|Year : 2019 | Volume
| Issue : 1 | Page : 12-18
The Sidney Licht Lectureship Award 2017: Novel Options for Restoration of Discrete Functions Following Brain Damage
Department of Neurological Rehabilitation, Loewenstein Hospital Rehabilitation Center, Raanana, and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
|Date of Web Publication||22-May-2019|
Department of Neurological Rehabilitation, Loewenstein Hospital Rehabilitation Center, Raanana, and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv
Source of Support: None, Conflict of Interest: None
The presence of aphasia following left hemisphere damage and of spatial neglect following right hemisphere damage are both associated with a significant negative impact on the functional outcome of stroke patients referred to rehabilitation. In aphasia, interpersonal variance in structure-function mapping, and findings related to pragmatics, points to exciting new options for rehabilitation research. In the case of neglect rehabilitation, promising novel options are pointed by experiments showing abolishment of neglect when spatial attention is modulated shortly after stimulus capture (at a stage where perceptual information is maintained in the iconic buffer) and by studies showing amelioration following electroencephalogram-biofeedback treatment aimed to enhance the level of arousal in perilesional cortex.
Keywords: Electroencephalogram-biofeedback, iconic memory, language neuroanatomy, neuropragmatics, Sidney Licht Award, spatial attention, unilateral spatial neglect
|How to cite this article:|
Soroker N. The Sidney Licht Lectureship Award 2017: Novel Options for Restoration of Discrete Functions Following Brain Damage. J Int Soc Phys Rehabil Med 2019;2:12-8
|How to cite this URL:|
Soroker N. The Sidney Licht Lectureship Award 2017: Novel Options for Restoration of Discrete Functions Following Brain Damage. J Int Soc Phys Rehabil Med [serial online] 2019 [cited 2022 May 20];2:12-8. Available from: https://www.jisprm.org/text.asp?2019/2/1/12/258765
| Novel Options in the Treatment of Impaired Language|| |
Remapping options pointed by interpersonal variance in language neuroanatomy
Broca, Wernicke, and most of their followers up to the 1980s thought about the mapping of language functions in the left perisylvian cortical regions in terms of a deterministic relationship, i.e., the posterior left inferior frontal gyrus and the posterior left superior temporal gyrus relate to speech fluency and language comprehension, respectively, more or less as eyes and ears relate to seeing and hearing. In the classical model of language organization in the brain ascribed to Wernicke, Lichtheim, Damasio, and Geschwind [Figure 1], the location of damage is thought to yield a specific impact on the presentation of aphasia, such that damage located anterior to the central sulcus is associated with nonfluent aphasia, damage located posterior to the central sulcus is associated with fluent aphasia, perisylvian damage is associated with aphasia “with repetition disorder,” and damage away from the sylvian fissure is associated with “aphasia without repetition disorder.” Fibers connecting Wernicke's area with regions of unimodal and heteromodal association cortex enable activation of appropriate representations (visual and other) upon hearing words – a process which is essential for language comprehension. Likewise, fibers connecting Broca's area with other cortical regions enable translation of thoughts into expressive speech.
|Figure 1: Schematic outline of the classical model of language organization in the brain. Purple and green arrows on the top indicate prerolandic and retro-rolandic cortical areas where damage causes nonfluent (NF) and fluent (F) types of aphasia, respectively. Damage to different perisylvian regions (within the red ellipse) is associated with aphasia “with repetition disorder” (as in Broca's, Wernicke's, conduction, and global aphasia types), whereas extrasylvian damage causing aphasia is associated with “aphasia without repetition disorder” (as in transcortical motor, sensory, and mixed aphasia types and also in anomic aphasia). Fibers connecting Wernicke's and Broca's areas with other cortical regions (green and purple bidirectional arrows) are crucial for speech comprehension and production|
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In the 1980s, soon after the introduction of computerized tomography, studies that analyzed the relationship between lesion location and the type of language impairment experienced by stroke patients started to note more and more cases where the predictions of the classical model failed. For example, using normalized lesion data to examine the location of damage in stroke patients with fluent paraphasic speech and marked comprehension deficits compatible with Wernicke's aphasia, we noted cases where the lesion not only spared Wernicke's area but also involved extensively Broca's area [patient FZ in [Figure 2] is an example for that]. We have found also cases with the opposite pattern – nonfluent speech with preserved comprehension and impaired repetition, compatible with Broca's aphasia, where the visible damage in CT/MR scans spares Broca's area. Significant variance was found not only in the location of damage underlying aphasic syndromes but also in the effects of lesions on specific communicative abilities such as naming, auditory-verbal comprehension, repetition, and speech fluency. Lesion analyses failed also to distinguish clearly between patients who performed correctly and patients who failed to perform tasks demanding the use of discrete specific linguistic rules, for example, syntactic movement (Gvion A, Grodzinsky Y, and Soroker N, unpublished material).
|Figure 2: Normalized lesion data from five stroke patients with Wernicke's aphasia (diagnosis based on patients' performance in the Hebrew version of the Western Aphasia Battery). As could be expected, in most patients, the damage involves the superior temporal gyrus, but note the location of structural damage in patient FZ (second from the top): despite intactness of the superior temporal lobe (Wernicke's area) in this patient, his comprehension of heard words was severely impaired. Moreover, one can see that this patient had an extensive damage in the inferior frontal gyrus (Broca's area), yet his speech was fluent, paraphasic, typical of patients with Wernicke's aphasia. The case of patient FZ, and other cases reported in the literature, points to the large variance that exists in the mapping of language functions in the cortical mantle|
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Classifying individual patients into this or that aphasic syndrome, and attempting to localize the damage underlying the different syndromes, are much less important than obtaining, for each patient, a detailed profile of preserved and impaired discrete operations pertinent to language information processing. Based on such a profile, tailor-made rehabilitation treatment can be structured to best answer the patient's needs, which are always somewhat different than those of other aphasic patients.
From the perspective of rehabilitation medicine, the interpersonal variance shown in language neuroanatomy at the level of discrete operations is very important, as it shows that in humans, mapping of operations taking place in the processing of language is not restricted obligatorily to a particular portion of the cortex. This fact makes it likely that with appropriate rehabilitation means, patients losing a given language capacity following a focal brain damage might be able to develop adaptive remapping of the lost operation in a region with preserved synaptic space – one that is shown to carry that same operation in other humans.
Observations of lesion effects that contradict the predictions of the classical model, and functional magnetic resonance imaging (fMRI) activation patterns of healthy individuals performing language tasks, led eventually to replacement of the classical model formulated in its final form by Damasio and Geschwind by more recent accounts (e.g., the dual-stream model proposed by Hickok and Poeppel). It remains to be shown whether the variance in language neuroanatomy is accommodated in the newer model better than in the classical model.
Accurate characterization of the variance in functional neuroanatomy of language, especially at the level of discrete language operations, is likely to contribute to the emerging practice of using noninvasive brain stimulation (NIBS) as an adjuvant factor in aphasia rehabilitation (NIBS is employed regularly by either repetitive transcranial magnetic stimulation [rTMS] or by transcranial direct-current stimulation [tDCS]). Such treatments usually aim to manipulate the interhemispheric dynamics to release perilesional areas of the left hemisphere from inhibition exerted by homologous regions of the right hemisphere. They also aim to increase the level of cortical arousal in perilesional nonimpaired synaptic space, to facilitate adaptive remapping there. Identification of the cortical areas that provide the structural basis for distinct language operations – in different people – will provide useful cues to selection of the target regions for stimulation.
Pathways for remediation hinted by neuro-pragmatics
Rehabilitation of acquired disorders of language tends to focus on impairments revealed in core operations, i.e., impaired phonology, lexical semantics and syntax, as expressed in language comprehension and production. Disorders of pragmatics usually receive much less attention. The field of pragmatics deal with issues related to language use in context, where “context” here means – parts that precede or follow a passage and fix its meaning, or the circumstances in which communication occurs. In our neuropragmatics research project, we have studied the neural substrate of distinct operations within the field of pragmatics, as revealed by impairments that stem from localized damage in different cortical regions.,,,, Our studies pointed, on the one hand, to important domains of acquired disability that is usually neglected and on the other hand to potential pathways for remediation in aphasia.
Among the communicative abilities that usually receive little attention are those that comprise Gardner and Brunnel's “right hemisphere communication battery,” i.e., comprehension of humor, emotional prosody, indirect requests, metaphors, inferences, sarcasm, alternative word meanings, and narrative. We have found that these communicative abilities are severely affected by damage in either the right or the left hemispheres., Likewise, both right and left hemispheric strokes were found to affect significantly the capacity of patients to process implicatures. Disturbances revealed in these aspects of human functioning, while of secondary importance relative to impairments revealed in core language functions, are still important elements in human interpersonal communication that received little place in rehabilitation research so far although they may restrict participation significantly in certain individuals.
Another aspect of our neuropragmatics research dealt with basic speech acts (BSAs). According to the legacy of prominent philosophers of language such as Austin, Grice, Searle, and Kasher, the proper unit of analysis in studying verbal communication is not the sentence but the speech act, i.e., the utterance of a sentence in a particular context. Four speech acts are more basic than others and reflect elementary uses of sentences in verbal communication. The BSAs are assertion, question, request, and command. By analyzing the effects of normalized brain lesions, we have found a significant negative correlation between lesion extent in different left perisylvian regions and the capacity of stroke patients to comprehend sentences used to convey each of the four BSAs [Figure 3].
|Figure 3: The figure depicts in a schematic way the different localization patterns of the four basic speech acts. The marked areas are those where the negative correlation between the extent of damage (number of involved voxels within the region of interest) and performance level reached statistical significance at the. 05 level. (a) Assertion: inferior frontal gyrus; (b) question: inferior and middle frontal gyri; (c) request: inferior and middle frontal gyri and superior and middle temporal gyri; (d) command: superior and middle temporal gyri, angular gyrus, and supramarginal gyrus. Based on analysis of normalized lesion data of 31 left-hemisphere damaged stroke patients|
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It should be noted that nonaphasic right-hemisphere damaged (RHD) patients also showed significant disadvantage relative to healthy controls, in their ability to process BSAs, although their impairment was less severe than that of left-hemisphere damaged (LHD) patients. Thus, damage to a variety of the left and right cortical regions can result in pragmatic incompetence (i.e., inability to appreciate context-derived meanings or to expressively use language in a form appropriate to the context). The occurrence of impaired pragmatic competence following RHD shows that pragmatic functions can be lost independently of syntax, semantics, and phonology. It is of interest that localization of BSAs was observed only in the LHD group, implying that pragmatic control in the left hemisphere is localized whereas in the right hemisphere it is more distributed.
The finding of a distinct localization pattern for the different BSAs is of significant clinical importance. It suggests marked differences in the abilities of aphasic patients to process sentences according to their SA context. Recognition of individual patterns of preservation and loss of BSAs (by introduction of appropriate testing for that into clinical speech rehabilitation practice) is likely to facilitate the development of novel treatment strategies, to be adapted in a tailor-made fashion in accord with the needs of each individual aphasic patient.
| Novel Options in the Treatment of Impaired Spatial Attention|| |
Access to conscious awareness regained by modulation of spatial attention shortly after stimulus capture
Unilateral spatial neglect (USN) is a multifactorial symptom complex, emerging mainly but not exclusively following damage in the right temporoparietal cortex. In USN, salient objects and events in contralesional space receive inadequate search and less or no attention (hence, remain outside conscious awareness), and processing of contralesional stimuli that do reach awareness is attenuated. This condition is thought to result from impaired space representation (organization of data in spatial coordinates) and/or impaired distribution and mobilization of attention in space. Much in USN phenomenology remains unclear – for example, why actually is the left missing in figures made by neglect patients? [Figure 4] – is it due to the lack of adequate sensory feedback or due to impaired access to parts of stored representations?
|Figure 4: Representational drawing is a paper-and-pencil test frequently used in clinical practice for the diagnosis of neglect. Drawings of a clock face, a butterfly, or a human figure reveal in unilateral spatial neglect patients a perplexing asymmetry. The drawings here were made by seven unilateral spatial neglect patients hospitalized for rehabilitation in our department|
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USN poses a big challenge for rehabilitation medicine, being related to significant prolongation of rehabilitation hospital stay (direct cost), and poor functional outcome at discharge expressed in various domains of cognitive and motor activity. Many treatments have been proposed but only few were shown to reduce neglect-related disability.
USN results usually from a stroke in the right middle cerebral artery (R-MCA) territory [Figure 5]. The optic pathways and the primary visual cortex are seldom involved. Therefore, after the acute poststroke period, when a more or less central gaze replaces the initial strong tendency to maintain the head and eyes turned persistently toward the right, one could expect stimuli to receive adequate visual processing. Why then salient visual stimuli fail to reach conscious awareness at this stage?
|Figure 5: Normalized lesion data from two-stroke patients with unilateral spatial neglect, following an ischemic infarction in the right middle-cerebral-artery territory. As can be seen in these two typical lesion distributions, the area of damage does not involve the visual cortex and usually spares also the optic radiation in the depths of the parietal lobe. The question raised by this lesion pattern is in what stage of visual information processing data is blocked and access to conscious awareness is denied|
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The following is an initial report of data obtained by us in a study aimed to shed light on this question. We examined 17 right-handed patients with stroke in R-MCA territory, in whom USN was evidenced by rightward deviation in line bisection and left-side disadvantage in cancellation tasks and in a computerized visual search task [Figure 6].
|Figure 6: Results of visual-search task performance (“starry-night test,”) used by us to establish the diagnosis of unilateral spatial neglect and to quantitate the left-side disadvantage in terms of reaction time to stimuli appearing in different parts of the computer screen (red color: long reaction time and blue color: short reaction time). Graphical representation of starry-night test results shown here for four patients with left-side neglect, as an example|
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We asked whether left-sided visual information, which regularly does not reach conscious awareness in USN, can be retrieved explicitly (i.e., by way of direct verbal report), from a stage of data processing defined as iconic memory (“iconic memory,” or “sensory memory,” or “very-short term memory” [VSTM] denotes a hypothetical memory store with rapid decay of the memory trace (~500 ms).
Sperling's classical method of partial report was used to manipulate the retrieval mode, such that patients had to report not everything they saw but only the stimuli in the side marked by either a precue or a postpresentation cue [a central arrow pointing either to the right or to the left, in random order, [Figure 7].
|Figure 7: Pairs of digits, one in each side, presented simultaneously for 32 ms, served as stimuli; Partial report was operated either by way of a precue (presented shortly before stimulus exposure) or a postcue (presented shortly after stimulus disappearance), in both cases, the cue was a central arrow pointing to one side. While in conditions of “whole report,” the patients were asked to report all they saw (in both sides), in the cued conditions, they were demanded to report just the digit on the cued location|
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In this study, we obtained direct evidence for the integrity of primary visual processing in USN. We were able to demonstrate almost complete abolishment of neglect by manipulation of the retrieval strategy (i.e., replacing “whole report” by “partial report”), as long as this manipulation was conducted during data maintenance in the iconic buffer, that is, in the short period (<500 ms) that follows stimulus capture by the eyes. The effect reached its peak when stimulus-onset asynchrony (the time from stimulus appearance to cue appearance) was 100 ms [Figure 8].
|Figure 8: This figure summarizes the essential finding of the study. It shows the significant disadvantage in the identification of left-sided visual stimuli, as compared to identification of right-sided stimuli. This disadvantage is manifested in the natural “whole report” condition (correct identification - 15% on the left and 60% on the right), as well as in “precue” and delayed “postcue” conditions. Stimulus onset asynchrony values (ms): SOA = 0 denotes time of stimulus appearance; SOA = −500 and −100 ms are precue conditions; SOA = 50, 100, 200, 300, 400 and 500 ms are postcue conditions. When the spatial cue indicating the side selected for partial report is provided at SOA = 100 ms, the rate of stimulus identification on the left is equal to the right, i.e., neglect is abolished in this condition. Note that by the time this effective postcue appears, the stimulus is no longer in the field of vision. Also note that with SOA of 500 ms (usually considered the upper limit of time for data maintenance in the iconic buffer), there is no more benefit from partial report relative to whole report|
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Thus, left-sided visual information destined to be neglected can be made available for conscious awareness and verbal report, using postexposure spatial cues within the short-time interval of data maintenance in iconic memory. The optimal timing for the provision of the spatial cue is 100 ms after stimulus presentation. This is an explicit direct demonstration, as opposed to earlier implicit demonstrations, that neglected information is captured and processed by the visual system.
The above findings pose a challenge for rehabilitation medicine – to explore further whether repeated use of postexposure spatial cues for partial report, within a 2–3 weeks training program, is likely to shorten the period where uneven distribution of attention exerts a deleterious effect on patients' progress in the rehabilitation process. The final goal of such a clinical research will be to assess whether amelioration of USN induced in this way is likely to generate to real-life situations and be accompanied by reduction of neglect-related disability.
Induction of focal changes in cortical excitability using electroencephalogram biofeedback – A promising new treatment for unilateral spatial neglect
Stroke patients with USN were shown to benefit from noninvasive neuromodulatory interventions (rTMS, tDCS) aimed to change the level of arousal in the parietal cortex. A good example for that is a work published by Sparing et al., where both, excitatory stimulation over the right parietal cortex (using anodal tDCS) and inhibitory stimulation over the left parietal cortex (using cathodal tDCS), were shown to induce a temporary amelioration in USN.
Electroencephalogram biofeedback (EEG-BF) is another means for induction of changes in cortical arousal, using the natural arousing capacity of the ascending reticular activating system (ARAS). Computer generated visual or auditory cues, triggered by the EEG activity of the trained person, indicate that his/her ongoing mental activity is or is not in the desired direction with respect to the goal set for the training.
Cortical regions adjacent to the area affected by stroke are usually the prime target for neuromodulatory interventions, whether using an external source acting transcranially (like rTMS or tDCS), or exploiting the intrinsic capacity of the ARAS, by way of EEG-BF. The reason for that is that adaptive structure-function remapping supporting functional recovery is accomplished usually by recruitment of a perilesional preserved synaptic space.
Neuromodulatory interventions aim to secure an adequate level of arousal in perilesional cortical regions, either by excitatory stimulation of these regions or by inhibitory stimulation of their homologous regions in the healthy hemisphere. The rationale for attempted downregulation of the healthy hemisphere is based on the concept of reciprocal interhemispheric inhibition becoming unbalanced following unilateral damage. It is assumed that downregulation of the healthy hemisphere releases the perilesional cortex from excessive inhibition exerted by the healthy hemisphere.
In the case of USN, there seems to be a specific interest in securing an adequate level of arousal in the dorsal regions of the posterior parietal cortex (PPC). These perilesional regions, which are part of the dorsal attention network (DAN), were found in an fMRI study to play a crucial role in recovery from USN. A change in intrahemispheric connectivity (between the right-sided DAN and the structurally-damaged right-sided VAN (ventral attention network) and a change in interhemispheric connectivity between the homologous right and left components of the DAN are assumed to take place in the recovery process.,
In a feasibility EEG-BF study recently completed, we trained RHD stroke patients with USN to increase the level of arousal in the right dorsal PPC regions. We used the ongoing β/θ ratio recorded from the P4 electrode for activation of the reward signal in the computer screen. There were ten daily sessions (30 min each) of EEG-BF training preceded and immediately followed by patients performing a short computerized visual-search task, done under EEG monitoring.
[Figure 9] shows the improvement obtained by eight USN patients following ten daily sessions of EEG-BF. As can be seen, all the patients manifested shortening of the reaction time to left-sided stimuli (in the SNT visual-search task mentioned previously) although the degree of improvement varied significantly.
|Figure 9: Percent improvement in reaction time to left-sided visual stimuli following 10 days of electroencephalogram biofeedback training, relative to baseline pretreatment performance. The group average improvement is 22.9% with two patients showing more than 30% improvement while one patient improved by only 6%|
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This feasibility study showed us that EEG-BF is able to influence the pattern of cerebral electrical activity and to improve neglect patients' ability to respond to left-sided stimuli. Therefore, we propose that EEG-BF is likely to become an effective tool in the rehabilitation treatment of this highly disabling condition. Yet, variant clinical response points to a need for careful analysis of the physiological response and of lesion characteristics in each patient, in an effort to delineate the factors determining the likelihood of benefit from this intervention.
| Concluding Remarks|| |
I chose to concentrate in the Sidney Licht Award Lecture on impairments of language use and of spatial attention, as expressed in aphasia and spatial neglect – two of the most disabling conditions encountered in stroke rehabilitation practice. The information provided here is derived largely from preliminary results of ongoing studies, which in my view point to promising new options for rehabilitation treatment. In these studies, as in almost all other research we do, we used four generic elements: lesion analysis: recognition of constraints imposed by lesion variance, using normalized lesion data to enable group statistics, and lesion analyses aimed to identify the target synaptic space for stimulation on an individual basis; function analysis: longitudinal testing of performance using reliable yet sensitive assessment tools, enabling discrimination between functional gains reflecting restoration of basic modular functions versus gains stemming from adoption of compensatory behavioral strategies. Neurophysiological analysis: EEG monitoring of the brain's immediate and persisting neurophysiological response to treatment, including the use of biomarkers based on quantitative EEG analysis. Control of confounding variables: for example, time after stroke onset, premorbid cognitive state, etc., and careful setting of inclusion/exclusion criteria for research. The combined use of these elements of assessment is recommended for clinical research targeting the rehabilitation of discrete brain functions.
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Conflicts of interest
There are no conflicts of interest.
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