Plasticity and awareness of bodily distortion

Knowledge of the body is filtered by perceptual information, recalibrated through predominantly innate stored information, and neurally mediated by direct sensory motor information. Despite multiple sources, the immediate prediction, construction, and evaluation of one’s body are distorted. The origins of such distortions are unclear. In this review, we consider three possible sources of awareness that inform body distortion. First, the precision in the body metric may be based on the sight and positioning sense of a particular body segment. This view provides information on the dual nature of body representation, the reliability of a conscious body image, and implicit alterations in the metrics and positional correspondence of body parts. Second, body awareness may reflect an innate organizational experience of unity and continuity in the brain, with no strong isomorphism to body morphology. Third, body awareness may be based on efferent/afferent neural signals, suggesting that major body distortions may result from changes in neural sensorimotor experiences. All these views can be supported empirically, suggesting that body awareness is synthesized from multimodal integration and the temporal constancy of multiple body representations. For each of these views, we briefly discuss abnormalities and therapeutic strategies for correcting the bodily distortions in various clinical disorder

Brain motor system function after chronic, complete spinal cord injury.

Most therapies under development to restore motor function after spinal cord injury (SCI) assume intact brain motor functions. To examine this assumption, 12 patients with chronic, complete SCI and 12 controls underwent functional MRI during attempted, and during imagined, right foot movement, each at two force levels. In patients with SCI, many features of normal motor system function were preserved, however, several departures from normal were apparent: (i) volume of activation was generally much reduced, e.g. 4-8% of normal in primary sensorimotor cortex, in the setting of twice normal variance in signal change; (ii) abnormal activation patterns were present, e.g. increased pallido-thalamocortical loop activity during attempted movement and abnormal processing in primary sensorimotor cortex during imagined movement; and (iii) modulation of function with change in task or in force level did not conform to patterns seen in controls, e.g. in controls, attempted movement activated more than imagined movement did within left primary sensorimotor cortex and right dorsal cerebellum, while imagined movement activated more than attempted movement did in dorsolateral prefrontal cortex and right precentral gyrus. These modulations were absent in patients with SCI. Many features of brain motor system function during foot movement persist after chronic complete SCI. However, substantial derangements of brain activation, poor modulation of function with change in task demands and emergence of pathological brain events were present in patients. Because brain function is central to voluntary movement, interventions that aim to improve motor function after chronic SCI likely also need to attend to these abnormalities of brain function

Cognitive social and affective neuroscience of patients with spinal cord injury

A successful human-environment interaction requires a continuous integration of information concerning body parts, object features and affective dynamics. Multiple neuropsychological studies show that tools can be integrated into the representation of one's own body. In particular, a tool that participates in the conscious movement of the person is added to the dynamic representation the body – often called “Body schema” – and may even affect social interaction. In light of this the wheelchair is treated as an extension of the disabled body, essentially replacing limbs that don't function properly, but it can also be a symbol of frailty and weakness. In a series of experiments, I studied plastic changes of action, tool and body representation in individuals with spinal cord injury (SCI). Due to their peripheral loss of sensorimotor functions, in the absence of brain lesions and spared higher order cognitive functions, these patients represent an excellent model to study this topic in a multi-faceted way, investigating both fundamental mechanisms and possible therapeutic interventions. In a series of experiments, I developed new behavioral methods to measure the phenomenological aspects of tool embodiment (Chapter 3), to study its functional and neural correlates (Chapter 4) and to assess the possible computational model underpinning these phenomena (Chapter 5). These tasks have been used to describe changes in tool, action and body representation following the injury (Chapter 3 and 4), but also social interactions (Chapter 7), with the aim of giving a complete portrait of change following such damage. I found that changes in the function (wheelchair use) and the structure (body brain disconnection) of the physical body, plastically modulate tool, action and body representation. Social context and social interaction are also shaped by the new configuration of bodily representations. Such a high degree of plasticity suggests that our sense of body is not given at once, but rather it is constantly constructed and adapted through experience

Uner Tan Syndrome: History, Clinical Evaluations, Genetics, and the\ud Dynamics of Human Quadrupedalism

Abstract: This review includes for the first time a dynamical systems analysis of human quadrupedalism in Uner Tan syndrome, which is characterized by habitual quadrupedalism, impaired intelligence, and rudimentary speech. The first family was discovered in a small village near Iskenderun, and families were later found in Adana and two other small villages near Gaziantep and Canakkale. In all the affected individuals dynamic balance was impaired during upright walking,and they habitually preferred walking on all four extremities. MRI scans showed inferior cerebellovermian hypoplasia with slightly simplified cerebral gyri in three of the families, but appeared normal in the fourth. PET scans showed a decreased glucose metabolic activity in the cerebellum, vermis and, to a lesser extent the cerebral cortex, except for one patient,\ud whose MRI scan also appeared to be normal. All four families had consanguineous marriages in their pedigrees,\ud suggesting autosomal recessive transmission. The syndrome was genetically heterogeneous. Since the initial discoveries\ud more cases have been found, and these exhibit facultative quadrupedal locomotion, and in one case, late childhood onset. It has been suggested that the human quadrupedalism may, at least, be a phenotypic example of reverse evolution. From the viewpoint of dynamic systems theory, it was concluded there may not be a single factor that predetermines human quadrupedalism in Uner Tan syndrome, but that it may involve self-organization, brain plasticity, and rewiring, from the many decentralized and local interactions among neuronal, genetic, and environmental subsystems

Seljaajutraumade epidemioloogia Eestis. Peaaju aktivatsioonimuster seljaajutrauma ägedas faasis

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Seljaajutrauma (SAT) korral saavad seljaajus paiknevad närvirakud otseselt või kaudselt kahjustada. Suurel osal patsientidest jääb seetõttu eluaegne täielik või osaline jalgade ja/või käte halvatus ning tundlikkushäired, sest kahjustunud närvirakud seljaajus ei taastu endisele tasemele. SAT invaliidistab maailmas igal aastal üle saja tuhande inimese. SAT haigestumuskordajad erinevad riigiti. Arenenud riikide haigestumuskordajad on arenguriikidest suuremad ning seda seletatakse andmete erineva kättesaadavuse, meditsiinilise abi taseme ning üldise erineva elukvaliteediga. Eestis saab igal aastal SAT 39,7 isikut 1 000 000 inimese kohta ehk umbes 50 inimest aastas. Euroopas on see suurim haigestumus. Eestis on ohviteks noored 16–30-aastased mehed, kes kukuvad kõrgusest või saavad viga autoavariis. Oluline traumapõhjus on noortel ka sporditrauma, millest 90% on tingitud sukeldumisest. Selgub, et Eestis on peaaegu pooled patsiendid trauma saamise ajal alkohoolses joobes. SAT järel hakkab organism oodatust kiiremini vananema. Kuna häiruvad paljud füsioloogilised protsessid, esineb neil patsientidel palju traumajärgseid tüsistusi ning suurem suremus võrreldes tervete isikutega. Eestis sureb trauma järel naisi rohkem kui mehi. Suremus on suurim esimesel traumajärgsel aastal. Peamisteks surmapõhjusteks on välised põhjused, sepsis ja südame-veresoonkonnahaigused. Kahjuks on SAT-patsientide hulgas suur ka enesetappude hulk. SAT järel tekivad olulised muutused ja ümberkorraldused ka peaajus. Peaaju aktivatsioonimuster muutub selle järgi, kas patsient paraneb või mitte. Uurimistöö tulemusel selgus, et paranejatel on esimestel traumajärgsetel kuudel peaajukoore aktivatsioon laialdasem ja intensiivsem kui mitteparanejatel. Seetõttu võib arvata, et funktsionaalne magnetresonantstomograafiline uuring, millega saab aju aktivatsioonimustrit uurida, on SAT-patsientide paranemise võimalik ennustaja. SAT-ravi tänapäeval puudub, seega on tähtsaim ennetus.Traumatic spinal cord injury (TSCI) is either a direct or an indirect damage to the nerve cells in the spinal cord. According to the height of the lesion, the clinical picture is variable. Injury to the spinal cord in the cervical region is associated with loss of muscle strenght and/or sensibility in all four extremities. Injury to the lower spinal cord causes loss of strenght and/or sensibility only in legs. Every year more than 100,000 people acquire TSCI around the world. The reported incidence is the highest in the United States and the lowest in the Netherlands. The incidence of TSCI is 39.7 per million population in Estonia, which means that almost 50 individuals sustain TSCI every year in Estonia. The incidence is unfortunately one of the highest in Europe. The rates are significantly higher for men compared with women and especially among the youngest men (age-group 16 to 30 years). The leading cause of TSCI are falls, followed by motor vehicle accidents and diving. A significant proportion of injuries are related to alcohol consumption before trauma in Estonia. As the time passes, the accelerated aging is taking place in those with TSCI. This is particulary evident in musculoskeletal, endocrine, and cardiovascular systems. Life expectancy is significantly decreased in TSCI patients in Estonia compared with the general population. During the first year, the leading underlying causes of death were external causes of injury, cardiovascular diseases and different infections. Later, the cardiovascular diseases became predominant, followed by suicides. TSCI does not affect the brain, although changes in brain function have been identified by different studies. Our study found broadening of cortical activation and a shift of the centre of gravity during the first year after TSCI depending on the recovery. These results show that during the first post-TSCI year, compensatory changes of brain function will take place. We suggest that the results offer unique evidence for the usefulness of functional magnetic resonance imaging as a predictor for outcome after TSCI. As there is no cure for TSCI today, prevention is very important

Locomotor activity in spinal man: significance of afferent input from joint and load receptors

The aim of this study was to differentiate the effects of body load and joint movements on the leg muscle activation pattern during assisted locomotion in spinal man. Stepping movements were induced by a driven gait orthosis (DGO) on a treadmill in patients with complete para‐/tetraplegia and, for comparison, in healthy subjects. All subjects were unloaded by 70% of their body weight. EMG of upper and lower leg muscles and joint movements of the DGO of both legs were recorded. In the patients, normal stepping movements and those mainly restricted to the hips (blocked knees) were associated with a pattern of leg muscle EMG activity that corresponded to that of the healthy subjects, but the amplitude was smaller. Locomotor movements restricted to imposed ankle joint movements were followed by no, or only focal EMG responses in the stretched muscles. Unilateral locomotion in the patients was associated with a normal pattern of leg muscle EMG activity restricted to the moving side, while in the healthy subjects a bilateral activation occurred. This indicates that interlimb coordination depends on a supraspinal input. During locomotion with 100% body unloading in healthy subjects and patients, no EMG activity was present. Thus, it can be concluded that afferent input from hip joints, in combination with that from load receptors, plays a crucial role in the generation of locomotor activity in the isolated human spinal cord. This is in line with observations from infant stepping experiments and experiments in cats. Afferent feedback from knee and ankle joints may be involved largely in the control of focal movement

Complete Division of the Spinal Cord in Lower Dorsal Region: A Case With Conservation of Spinal Reflexes Below Level of Lesion

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Üner Tan Syndrome: Review and Emergence of Human Quadrupedalism in Self-Organization,\ud Attractors and Evolutionary Perspectives\ud

The first man reported in the world literature exhibiting habitual quadrupedal locomotion was discovered by a British traveler and writer on the famous Baghdat road near Havsa/Samsun on the middle Black-Sea coast of Turkey (Childs, 1917). Interestingly, no single case with human quadrupedalism was reported in the scientific literature after Child's first description in 1917 until the first report on the Uner Tan syndrome (UTS: quadrupedalism, mental retardation, and impaired speech or no speech)in 2005 (Tan, 2005, 2006). Between 2005 and 2010, 10 families exhibiting the syndrome were discovered in Turkey with 33 cases: 14 women (42.4%) and 19 men (57.6%). Including a few cases from other countries, there were 25 men (64.1%)and 14 women (35.9%). The number of men significantly exceeded the number of women (p < .05). Genetics alone did not seem to be informative for the origins of many syndromes, including the Uner Tan syndrome. From the viewpoint of dynamical systems theory, there may not be a single factor including the neural and/or genetic codes that predetermines the emergence of the human quadrupedalism.Rather, it may involve a self-organization process, consisting of many decentralized and local interactions among neuronal, genetic, and environmental subsystems. The most remarkable characteristic of the UTS, the diagonal-sequence quadrupedalism is well developed in primates. The evolutionarily advantage of this gait is not known. However, there seems to be an evolutionarily advantage of this type of locomotion for primate evolution, with regard to the emergence of complex neural circuits with related highly complex structures. Namely, only primates with diagonal-sequence quadrupedal locomotion followed an evolution favoring larger brains, highly developed cognitive abilities with hand skills, and language, with erect posture and bipedal locomotion, creating the unity of human being. It was suggested that UTS may be considered a further example for Darwinian diseases, which may be associated with an evolutionary understanding of the disorders using evolutionary principles, such as the natural selection. On the other hand, the human quadrupedalism was proposed to be a phenotypic example of evolution of reverse, i.e., the reacquisition by derived populations of the same character states as those of ancestor populations. It was also suggested that the emergence of the human quadrupedalism may be related to self-organizing processes occurring in complex systems, which select or attract one preferred behavioral state or locomotor trait out of many possible attractor states. Concerning the locomotor patterns, the dynamical systems in brain and body of the developing child may prefer some kind of locomotion, according to interactions of the internal components and the environmental conditions, without a direct role of any causative factor(s), such as genetic or neural codes, consistent with the concept of self-organization, suggesting no single element may have a causal priority

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease- causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15. Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson’s disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes