

fNIRS is sensitive to leg activity in the primary motor cortex after systemic artifact correction.

BACKGROUND: functional near-infrared spectroscopy (fNIRS) is an increasingly popular tool to study cortical activity during movement and gait that requires further validation. This study aimed to assess (1) whether fNIRS can detect the difficult-to-measure leg area of the primary motor cortex (M1) and distinguish it from the hand area; and (2) whether fNIRS can differentiate between automatic (i.e., not requiring one's attention) and non-automatic movement processes. Special attention was attributed to systemic artifacts (i.e., changes in blood pressure, heart rate, breathing) which were assessed and corrected by short channels, i.e., fNIRS channels which are mainly sensitive to superficial scalp hemodynamics. METHODS: Twenty-three seated, healthy participants tapped four fingers on a keyboard or tapped the right foot on four squares on the floor in a specific order given by a 12-digit sequence (e.g., 434141243212). Two different sequences were executed: a beforehand learned (i.e., automatic) version and a newly learned (i.e., non-automatic) version. A 36-channel fNIRS device including 12 short channels covered multiple motor-related cortical areas including M1. The fNIRS data were analyzed with a general linear model (GLM). Correlation between the expected functional hemodynamic responses (i.e. task regressor) and the short channels (i.e. nuisance regressors), necessitated performing a separate short channel regression instead of integrating them in the GLM. RESULTS: Consistent with the M1 somatotopy, we found significant HbO increases of very large effect size in the lateral M1 channels during finger tapping (Cohen's d = 1.35, p<0.001) and significant HbO increases of moderate effect size in the medial M1 channels during foot tapping (Cohen's d = 0.8, p<0.05). The cortical activity differences between automatic and non-automatic tasks were not significantly different. Importantly, leg movements produced large systemic fluctuations, which were adequately removed by the use of all available short channels. DISCUSSION: Our results indicate that fNIRS is sensitive to leg activity in M1, though the sensitivity is lower than for finger activity and requires rigorous correction for systemic fluctuations. We furthermore highlight that systemic artifacts may result in an unreliable GLM analysis when short channels show signals that are similar to the expected hemodynamic responses.

Performing a vibrotactile discrimination task modulates finger representations in primary somatosensory cortex.

It is well established that vibrotactile stimuli are represented in somatotopic maps. However, less is known about whether these somatotopic representations are modulated by task demands and maybe even in the absence of tactile input. Here, we used a vibrotactile discrimination task as a tool to investigate these questions in further detail. Participants were required to actively perceive and process tactile stimuli in comparison to a no-task control condition where identical stimuli were passively perceived (no-memory condition). Importantly, both vibrotactile stimuli were either applied to the right index or little finger, allowing us to investigate whether cognitive task demands shape finger representations in primary somatosensory cortex (S1). Using multivoxel pattern analysis and representational similarity analysis, we found that S1 finger representations were more distinct during the memory than the no-memory condition. Interestingly, this effect was not only observed while tactile stimuli were presented but also during the delay period (i.e., in the absence of tactile stimulation). Our findings imply that when individuals are required to focus on tactile stimuli, retain them in their memory, and engage in active processing of distinctive stimulus features, this exerts a modulatory effect on the finger representations present in S1.NEW & NOTEWORTHY Using multivoxel pattern analysis, we found that discrimination task demands shape finger representations in the contralateral primary somatosensory cortex (S1), and that somatotopic representations are modulated by task demands not only during tactile stimulation but also to a certain extent in the absence of tactile input.

Functional brainstem representations of the human trigeminal cervical complex.

BACKGROUND: The human in-vivo functional somatotopy of the three branches of the trigeminal (V1, V2, V3) and greater occipital nerve in brainstem and also in thalamus and insula is still not well understood. METHODS: After preregistration (clinicaltrials.gov: NCT03999060), we mapped the functional representations of this trigemino-cervical complex non-invasively in 87 humans using high-resolution protocols for functional magnetic resonance imaging during painful electrical stimulation in two separate experiments. The imaging protocol and analysis was optimized for the lower brainstem and upper spinal cord, to identify activation of the spinal trigeminal nuclei. The stimulation protocol involved four electrodes which were positioned on the left side according to the three branches of the trigeminal nerve and the greater occipital nerve. The stimulation site was randomized and each site was repeated 10 times per session. The participants partook in three sessions resulting in 30 trials per stimulation site. RESULTS: We show a large overlap of peripheral dermatomes on brainstem representations and a somatotopic arrangement of the three branches of the trigeminal nerve along the perioral-periauricular axis and for the greater occipital nerve in brainstem below pons, as well as in thalamus, insula and cerebellum. The co-localization of greater occipital nerve with V1 along the lower part of brainstem is of particular interest since some headache patients profit from an anesthetic block of the greater occipital nerve. CONCLUSION: Our data provide anatomical evidence for a functional inter-inhibitory network between the trigeminal branches and greater occipital nerve in healthy humans as postulated in animal work. We further show that functional trigeminal representations intermingle perioral and periauricular facial dermatomes with individual branches of the trigeminal nerve in an onion shaped manner and overlap in a typical within-body-part somatotopic arrangement.Trial registration: clinicaltrials.gov: NCT03999060.

Onset pattern of nigrostriatal denervation in early Parkinson's disease.

The striatal dopaminergic deficit in Parkinson's disease exhibits a typical pattern, extending from the caudal and dorsal putamen at onset to its more rostral region as the disease progresses. Clinically, upper-limb onset of cardinal motor features is the rule. Thus, according to current understanding of striatal somatotopy (i.e. the lower limb is dorsal to the upper limb) the assumed pattern of early dorsal striatal dopaminergic denervation in Parkinson's disease does not fit with an upper-limb onset. We have examined the topography of putaminal denervation in a cohort of 23 recently diagnosed de novo Parkinson's disease patients and 19 age-/gender-matched healthy subjects assessed clinically and by 18F-DOPA PET; 15 patients were re-assessed after 2 years. There was a net upper-limb predominance of motor features at onset. Caudal denervation of the putamen was confirmed in both the more- and less-affected hemispheres and corresponding hemibodies. Spatial covariance analysis of the most affected hemisphere revealed a pattern of 18F-DOPA uptake rate deficit that suggested focal dopamine loss starting in the posterolateral and intermediate putamen. Functional MRI group-activation maps during a self-paced motor task were used to represent the somatotopy of the putamen and were then used to characterize the decline in 18F-DOPA uptake rate in the upper- and lower-limb territories. This showed a predominant decrement in both hemispheres, which correlated significantly with severity of bradykinesia. A more detailed spatial analysis revealed a dorsoventral linear gradient of 18F-DOPA uptake rate in Parkinson's disease patients, with the highest putamen denervation in the caudal intermediate subregion (dorsoventral plane) compared to healthy subjects. The latter area coincides with the functional representation of the upper limb. Clinical motor assessment at 2-year follow-up showed modest worsening of parkinsonism in the primarily affected side and more noticeable increases in the upper limb in the less-affected side. Concomitantly, 18F-DOPA uptake rate in the less-affected putamen mimicked that recognized on the most-affected side. Our findings suggest that early dopaminergic denervation in Parkinson's disease follows a somatotopically related pattern, starting with the upper-limb representation in the putamen and progressing over a 2-year period in the less-affected hemisphere. These changes correlate well with the clinical presentation and evolution of motor features. Recognition of a precise somatotopic onset of nigrostriatal denervation may help to better understand the onset and progression of dopaminergic neurodegeneration in Parkinson's disease and eventually monitor the impact of putative therapies.

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.

Activation of Cerebellum, Basal Ganglia and Thalamus During Observation and Execution of Mouth, hand, and foot Actions.

Humans and monkey studies showed that specific sectors of cerebellum and basal ganglia activate not only during execution but also during observation of hand actions. However, it is unknown whether, and how, these structures are engaged during the observation of actions performed by effectors different from the hand. To address this issue, in the present fMRI study, healthy human participants were required to execute or to observe grasping acts performed with different effectors, namely mouth, hand, and foot. As control, participants executed and observed simple movements performed with the same effectors. The results show that: (1) execution of goal-directed actions elicited somatotopically organized activations not only in the cerebral cortex but also in the cerebellum, basal ganglia, and thalamus; (2) action observation evoked cortical, cerebellar and subcortical activations, lacking a clear somatotopic organization; (3) in the territories displaying shared activations between execution and observation, a rough somatotopy could be revealed in both cortical, cerebellar and subcortical structures. The present study confirms previous findings that action observation, beyond the cerebral cortex, also activates specific sectors of cerebellum and subcortical structures and it shows, for the first time, that these latter are engaged not only during hand actions observation but also during the observation of mouth and foot actions. We suggest that each of the activated structures processes specific aspects of the observed action, such as performing internal simulation (cerebellum) or recruiting/inhibiting the overt execution of the observed action (basal ganglia and sensory-motor thalamus).

Somatotopic Specificity of Perceptual and Neurophysiological Changes Associated with Visuo-proprioceptive Realignment.

When visual and proprioceptive estimates of hand position disagree (e.g., viewing the hand underwater), the brain realigns them to reduce mismatch. This perceptual change is reflected in primary motor cortex (M1) excitability, suggesting potential relevance for hand movement. Here, we asked whether fingertip visuo-proprioceptive misalignment affects only the brain's representation of that finger (somatotopically focal), or extends to other parts of the limb that would be needed to move the misaligned finger (somatotopically broad). In Experiments 1 and 2, before and after misaligned or veridical visuo-proprioceptive training at the index finger, we used transcranial magnetic stimulation to assess M1 representation of five hand and arm muscles. The index finger representation showed an association between M1 excitability and visuo-proprioceptive realignment, as did the pinkie finger representation to a lesser extent. Forearm flexors, forearm extensors, and biceps did not show any such relationship. In Experiment 3, participants indicated their proprioceptive estimate of the fingertip, knuckle, wrist, and elbow, before and after misalignment at the fingertip. Proprioceptive realignment at the knuckle, but not the wrist or elbow, was correlated with realignment at the fingertip. These results suggest the effects of visuo-proprioceptive mismatch are somatotopically focal in both sensory and motor domains.

Somatosensory cortex of macaque monkeys is designed for opposable thumb.

The evolution of opposable thumb has enabled fine grasping ability and precision grip, therefore the ability to finely manipulate the objects and refined tool use. Since tactile inputs to an opposable thumb are often spatially and temporally out of sync with inputs from the fingers, we hypothesized that inputs from the opposable thumb would be processed in an independent module in the primary somatosensory cortex (area 3b). Here we show that in area 3b of macaque monkeys, most neurons in the thumb representation do not respond to tactile stimulation of other digits and receive few intrinsic cortical inputs from other digits. However, neurons in the representations of other 4 digits respond to touch on any of the 4 digits and interconnect significantly more. The thumb inputs are thus processed in an independent module, whereas there is a significantly more interdigital information exchange between the other digits. This cortical organization reflects behavioral use of a hand with an opposable thumb.

Representational similarity scores of digits in the sensorimotor cortex are associated with behavioral performance.

Previous studies aimed to unravel a digit-specific somatotopy in the primary sensorimotor (SM1) cortex. However, it remains unknown whether digit somatotopy is associated with motor preparation and/or motor execution during different types of tasks. We adopted multivariate representational similarity analysis to explore digit activation patterns in response to a finger tapping task (FTT). Sixteen healthy young adults underwent magnetic resonance imaging, and additionally performed an out-of-scanner choice reaction time task (CRTT) to assess digit selection performance. During both the FTT and CRTT, force data of all digits were acquired using force transducers. This allowed us to assess execution-related interference (i.e., digit enslavement; obtained from FTT & CRTT), as well as planning-related interference (i.e., digit selection deficit; obtained from CRTT) and determine their correlation with digit representational similarity scores of SM1. Findings revealed that digit enslavement during FTT was associated with contralateral SM1 representational similarity scores. During the CRTT, digit enslavement of both hands was also associated with representational similarity scores of the contralateral SM1. In addition, right hand digit selection performance was associated with representational similarity scores of left S1. In conclusion, we demonstrate a cortical origin of digit enslavement, and uniquely reveal that digit selection is associated with digit representations in primary somatosensory cortex (S1). Significance statement In current systems neuroscience, it is of critical importance to understand the relationship between brain function and behavioral outcome. With the present work, we contribute significantly to this understanding by uniquely assessing how digit representations in the sensorimotor cortex are associated with planning- and execution-related digit interference during a continuous finger tapping and a choice reaction time task. We observe that digit enslavement (i.e., execution-related interference) finds its origin in contralateral digit representations of SM1, and that deficits in digit selection (i.e., planning-related interference) in the right hand during a choice reaction time task are associated with more overlapping digit representations in left S1. This knowledge sheds new light on the functional contribution of the sensorimotor cortex to everyday motor skills.

Cortical response variability is driven by local excitability changes with somatotopic organization.

Identical sensory stimuli can lead to different neural responses depending on the instantaneous brain state. Specifically, neural excitability in sensory areas may shape the brain´s response already from earliest cortical processing onwards. However, whether these dynamics affect a given sensory domain as a whole or occur on a spatially local level is largely unknown. We studied this in the somatosensory domain of 38 human participants with EEG, presenting stimuli to the median and tibial nerves alternatingly, and testing the co-variation of initial cortical responses in hand and foot areas, as well as their relation to pre-stimulus oscillatory states. We found that amplitude fluctuations of initial cortical responses to hand and foot stimulation - the N20 and P40 components of the somatosensory evoked potential (SEP), respectively - were not related, indicating local excitability changes in primary sensory regions. In addition, effects of pre-stimulus alpha (8-13 Hz) and beta (18-23 Hz) band amplitude on hand-related responses showed a robust somatotopic organization, thus further strengthening the notion of local excitability fluctuations. However, for foot-related responses, the spatial specificity of pre-stimulus effects was less consistent across frequency bands, with beta appearing to be more foot-specific than alpha. Connectivity analyses in source space suggested this to be due to a somatosensory alpha rhythm that is primarily driven by activity in hand regions while beta frequencies may operate in a more hand-region-independent manner. Altogether, our findings suggest spatially distinct excitability dynamics within the primary somatosensory cortex, yet with the caveat that frequency-specific processes in one sub-region may not readily generalize to other sub-regions.

In the back of your mind: Cortical mapping of paraspinal afferent inputs.

Topographic organisation is a hallmark of vertebrate cortex architecture, characterised by ordered projections of the body's sensory surfaces onto brain systems. High-resolution functional magnetic resonance imaging (fMRI) has proven itself as a valuable tool to investigate the cortical landscape and its (mal-)adaptive plasticity with respect to various body part representations, in particular extremities such as the hand and fingers. Less is known, however, about the cortical representation of the human back. We therefore validated a novel, MRI-compatible method of mapping cortical representations of sensory afferents of the back, using vibrotactile stimulation at varying frequencies and paraspinal locations, in conjunction with fMRI. We expected high-frequency stimulation to be associated with differential neuronal activity in the primary somatosensory cortex (S1) compared with low-frequency stimulation and that somatosensory representations would differ across the thoracolumbar axis. We found significant differences between neural representations of high-frequency and low-frequency stimulation and between representations of thoracic and lumbar paraspinal locations, in several bilateral S1 sub-regions, and in regions of the primary motor cortex (M1). High-frequency stimulation preferentially activated Brodmann Area (BA) regions BA3a and BA4p, whereas low-frequency stimulation was more encoded in BA3b and BA4a. Moreover, we found clear topographic differences in S1 for representations of the upper and lower back during high-frequency stimulation. We present the first neurobiological validation of a method for establishing detailed cortical maps of the human back, which might serve as a novel tool to evaluate the pathological significance of neuroplastic changes in clinical conditions such as chronic low back pain.

Tiling and somatotopic alignment of mammalian low-threshold mechanoreceptors.

Innocuous mechanical stimuli acting on the skin are detected by sensory neurons, known as low-threshold mechanoreceptors (LTMRs). LTMRs are classified based on their response properties, action potential conduction velocity, rate of adaptation to static indentation of the skin, and terminal anatomy. Here, we report organizational properties of the cutaneous and central axonal projections of the five principal hairy skin LTMR subtypes. We find that axons of neurons within a particular LTMR class are largely nonoverlapping with respect to their cutaneous end organs (e.g., hair follicles), with Aß rapidly adapting-LTMRs being the sole exception. Individual neurons of each LTMR class are mostly nonoverlapping with respect to their associated hair follicles, with the notable exception of C-LTMRs, which exhibit multiple branches that redundantly innervate individual hair follicles. In the spinal cord, LTMR central projections exhibit rostrocaudal elongation and mediolateral compression, compared with their cutaneous innervation patterns, and these central projections also exhibit a fine degree of homotypic topographic adjacency. These findings thus reveal homotypic tiling of LTMR subtype axonal projections in hairy skin and a remarkable degree of spatial precision of spinal cord axonal termination patterns, suggesting a somatotopically precise tactile encoding capability of the mechanosensory dorsal horn.

Resting-State functional networks of different topographic representations in the somatosensory cortex of macaque monkeys and humans.

Information processing in the brain is mediated through a complex functional network architecture whose comprising nodes integrate and segregate themselves on different timescales. To gain an understanding of the network function it is imperative to identify and understand the network structure with respect to the underlying anatomical connectivity and the topographic organization. Here we show that the previously described resting-state network for the somatosensory area 3b comprises of distinct networks that are characteristic for different topographic representations. Seed-based resting-state functional connectivity analysis in macaque monkeys and humans using BOLD-fMRI signals from the face, the hand and rest of the medial somatosensory representations of area 3b revealed different correlation patterns. Both monkeys and humans have many similarities in the connectivity networks, although the networks are more complex in humans with many more nodes. In both the species face area network has the highest ipsilateral and contralateral connectivity, which included areas 3b and 4, and ventral premotor area. The area 3b hand network included ipsilateral hand representation in area 4. The emergent functional network structures largely reflect the known anatomical connectivity. Our results show that different body part representations in area 3b have independent functional networks perhaps reflecting differences in the behavioral use of different body parts. The results also show that large cortical areas if considered together, do not give a complete and accurate picture of the network architecture.

Distinct representation of ipsilateral hand movements in sensorimotor areas.

There is ample evidence that the contralateral sensorimotor areas play an important role in movement generation, with the primary motor cortex and the primary somatosensory cortex showing a detailed spatial organization of the representation of contralateral body parts. Interestingly, there are also indications for a role of the motor cortex in controlling the ipsilateral side of the body. However, the precise function of ipsilateral sensorimotor cortex in unilateral movement control is still unclear. Here, we show hand movement representation in the ipsilateral sensorimotor hand area, in which hand gestures can be distinguished from each other and from contralateral hand gestures. High-field functional magnetic resonance imaging (fMRI) data acquired during the execution of six left- and six right-hand gestures by healthy volunteers showed ipsilateral activation mainly in the anterior section of precentral gyrus and the posterior section of the postcentral gyrus. Despite the lower activation in ipsilateral areas closer to the central sulcus, activity patterns for the 12 hand gestures could be mutually distinguished in these areas. The existence of a unique representation of ipsilateral hand movements in the human sensorimotor cortex favours the notion of transcallosal integrative processes that support optimal coordination of hand movements.

Motor Onset Topography and Progression in Parkinson's Disease: the Upper Limb Is First.

OBJECTIVE: To define the motor onset and progression of Parkinson's disease (PD) in a prospective cohort of early unmedicated patients. METHODS: We enrolled a consecutive cohort of recently diagnosed (<18 months) PD patients with unilateral manifestations using age and gender-matched controls. The most affected body region was determined using various clinical standard metrics and objective quantitative kinematic measurements. Parkinson's Progression Markers Initiative data were used for external validation of the results. RESULTS: Twenty-five drug-naive patients and 21 controls were studied. Upper limbs were (92%) the most affected body region at onset as ascertained by patients' self-assessment, neurologists' impression, and Movement Disorders Society Unified Parkinson's Disease Rating Scale score. The upper limb (ie, hand) was the site of onset in 80% of patients. Motor features progressed to involve the lower limb but remained limited to the initially affected body side over a 2-year follow-up. Agreement among the different metrics (96%) confirmed focal upper limb predominant motor impairment at onset. The findings were confirmed by quantitative kinematic analyses and from a cohort of 34 similar patients from the Parkinson's Progression Markers Initiative database. CONCLUSIONS: Motor manifestations in PD start distally in one upper limb. The complexity of the motor repertoire and, consequently, the presumed larger dopaminergic striatal demand for maintaining skillful motor function in the upper limb, may contribute to greater vulnerability of dopaminergic striatal terminals. Recognition of this motor pattern could be used to monitor the evolution of nigrostriatal degeneration and the putative impact of therapies. © 2021 International Parkinson and Movement Disorder Society.

Topography of the pain in classical trigeminal neuralgia: insights into somatotopic organization.

Trigeminal neuralgia is defined by its clinical characteristics of paroxysmal unilateral facial pain in a well-defined territory. Distribution of the pain may be in one or several of the cutaneous and/or mucous territories of the three divisions with V2 pain being the most frequent territory followed by V3 and V1. Factors determining the distribution of pain have not yet been systematically investigated. It is now well recognized that vascular compression factor is a predominant aetiology of classical trigeminal neuralgia. In this study we aimed to find whether there is a relation between the location of the vascular compression and the peripheral distribution of the pain. Patients with classical trigeminal neuralgia in whom microvascular decompression was performed were included. Data recorded pertained to the nature of the conflict, its degree and, most importantly, location around the root: supero-median, supero-lateral or inferior. Equally, clinical data for the distribution of pain were recorded. Most of the patients 318 (89.3%) had the compression coming from above, i.e. 220 (61.7%) had compression from a supero-medial direction and 98 (27.5%) from a supero-lateral direction; inferior compression was present in 38 patients (10.7%). Distribution of the pain was significantly different according to the location of the conflict (P = 0.0005, Fisher Exact test). Odds ratios were computed for each location of compression and painful territory involved. According to the overall distribution of pain, patients with supero-medial compression had an odds ratio of 2.7 [95% confidence interval (CI) 1.66-4.41] of manifesting with V1 pain. Conversely V3 pain was less likely to occur with supero-median compression than the other types of pain (odds ratio 0.53, 95% CI 0.34-0.83). Inferior compression on the other hand was more likely to manifest with V3 pain with an odds ratio of 2.56 (95% CI 1.21-5.45). Overall V2 pain had an odds ratio close to 1 regardless of the type of compression. These findings suggest an association between the location of the neurovascular conflict with its resulting insult and the distribution of pain supporting a somatotopic view of the organization of the trigeminal root and a role of the conflict in the clinical manifestation of trigeminal neuralgia.

Two Distinct Systems Represent Contralateral and Ipsilateral Sensorimotor Processes in the Human Premotor Cortex: A Dense TMS Mapping Study.

Animal brains contain behaviorally committed representations of the surrounding world, which integrate sensory and motor information. In primates, sensorimotor mechanisms reside in part in the premotor cortex (PM), where sensorimotor neurons are topographically clustered according to functional specialization. Detailed functional cartography of the human PM is still under investigation. We explored the topographic distribution of spatially dependent sensorimotor functions in healthy volunteers performing left or right, hand or foot, responses to visual cues presented in the left or right hemispace, thus combining independently stimulus side, effector side, and effector type. Event-related transcranial magnetic stimulation was applied to single spots of a dense grid of 10 points on the participants' left hemiscalp, covering the whole PM. Results showed: (1) spatially segregated hand and foot representations, (2) focal representations of contralateral cues and movements in the dorsal PM, and (3) distributed representations of ipsilateral cues and movements in the ventral and dorso-medial PM. The present novel causal information indicates that (1) the human PM is somatotopically organized and (2) the left PM contains sensory-motor representations of both hemispaces and of both hemibodies, but the hemispace and hemibody contralateral to the PM are mapped on a distinct, nonoverlapping cortical region compared to the ipsilateral ones.