Olfactory sniffing signals consciousness in unresponsive patients with brain injuries.

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious1, and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions2,3. Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries4,5. Olfaction relies on brain structures that are involved in the basic mechanisms of arousal6, and we therefore hypothesized that it may serve as a biomarker for consciousness7. Here we use a non-verbal non-task-dependent measure known as the sniff response8-11 to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function10-15. We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

Unilateral Spatial Neglect without Hemiplegia: The Output-Mode Effect Revisited.

BACKGROUND: The occurrence of unilateral spatial neglect (USN) in non-hemiplegic right-hemisphere damaged patients is rare. Earlier studies of such patients revealed a significant advantage when typical neglect tests were performed by the patient's left hand as compared to the dominant right hand. The mechanism underlying this "output-mode effect" remains elusive. METHODS: We analyzed the temporal dynamics of this effect using line-bisection task in 9 non-hemiplegic stroke patients with left-USN. RESULTS: In 4 patients tested shortly after stroke onset (≤ 6 weeks), the impact of hand laterality was variable (left-hand advantage in one patient; right-hand advantage in 2 patients; similar performance in both hands in one patient). Only later (> 6 weeks) a clear advantage of the left hand emerged in the majority of patients, similar to the earlier reports which were all based on late testing. CONCLUSIONS: We found variable dynamics in the expression of the output-mode effect in the first weeks following stroke onset, which may reflect changes of inter-hemispheric balance, related to recovery processes. We propose that therapeutic interventions aiming to manipulate the inter-hemispheric balance (e.g., by non-invasive brain stimulation) take into account the existence of such dynamics and their highly variate nature.

Effects of aquatic physical intervention on fall risk, working memory and hazard-perception as pedestrians in older people: a pilot trial.

BACKGROUND: Normal aging is associated with balance, mobility and working memory decline that increase fall risk and influence activity of daily living functions. Mounting evidence suggests that physical activity is beneficial for decreasing aging effects. Previous studies have focused on land-based physical activity. Research concerning the aquatic environment is scarce. The primary objectives of this three arm intervention pilot study were to examine the effects of an aquatic physical intervention program on balance, gait, fall risk and working memory among community-dwelling older individuals. The secondary objective was to examine the effects of an aquatic physical intervention program on safety of street-crossing among community-dwelling older individuals. METHODS: Forty-two healthy participants aged 65 or older were enrolled into one of three intervention groups: aquatic physical intervention (API) (N = 13), on-land physical intervention (OLPI) (N = 14) or non-physical intervention (NPI) (N = 15). The intervention took place from 2018 until 2019 at Tel-Aviv University, Sheba medical center and Reich Center. The protocol included 30-min sessions twice a week for 12 weeks. Balance, gait and fall risk were assessed by the Tinneti test, working memory abilities were assessed by digit span and Corsi blocks tests and simulated safe streets-crossing was assessed by the hazard perception test for pedestrians. Testing and data collection was conducted at baseline, after six weeks and 12 weeks of intervention. All members of the professional team involved in evaluating participants were blind to the intervention group to which participants were allocated. RESULTS: The differences in Tinetti balance (F (2, 39)=10.03, p < 0.01), fall risk (F (2, 39)=5.62, p0 > .05), digit span forward (F (2, 39)=8.85, p < 0.01) and Corsi blocks forward (F (2, 39)=3.54, p < 0.05) and backward (F (2, 39)=6.50, p < 0.05) scores after 12 weeks between the groups were significant. The API group showed improved scores. The differences in hazard perception test for pedestrians scores after 12 weeks of intervention between the groups were marginally significant (F (2, 39)=3.13, p = 0.055). The API group showed improved scores. CONCLUSIONS: These findings may affect experts working with the elderly population when making decisions concerning therapeutic prevention interventions for the deficiencies of elderly patients. Older adults practicing aquatic physical activity could contribute to their increased safety. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov Registry NCT03510377. Date of registration: 10/31/2017.

Cogstate Brief Battery: Cognition and the feigning of cognitive impairment in chronic pain.

Chronic pain (CP) is often associated with cognitive impairment. The Cogstate Brief Battery (CBB), a computerized assessment battery, has been studied in several neuropsychiatric disorders but not in CP. Since feigning of cognitive impairment is common in CP, the current study aimed to assess the CBB's utility in differentiating CP patients (n = 64) from healthy participants (n = 33), as well as to assess the effect of simulating cognitive impairment by CP patients on performance in the battery. CP outpatients were randomly assigned to one of two groups: (a) Patients performing the CBB to the best of their ability. (b) Patients simulating cognitive impairment. Independent-samples t-tests indicated that three of four CBB tasks successfully differentiated CP patients from matched healthy controls. Additionally, an analysis of covariance (ANCOVA) indicated that CP patients who simulated cognitive impairment performed more poorly in all four CBB tasks, with the detection task having the strongest discrimination capacity. This is the first study to point toward the usefulness and sensitivity of the CBB for assessment of cognition and detection of feigned cognitive impairment in CP. Further studies are required to validate these preliminary findings and assess the CBB's utility in daily clinical practice.

Skill-learning by observation-training with patients after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability in Western society, and often results in functional and neuropsychological abnormalities. Memory impairment is one of the most significant cognitive implications after TBI. In the current study we investigated procedural memory acquisition by observational training in TBI patients. It was previously found that while practicing a new motor skill, patients engage in all three phases of skill learning-fast acquisition, between-session consolidation, and long-term retention, though their pattern of learning is atypical compared to healthy participants. A different set of studies showed that training by observing a motor task, generally prompted effective acquisition and consolidation of procedural knowledge in healthy participants. The aim of our study was to (i) evaluate the potential benefit of action observation in TBI patients. (ii) Examine the possibility of general improvement in performance between the first (24 h post-training) and second (2 weeks post-training) stage of the study. (iii) Investigate the link between patients' ability to benefit from observational learning (via performance gains-speed and accuracy) and common measures of injury (such as severity of injury, functional and cognitive measures). Materials and methods: Patients hospitalized after moderate to severe TBI, were trained by observation for the finger opposition sequence (FOS) motor task. They were then tested for the observation-trained sequence (A) and a similar control sequence (B), at two different time-points (24 h post-training and 2 weeks later). Results revealed: (i) a significant difference in performance between the trained (A) and untrained (B) sequences, in favor of the trained sequence. (ii) An increase in performance for both sequences A and B toward the second (retention) session. (iii) The advantage for sequence A was stable and preserved also in the second session. (iv) Participants with lower moderate Functional Independence Measure (FIM) scores gained more from observational-procedural learning, compared with patients with higher functional abilities. Conclusion: Overall, these findings support the notion that TBI patients may achieve procedural memory consolidation and retention through observational learning. Moreover, different functional traits may predict the outcomes of observational training in different patients. These findings may have significant practical implications in the future, regarding skill acquisition methods in TBI patients.

New insights in implicit sequence learning of adults with traumatic brain injury: As measured by an ocular serial reaction time (O-SRT) task.

Objective: We investigated the effect of traumatic brain injury (TBI) on implicit sequence learning (ISL) and its relation with demographic, clinical, and working memory (WM) capacity using an eye-tracked variant of the standard serial reaction time (RT; SRT) task. Besides RT, this ocular SRT (O-SRT) task enables generation of correct anticipations (CA) and stucks, reflecting other critical aspects of ISL. Method: ISL was tested in 26 individuals with TBI and 28 healthy controls using the O-SRT task. Mixed analyses of variance were conducted to analyze RT and CA in three phases: learning, interference, and recovery from interference. The average number of stucks was compared with an independent-samples t test. Finally, Pearson correlation analyses of ISL with demographic, clinical, and WM capacity measures were performed. Results: Based on RT, ISL was impaired in the TBI group. However, CA demonstrated improved learning, but with deficits in the interference and recovery from interference phases. Stucks were more frequent in the TBI group, which affected RT and CA measures. Neither demographic nor clinical factors were associated with ISL. Verbal, but not spatial, WM capacity was impaired in the TBI group, and spatial WM capacity positively correlated with ISL in controls only. Conclusion: We suggest that the high TBI group stuck rate can be attributed to lack of initiative and/or conservative response bias associated with TBI, and view it as a main cause leading to deficits in ISL. Unlike controls, the TBI group could not muster their relatively preserved spatial WM capacity to support their ISL performance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Effects of Ai-Chi Practice on Balance and Left Cerebellar Activation during High Working Memory Load Task in Older People: A Controlled Pilot Trial.

BACKGROUND: Normal aging is associated with balance and working memory decline. From a neurobiological standpoint, changes in cerebellar functional plasticity may mediate the decline in balance and working memory for older adults. Mounting evidence suggests that physical activity is beneficial for decreasing aging effects. Previous studies have focused on land-based physical activity and research concerning the aquatic environment is scarce. This study investigated the effectiveness of Ai-Chi on balance abilities and cerebral activation during a high working memory load task among community-dwelling older people. METHODS: A total of 19 people aged 65-86 years were allocated to receive Ai-Chi practice (n = 6), structured on-land Ai-Chi practice (n = 7) or guided-imagery of Ai-Chi practice (n = 6) for a bi-weekly, 30-min exercise session for 12 weeks. Balance was measured by the Tinetti balance sub-test and working memory was measured by the N-back test during functional-MRI scan. RESULTS: The Ai-Chi practice group presented a significant change in balance between pre and post intervention (balance t = -4.8, p < 0.01). In the whole-brain analysis, during high working memory load task, the Ai-Chi practice group presented a decrease in left cerebellar activation. Region of interest analyses yielded similar results by which pre-cerebellar activation was higher than post-intervention (t = 2.77, p < 0.05). CONCLUSIONS: Ai-Chi is an available, non-invasive intervention method that may serve as a tool to improve cerebellar activation that in turn might improve balance. In addition, our findings may provide new insights into the neuronal mechanisms that underlie both motor and cognitive abilities.

Spared and impaired olfactory abilities after thalamic lesions.

Olfactory information reaches olfactory cortex without a thalamic relay. This neuroanatomical substrate has combined with functional findings to suggest that, in olfaction, the typical thalamic role in sensory processing has shifted to the olfactory bulb or olfactory cortex. With this in mind, we set out to ask whether the thalamus at all plays a significant functional role in human olfaction. We tested olfactory function in 17 patients with unilateral focal thalamic lesions and in age-matched healthy controls. We found that thalamic lesions did not significantly influence olfactory detection but significantly impaired olfactory identification, and only right lesions altered olfactory hedonics by reducing the pleasantness of pleasant odors. An auditory control revealed that this shift in pleasantness was olfactory specific. These olfactory impairments were evident in explicit measures of perception, as well as in patterns of sniffing. Whereas healthy subjects modulated their sniffs in accordance with odorant content, thalamic patients did not. We conclude that, although the thalamus is not in the path of olfactory information from periphery to cortex, it nevertheless plays a significant functional role in human olfaction.

Self-efficacy and acceptance of disability following mild traumatic brain injury: A pilot study.

Recovery from mild traumatic brain injury (mTBI) and regaining emotional equilibrium afterward can take much longer than the typical three months. Recent works attribute persisting complaints to psychological factors, primarily the negative perception of mTBI. However, research has yet to demonstrate how self-beliefs concerning capability are linked to perception and ability to accept injury. The objective of this study was to investigate how perceived general self-efficacy (GSE) and acceptance of disability (AD) relate to emotional outcome following mTBI. Thirty individuals aged 21-57, all of whom were at least three-month post diagnosis of mTBI, underwent a psychiatric clinical interview assessing depression, post-traumatic stress disorder (PTSD), and quality of life (QoL), and completed self-report scales to evaluate psychological factors. Scores on AD, depression, and QoL for most life domains were significantly lower and worse than among the normative population. Pearson coefficients indicated significant correlations between psychological factors and emotional outcome. Mediation analysis showed a significant role of AD in mediating the correlation between GSE and depression/general QoL, irrespective of PTSD. Low self-efficacy accentuates negative perception of the injury which, in turn, leads to poor emotional outcomes post mTBI. Therefore, AD should become the focus of therapeutic interventions.

Traumatic brain injury hinders learning of road hazard awareness by repeated exposure to video-based hazards.

OBJECTIVE: To better understand hazard awareness abilities among traumatic brain injury (TBI) survivors of which little is currently known. TBI survivors express degradation in driving abilities, particularly the proactive strategy in which indicators of potentially hazardous situations are sought and identified. The current study examined differences in hazard awareness learning between TBI survivors and noninjured control individuals matched for age and driving experience. METHOD: Forty individuals equally divided among the 2 groups were assessed by exposure to repetitive video-based hazard scenarios, which have been shown to improve hazard awareness in noninjured individuals. Differences in participants' eye movements and behavioral response while watching video clips of genuine traffic scenes were recorded. RESULTS: Although survivors of TBI demonstrated relatively intact hazard awareness abilities under baseline conditions, they failed to learn from repetitive presentation of the same hazardous situation (i.e., they did not improve hazard detection) and thus failed to adjust their scanning and behavioral reaction (e.g., time to reaction, adapt of scanning behavior). Differences were more prominent for hidden hazards. Our results show impoverished anticipation abilities in driving simulation tasks performed in the subacute recovery phase after TBI and that differences in materialized hazards awareness are distinguishable between TBI survivors and noninjured drivers of similar age and driving experience. CONCLUSIONS: Our findings signal the need for further research to clarify the relationship between TBI and hazard awareness training that might be supportive of driving rehabilitation after TBI. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Direct and indirect measures of context in patients with mild-to-severe traumatic brain injury (TBI): The additive contribution of eye tracking.

Introduction: The facilitation of memory for target stimuli due to the similarity of context in the learning and testing phases is known as the "Context-Effect" (CE). Previous studies reported that TBI affects memory for contextual information when tested directly. However, the indirect effect of contextual information on memory of target (i.e., CE) is preserved. Several studies have demonstrated that CE is composed of multiple, distinct cognitive processes. The present study includes four context conditions to enable identification of the exact process affected by TBI. In addition, eye movements were monitored to test three hypotheses: first, that the TBI group's dwell time on target (DTOT) at encoding would be less than that of controls. Second, that DTOT at encoding would be more highly associated with recognition at test for the control group than for the TBI group. Third, that overall DTOT at encoding on new, as compared to old items ("repetition effect"), would be less pronounced for the TBI group as compared to controls. Methods: Twenty-four patients with mild-to-severe TBI and 23 matched controls participated in this study. We presented participants with photographs of male faces shown wearing distinctive, trial-unique hats (yielding specific Target-Context pairing). Eye movements were recorded throughout the test task. Results: Memory for faces following TBI is impaired compared to that of controls. The magnitude and pattern of CE are the same for both groups. The TBI group has a lower DTOT compared to that of controls. However, the relative length of DTOT in the various conditions is similar in both groups. Conclusions: Behavioral results indicate that although the TBI group has impaired memory for faces, the CE pattern is similar to that of controls. Similarly, in terms of eye movements, although the TBI group focuses less on target, relations between the various conditions are similar in both groups.

Atypical Within-Session Motor Procedural Learning after Traumatic Brain Injury but Well-Preserved Between-Session Procedural Memory Consolidation.

Using the finger-to-thumb opposition sequence (FOS) learning task, we characterized motor skill learning in sub-acute patients hospitalized for rehabilitation following traumatic brain injury (TBI). Ten patients (Trained TBI) and 11 healthy participants (Trained Healthy) were trained using a multi-session protocol: a single session was afforded in the first week of the study, and four daily sessions were afforded during the second week. Intensity of practice was adapted to patients. Performance speed and accuracy were tested before and after each session. Retention was tested 1 month later. Ten patients (Control TBI) had no FOS training and were tested only at the beginning and the end of the 6 week period. Although baseline performance on the FOS was very slow, all three phases of skill learning found in healthy adults (acquisition, between-session consolidation gains, and long-term retention) could be identified in patients with TBI. However, their time-course of learning was atypical. The Trained TBI group improved in speed about double the spontaneous improvements observed in the Control TBI group, with no speed-accuracy tradeoff. Normalized to their initial performance on the FOS, the gains accrued by the Trained TBI group after a first training were comparable to those accrued by healthy adults. Only during the second week with daily training, the rate of improvement of the Trained TBI group lagged behind that of the Trained Healthy group, due to increasing within-sessions losses in performance speed; no such losses were found in healthy participants. The Functional Independence Measure scores at the start of the study correlated with the total gains attained at the end of the study; no correlations were found with severity of injury or explicit memory impairments. Despite within-sessions losses in performance, which we propose reflect cognitive fatigue, training resulted in robust overall learning and long-term retention in patients with moderate-severe TBI. Given that the gains in performance evolved mainly between sessions, as delayed, offline, gains, our results suggest that memory consolidation processes can be effectively engaged in patients with TBI. However, practice protocols and schedules may need to be optimized to better engage the potential for long-term plasticity in these patients.

Implicit integration in a case of integrative visual agnosia.

We present a case (SE) with integrative visual agnosia following ischemic stroke affecting the right dorsal and the left ventral pathways of the visual system. Despite his inability to identify global hierarchical letters [Navon, D. (1977). Forest before trees: The precedence of global features in visual perception. Cognitive Psychology, 9, 353-383], and his dense object agnosia, SE showed normal global-to-local interference when responding to local letters in Navon hierarchical stimuli and significant picture-word identity priming in a semantic decision task for words. Since priming was absent if these features were scrambled, it stands to reason that these effects were not due to priming by distinctive features. The contrast between priming effects induced by coherent and scrambled stimuli is consistent with implicit but not explicit integration of features into a unified whole. We went on to show that possible/impossible object decisions were facilitated by words in a word-picture priming task, suggesting that prompts could activate perceptually integrated images in a backward fashion. We conclude that the absence of SE's ability to identify visual objects except through tedious serial construction reflects a deficit in accessing an integrated visual representation through bottom-up visual processing alone. However, top-down generated images can help activate these visual representations through semantic links.

Role of disengagement failure and attentional gradient in unilateral spatial neglect - a longitudinal study.

PURPOSE: To assess the importance of 'disengagement failure' and 'attentional gradient' in unilateral spatial neglect (USN) and in recovery from neglect. METHOD: Eight right-hemisphere-damaged stroke patients performed the standardized Behavioural-Inattention-Test battery for visual neglect, line-bisection tests, and two computerized reaction-time (RT) tasks: a variant of Posner's 'Spatial-Cueing' paradigm (with special emphasis on the magnitude of leftward disengagement time) and a signal-detection task (marking the spatial gradient of attention by the distribution of RTs to target stimuli in different spatial locations). The correlation between the different measures was assessed at two points in time, before and after a period of rehabilitation treatment. RESULTS: A recovery pattern could be identified in both RT paradigms. However, the correlation between standard measures of neglect and performance on both, spatial-cueing and signal-detection tasks, was weak. CONCLUSION: Neither difficulty disengaging attention from an ipsilesional stimulus nor changes in the attentional gradient can fully explain the processes underlying USN and its recovery. A large interpersonal variance exists among USN patients in the expression of disengagement and other spatial-attention deficits. Hence, individual patients should be tested by measuring different factors known to play a role in USN. This information is crucial for assigning the appropriate treatment for each patient in accord with the specific deficit revealed.

Effectiveness of executive functions training within a virtual supermarket for adults with traumatic brain injury: a pilot study.

Impairments of executive functions (EF) significantly affect the ability to lead an independent lifestyle. Virtual environments offer a way to rehabilitate EF due to their ecological validity. The purpose of this pilot study was to examine the effectiveness of a virtual reality (VR) supermarket (VMall) for treatment of EF in patients with Traumatic Brain Injury (TBI), compared to conventional occupational therapy (OT), in order to provide initial data regarding the effect sizes for calculation of sample size as well as to establish an intervention protocol for future Randomized Control Trials (RCTs). Twelve men and women, aged 19-55 years, who had TBI resulting in EF impairments participated in this study. Outcome measures were the Multiple Errands Test-Simplified Version (MET-SV) and the Executive Function Performance Test (EFPT). Cognitive treatment provided to both groups was based on the same principles; the participants in the experimental group received 10 45-min VR-based treatment sessions and the control group participants received 10 sessions of occupational therapy cognitive retraining without VR. Baseline performance prior to intervention showed no statistically significant differences between groups. Most participants improved their performance after therapy. Following a Bonferroni correction for multiple comparisons, no significant between or within group differences were found, Nevertheless, large effect sizes (0.51) for the percent (%) relative change of the MET-SV total score and EFPT total score after intervention were high in favor of the experimental group indicating a larger improvement in EF. Based on this pilot study, results show a trend towards an advantage to VR therapy compared to cognitive retraining OT without VR, as it leads to greater improvement in complex everyday activities.

Assessment of spatial attention after brain damage with a dynamic reaction time test.

Lateralized spatial biases after brain damage are commonly assessed using batteries of paper-and-pencil tests. These tests hardly allow quantification of performance in different locations in space, and they tend to lose sensitivity along the course of recovery. We tested the dynamic Starry Night Test (SNT), a novel computerized test measuring reaction time and detection accuracy for visual target stimuli in a dynamic background, in 32 inpatients with right hemisphere stroke (RHS), 16 patients with left hemisphere stroke (LHS), and 9 healthy controls. As a group, only the RHS patients were significantly slower to respond to contralesional targets. Individually, 21 (66%) RHS patients and 5 (31%) LHS patients showed statistically significant contralateral deficits. In a number of RHS patients the SNT was more sensitive to the ipsilesional bias of spatial attention than the Behavioral Inattention Test (BIT), a standardized paper-and-pencil test battery of unilateral spatial neglect. Two illustrative case reports show that the dynamic SNT, but not the BIT, was sensitive to the spatial deficit in recovered patients, one of whom was involved in repeated car accidents. The SNT overcomes serious shortcomings of paper-and-pencil tests of unilateral neglect. It provides a simple quantitative tool for monitoring the natural and treatment-induced recovery of patients.

Blood homocysteine levels in stroke patients undergoing rehabilitation.

BACKGROUND: One of the major concerns of a stroke victim is the threatening possibility of loosing all the functional achievements attained through prolonged rehabilitation effort, in case of a recurrent cerebrovascular event. Recently, elevated serum homocysteine (Hcy) level was found to be associated with an increased risk for atherosclerotic vascular disease. The aim of the present study was to assess the yield of screening stroke patients for hyperhomocysteinemia, as part of the measures taken to reduce the risk of stroke recurrence. MATERIAL/METHODS: Blood Hcy levels of stroke patients undergoing rehabilitation were compared to the Hcy levels of patients admitted for rehabilitation following brain damage of non-vascular etiologies. RESULTS: The mean Hcy level was found to be significantly higher in the former group (10.21+/-7.81 micromol/L and 6.16+/-4.28 micromol/L in the stroke group and in the non-vascular group, respectively [p<0.003]). However, when analysis of variance was applied and the correlation with age was accounted for, the difference between the groups became insignificant. CONCLUSIONS: Considering the current high cost of blood Hcy tests, the above findings do not support adoption of an overall, non-selective screening policy for hyperhomocysteinemia in stroke patients. However, it may be justified to measure Hcy levels, as well as folic acid, vitamin B6 and vitamin B12 levels, in selected stroke cases. Further study is needed in order to set clear guidelines for the search after this possible risk factor of stroke, one of the major causes of morbidity and mortality in modern society.