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A novel use of virtual reality in the treatment of cognitive and motor deficit in spinal cord injury A case report

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Rationale: Aim of this study is to evaluate the cognitive and motor outcomes after a combined rehabilitative training using a standard cognitive approach and virtual reality (VR), in a patient with spinal cord injury (SCI). Patient's concerns: A
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   A novel use of virtual reality in the treatment of cognitive and motor de fi cit in spinal cord injury   A case report Giuseppa Maresca, PsyD, Maria Grazia Maggio, PsyD, Antonio Buda, PT, Gianluca La Rosa, MSc, Alfredo Manuli, MSc, Placido Bramanti, MD, Rosaria De Luca, MSc, Rocco Salvatore Calabrò, MD, PhD ∗  AbstractRationale:  Aim of this study is to evaluate the cognitive and motor outcomes after a combined rehabilitative training using astandard cognitive approach and virtual reality (VR), in a patient with spinal cord injury (SCI). Patient ’ s concerns:  A 60-year-old right-handed man, affected by incomplete cervical SCI, came to our observation for amoderate tetraparesis, mainly involving the left side, after about 6-months from the acute event. The neurological examinationshowed imbalance with upper limb incoordination, besides the paresis mainly involving the left side. At a neuropsychologicalevaluation, he presented important impairment in cognitive and behavioural status, with temporal and spatial disorientation, areduction of attention and memory process, de fi cit of executive function and a severe depression of mood, which was not detectedduring the previous recovery. Diagnosis:  Motor and cognitive de fi cits in SCI. Interventions:  Thepatientwas1stsubmittedtostandardcognitivetrainingandtraditionalphysiotherapy,andthentoacombinedtherapeutic approach, in which virtual reality training was provided by means of the virtual reality rehabilitation system (VRRS,Khymeia, Italy). Outcomes:  After the combined therapeutic approach with the VRRS training, we observed a signi fi cant improvement in differentcognitive domains, a notable reduction of anxiety and depressive symptoms, as well as motor performance, and balanceimprovement. Lessons:  Virtual reality can be considered a promising tool for the rehabilitation of different neurological disorders, includingpatients with both motor and cognitive de fi cits following SCI.  Abbreviations:  ATP  =  attention process training, BBS  =  Berg balance scale, CAM  =  attentive matrices test, FIM  =  functionalindependencemeasure,HRS-A  = Hamiltonratingscaleforanxiety,HRS-D = Hamiltonratingscalefordepression,MoCA  = Montrealcognitive assessment, MSCIS  =  the model spinal cord injury system, PT   =  physiotherapy, RAVLI  =  Rey auditory verbal learningimmediate, RAVLR = Rey auditory verbal learning recall, RCI = reliable change index, ROT  = reality orientation therapy, SCI = spinalcord injury, SCT  = standard cognitive training, SD = standard deviation, SFT  = semantic  fl uency test,TMT  = trail making test, VFT  = verbal  fl uency test, VR  =  virtual reality, VRRS  =  virtual reality rehabilitation system. Keywords:  neurorehabilitation, spinal cord injury, virtual reality, VRRS 1. Introduction Spinal cord injury (SCI) consists of temporary or permanentlyloss of motor, sensory, or autonomic functions after eithertraumatic or non-traumatic spinal cord damage. Every year,spinal trauma, affects about an individual in a thousand. AnItalian epidemiologic survey [1] has found 1014 new cases of spinalcordinjury(SCI)in2years,mosttrauma(67.5%).Amongthese, almost the 57% showed a SCI close to the neck, which cancausetotalorpartialquadriplegiaandanalterationofthemuscletone, depending on the speci fi c position, and the seriousness of the trauma. [2] The location and type of spinal cord damagedetermine the different clinical pictures (ranging from variouslevels of incomplete forms up to a complete SCI), and thefunctional and rehabilitation outcomes. [3] The SCI can cause important disability, mainly involving themotor function. Sensory-motor as well as genito-urinary, neuro-vegetativeorbreathingalterationsmayalsobepresent.Cognitivedysfunctions sometimes may be detected, but they are not relatedto the injury. The model spinal cord injury system (MSCIS) [4] observed that 28% of the patients affected by acute SCI tend tohave minor brain injuries, and among these, only 12% presentscognitive or behavioral alterations. Kreutzer et al [5] haveobserved a chronic de fi cit in visual verbal learning, in the visualorganization and attention in 30 patients affected by SCI, even if they did not reveal evident traumatic brain injuries. Moreover,patients affected by SCI shows high levels of depression and Editor: N/A.The authors have no funding and con fl   icts of interest to disclose.IRCCS Centro Neurolesi   “  Bonino Pulejo ”  , Messina, Italy. ∗ Correspondence: Rocco Salvatore Calabrò, IRCCS Centro Neurolesi   “  BoninoPulejo ”  , Messina, Italy, S.S. 113, Contrada Casazza, 98124 Messina, Italy (e-mail: salbro77@tiscali.it, roccos.calabro@irccsme.it).Copyright   ©  2018 the Author(s). Published by Wolters Kluwer Health, Inc.This is an open access article distributed under the terms of the CreativeCommons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.Medicine (2018) 97:50(e13559)Received: 23 August 2018 / Accepted: 14 November 2018 http://dx.doi.org/10.1097/MD.0000000000013559 Clinical Case Report  Medicine ® OPEN 1  anxiety, which tend to decrease during their rehabilitative periodeven if their prevalence remains unexpectedly high. [6] Inliterature, some studies [7,8] highlighted that cognitive andemotional-behavioral symptoms in SCI (concentration, attentionand memory de fi cits) can be a consequence of the loss of consciousness or of a post-traumatic amnesia. Nonetheless, thesesymptoms can also be a consequence of predisposing risk factorsconnected to some aspects of the patients ’  everyday life, [9,10] totheir level of education, [6] to their stress and other socio-demographic factors, or to prolonged anesthesia. Manytraditional and innovative techniques can be useful for therehabilitation of motor and cognitive de fi cits, [11,12] however; inthe last decade, virtual reality (VR) has had a growing role in thetreatment of different neurological disorders. [13,14] The VR is the term used to indicate a simulated reality: itconsists in the use of computer technologies to create arti fi cialenvironments, similar to the real ones with which the patient caninteract. The  “ virtual rehabilitation ”  puts together the advan-tagesofacognitiveandmotorstimulationwitharecreationalandhighlyecologicrole, sothatthepatients ’  motivationandpleasuregrows during the rehabilitative session, with a simulation of everyday life activities. These aspects have relevant consequenceson both motor and cognitive abilities, with regard to attention,memory and executive processes, [15] supporting higher aware-ness and knowledge of results and performance. Indeed, thanksto these virtual scenarios, the central nervous system receives anincreased sensory feedback, which is able to produce changesin the synaptic plasticity, to reinforce motor learning. [16] Among the various tools using VR, the virtual realityrehabilitation system (VRRS) is a promising device for therehabilitationofawiderangeofneurologicaldisorders,thankstoits modularity. The VRSS has 3 main rehabilitative modules:Neurologic (including motor, cognitive; and logopedic activities;Cardiorespiratory, and Orthopedic, whose use is giving promis-ing results. [17 – 19] The aim of this study is to evaluate the cognitive and motoroutcomes after combined rehabilitative training using a standardcognitive approach and virtual reality, in a patient with SCI. 2. Case description A 60-year-old right-handed man, affected by incomplete cervicalvertebro-spinal trauma, presented with a moderate tetraparesis,mainly involving the left side. The patient, an oncologist lining inMessina(Sicily,Italy),wasmarriedandhas2children(a27-year-old male and 23-year-old female). His parents were both dead:the father for natural causes and mother from breast cancer,while he and her older sisters were healthy. The psychomotordevelopment of the patient was normal and he practiced sportregularly; at a young age, he was a soccer player, and he likedcycling. The patient also liked reading, swimming and travelling,and he had a very intense social life. He was a moderate coffeedrinker; he did not drink alcohol and was a non-smoker.In November 2016, following asevere caraccident resulting inSCI, he was admitted to a neurosurgical ward for a totaldecompressive laminectomy at C3 – 4 level. He attended therehabilitation center for about 4 months, with moderate motorimprovements. At discharge, an assessment of cognitive statuswas not performed. The patient was then admitted to the(blinded), to undergo a speci fi c neurorehabilitation cycle (i.e.around 6 months after the SCI).At our observation, the neurological examination showed amoderate left-hemiparesis and imbalance with upper limbincoordination(thatwaspresentonlyintheeye-closedcondition)and reduced sensitivity (hypoesthesia). At a neuropsychologicalevaluation, he presented several alterations in the cognitive andbehavioral status, with temporal, spatial and autobiographicdisorientation, reduction of attention and memory processes,de fi cit of the executive function and severe anxious-depressivesymptoms. No other medical comorbidities were detected, andhematochemical tests, as well as cardiac evaluation, and cerebralmagnetic resonance, were normal.Patient gave informed consent for the diagnostic procedures,treatment, and publication of the case.  2.1. Procedures As the patient was in a post-traumatic chronic phase, to managehis cognitive, motor and emotional status, we decided to treathim by using a speci fi c rehabilitation protocol, including 2different types of training. The patient was adequately informedabout the study and offered his collaboration and writtenconsent. In the 1st phase, the patient was submitted to aconventional treatment, including psychological counselling,standard cognitive training (SCT) and physiotherapy (PT). Afterthe 1st phase, 4 weeks of latency have elapsed before the nextphase, in which the patient was only treated with physiotherapy(to avoid a cumulative effect). Then, the patient was submittedto the experimental protocol (second phase; i.e. a combinedtherapeutic approach, cognitive and sensory-motor training wasprovided by means of the virtual reality rehabilitation system(VRRS, by Khymeia, Italy), besides the standard Bobath physicaltherapy).However, the patient was provided with the same amount of treatmentbothinphase1and2;inparticular,inthe1stphasethepatient underwent 72 sessions of PT and 72 of SCT, whereas inthe2ndphasethepatientwassubmittedto36PTsessionsand36SCT sessions, besides 72 VRRS sessions (both cognitive andmotor). The entire rehabilitation treatment lasted about 6months: the patient was hospitalized for 3 months, then, hestayedathomefor1month,andcamebackasinpatientforother3 months (for more details see Table 1).  2.2. Functional assessment  Thepatientwasevaluatedbyaskilledneuropsychologistthroughthe administration of speci fi c neuropsychological battery,including Montreal cognitive assessment (MoCA) to evaluategeneral cognitive status, attentive matrices test (CAM); trailmaking test (TMT), digit span and the Rey auditory verballearning immediate and recall (RAVLI, RAVLR), Weigl ’ s sortingtest, Raven ’ s coloured matrices; verbal  fl uency test (VFT) andsemantic  fl uency test (SFT) to assess spontaneous speech,comprehension and communication skills, Hamilton rating scalefor depression (HRS-D) and Hamilton rating scale for anxiety(HRS-A).A physiotherapist administered the functional independencemeasure (FIM) (after discussion with the rehabilitation team),andtheBergbalancescale(BBS)toassessfunctionalrecoveryandbalance (Table 2). Both the neuropsychologist and physiothera-pist were blinded to the patient ’ s treatment. We evaluated thepatient ’ s cognitive and motor pro fi le in 2 separate phases, beforeand after the 2 different trainings (T0: baseline; T1: at the end of the traditional neurorehabilitation training; T2: at the beginningof the combined experimental approach; and T3: after thecombined approach). Reliable change index (RCI) was used to Maresca et al. Medicine (2018) 97:50  Medicine 2  evaluate whether a change in an individual ’ s score (i.e., betweenT0 and T1, and T2 and T3) was signi fi cant or not (based on howreliable the measure is). The RCI allows to de fi ne if the changeobservedinapatientisclinicallyandpracticallysigni fi cant,basedon the amount of change that a patient has to show on a speci fi cpsychometric instrument between the measurement occasions insuch a way that a difference is more signi fi cant than reasonablyexpected for any measurement errors. The RCI is a statistic usedtodetermineifachangeoccurringinthescoreofanindividual(orgroup)isstatistically signi fi cantbased onthetest-retest reliabilityof the measurement. [20] This provides information about thelikelihood that a change in test scores  “ results from ”  true orreliable change or results from the case. To calculate RCI assuggested by Bauer et al [21] we used a speci fi c formula. In thisstudy, we added other scores. We administered same criteria to ahalf-treatment evaluation,to monitorthechanges, andin theendthe post-treatment scores. We used the standard deviation (SD)fromthefunctionalnormativesample,andcoef  fi cientalphafromthenormativesampleforthescaletoobtaintheminimumchangein a scale score calculation. The standard error of the differencewill be dependent on the measure ’ s standard error, whichinvolves the standard deviation of the normative sample of theinstrument and the test reliability. The result represents astandard score. Values  ≥  1.96 or    1.96 are representative of atrue change at a 95% con fi dence level ( P -value = .05), unlikely tobe explained by measurement error. Given that it has beendemonstratedthatRCIcouldbeusefulinassessingchangesintheneuropsychological  fi eld, [22] we used this index also for motorfunctional outcomes.  2.3. Conventional rehabilitation training The conventional treatment consisted of psychological counsel-ling, standard cognitive training (SCT) and physiotherapy (PT).Counselling was focused to reduce anxiety and depressionsymptoms, using a narrative and introspective training to helpboth the patient and his family. The SCT was based on a face-to-face approach between the therapist and the patient using paperand pencil tools. It was mainly focused on strengtheningorientation with a speci fi c cognitive program based on thereality orientation therapy (ROT); autobiographic memory,temporal and spatial orientation, and simple relationships andlogic associations were also trained. To improve attention, weused the attention process training (ATP) that includes task  Table 1 Standard and experimental training performed by the patient. Rehabilitation program Rehabiliative approach Session duration Types of treatment Phase 13 monthsNov-Jan(2016 – 2017)conventionalneurorehabilitationPsychological counseling 2 weekly sessions of60 minutes (24 totaltreatments)60 minutes of psychological counselingStandard cognitive training 6 weekly sessions of60 minutes (72 totaltreatments)15 minutes of reality orientation therapy15 minutes of attention process training15 memory training15 problem solvingTraditional physiotherapy 6 weekly sessions of60 minutes (72 totaltreatments)10 minutes: stretching and mobilization in supine position10 minutes: assisted exercises, exercises against resistance, and free exercises15 minutes: exercises for trunk control, and balance in sitting position10 minutes: balance exercises with weight shift15 minutes: cycling/gait trainingPHASE 23 months Apr-June(2017)combined rehabilitativeapproachPsychological counseling 2 weekly sessions of60 minutes (24 totaltreatments)60 minutes of psychological counselingStandard cognitive training 3 weekly sessions of60 minutes (36 totaltreatments)15 minutes reality orientation therapy15 minutes attention process training15 memory training15 problem solvingTraditional physiotherapy 3 weekly sessions of60 minutes (36 totaltreatments)10 minutes: stretching and mobilization in supine position10 minutes: assisted exercises, exercises against resistance, and free exercises15 minutes: exercises for trunk control, and balance in sitting position10 minutes: balance exercises with weight shift15 minutes: cycling/gait trainingVirtual reality rehabilitationsystem (VRRS) — cognitiveModule3 weekly sessions of60 minutes (36 totaltreatments)15 minutes reality orientation therapy15 minutes attention process training15 memory training15 Problem SolvingVirtual reality rehabilitationsystem (VRRS) — sensory-motor module3 weekly sessions of60 minutes (36 totaltreatments)30 minutes: trunk control training, static and dynamic balance.30 minutes: symmetrical load and weight shifting Maresca et al. Medicine (2018) 97:50 www.md-journal.com 3  targeting for the sustained, selective, split and alternatingattention. The memory enhancement goal was achieved byworking on recognition and remembrance tasks with verbal andnonverbal material, reminiscence and validation therapy,mnemonic techniques and strategic skills. The training of theexecutive function was reached by working on categorization,planning, associationandanalogical reasoning(Table 3). ThePTwasprovidedaccordingtoBobathapproach,aimedatimprovingbalance, reducing spasticity and increasing left side muscle force.  2.4. Combined neurorehabilitation approach The combined neurorehabilitation approach consisted of thevirtual reality (VR) treatments, in addition to the conventionalrehabilitation approach. This kind of approach was provided bythe virtual reality rehabilitation system (VRRS), one of the mostadvanced comprehensive and clinically proven VR system forrehabilitation [19,23] and telerehabilitation. [24] Extremely easy touse, high customization capacity, complete automated reporting,functionaltelerehabilitation,aresomeoftheguidingprinciplesof continuous system development. The VRRS, in fact, is conceivedas a  “ central HUB ”  to which you can connect via USB a series of specialized peripherals, fully synchronized and integrated withthe system. The VRRS can be used in many neurologicaldisorders,thankstothedifferentmodulesforcognitive,language,postural, and motor rehabilitation.Duringthecognitivetraining,thepatientwassittinginfrontof the device, actively interacting with the platform. The VRRScognitive module consists in a large set of activities forrehabilitation, with more than 50 exercises already availableand many others under development. All activities are organizedby cognitive function: memory, attention, language, spatial-temporal orientation, planning, reasoning and other executivefunction, calculation, and praxis. Cognitive exercises providedthrough the VRRS can be classi fi ed in 2 main categories. The 1stcategory includes 2D exercises where the patient interacts withobjects and scenarios through the touch screen or through aparticular magnetic tracking sensor coupled with a squeezableobject, thus emulating mouse-like interaction capabilities. The2ndcategoryconsistsof3Dexercises,wherethepatientsinteractswith 3D on immersive virtual scenarios and objects through amagnetic tracking sensor generally placed over the hand (thatpermits a 3D position tracking of the end effector). Furthermore,cognitive tasks are generally coded as pick and place activities,ordering activities, selection activities, and sequential selectionactivities (Table 3).The VRRS motor program includes speci fi c tasks of the virtualsensory motor to stimulate muscle strengthening, strengthen legtendons and ligaments, improve posture, pelvis movements, andbalance reactions. All virtual exercises have been planned andorganized by the therapist (after consultation with the neurolo-gist),withincreasingdif  fi cultyinrelation tothetimeofexecutionand the category of activity. In fact, in the 1st training phase, thetherapist used the stabilometric platform to increase the staticbalance. Supine mobilization and assisted and free exercises fortrunk control and balance in a sitting position, along withexercises with weight shift and walking, were carried out. At alaterstage,thetherapistusedaproprioceptive/dynamicplatform,  Table 2 shows the patient ’ s neuropsychological and motor assessment. Test/scale Domain Description Montreal cognitiveassessment (MoCA)Cognition The Montreal cognitive assessment is a brief cognitive screening assessing: short-term memory, visuo-spatial abilities,executive functions, attention, concentration and working memory, language and orientation to time and placeHamilton anxiety ratingscale (HARS-A) Anxiety The Hamilton anxiety rating scale is a rating scale developed to measure the severity of anxiety symptoms; the scaleconsists of 14 items, each de fi ned by a series of symptoms, and measures both psychic and somatic anxietyHamilton depressionrating scale (HRS-D)Depression The Hamilton depression rating scale is a multiple item questionnaire used to provide an indication of depression; it isdesigned for adults and is used to rate the severity of their depression by feelings of guilt, suicidal ideation, insomnia,apprehension or retardation, anxiety, weight loss and somatic symptoms Attentive matrix test Attention It is used to evaluate the selective visual attention. There are 3 matrices that are shown to the subject. Each of themconsists of 13 lines of 10 numbers from 0 to 9 each, arranged in a random sequence. The subject must block allnumbers equal to those printed at the top of the matrix. Matrices should be presented from the simplest to the mostdif fi cultTrail making test Attention andvisuo-spatialfunctionTMT assesses spatial planning capability in a visuo-motor task. TMT is composed of two parts, A and B. The trail Aevaluates the sustained attention, the trail B measures split and alternate attention, and the difference in timebetween the 2 tests (B –  A) is a factor of cognitive  fl exibility and shifting abilityDigit span Memory This test evaluate the verbal memory span (digit memory). It consists of 2 different tests: 1. Forward digits (repeat digitsforwards); 2. Back digits (repeating digits in reverse)Rey auditory verbal learningimmediate and recall(RAVLI, RAVLR)Memory This test measures the immediate memory span and provides an analysis of learning. The test consists of 5presentations, with re-enactment, a list of 15 wordsVerbal  fl uency test (VFT) Fluency It evaluates the amplitude of the lexical stock, the ability to access the lexicon and the lexical organization. It consists in2 parts: Verbal  fl uency for phonemic categories and Verbal  fl uency for semantic categoriesRaven ’ s coloured matrices Executive functions The test measures the  fl uid Intelligence. They are used with adults of low intellect or old ageWeigl ’ s sorting test Executive functions This test measures the ability of categorical thinking and it is composed by 12 wood stimuli classi fi able for form, colour,suit thickness and dimensions. The test can be done in 2 ways (active and passive)Berg balance scale (BBS) Balance The Berg balance scale (BBS), consisting in 14 item and built on 4-points Likert Scale. It is a widely used clinical testfor the evaluation of the effectiveness of interventions and for the quantitative descriptions of the motor functions ofthe older adultFunctional independencemeasure (FIM)Disability The functional independence measure is an assessment tool that allows to measure the disability, it also inspects 18activities of everyday life (13 motor sphincters, 5 cognitive). Each activity can receive a variable score of 1 (completedependence on others) and 7 (full self-suf fi ciency) Maresca et al. Medicine (2018) 97:50  Medicine 4  characterized by greater instability and greater executivedif  fi culty, with training of the trunk control, in static anddynamic equilibrium and weight displacement (Figure 1).At the end of the traditional treatment (T1) using standardtechniques, the patient presented a mild improvement only inorientation and mood, with a reduction of negative thoughts,besides a better postural control. Only at the end of combinedapproach using VRRS, we observed asigni fi cant improvement indifferent cognitive domains such as executive process, selectiveattention, memory abilities, and spatial cognition; moreover, wehaveseenasubstantialreductioninanxiety ’ slevelanddepressivesymptoms (Table 4), with the optimization of global motorperformance and balance improvement, in both static anddynamic control, as per Berg balance scale (BBS) score (Table 5). 3. Discussion Spinalcordinjuryisaconditionthatcausestotalorpartialtetraorparaplegia and alteration of the muscle tone [2] with possiblesensory de fi cit, genito-urinary, neurovegetative, and respiratorysymptoms. Generally speaking, no cognitive impairment isfound [2] although, as described by Hartmann et al, [25] our caseshows that the evaluation and treatment of neuropsychologicalandmotorde fi citsmayeventuallycontributetoabetterfunctionaloutcome.Wearenotcompletelyabletostateifcognitivede fi citpre-existedtheaccidentortotalanaesthesia;however,theimpairmentappeared after this event, and it was neglected during the 1strehabilitative intervention. The accurate neuropsychologicalevaluation we carried out led us to the detection of the cognitivedecline for which allowed us proper management of the disorder.Therefore, the rehabilitative team should consider appliedneuropsychology as an integral part of the rehabilitation process,evenwhennocognitivede fi citsarereferred [26] inpatientsincludingthose with spinal cord injury (SCI).In this report, we want to underline the important role of innovative devices using virtual reality (VR) in improving bothmotor and cognitive performances.In the last decades, in the  fi eld of rehabilitation, we havewitnessed the development of innovative tools that make use of VR. This consists of a set of computing technologies that cancreate interactive environments involving the user in simulatingreal world activities. Several clinical and experimental applica-tions demonstrated the effectiveness of these technologies onpeople of all ages, affected by neurological and motor disordersand spasticity of different etiologies. [11,14] In addition, VR maypromotepsychologicalwellbeing,participationandautonomyof   Table 3 Cognitive rehabilitative program, including the standard and the experimental (VRRS) one. COGNITIVE domain VRRS cognitive training STANDARD cognitive training Orientation To select and sort in the right sequence the days of the week and themonths of the year. To indicate the position of the objects on thescreen (right, left, up, down). To recognize the rotation type of animalsand objects (clockwise and anti-clockwise) and to position the itemsaccording to the type of rotation indicated. The level of dif  fi  culty increases with the increase of the numbers of elements  To stimulate temporal and spatial orientation through the recall of days,months, years, festivities, events or personal data, personal stories,places, itiniraries and spatial locations. The informations are repeatedlytransmitted in visual, verbal, written or auditory mode. Cognitive therapist uses tasks with increasing dif  fi  culty, enhancing the speci  fi  city of the requests. The patient was gradually requested to give more temporal, spatial and autobiographical details   Attention To select, with an immediate and recall feedback (audio and video), somevarious elements (colors; musical strings; geometric or not form;animals . . . ) observed in the virtual environment. These elementsremain visible to the observer for a variable time, established by theinteraction between the virtual system, therapist and patient. The patienttouches the virtual target element, in a speci fi c time; this action causesa visual change with a speci fi c audio feedback (positive reinforce);otherwise the element disappear (negative reinforce) The level of dif  fi  culty increases with the increase of the numbers of distracters and reducing the usable time of execution. To indicate and touch the speci fi c target-stimuli in relation to speci fi ccharacteristics (color; image; animal, function . . . ), neglecting thedistracters, which consist in other picture, different for number andcomplexity of criteria. The therapist gives the verbal commands to thepatient, which combines the different selected images. Cognitive therapist uses tasks with increase dif  fi  culty, according to speci  fi  c parameters, such as number and type of the target, number and type of distracters; complexity of the consign. Memory To observe at 1st particular elements, and then (in the immediate andrecall time) to remember these (egg; season; colors, boll; numbers;environments, animals; geometric form or not; fruit; job . . . ) with adynamic interaction in semi-immersive virtual environment  (sprites task). The patient remembers the place (the position; visuo-spatial memory)and the name (verbal information) of the element/s observed. The level of dif  fi  culty increases with the increase of the number of elements to remember and with the reduction of the time to execution. Memory training tasks are conducted on paper and pencil approach in aface to face rehabilitative setting with an interaction only betweentherapist and patient. The forms of these tasks include recalling aseries of locations of items on a speci fi c rehabilitative table (in acognitive room), recalling digits or letters in either the order presentedor reverse order, or recalling speci fi cally where a particular number or name, digit was in a sequence. The memory training is articulated in 3 levels of complexity (easy; medium and high dif  fi  culty) in relation to time and number of verbal and not stimuli to remember. Executive andvisuospatialfunctionsTo program some movements  fi nalized to virtual touch, to move or manipulate speci fi c objects, in different directions (i.e. balls;  fl owers;butter  fl y.); or to realize speci fi c associations (i.e. number- color) with adynamic interaction in virtual environment. When the patient touchesvirtual objects, he/she obtains a video and audio feedback   (using sprites task).  In particular, the subject realizes ideo-motor sequences (fromsimple to complex series of actions), after the verbal consign bytherapist. The level of dif  fi  culty increases (from   fi  rst to third level) with the increase of the complexity of virtual ideo-motor serious to realize. To program some movements  fi nalized to direct touch and to move thespeci fi c objects (i.e. pencil; pen) in different directions (i.e. left; right;according to therapist ’ s indication) in a speci fi c space (i.e. rehabilitativetable); or to realize speci fi c associations (i.e. letter- color), using a penand pencil approach, organized in a face to face rehabilitative session. Each training is articulated in three different levels of dif  fi  culty in relation to the complexity of the ideo-motor sequences and executive increased tasks to administer. Maresca et al. Medicine (2018) 97:50 www.md-journal.com 5
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