Cerebral processing of auditory and noxious stimuli in severely brain injured patients: differences between VS and MCS

We review cerebral processing of auditory and noxious stimuli in minimally conscious state (MCS) and vegetative state (VS) patients. In contrast with limited brain activation found in VS patients, MCS patients show activation similar to controls in response to auditory, emotional and noxious stimuli. Despite an apparent clinical similarity between MCS and VS patients, functional imaging data show striking differences in cortical segregation and integration between these two conditions. However, in the absence of a generally accepted neural correlate of consciousness as measured by functional neuroimaging, clinical assessment remains the gold standard for the evaluation and management of severely brain damaged patients.     

视觉威胁反应在判断严重意识障碍程度的应用

目的用强弱光源作为视觉威胁刺激物,与CRS-R量表中以手指为刺激物的视觉威胁反应进行对比,比较严重意识障碍患者对不同视觉威胁刺激物的敏感性差异;在此基础上研究视觉威胁反应能否作为意识的指标。方法随机选择89例严重意识障碍(DOC)患者,采用The JFK Coma Recovery Scale-Revise(JFK改进的昏迷恢复量表,以下简称CRS-R)对其进行床边测量。对于视觉威胁反应项,分别对患者采取手指、弱光、强光刺激物进行刺激,比较反应的差异。结果植物状态(VS)和最小意识状态(MCS)患者对手指视觉威胁刺激的反应具有显著的差异(P0.001),植物状态和最小意识状态患者对强光视觉威胁刺激的反应具有显著的差异(P0.001)。最小意识障碍患者对手指、强光两种视觉威胁刺激的反应没有显著性的差异(P0.05),植物状态患者对手指、强光两种视觉威胁刺激的反应没有显著性的差异(P0.05)。结论严重意识障碍患者(n=89)对不同刺激物(手指、弱光、强光)的反应无显著性差异;视觉威胁反应(手指和光)能反映意识。     

Clinical neurophysiology of prolonged disorders of consciousness: From diagnostic stimulation to therapeutic neuromodulation

The identification of signs of awareness in patients with prolonged disorders of consciousness (DoC) after severe brain injury is a challenging task for clinicians. Differentiating on behavioural examination the vegetative state (VS) from the minimally conscious state (MCS) can lead to a high misdiagnosis rate. Advanced neuroimaging and neurophysiological techniques can supplement clinical evaluation by providing physiological evidence of brain activity. However, an open issue remains whether these empirical results are directly or indirectly associated with covert consciousness and limitations emerge for their diagnostic application at the single-patient level. On the therapeutic side, the efficacy of both non-invasive and invasive brain stimulation/modulation trials is matter of debate. The present review provides an updated analysis of the diagnostic and prognostic impact that the different neurophysiological techniques of stimulation [including short-latency evoked potentials, long-latency event related potentials (ERPs), transcranial magnetic stimulation (TMS), TMS-EEG co-registration] offer in prolonged DoC. The results of the therapeutic stimulation techniques are also evaluated. It is concluded that TMS-EEG emerges as the most promising tool for differentiating VS from MCS whereas ERPs allow neurophysiologists to probe covert cognitive capacities of each patient. Significant behavioural improvements in prolonged DoC with brain stimulation techniques are still anecdotical and further treatment options are awaited.     

Visual search in patients with subcortical vascular dementia: short fixations but long reaction times

Visual search is a cognitive function of high ecological relevance. It involves rapid alternations between allocating and shifting attention. In patients with Alzheimer's disease, the duration of fixations during visual search increases already in the early stage of the illness. Subcortical vascular dementia (SVD), a newly defined subgroup of vascular dementia, has not yet been examined in this respect. SVD affects patients with a history of lacunar infarctions and/or transient ischemic attacks, focal neurological signs and evidence of subcortical white matter lesions as well as lacunes in the deep grey matter. Here, we report our findings from tracking eye movements during a visual search task with different array sizes in 9 patients with SVD and compare the number and duration of eye fixations they made with the values obtained in 9 healthy elderly control subjects. While patients with SVD were significantly slower in the tasks with longer center to target distances (mean reaction time), the number and duration of fixations they made did not differ from those in controls. Impairment of visual search in patients with SVD seems to be an effect of general cognitive slowing in more demanding arrays of visual search rather than a specific deficit in parameters of eye fixation.     

Eye movements of patients with schizophrenia in a natural environment

Alterations of eye movements in schizophrenia patients have been widely described for laboratory settings. For example, gain during smooth tracking is reduced, and fixation patterns differ between patients and healthy controls. The question remains, whether such results are related to the specifics of the experimental environment, or whether they transfer to natural settings. Twenty ICD-10 diagnosed schizophrenia patients and 20 healthy age-matched controls participated in the study, each performing four different oculomotor tasks corresponding to natural everyday behavior in an indoor environment: (I) fixating stationary targets, (II) sitting in a hallway with free gaze, (III) walking down the hallway, and (IV) visually tracking a target on the floor while walking straight-ahead. In all conditions, eye movements were continuously recorded binocularly by a mobile lightweight eye tracker (EyeSeeCam). When patients looked at predefined targets, they showed more fixations with reduced durations than controls. The opposite was true when participants were sitting in a hallway with free gaze. During visual tracking, patients showed a significantly greater root-mean-square error (representing the mean deviation from optimal) of retinal target velocity. Different from previous results on smooth-pursuit eye movements obtained in laboratory settings, no such difference was found for velocity gain. Taken together, we have identified significant differences in fundamental oculomotor parameters between schizophrenia patients and healthy controls during natural behavior in a real environment. Moreover, our data provide evidence that in natural settings, patients overcome some impairments, which might be present only in laboratory studies, by as of now unknown compensatory mechanisms or strategies.     

Visual scanning deficits in schizophrenia and their relationship to executive functioning impairment

Abnormal visual scanning of faces, objects, and line drawings has been observed in patients with schizophrenia and is thought to reflect neurocognitive impairment. In this study, a simultaneous measurement approach was used to assess whether schizophrenia patients demonstrate restricted visual scanning when confronted with a complex problem-solving stimulus, and whether visual scanning deficits are predictive of inflexible thinking. Thirty-eight schizophrenia patients and 30 comparison participants were presented with Rorschach inkblots while eye movements were monitored and verbal responses to the stimuli were recorded and scored for inflexible thinking using the Rorschach Repetition and Perseveration Scale. Schizophrenia patients demonstrated fewer and longer visual fixations and shorter total scanpath relative to comparison participants but did not differ on mean scanpath length. Among patients, fewer fixations were associated with a higher frequency of verbal perseverations. Correlations between scanning measures and symptoms showed that negative symptoms were related to a minimal scanning or "staring" approach. Results support previous findings of restricted visual scanning in schizophrenia patients, are consistent with previously observed relationships between visual scanning and symptom profiles, and suggest that visual organizational deficits during complex problem-solving tasks may be related to cognitive inflexibility and frontal-executive dysfunction.     

Object identification in cerebral visual impairment characterized by gaze behavior and image saliency analysis

Individuals with cerebral visual impairment (CVI) have difficulties identifying common objects, especially when presented as cartoons or abstract images. In this study, participants were shown a series of images of ten common objects, each from five possible categories ranging from abstract black & white line drawings to color photographs. Fifty individuals with CVI and 50 neurotypical controls verbally identified each object and success rates and reaction times were collected. Visual gaze behavior was recorded using an eye tracker to quantify the extent of visual search area explored and number of fixations. A receiver operating characteristic (ROC) analysis was also carried out to compare the degree of alignment between the distribution of individual eye gaze patterns and image saliency features computed by the graph-based visual saliency (GBVS) model. Compared to controls, CVI participants showed significantly lower success rates and longer reaction times when identifying objects. In the CVI group, success rate improved moving from abstract black & white images to color photographs, suggesting that object form (as defined by outlines and contours) and color are important cues for correct identification. Eye tracking data revealed that the CVI group showed significantly greater visual search areas and number of fixations per image, and the distribution of eye gaze patterns in the CVI group was less aligned with the high saliency features of the image compared to controls. These results have important implications in helping to understand the complex profile of visual perceptual difficulties associated with CVI.     

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.     

Sham-controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness

Background and purpose

Transcranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double-blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS.

Methods

Patients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months’ follow-up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non-traumatic). Interim analyses were planned to continue or stop the trial.

Results

The trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post-injury, 18 women, 32 MCS, 39 non-traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months’ follow-up revealed a significant improvement for patients in MCS and with traumatic aetiology.

Conclusions

Transcranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.     

Eye tracking and physiological reactivity to threatening stimuli in posttraumatic stress disorder

This study tested the vigilance-avoidance model of anxiety and attention bias in posttraumatic stress disorder (PTSD). This study used eye tracking technology to record initial fixations, pupil dilation, fixation time and concurrent skin conductance response to examine initial orienting towards threat stimuli and subsequent fixations. Twenty-one traumatized participants (11 diagnosed with PTSD and 10 trauma-exposed participants without PTSD) viewed 32 stimuli (with four words in each quadrant). Sixteen trials contained a trauma-relevant word in one quadrant and 16 had four neutral words. PTSD patients reported significantly greater number of initial fixations to trauma words, and a greater number of skin conductance responses to initial threat fixations. There were no significant differences in subsequent fixations to trauma words between groups. Although this study provides evidence of attentional bias towards threat that is accompanied by specific autonomic arousal, it does not indicate subsequent avoidance of threat stimuli in PTSD.     

Two distinct deficits of visual tracking caused by unilateral lesions of cerebral cortex in humans

We studied horizontal visual tracking in 20 patients with unilateral cerebral lesions and in 10 age-matched control subjects. Five patients, all with posterior lesions, showed impaired smooth pursuit of predictable targets moving toward the side of the cerebral lesion. Using nonpredictable step-ramp stimuli, we identified two distinct deficits of visual tracking. The first was a unidirectional deficit of smooth pursuit, for targets moving toward the side of the lesion, in response to stimuli presented into either visual hemifield. The second deficit, identified in a sixth patient who did not show pursuit asymmetry to predictable targets, was a bidirectional inability to estimate the speed of a moving target in the visual hemifield contralateral to the side of the lesion; this caused inaccurate saccades to moving (but not stationary) targets and impaired smooth pursuit initiation. These visual tracking deficits were independent of homonymous hemianopia or hemispatial neglect. These two tracking deficits are similar to those described in rhesus monkeys with lesions of the medial superior temporal and middle temporal visual areas.     

Oxytocin increases eye-gaze towards novel social and non-social stimuli

ABSTRACT

Research on oxytocin (OT) has revealed a substantial involvement of this neuropeptide in social cognition processes and attachment behavior.

The rationale of the present project was to decipher the differential role of OT in basic social cognition processes towards non-erotic attachment stimuli vs. reproduction-related stimuli in human subjects.

In a randomized double-blind repeated-measures cross-over design, N = 82 participants were investigated twice and received either intranasal OT or placebo at the first assessment followed by placebo or OT at second assessment. Participants were presented with standardized pictures of parent-child dyads, romantic couples engaging in non-erotic or explicit sexual activities, and non-social pictures while we assessed pupil dilation and eye focus on specific pre-defined areas of interest. Multilevel analyses suggest that during the initial presentation, OT increased pupil dilation towards all categories of stimuli and led the eye focus towards the eyes and body regions, followed by a strong decrease in pupil dilation and fixations at the second session.

These carry-over effects indicate that hormonal treatment at an initial contact to social stimuli can determine how these stimuli are processed later. These results might have implications for OT as a treatment in interventions with repeated exposure to social material.     

Visual search disorders beyond pure sensory failure in patients with acute homonymous visual field defects

Patients with homonymous visual field defects (HVFD) are often crucially disabled during self-guided visual exploration of their natural environment. Abnormal visual search may be related to the sensory deficit, deficient spatial orientation or compensatory eye movements. We tested the hypothesis that visual search in HVFD is purely determined by the visual–sensory deficit by comparing nine patients with HVFD due to occipital stroke in an acute stage to nine healthy subjects with technically simulated “virtual” homonymous visual field defects (vHVFD) and to nine controls with normal visual fields. The simulated gaze-contingent visual field defects in vHVFD subjects were individually matched to the patients’ HVFD with respect to their size and side. Eye movements were recorded while subjects searched for targets among distractors and indicated target detection by clicks.All patients, in particular those with lesions involving the inferior occipito-temporal (fusiform) gyrus, but also those with small lesions restricted to the visual cortex, showed longer search durations than vHVFD subjects. This was tightly related to the higher number of fixations and particularly “re-fixations” (repeated scanning of fixated items). Working memory across saccades during the search was intact (no increased “re-clicks”). Scanpath strategies were similar in patients and vHVFD subjects. For both groups amplitude and frequency of saccades did not differ between the hemifields.In HVFD patients with acute occipital brain lesions, visual input failure does not fully account for abnormal visual search. It might either result from disconnections of the primary visual cortex to associated occipital and temporal brain areas or reflect an early stage of compensatory eye movements which differ from chronic HVFD patients.     

Simple method of differential diagnosis of peripheral and central vertigo--development of diagnostic method and studies of 178 cases]

In patients who complain of vertigo or who have equilibrium disorders, it is often difficult to determine the etiology of the disorder, that is to determine whether it is dependent on a peripheral or central vestibular disorder. To attempt to determine the etiology in these cases, we divised a new method, the caloric eye tracking pattern test (CETP-Test). Seventeen normal subjects and 161 patients were tested. The latter group included 33 with peripheral disorders such as Meniere's disease, benign paroxysmal positional nystagmus, and others, and 128 with central disorders such as vertebral basilar artery insufficiency, cervical vertigo, and others, were tested. The cases of central disorders were limited to those patients whose eye tracking pattern before the caloric stimulation was normal. In normal subjects and in patients with peripheral disorders, it is well known that caloric nystagmus has little influence on the eye tracking pattern. In contrast, in patients with central vestibular disorders, caloric nystagmus evokes abnormalities on the eye tracking pattern, either superimposed or saccades, despite the fact that the eye tracking pattern before the caloric stimulation is normal. First we administer the eye tracking stimulation test using a target which moves horizontally at 0.3 cycle per second. Next, we perform the caloric test on the right ear, using 20 c.c. of ice water for 10 seconds. During the evoked caloric nystagmus we administer the eye tracking test once again. The eye tracking pattern is recorded for 20 seconds beginning 50 seconds after the start of the ice water injection. The procedure repeated on the left ear. The results on each case are presented as three patterns of ENG-recording. We may stat that in normal subjects and in patients with peripheral vestibular disorders, visual suppression of caloric nystagmus remains functional. Caloric induced nystagmus does not affect the CETP. In patients with central vestibular disorders, visual suppression of caloric nystagmus does not function properly because of defects in the visual suppression mechanism. Therefore, caloric nystagmus greatly influences the CETP. Consequently, the CETP may not be smooth when CETP test is administered to patients with central vestibular disorders. We may say also that the visual suppression to the vestibular nystagmus is evoked more strongly by pursuing a moving visual stimulus than by gazing a stational target. These results allow for a differential diagnosis between peripheral and central disorders.     

Non-oriented cells of the striate cortex activated during smooth pursuit eye movements and steady fixations in behaving monkeys

Extracellular recordings were carried out in the primary visual cortex of behaving monkeys. Neurons were activated by moving a visual stimulus on their receptive fields during periods of steady fixation and by moving their receptive fields (smooth pursuit eye movements) on a motionless visual stimulus. Regarding non-oriented cells, they turned out to be activated by the visual stimulation both during steady fixations and smooth pursuit eye movements. Therefore, the non-oriented cells we studied seem not to receive an extraretinal signal related to the slow eye movements.     

Brain response to one's own name in vegetative state, minimally conscious state, and locked-in syndrome

BACKGROUND: A major challenge in the management of severely brain-injured patients with altered states of consciousness is to estimate their residual perception of the environment. OBJECTIVE: To investigate the integrity of detection of one's own name in patients in a behaviorally well-documented vegetative state (VS), patients in a minimally conscious state (MCS), and patients with locked-in syndrome. DESIGN: We recorded the auditory evoked potentials to the patient's own name and to 7 other equiprobable first names in 15 brain-damaged patients. RESULTS: A P3 component was observed in response to the patient's name in all patients with locked-in syndrome, in all MCS patients, and in 3 of 5 patients in a VS. P3 latency was significantly (P<.05) delayed for MCS and VS patients compared with healthy volunteers. CONCLUSIONS: These results suggest that partially preserved semantic processing could be observed in noncommunicative brain-damaged patients, notably for the detection of salient stimuli, such as the subject's own name. This function seems delayed in MCS and (if present) in VS patients. More important, a P3 response does not necessarily reflect conscious perception and cannot be used to differentiate VS from MCS patients.     

fMRI of optokinetic eye movements with and without a contribution of smooth pursuit.

BACKGROUND AND PURPOSE: Optokinetic eye movements are elicited when tracking a moving pattern. It can be argued that a moving pattern of stripes invokes both the optokinetic and the smooth pursuit eye movement system, which may confound the observed brain activation patterns using functional magnetic resonance imaging (fMRI). A moving pattern of limited-lifetime-dot stimulation does not target the smooth pursuit eye movement system. METHODS: fMRI was used to compare the cortical activity elicited by an optokinetic eye movement response evoked by a moving pattern of stripes and a moving pattern of limited lifetime dots. RESULTS: The eye movement behavior showed that both types of stimuli evoked an adequate and similar optokinetic eye movement response, but stimulation with stripes evoked more activation in the frontal and parietal eye fields, MT/V5, and in the cerebellar area VI than stimulation with limited-lifetime dots. CONCLUSIONS: These brain areas are implicated in smooth pursuit eye movements. Our results suggest that indeed both the optokinetic and the smooth pursuit eye movement system are involved in tracking a moving pattern of stripes.     

Using eye movement responses to index auditory comprehension: An adaptation of the Revised Token Test

Background: Tracking spontaneous eye movement responses may improve the accuracy of comprehension assessment in patients with neurological impairments. Eye movement methods provide an on-line response mode that does not require an overt planned motoric response, tax participants' understanding of instructions, or interrupt the comprehension process with intervening instructions or prompts. Aims: The purpose of this study was to examine an adaptation of a standardised test of auditory comprehension for adults with neurological impairments, using eye movement responses. Individuals with normal language comprehension should demonstrate a consistent pattern of eye movement responses indicating comprehension. Methods & Procedures: Nineteen adults with no history of neurological involvement were presented with auditory comprehension stimuli from the Revised Token Test (RTT) (McNeil & Prescott, 1978) in each of three conditions: traditional, pointing, and eye movement. In the traditional condition, the standardised version of the RTT was administered. In the pointing condition, RTT stimuli were manipulated to fit a multiple-choice format; participants responded to modified verbal stimuli for each item by pointing to one of four images shown in a printed test manual. In the eye movement condition, participants viewed the same stimuli presented in the multiple-choice pointing version, shown on a computer monitor rather than in a test manual. A remote pupil centre/corneal reflection system was used to monitor eye movements. Participants were not instructed to look at anything in particular, and were not told that there were target images within the displays. The eye movement condition was presented first to avoid participants/ perceptions that they were expected to select a target image with their eyes. Dependent variables included the proportion of total viewing time that participants fixated on target images and non-target foils. Outcomes & Results: Traditional RTT scores indicated normal comprehension for all participants, according to published norms. Likewise, pointing condition scores indicated good comprehension. For each of the subtests in the eye movement condition, the proportional amount of time that fixations were allocated to target images significantly exceeded chance expectations.     

Eye movements during the Rorschach test in schizophrenia

In order to understand relationships between scanning behaviors, characteristics of visual stimuli and the clinical symptoms in schizophrenia, eye movements of 37 schizophrenic patients and 36 controls were recorded using an eye-mark recorder during a free-response period in a Rorschach test. Four cards (I, II, V and VIII) were used. Data were analyzed during 15 s from the presentation of each card. For all cards, the number of eye fixations and the number of eye fixation areas were fewer, and total scanning length and mean scanning length were shorter for schizophrenic patients than for controls. For card II, in the non-popular response group, eye fixation frequency upon area 5 + 6 (red) was higher for schizophrenic patients. For card VIII, in the popular response group, eye fixation frequency upon area 5 + 6 (pink) was lower for schizophrenic patients. For cards II and VIII, the number of eye fixations was inversely correlated with negative symptoms. For card II, total scanning length tended to be inversely correlated with negative symptoms, and mean eye fixation time was correlated with negative symptoms. The number of eye fixation areas was inversely correlated with positive symptoms. For card VIII, eye fixation frequency in a stimulative area tended to be correlated with positive symptoms. Scanning behaviors in schizophrenic patients are affected by characteristics of visual stimuli, and partially by clinical symptoms.     

Free viewing exploration in schizophrenia: Review of evidence from laboratory settings to natural environment

Several studies have investigated visual processing impairment in schizophrenia. The literature on visual exploration has described restricted scanning in schizophrenia patients. This gaze behavior is characterized by increased fixation duration, a reduced scan path length and avoidance of salient features of the face with emotional content. The aim of this paper is to give an insight on the latest update on scan path deficit. Abnormal gaze exploration was replicated in various visual stimuli. This review describes gaze patterns with stimuli that imply minimal to high cognitive process: figures, objects, faces, and scenes. Interestingly, schizophrenia patients have shown cognitive flexibility by modulating gaze scanning when they are involved in an active assignment. We will also consider scanning abnormalities in real-life environment and discuss the potential therapeutic use of eye tracking in schizophrenia. The therapeutic application of eye tracking in schizophrenia is a young emerging field in psychiatry research. The recent remediation program is based on the reorientation of visual attention on the salient features of faces. For now, this program has shown encouraging results. Further studies are needed to explore behavior in real-world situations to complement laboratory measurements to move toward a full understanding of the mechanisms underlying atypical scanning in patients with schizophrenia.