Novel Virtual Reality Application in Field of Neurorehabilitation

Virtual reality (VR) therapy has many benefits to promote neurological and functional recovery in the field of neurorehabilitation after brain injury. VR-assisted neurorehabilitation can be applied in motor, sensori-motor, cognitive, activities of daily living (ADL), and telerehabilitation. Recent reports found that VR therapy appears to be a safe intervention that is effective at improving arm function and ADL function following stroke. Greater improvements were seen at a higher VR therapeutic dose. There has been insufficient evidence that VR therapy improved lower extremity gait speed, balance, and cognitive function after brain injury. As a result, the number of commercially available devices have increased and large-scale controlled trials have reported positive effects recently. Interface devices, various feedback methods, and the advancement of augmented reality technology are quickly developing, therefore, the potential value of VR therapy in neurorehabilitation will be high and its clinical application will be diversified.

Flickering exercise video produces mirror neuron system (MNS) activation and steady state visually evoked potentials (SSVEPs)

The action of observing can be used as an effective rehabilitation paradigm, because it activates the mirror neuron system. However, it is difficult to fully use this paradigm because it is difficult to get patients to engage in watching video clips of exercise. In this study, we proposed a steady state visually evoked potential (SSVEP) based paradigm that could be used in a Brain Computer Interface, and examined its feasibility by investigating whether flickering video could activate the mirror neuron system and evoke SSVEPs at the same time. Twenty subjects were recruited and asked to watch the flickering videos at a rate of 20 Hz of upper limb motion and visual white noise, while an EEG signal was recorded. The mu rhythm (8–13 Hz) suppression and the SSVEP (19–21 Hz) evocation were analyzed from recorded EEG. The results showed that SSVEPs, evoked by the flickering stimulus, was observed in both conditions on O1 and O2, but the mu rhythm suppression on C3 and C4 was observed only in the exercise video condition. These results could signify that the flickering video is applicable for the BCI rehabilitation game, activating the mirror neuron system at the same time.

Upper Extremity Rehabilitation using Virtual Reality after Stroke

There is limited evidence regarding the use of virtual reality (VR) and interactive video gaming for improving arm function because there are few such commercial devices and little relevant research. However, evidence of the greater effectiveness of upper extremity VR training over that of conventional therapy after stroke has recently grown due to the adoption of various therapeutic devices. VR applications are novel and potent technologies for upper extremity rehabilitation after stroke because the interface technologies, augmented reality technologies, and various sensorimotor feedback techniques are rapidly advancing. Going forward, VR technology should be designed to provide the possibility of intense functional repetitive practice for patients. The combination of VR with robotic devices, neuromodulation, mirror therapy, and telerehabilitation may synergistically improve upper extremity function after stroke. In severely injured patients, robotic interfaces should be considered, the level of difficulty should be fitted appropriately to the severity of the deficits, and the fact that it is difficult to train patients repeatedly and effectively in a real-world environment should be considered. Further research should be conducted on the application of VR programs in larger populations, VR involving various training paradigms, VR at different exercise levels, and the long-term sustained effects of VR. In addition, synergistically enhanced effects of combining other treatments and feedback paradigms with well-designed interfaces should be investigated.

T2 Relaxometry Using 3.0-Tesla Magnetic Resonance Imaging of the Brain in Early- and Late-Onset Restless Legs Syndrome

BACKGROUND AND PURPOSE: Previous T2 relaxometry studies have provided evidence for regional brain iron deficiency in patients with restless legs syndrome (RLS). Measurement of the iron content in several brain regions, and in particular the substantia nigra (SN), in early- and late-onset RLS patients using T2 relaxometry have yielded inconsistent results. In this study the regional iron content was assessed in patients with early- and late-onset RLS using magnetic resonance imaging (MRI), and compared the results with those in controls. METHODS: Thirty-seven patients with idiopathic RLS (20 with early onset and 17 with late onset) and 40 control subjects were studied using a 3.0-tesla MRI with a gradient-echo sampling of free induction decay and echo pulse sequence. The regions of interest in the brain were measured independently by two trained analysts using software known as medical image processing, analysis, and visualization. The results were compared and a correlation analysis was conducted to investigate which brain areas were related to RLS clinical variables. RESULTS: The iron index in the SN was significantly lower in patients with late-onset RLS than in controls (p=0.034), while in patients with early-onset RLS there was no significant difference. There was no significant correlation between the SN iron index of the late-onset RLS group and clinical variables such as disease severity. CONCLUSIONS: Late-onset RLS is associated with decreased iron content in the SN. This finding supports the hypothesis that regional brain iron deficiency plays a role in the pathophysiology of late-onset RLS.

Randomized, Sham Controlled Trial of Transcranial Direct Current Stimulation for Painful Diabetic Polyneuropathy

OBJECTIVE: To investigate the analgesic effect of transcranial direct current stimulation (tDCS) over the primary motor (M1), dorsolateral prefrontal cortex (DLPFC), and sham tDCS in patients with painful diabetic polyneuropathy (PDPN). METHODS: Patients with PDPN (n=60) were divided randomly into the three groups (n=20 per group). Each group received anodal tDCS with the anode centered over the left M1, DLPFC, or sham stimulation for 20 minutes at intensity of 2 mA for 5 consecutive days. A blinded physician rated the patients' pain using a visual analog scale (VAS), Clinical Global Impression (CGI) score, anxiety score, sleep quality, Beck Depression Inventory (BDI), and the pain threshold (PT) to pressure. RESULTS: After the tDCS sessions, the M1 group showed a significantly greater reduction in VAS for pain and PT versus the sham and DLPFC groups (p<0.001). The reduction in VAS for pain was sustained after 2 and 4 weeks of follow-up in the M1 group compared with the sham group (p<0.001, p=0.007). Significant differences were observed among the three groups over time in VAS for pain (p<0.001), CGI score (p=0.01), and PT (p<0.001). No significant difference was observed among the groups in sleep quality, anxiety score, or BDI score immediately after tDCS. CONCLUSION: Five daily sessions of tDCS over the M1 can produce immediate pain relief, and relief 2- and 4-week in duration in patients with PDPN. Our findings provide the first evidence of a beneficial effect of tDCS on PDPN.

Disruption of Orbitofronto-Striatal Functional Connectivity Underlies Maladaptive Persistent Behaviors in Alcohol-Dependent Patients

OBJECTIVE: Alcohol dependence is characterized by persistent alcohol-seeking despite negative consequences. Previous studies suggest that maladaptive persistent behaviors reflect alcohol-induced brain changes that cause alterations in the cortico-striatal-limbic circuit. METHODS: Twenty one alcohol dependent patients and 24 age-matched healthy controls performed a decision-making task during functional MRI. We defined the medial orbitofrontal cortex (mOFC) as a region-of-interest and performed seed-based functional connectivity analysis. RESULTS: Healthy controls were more flexible in adapting an alternative behavioral strategy, which correlated with stronger mOFC-dorsal striatum functional connectivity. In contrast, alcohol dependent patients persisted to the first established behavioral strategy. The mOFC-dorsal striatum functional connectivity was impaired in the alcohol-dependent patients, but increased in correlation with the duration of abstinence. CONCLUSION: Our findings support that the disruption of the mOFC-striatal circuitry contribute to the maldaptive persistent behaviors in alcohol dependent patients.

Imaging Findings of Brain Death on 3-Tesla MRI

OBJECTIVE: To demonstrate the usefulness of 3-tesla (3T) magnetic resonance imaging (MRI) including T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), time-of-flight (TOF) magnetic resonance angiography (MRA), T2*-weighted gradient recalled echo (GRE), and susceptibility weighted imaging (SWI) in diagnosing brain death. MATERIALS AND METHODS: Magnetic resonance imaging findings for 10 patients with clinically verified brain death (group I) and seven patients with comatose or stuporous mentality who did not meet the clinical criteria of brain death (group II) were retrospectively reviewed. RESULTS: Tonsilar herniation and loss of intraarterial flow signal voids (LIFSV) on T2WI were highly sensitive and specific findings for the diagnosis of brain death (p < 0.001 and < 0.001, respectively). DWI, TOF-MRA, and GRE findings were statistically different between the two groups (p = 0.015, 0.029, and 0.003, respectively). However, cortical high signal intensities in T2WI and SWI findings were not statistically different between the two group (p = 0.412 and 1.0, respectively). CONCLUSION: T2-weighted imaging, DWI, and MRA using 3T MRI may be useful for diagnosing brain death. However, SWI findings are not specific due to high false positive findings.

Facilitation of Corticospinal Excitability According to Motor Imagery and Mirror Therapy in Healthy Subjects and Stroke Patients

OBJECTIVE: To delineate the changes in corticospinal excitability when individuals are asked to exercise their hand using observation, motor imagery, voluntary exercise, and exercise with a mirror. METHOD: The participants consisted of 30 healthy subjects and 30 stroke patients. In healthy subjects, the amplitudes and latencies of motor evoked potential (MEP) were obtained using seven conditions: (A) rest; (B) imagery; (C) observation and imagery of the hand activity of other individuals; (D) observation and imagery of own ipsilateral hand activity; (E) observation and imagery of the hand activity of another individual with a mirror; (F) observation and imagery of own symmetric ipsilateral hand activity (thumb abduction) with a mirror; and (G) observation and imagery of own asymmetric ipsilateral hand activity (little finger abduction) with a mirror. In stroke patients, MEPs were obtained in the A, C, D, E, F conditions. RESULTS: In both groups, increment of the percentage MEP amplitude (at rest) and latency decrement of MEPs were significantly higher during the observation of the activity of the hand of another individual with a mirror and during symmetric ipsilateral hand activity on their own hand with a mirror than they were without a mirror. In healthy subjects, the increment of percentage MEP amplitude and latency decrement were significantly higher during the observation of the symmetric ipsilateral hand activity with a mirror compared to the observation of the activity of the asymmetric ipsilateral hand with a mirror of their own hand. CONCLUSION: In both groups, corticospinal excitability was facilitated by viewing the mirror image of the activity of the ipsilateral hand. These findings provide neurophysiological evidence supporting the application of various mirror imagery programs during stroke rehabilitation.

Comparison of the Characteristics of Anhedonia between Patients with Schizophrenia and Depressive Disorder / 신경정신의학

OBJECTIVES: Anhedonia, defined as an inability to experience pleasure, has been considered to be a core feature of schizophrenia and depression. The purpose of the present study was to compare the specific characteristics of anhedonia in patients with the two illnesses by examining hedonic capacity during phased hedonic experience. METHODS: Hedonic rating tasks, using the film clips of physical and social hedonic stimuli and neutral stimuli, were performed by 29 patients with schizophrenia, 20 patients with depression, and 29 normal controls. Each task consisted of 'preview phase' with insufficient emotional information, and a subsequent 'theme phase' with sufficient emotional information. RESULTS: In normal controls, the mean hedonic score was increased in the theme phase compared with the preview phase, suggesting an appropriate augmentation of the hedonic response. In patients with schizophrenia, hedonic scores in the preview phase were comparable with those in normal controls, but showed deficient augmentation in the theme phase. In patients with depressive disorder, the range of increments in scores between the preview and theme phases was normal, but the scores themselves were lower in both phases than in the other two groups. CONCLUSION: The results indicate that patients with schizophrenia show a deficient augmentation of the hedonic response, whereas patients with depressive disorder have a pervasive lack of hedonic capacity.

Characteristics of Eye Gaze Distribution of Patients with Schizophrenia during the Emotion-Provoking Conversation with Several Virtual Persons / 신경정신의학

OBJECTIVES: Impairment of social cognition affects the social functioning of patients with schizophrenia. For example, patients with schizophrenia have been shown to display abnormal eye contact during a one-on-one conversation. This study was designed to investigate the behavioral characteristics of patients with schizophrenia while talking with two people. METHODS: Twenty six patients with schizophrenia and 26 normal controls performed virtual reality conversation tasks, in which they talked with main and assistant avatars under positive or negative emotional conditions. While listening and speaking, the durations of eye gaze with the main and minor avatars were measured from the head orientations of the participants using a positional tracker. RESULTS: Compared with normal controls, the patient group showed a shorter duration of gaze towards the main avatar and a longer duration of gaze towards the assistant avatar. This pattern was more apparent in the negative situation. CONCLUSION: The results suggest a defect in social cognition, in which patients with schizophrenia fail to distribute their gaze appropriately during a conversation with more than one other person.

Social Pressure-Induced Craving in Patients with Alcohol Dependence: Application of Virtual Reality to Coping Skill Training

OBJECTIVE: This study was conducted to assess the interaction between alcohol cues and social pressure in the induction of alcohol craving. METHODS: Fourteen male patients with alcohol dependence and 14 age-matched social drinkers completed a virtual reality coping skill training program composed of four blocks according to the presence of alcohol cues (x2) and social pressure (x2). Before and after each block, the craving levels were measured using a visual analogue scale. RESULTS: Patients with alcohol dependence reported extremely high levels of craving immediately upon exposure to a virtual environment with alcohol cues, regardless of social pressure. In contrast, the craving levels of social drinkers were influenced by social pressure from virtual avatars. CONCLUSION: Our findings imply that an alcohol cue-laden environment should interfere with the ability to use coping skills against social pressure in real-life situations.

The Relationship between Cortical Activation during an Inference Task and Presence in the Virtual Environment in Patients with Schizophrenia: An fMRI Study / 신경정신의학

OBJECTIVES: Virtual reality has been increasingly used in the psychiatric field. Presence, the sense of "being there," is an essential concept in terms of the effectiveness of the virtual reality. The present study aimed to investigate the characteristics of the presence-related brain regions in patients with schizophrenia. METHODS: Using fMRI, brain activities were measured while performing the virtual reality tasks in fifteen healthy normal subjects and fifteen patients with schizophrenia. The tasks consisted of listening to some stories and inferring the content of the previous events. Ambiguous information was given for the experimental task, whereas clear information was given for the control task. Correlations between the image contrast values and the presence scores were analyzed. RESULTS: The presence-related brain regions in healthy controls were identified in the two discrete region groups that could be referred to as the cognitive neural correlates and the perceptual neural correlates. The former included the anterior cingulate, the left inferior temporal gyrus, the right lingual gyrus, and the right cuneus, whereas the latter consisted of the right posterior cingulate, the left lingual gyrus and the right fusiform gyrus. Compared with healthy controls, regional correlation patterns were different in patients with schizophrenia, including that the posterior cingulate had significant correlations. CONCLUSION: These results suggest that patients with schizophrenia utilize perceptual apparatus for the presence more than the cognitive aspect. A peculiar pattern of the presence in schizophrenia may be related to increased correlations between the posterior cingulate and other brain regions.

Perseverative Pattern of Decision-Making in Alcohol Dependent Patients / 신경정신의학

OBJECTIVES: The relationship between substance dependence and poor decision making has received much attention in recent years. This study aimed to test the hypothesis that alcohol dependent subjects would demonstrate a more perseverative decision-making pattern, during ambiguous situations. METHODS: 15 alcohol dependent patients and 15 healthy normal controls performed a novel computerized decision-making task, which presented figures of coins. The subjects were instructed to guess whether the total number of coins was 'odd' or 'even'. Besides these two response, one could select a third alternative - 'pass' - in case the chances were assumed to be low. RESULTS: There was significant difference in performance between the two groups (F=4.339, p=0.008). The control group gained 15.4+/-14.4 points, whereas the alcohol dependent group lost 0.6+/-5.3 points. The normal control group demonstrated a tendency to make more pass responses as the trials were repeated. In contrast, the alcohol dependent group didn't make use of the alternative, but kept challenging between 'odd' and 'even', although they sensed that the chances were low. CONCLUSION: The alcohol dependent patients demonstrated a more rigid and perseverative response pattern and showed deficits in making use of compromise alternatives.

Effects of Nicotine on Interpersonal Distance of Patients with Schizophrenia in Immersive Virtual Environments: a Preliminary Study / 대한정신약물학회지

OBJECTIVE: Using immersive virtual environment technique, we aimed to preliminarily examine whether nicotine affects the interpersonal distance, as the size of personal space, in schizophrenic patients, which have extraordinarily high smoking rate. METHOD: Ten male schizophrenic patients who were at least moderate current smokers smoked a high (0.9 mg nicotine as an active drug) or low (0.1 mg nicotine as a placebo) nicotine-yielding cigarette after overnight-abstinence in randomized, double blind, cross-over design. Following the smoking session, subjects performed the 'self-introduction task' in virtual environment by introducing themselves consecutively to six different avatars, which varied in gender and facial/verbal expressions (neutral, angry, and happy). In the tasks, subjects were asked to step forward to each avatar until they felt most comfortable to greet the avatar first. The distance was measured by the head-tracking device, which was transmitting real-time data to the computer. Affective valence and arousal to each avatar were also rated by subjects following the tasks. RESULTS: The overall interpersonal distance of the drug group was significantly greater than that of placebo group (Z = -2.93, p = 0.022). The distances with emotionally neutral avatars (male/female) of the six were significantly different between the two groups (Z = -2.19, p = 0.028 ; Z = -2.09, p = 0.037). Within-group analysis revealed a significant difference among the distances with the six avatars in the placebo group (x2 = 17.03, df = 5, p = 0.004), but there was no significant within-group difference in the drug group (x2 = 6.11, df = 5, p = 0.295). CONCLUSION: These preliminary findings suggest that nicotine may increase the size of personal space of schizophrenic patients probably by enhancing the social stimuli perception through affecting the patients' cognitive function.