The neural correlates of topographical disorientation-a lesion analysis study.

Topographical disorientation refers to the selective inability to orient oneself in familiar surroundings. However, to date its neural correlates remain poorly understood. Here we use quantitative lesion analysis and a lesion network mapping approach in order to investigate seven patients with topographical disorientation. Our findings link not only the posterior parahippocampal gyrus (PHG) and retrosplenial cortex but also the lingual gyrus, the precuneus and the fusiform gyrus to topographical disorientation. We propose that topographical disorientation is due to the inability to integrate familiar landmarks within a framework of allocentric and egocentric orientation, supported by a neural network including the posterior PHG, the retrosplenial and the lingual cortex.

Attention to attention in aphasia - elucidating impairment patterns, modality differences and neural correlates.

It is increasingly acknowledged that patients with aphasia following a left-hemisphere stroke often have difficulties in other cognitive domains. One of these domains is attention, the very fundamental ability to detect, select, and react to the abundance of stimuli present in the environment. Basic and more complex attentional functions are usually distinguished, and a variety of tests has been developed to assess attentional performance at a behavioural level. Attentional performance in aphasia has been investigated previously, but often only one specific task, stimulus modality, or type of measure was considered and usually only group-level analyses or data based on experimental tasks were presented. Also, information on brain-behaviour relationships for this cognitive domain and patient group is scarce. We report detailed analyses on a comprehensive dataset including patients' performance on various subtests of two well-known, standardised neuropsychological test batteries assessing attention. These tasks allowed us to explore: 1) how many patients show impaired performance in comparison to normative data, in which tasks and on what measure; 2) how the different tasks and measures relate to each other and to patients' language abilities; 3) the neural correlates associated with attentional performance. Up to 32 patients with varying aphasia severity were assessed with subtests from the Test of Attentional Performance (TAP) as well as the Test of Everyday Attention (TEA). Performance was compared to normative data, relationships between attention measures and other background data were explored with principal component analyses and correlations, and brain-behaviour relationships were assessed by means of voxel-based correlational methodology. Depending on the task and measure, between 3 and 53 percent of the patients showed impaired performance compared to normative data. The highest proportion of impaired performance was noted for complex attention tasks involving auditory stimuli. Patients differed in their patterns of performance and only the performance in the divided attention tests was (weakly) associated with their overall language impairment. Principal components analyses yielded four underlying factors, each being associated with distinct neural correlates. We thus extend previous research in characterizing different aspects of attentional performance within one sample of patients with chronic post stroke aphasia. Performance on a broad range of attention tasks and measures was variable and largely independent of patients' language abilities, which underlines the importance of assessing this cognitive domain in aphasic patients. Notably, a considerable proportion of patients showed difficulties with attention allocation to auditory stimuli. The reasons for these potentially modality-specific difficulties are currently not well understood and warrant additional investigations.

Assessing executive functions in post-stroke aphasia-utility of verbally based tests.

It is increasingly acknowledged that, often, patients with post-stroke aphasia not only have language impairments but also deficits in other cognitive domains (e.g. executive functions) that influence recovery and response to therapy. Many assessments of executive functions are verbally based and therefore usually not administered in this patient group. However, the performance of patients with aphasia in such tests might provide valuable insights both from a theoretical and clinical perspective. We aimed to elucidate (i) if verbal executive tests measure anything beyond the language impairment in patients with chronic post-stroke aphasia, (ii) how performance in such tests relates to performance in language tests and nonverbal cognitive functions, and (iii) the neural correlates associated with performance in verbal executive tests. In this observational study, three commonly used verbal executive tests were administered to a sample of patients with varying aphasia severity. Their performance in these tests was explored by means of principal component analyses, and the relationships with a broad range of background tests regarding their language and nonverbal cognitive functions were elucidated with correlation analyses. Furthermore, lesion analyses were performed to explore brain-behaviour relationships. In a sample of 32 participants, we found that: (i) a substantial number of patients with aphasia were able to perform the verbal executive tests; (ii) variance in performance was not explained by the severity of an individual's overall language impairment alone but was related to two independent behavioural principal components per test; (iii) not all aspects of performance were related to the patient's language abilities; and (iv) all components were associated with separate neural correlates, some overlapping partly in frontal and parietal regions. Our findings extend our clinical and theoretical understanding of dysfunctions beyond language in patients with aphasia.

The verbal, non-verbal and structural bases of functional communication abilities in aphasia.

The ability to communicate, functionally, after stroke or other types of acquired brain injury is crucial for the person involved and the people around them. Accordingly, assessment of functional communication is increasingly used in large-scale randomized controlled trials as the primary outcome measure. Despite the importance of functional communication abilities to everyday life and their centrality to the measured efficacy of aphasia interventions, there is little knowledge about how commonly used measures of functional communication relate to each other, whether they capture and grade the full range of patients' remaining communication skills and how these abilities relate to the patients' verbal and non-verbal impairments as well as the underpinning lesions. Going beyond language-only factors is essential given that non-verbal abilities can play a crucial role in an individual's ability to communicate effectively. This study, based on a large sample of patients covering the full range and types of post-stroke aphasia, addressed these important, open questions. The investigation combined data from three established measures of functional communication with a thorough assessment of verbal and non-verbal cognition as well as structural neuroimaging. The key findings included: (i) due to floor or ceiling effects, the full range of patients' functional communication abilities was not captured by a single assessment alone, limiting the utility of adopting individual tests as outcome measures in randomized controlled trials; (ii) phonological abilities were most strongly related to all measures of functional communication and (iii) non-verbal cognition was particularly crucial when language production was relatively impaired and other modes of communication were allowed, when patients rated their own communication abilities, and when carers rated patients' basic communication abilities. Finally, in addition to lesion load being significantly related to all measures of functional communication, lesion analyses showed partially overlapping clusters in language regions for the functional communication tests. Moreover, mirroring the findings from the regression analyses, additional regions previously associated with non-verbal cognition emerged for the Scenario Test and for the Patient Communication Outcome after Stroke rating scale. In conclusion, our findings elucidated the cognitive and neural bases of functional communication abilities, which may inform future clinical practice regarding assessments and therapy. In particular, it is necessary to use more than one measure to capture the full range and multifaceted nature of patients' functional communication abilities and a therapeutic focus on non-verbal cognition might have positive effects on this important aspect of activity and participation.

Assessing and mapping language, attention and executive multidimensional deficits in stroke aphasia.

There is growing awareness that aphasia following a stroke can include deficits in other cognitive functions and that these are predictive of certain aspects of language function, recovery and rehabilitation. However, data on attentional and executive (dys)functions in individuals with stroke aphasia are still scarce and the relationship to underlying lesions is rarely explored. Accordingly in this investigation, an extensive selection of standardized non-verbal neuropsychological tests was administered to 38 individuals with chronic post-stroke aphasia, in addition to detailed language testing and MRI. To establish the core components underlying the variable patients' performance, behavioural data were explored with rotated principal component analyses, first separately for the non-verbal and language tests, then in a combined analysis including all tests. Three orthogonal components for the non-verbal tests were extracted, which were interpreted as shift-update, inhibit-generate and speed. Three components were also extracted for the language tests, representing phonology, semantics and speech quanta. Individual continuous scores on each component were then included in a voxel-based correlational methodology analysis, yielding significant clusters for all components. The shift-update component was associated with a posterior left temporo-occipital and bilateral medial parietal cluster, the inhibit-generate component was mainly associated with left frontal and bilateral medial frontal regions, and the speed component with several small right-sided fronto-parieto-occipital clusters. Two complementary multivariate brain-behaviour mapping methods were also used, which showed converging results. Together the results suggest that a range of brain regions are involved in attention and executive functioning, and that these non-language domains play a role in the abilities of patients with chronic aphasia. In conclusion, our findings confirm and extend our understanding of the multidimensionality of stroke aphasia, emphasize the importance of assessing non-verbal cognition in this patient group and provide directions for future research and clinical practice. We also briefly compare and discuss univariate and multivariate methods for brain-behaviour mapping.

Integrated Health Care Management of Moderate to Severe TBI in Older Patients-A Narrative Review.

PURPOSE OF REVIEW: Traumatic brain injuries are common, especially within the elderly population, which is typically defined as age 65 and older. This narrative review aims at summarizing and critically evaluating important aspects of their health care management in covering the entire pathway from prehospital care to rehabilitation and beyond. RECENT FINDINGS: The number of older patients with traumatic brain injury (TBI) is increasing, and there seem to be differences in all aspects of care along their pathway when compared to younger patients. Despite a higher mortality and a generally less favorable outcome, the current literature shows that older TBI patients have the potential to make significant improvements over time. More research is needed to evaluate the most efficient and integrated clinical pathway from prehospital interventions to rehabilitation as well as the optimal treatment of older TBI patients. Most importantly, they should not be denied access to specific treatments and therapies only based on age.

Trajectory of disability and quality-of-life in non-geriatric and geriatric survivors after severe traumatic brain injury.

OBJECTIVE: The objective was to investigate disability and health-related quality-of-life (HRQoL) 3, 6 and 12 months after traumatic brain injury (TBI) in non-geriatric (≤ 65 years) and geriatric patients (> 65 years). METHODS: Patients ≥ 16 years who sustained a severe TBI (Abbreviated Injury Scale of the head region > 3) were included in this prospective, multi-centre study. Outcome measures were Glasgow Outcome Scale Extended (GOSE; disability), SF-12 (HRQoL). Mixed linear model analyses were performed. RESULTS: Three hundred and fifty-one patients (median age = 50 years; interquartile range (IQR) = 27-67) were included; 73.2% were male and 27.6% were geriatric patients. Median GOSE at 3, 6 and 12 months was 5 (IQR = 3-7), 6 (IQR = 4-8) and 7 (IQR = 5-8); this increase (slopetime = 0.22, p < 0.0001) was age dependent (slopeage*time = -0.06, p = 0.003). Median SF-12 physical component scale score at 3, 6 and 12 months was 42.1 (IQR = 33.6-50.7), 46.6 (IQR = 37.4-53.9) and 50.4 (IQR = 39.2-55.1); this increase (slopetime = 1.52, p < 0.0001) was not age dependent (slopeage*time = -0.30, p = 0.083). SF-12 mental component scale scores were unchanged. CONCLUSIONS: Disability decreased and HRQoL improved after TBI between 3-12 months. In geriatric patients this improvement was relevant for HRQoL only.

Predictors of inpatient (neuro)rehabilitation after acute care of severe traumatic brain injury: An epidemiological study.

OBJECTIVE: To describe the discharge destination of patients with severe traumatic brain injury (sTBI) after acute care. To identify predictors associated with inpatient rehabilitation (vs discharge home) and to identify predictors associated with neurorehabilitation (vs general rehabilitation). METHODS: A national, multi-centre, prospective study with adult survivors after sTBI (abbreviated injury scale head score > 3). Univariate and multivariate logistic regression models included patient characteristics, pre-injury conditions, initial neuro-physiological assessment, trauma mechanisms, severity of TBI and pre-hospital conditions to find predictors of discharge destination. RESULTS: Out of the 566 included patients, 341 (60%) were referred to inpatient rehabilitation, thereof 249 (73%) to neurorehabilitation; 225 (40%) were discharged home or to a nursing home. Lower scores on the Glasgow Coma Scale at admission/at 14 days, higher injury severity scores and older age were predictors for inpatient rehabilitation. Younger age and male gender were predictors for neurorehabilitation. CONCLUSIONS: Patients' pathways after acute care are not only determined by the severity of their brain injury, but also by their overall injury severity and socio-biological factors. More than half of the patients after sTBI are not discharged to specialized inpatient neurorehabilitation and, therefore, efforts should be taken to optimize post-acute care.

Eye Gaze Behavior at Turn Transition: How Aphasic Patients Process Speakers' Turns during Video Observation.

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.

Comprehension of Co-Speech Gestures in Aphasic Patients: An Eye Movement Study.

BACKGROUND: Co-speech gestures are omnipresent and a crucial element of human interaction by facilitating language comprehension. However, it is unclear whether gestures also support language comprehension in aphasic patients. Using visual exploration behavior analysis, the present study aimed to investigate the influence of congruence between speech and co-speech gestures on comprehension in terms of accuracy in a decision task. METHOD: Twenty aphasic patients and 30 healthy controls watched videos in which speech was either combined with meaningless (baseline condition), congruent, or incongruent gestures. Comprehension was assessed with a decision task, while remote eye-tracking allowed analysis of visual exploration. RESULTS: In aphasic patients, the incongruent condition resulted in a significant decrease of accuracy, while the congruent condition led to a significant increase in accuracy compared to baseline accuracy. In the control group, the incongruent condition resulted in a decrease in accuracy, while the congruent condition did not significantly increase the accuracy. Visual exploration analysis showed that patients fixated significantly less on the face and tended to fixate more on the gesturing hands compared to controls. CONCLUSION: Co-speech gestures play an important role for aphasic patients as they modulate comprehension. Incongruent gestures evoke significant interference and deteriorate patients' comprehension. In contrast, congruent gestures enhance comprehension in aphasic patients, which might be valuable for clinical and therapeutic purposes.

Cue Recognition and Integration - Eye Tracking Evidence of Processing Differences in Sentence Comprehension in Aphasia.

PURPOSE: We aimed at further elucidating whether aphasic patients' difficulties in understanding non-canonical sentence structures, such as Passive or Object-Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations. METHODS: A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed. RESULTS: Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients' fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues. CONCLUSION: Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing delayed and therefore impaired recognition and integration of cues, as well as increased competition between interpretations.

Different visual exploration of tool-related gestures in left hemisphere brain damaged patients is associated with poor gestural imitation.

According to the direct matching hypothesis, perceived movements automatically activate existing motor components through matching of the perceived gesture and its execution. The aim of the present study was to test the direct matching hypothesis by assessing whether visual exploration behavior correlate with deficits in gestural imitation in left hemisphere damaged (LHD) patients. Eighteen LHD patients and twenty healthy control subjects took part in the study. Gesture imitation performance was measured by the test for upper limb apraxia (TULIA). Visual exploration behavior was measured by an infrared eye-tracking system. Short videos including forty gestures (20 meaningless and 20 communicative gestures) were presented. Cumulative fixation duration was measured in different regions of interest (ROIs), namely the face, the gesturing hand, the body, and the surrounding environment. Compared to healthy subjects, patients fixated significantly less the ROIs comprising the face and the gesturing hand during the exploration of emblematic and tool-related gestures. Moreover, visual exploration of tool-related gestures significantly correlated with tool-related imitation as measured by TULIA in LHD patients. Patients and controls did not differ in the visual exploration of meaningless gestures, and no significant relationships were found between visual exploration behavior and the imitation of emblematic and meaningless gestures in TULIA. The present study thus suggests that altered visual exploration may lead to disturbed imitation of tool related gestures, however not of emblematic and meaningless gestures. Consequently, our findings partially support the direct matching hypothesis.

Perception of co-speech gestures in aphasic patients: a visual exploration study during the observation of dyadic conversations.

BACKGROUND: Co-speech gestures are part of nonverbal communication during conversations. They either support the verbal message or provide the interlocutor with additional information. Furthermore, they prompt as nonverbal cues the cooperative process of turn taking. In the present study, we investigated the influence of co-speech gestures on the perception of dyadic dialogue in aphasic patients. In particular, we analysed the impact of co-speech gestures on gaze direction (towards speaker or listener) and fixation of body parts. We hypothesized that aphasic patients, who are restricted in verbal comprehension, adapt their visual exploration strategies. METHODS: Sixteen aphasic patients and 23 healthy control subjects participated in the study. Visual exploration behaviour was measured by means of a contact-free infrared eye-tracker while subjects were watching videos depicting spontaneous dialogues between two individuals. Cumulative fixation duration and mean fixation duration were calculated for the factors co-speech gesture (present and absent), gaze direction (to the speaker or to the listener), and region of interest (ROI), including hands, face, and body. RESULTS: Both aphasic patients and healthy controls mainly fixated the speaker's face. We found a significant co-speech gesture × ROI interaction, indicating that the presence of a co-speech gesture encouraged subjects to look at the speaker. Further, there was a significant gaze direction × ROI × group interaction revealing that aphasic patients showed reduced cumulative fixation duration on the speaker's face compared to healthy controls. CONCLUSION: Co-speech gestures guide the observer's attention towards the speaker, the source of semantic input. It is discussed whether an underlying semantic processing deficit or a deficit to integrate audio-visual information may cause aphasic patients to explore less the speaker's face.

A short tool to screen HIV-infected patients for mild neurocognitive disorders - a pilot study.

BACKGROUND: We aimed to evaluate the accuracy and acceptability of a short screening test battery for mild neurocognitive deficits. METHODS: HIV-infected individuals with a suppressed viral load were examined at the University Hospital Basel with a screening test consisting of a questionnaire and selected cognitive tests, administered by trained nurses, followed by an in-depth neuropsychological examination. Test acceptance was evaluated with a questionnaire. RESULTS: 30 patients were included in this study (median age of 52.5 years (interquartile range (IQR) 47-64), prior AIDS-defining condition in 37%, median CD4 cell count 658 (IQR 497-814) cells/µl). Overall, 25 (83%) patients were diagnosed with HIV-associated neurocognitive disorders (HAND) on in-depth neuropsychological assessment (16 patients had asymptomatic neurocognitive impairment (ANI), 8 a mild neurocognitive disorder (MND) and 1 patient HIV-associated dementia (HAD). Among 25 patients with HAND, only 9 patients (36%) were complaining of memory loss. The screening battery revealed neurocognitive deficits in 17 (57%) patients (sensitivity 64%, specificity 80%, positive predictive value 94% and negative predictive value 31%). Most patients (83%) estimated the screening test as valuable and not worrisome. CONCLUSIONS: A questionnaire combined with selected neuropsychological tests is a short, easy-to-perform very well accepted screening tool for mild neurocognitive disorders in asymptomatic HIV-infected individuals.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect.

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Theta burst stimulation over the right Broca's homologue induces improvement of naming in aphasic patients.

BACKGROUND AND PURPOSE: Improvements of language production in aphasic patients have been reported following repeated 1-Hz transcranial magnetic stimulation over the nondamaged right hemisphere. Most studies examined aphasic patients in the chronic phase. The effect of transcranial magnetic stimulation application in acute or subacute patients has not been systematically studied. We aimed to evaluate whether continuous theta burst stimulation, an inhibitory protocol with a shorter application time than the common 1-Hz protocol, is able to improve naming performance in aphasic patients in different poststroke phases. METHODS: Eighteen right-handed aphasic patients performed a picture naming task and a language independent alertness test before and after the application of theta burst stimulation over the intact right Broca's homologue localized by the 10-20 electroencephalogram system in a randomized, sham-controlled, crossover trial. RESULTS: We found that naming performance was significantly better, and naming latency was significantly shorter, after theta burst stimulation than after the sham intervention. Patients who responded best were in the subacute phase after stroke. CONCLUSIONS: This setting with the short theta burst stimulation application time and the simple stimulation localization procedure is suitable for clinical purposes.

ERP correlates of superordinate category activation.

The human semantic network is hierarchically organized, containing superordinate, basic and subordinate levels. Various impairments are thought to be connected with abnormal access to superordinate concepts. We devised an ERP paradigm to examine the activation of superordinate versus otherwise related concepts in 20 healthy participants. Following the presentation of a typical category member an arrow indicated whether the appropriate superordinate category had to be generated (categorization task) or an otherwise related word (relation task). To control task execution, a second word was presented for which a match-mismatch-judgment was required. Reaction times, accuracy rates and ERPs after the second word showed that participants successfully accessed the superordinate category name and that verification in the categorization task was faster and easier than in the relation task. Comparison of ERPs after the arrow revealed topographical, Global Field Power (GFP), and onset latency differences between the two tasks and thus indicated the involvement of at least partially different neural generators. Source localization analysis confirmed that brain regions were activated that were also identified in previous experiments with semantic task. The paradigm seems to be suitable for further examination of superordinate activation processes and evaluation of impairments such as thought disorders in schizophrenic patients.