Efficacy and limitation of cognitive rehabilitation]

The "higher brain dysfunction" illustrates various cognitive and behavioral consequences resulted from organic brain damage. Individually-tailored cognitive rehabilitation aims to directly and explicitly ameliorate disability of people with higher brain dysfunction. In this symposium, the efficacy and limitation of cognitive rehabilitation was discussed with particular interest in the two cognitive domains, i.e., language and memory. In the realm of aphasia rehabilitation, two mechanisms have been postulated for language restitution following aphasia: 1) partial recovery of left-hemisphere language-related areas, and 2) activation of their homologous counterparts in the right hemisphere. Although the both hemispheres may eventually contribute for functional reorganization of the language network, recent functional imaging studies of aphasic patients have demonstrated that the residual left hemisphere is primarily important for aphasia recovery. A recently presented hypothesis was described in which suppressing the right hemisphere may lead to better aphasia recovery. It is now widely accepted in the field of memory rehabilitation for individuals with amnesia/dementia that the theoretical framework of "errorless learning" is a guiding principle. Error elimination during learning is essential for favorable outcome of memory training. We should be aware of functional organization of the brain which underlies the efficacy of cognitive rehabilitation.     

Differential functional magnetic resonance imaging language activation in twins discordant for a left frontal tumor

Eight-year-old twins, one with a left frontal tumor and aphasic seizures, the other neurologically normal, underwent serial assessment of expressive language with functional magnetic resonance imaging and neuropsychology. The affected twin showed a significant amount of right hemisphere activation coincident with behavioral deterioration in expressive language and late growth in the tumor. This pattern of language dysfunction and the left language dominance of her co-twin suggested that the affected twin was also left dominant for language, and the significance of her right activation is discussed. We postulate that the right hemisphere activation represents a stabilizing mechanism in the context of a developmental and progressive lesion in language cortex rather than language transfer per se.     

Cortical language activation in stroke patients recovering from aphasia with functional MRI.

BACKGROUND AND PURPOSE: Two mechanisms for recovery from aphasia, repair of damaged language networks and activation of compensatory areas, have been proposed. In this study, we investigated whether both mechanisms or one instead of the other take place in the brain of recovered aphasic patients. METHODS: Using blood oxygenation level-dependent functional MRI (fMRI), we studied cortical language networks during lexical-semantic processing tasks in 7 right-handed aphasic patients at least 5 months after the onset of left-hemisphere stroke and had regained substantial language functions since then. RESULTS: We found that in the recovered aphasic patient group, functional language activity significantly increased in the right hemisphere and nonsignificantly decreased in the left hemisphere compared with that in the normal group. Bilateral language networks resulted from partial restitution of damaged functions in the left hemisphere and activation of compensated (or recruited) areas in the right hemisphere. Failure to restore any language function in the left hemisphere led to predominantly right hemispheric networks in some individuals. However, better language recovery, at least for lexical-semantic processing, was observed in individuals who had bilateral rather than right hemisphere-predominant networks. CONCLUSIONS: The results indicate that the restoration of left-hemisphere language networks is associated with better recovery and inversely related to activity in the compensated or recruited areas of the right hemisphere.     

Hemispheric asymmetries in cerebral cortical networks

Since the middle of the 19th century it has been recognized that several higher cognitive functions, including language, are lateralized in cerebral cortex. Neuropsychological studies on patients with brain lesions and rapid developments in brain imaging techniques have provided us with an increasing body of data on the functional aspects of language lateralization, but little is known about the substrate on which these specializations are realized. Much attention has been focused on the gross size and shape of cortical regions involved, but recent findings indicate that the columnar and connectional structure within auditory and language cortex in the left hemisphere are distinct from those in homotopic regions in the right hemisphere. These findings concern parameters that are closely linked to the processing architecture within the respective regions. Thus, the comparison of these microanatomical specializations with their respective functional counterparts provides important insights into the functional role of cerebral cortical organization and its consequences for processing of cortical information in the implementation of complex cognitive functions.     

Mechanisms of aphasia recovery and brain imaging]

Aphasia recovery may depend on right hemisphere or non-lesioned left hemisphere structures, pre-morbid brain language organization, and de novo learning of language. Here we review the brain imaging evidence supporting these different hypotheses. CT-scan studies have investigated the prognosis value of size and site of left hemisphere lesions. The size of the lesion is a global but not an individual predictor of the initial severity and subsequent recovery of aphasia. Studies on the site of the lesion have given different results for verbal expression and comprehension. There is no consensus on a single critical site for recovery of verbal expression in non-fluent aphasia, which may depend on sub-cortical more than cortical extend of the lesion. Conversely the extend of the lesion in the superior temporal gyrus emerges as a critical negative factor for comprehension recovery. Rest measurements of brain metabolism have consistently shown that aphasia severity depends much more on the degree of dysfunction of language-related areas in the left hemisphere than on the site of the lesion it-self. This suggests that aphasia recovery may depend on metabolic dysfunction recovery in peri-lesional structures. More recently, activation studies have shown consistent right hemisphere activation during language tasks in aphasic subjects, but their role in recovery remains debated. It is likely limited, and may depend on atypical pre-morbid language lateralization. Left hemisphere activations are also found in aphasic patients. They are often relocalized in peri-lesional areas, and emerge in most studies as the main factor of aphasia recovery.     

Atypical hemispheric dominance for attention: functional MRI topography.

The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention.     

Recovery from wernicke's aphasia: A positron emission tomographic study

Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke.     

Neural networks for sentence comprehension and production: An ALE‐based meta‐analysis of neuroimaging studies

Comprehending and producing sentences is a complex endeavor requiring the coordinated activity of multiple brain regions. We examined three issues related to the brain networks underlying sentence comprehension and production in healthy individuals: First, which regions are recruited for sentence comprehension and sentence production? Second, are there differences for auditory sentence comprehension vs. visual sentence comprehension? Third, which regions are specifically recruited for the comprehension of syntactically complex sentences? Results from activation likelihood estimation (ALE) analyses (from 45 studies) implicated a sentence comprehension network occupying bilateral frontal and temporal lobe regions. Regions implicated in production (from 15 studies) overlapped with the set of regions associated with sentence comprehension in the left hemisphere, but did not include inferior frontal cortex, and did not extend to the right hemisphere. Modality differences between auditory and visual sentence comprehension were found principally in the temporal lobes. Results from the analysis of complex syntax (from 37 studies) showed engagement of left inferior frontal and posterior temporal regions, as well as the right insula. The involvement of the right hemisphere in the comprehension of these structures has potentially important implications for language treatment and recovery in individuals with agrammatic aphasia following left hemisphere brain damage.     

Localization of language function in the brain

Since the first report of an aphasic patient by Paul Broca, the localization of brain function has been disputed for 150 years. In lesion studies, double dissociation has been a key concept to show the localization of particular cognitive functions. The advancement of non-invasive brain imaging methods enables us to investigate the brain activities under well-controlled conditions, further promoting the studies on the localization of the cognitive functions, including language function. Brain imaging studies, together with subtraction and correlation analyses, have accumulated evidence that syntax, phonology, and sentence comprehension are separately processed by modules in different cortical regions. More specifically, it has been clarified that the module for syntax localizes in the left lateral premotor cortex and the opercular/triangular parts of the left inferior frontal gyrus. This modular structure further suggests that aphasia is interpreted as deficits in either syntactic or phonological processing. Therefore, the classical model of contrasting speech production and comprehension should be updated. According to theoretical linguistics, on the other hand, the recursive computation of syntactic structures is an essential feature of human language faculty. One direction of research would be to contrast human beings and animals for the abilities of processing symbolic sequences. Another direction is to clarify that the human brain is indeed specialized in language processing, which can be revealed by well-controlled language tasks and functional imaging techniques. Here we will review recent studies that demonstrate the existence of grammar center in the left frontal cortex. The future studies in the neuroscience of language will eventually elucidate the cortical localization of language function in a more precise way, i.e., what is really computed in the human brain.     

Cerebral Processing of Timbre and Loudness: fMRI Evidence for a Contribution of Broca’s Area to Basic Auditory Discrimination

Sound timbre and sound volume processing are basic auditory discrimination processes relevant for human language abilities. Regarding lateralization effects, the prevailing hypotheses ascribe timbre processing to the right hemisphere (RH). Recent experiments also point to a role of the RH for volume discrimination. We investigated the relevance of the RH for timbre and volume processing, aiming at finding possible differences in cerebral representation of these acoustic parameters. Seventeen healthy subjects performed two auditory discrimination tasks on tone pairs, differing either in timbre or volume. FMRI was performed using an EPI-sequence on a 1.5 T scanner. Hemodynamic responses emerged in both tasks within a bilateral network of areas, including cingulate and cerebellum, peaking in primary and secondary auditory cortices (core and belt areas). Laterality analyses revealed a significant leftward dominance at the temporal cortex. Task comparison revealed significant activation within Broca’s area during the timbre task and a trend for an increase of right parietal responses during volume processing. These results contribute to a more differentiated view of timbre processing. Additionally to the engagement of the right temporal cortex during processing of musical timbre, there seem to be language related aspects of timbre that are preferentially processed in the left hemisphere. These findings are discussed within the framework of a model of timbre perception comprising two differentially lateralized subprocesses. Processing of spectral cues (harmonic structure) linked to the right hemisphere and processing of temporal cues (i.e. attack-decay dynamics) linked to the left hemisphere. Moreover, activation of Broca’s area linked to the timbre task indicates a participation of this area in discriminating phonetic changes of the vowel-like non-speech signals, encouraging the argument that basic acoustic cue processing at a pre- or non-speech level is represented within this “classical language area.”     

Comparison of the neural basis for imagined writing and drawing

Drawing and writing are complex processes that require the synchronization of cognition, language, and perceptual-motor skills. Drawing and writing have both been utilized in the treatment of aphasia to improve communication. Recent research suggests that the act of drawing an object facilitated naming, whereas writing the word diminished accurate naming in individuals with aphasia. However, the relationship between object drawing and subsequent phonological output is unclear. Although the right hemisphere is characteristically mute, there is evidence from split-brain research that the right hemisphere can integrate pictures and words, likely via a semantic network. We hypothesized that drawing activates right hemispheric and left perilesional regions that are spared in aphasic individuals and may contribute to semantic activation that supports naming. Eleven right-handed subjects participated in a functional MRI (fMRI) experiment involving imagined drawing and writing and 6 of the 11 subjects participated in a second fMRI experiment involving actual writing and drawing. Drawing and writing produced very similar group activation maps including activation bilaterally in the premotor, inferior frontal, posterior inferior temporal, and parietal areas. The comparison of drawing vs. writing revealed significant differences between the conditions in areas of the brain known for language processing. The direct comparison between drawing and writing revealed greater right hemisphere activation for drawing in language areas such as Brodmann area (BA) 46 and BA 37.     

Right Hemisphere Recruitment During Language Processing in Frontotemporal Lobar Degeneration and Alzheimer’s Disease

Right hemisphere recruitment of areas homotopical to affected left-sided language areas has classically been described in aphasia following stroke or brain tumors. It may also be a clinically significant mechanism in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). In a pooled analysis of previous functional magnetic resonance imaging studies of a modified version of the Pyramids and Palm Trees test, we probed the language network in 19 patients with primary progressive aphasia (nine semantic (SV) and ten agrammatic variant; neuropathologically confirmed FTLD in three cases to date), 15 patients with AD (14 clinically probable and one neuropathologically definite AD to date), and 37 healthy controls. The upper and lower bank of the left posterior superior temporal sulcus (STS) was affected in AD and the left anterior temporal pole (ATP) in primary progressive aphasia (PPA; mainly driven by SV). In the right hemisphere, the posterior STS showed an activity increase in both patient groups compared with controls. In AD, this activity increase correlated positively with naming accuracy. Both in AD and in PPA, the connection strength between right STS and right ATP was decreased compared with controls and this correlated with naming and comprehension scores, respectively. Only in PPA did the right anterior temporal pole show an activity increase, which correlated negatively with comprehension. Right-hemispheric recruitment and disconnections within the right temporal lobe may affect the degree of aphasia in cortical neurodegenerative disease.     

Crossed cerebro-cerebellar language dominance

In addition to its traditional role in motor control, the cerebellum has been implicated in various cognitive and linguistic functions. Lesion, anatomic, and functional imaging studies indicate a link between left frontal language regions and the right cerebellum. To probe the specificity of this circuit, we examined the association between language-related lateralized activation of the frontal cortex with lateralized activation of the cerebellum. Functional magnetic resonance imaging (fMRI) was carried out during letter-cued word generation in 14 healthy subjects: 7 subjects displayed typical left-hemisphere and 7 subjects displayed atypical right-hemisphere language dominance. We found activation of the cerebellar hemisphere contralateral to the language-dominant cerebral hemisphere in each subject. The cerebellar activation was confined to the lateral posterior cerebellar hemisphere (lobule VI, VII B, Cr I, Cr II). This study demonstrates that crossed cerebral and cerebellar language dominance is a typical characteristic of brain organization. The functional significance of the reported activations can now be tested in patients with lesions of the lateral posterior cerebellum.     

The contribution of the left and right hemispheres to early recovery from aphasia: A SPECT prospective study

This prospective study examined the relationship between post-stroke recovery of aphasia and changes in cerebral blood flow (CBF). To address the question of right hemisphere (RH) involvement in restitution of language, we tested the hypothesis that the increase in perfusion of the RH is crucial for early recovery from aphasia. Twenty-four right-handed patients with acute aphasia following left hemisphere (LH) ischaemic stroke were examined twice with a six-month interval. At each session CBF and language scores were measured on the same stroke patients. Language was measured by selected tasks derived from the Boston Diagnostic Aphasia Examination (BDAE). The SPECT scans were obtained using ^99mTc-ECD on a triple-head gamma camera Multispect-3. Although initial CBF measured for the whole group of aphasic patients was not a predictor for future language recovery for either hemisphere, increased perfusion of the RH during a six-month interval was found to parallel the recovery of aphasic disorders. There was a correlation between the change in the right parietal CBF (but not the left) and a change in numerous language abilities. Nevertheless, only CBF values on the left predicted performance on the language tests at initial and follow-up examinations. When the area damaged on structural imaging was excluded from perfusion analysis, only subcortical CBF change on the left showed a positive correlation with language improvement. Thus, the cerebral mechanism associated with early recovery from aphasia is a dynamic and complex process that may involve both hemispheres. Probably this mechanism involves functional reorganisation in the speech-dominant (damaged) hemisphere and regression of haemodynamic disturbances in the non-dominant (structurally intact) hemisphere.     

The right hemisphere language]

A large number of observations since the mid-nineteenth century have shown that damage to the left but not the right hemisphere destroys language function. These observations lead to the formation of the "classic" view that the left hemisphere has language function but not the right hemisphere. It thus came as a considerable surprise in the early 1960's when tests on commissurotomy or split-brain patients suggested the presence of a considerable capacity for reading comprehension in the right hemisphere. It has been suggested that the spared regions in the left hemisphere normally act to prevent the expression of latent language functions within the undamaged right hemisphere. Thus, only after the intact right hemisphere has been released from the disruptive and suppressive influences of the damaged left hemisphere by section of the corpus callosum, can its own residual function become effective. Some investigators have argued, however, that the split-brain evidence is misleading because the language of the split-brain patients is presented in both hemispheres even pre-operatively. Our investigation with functional MRI is in progress to decide which hypothesis is appropriate. In addition to the functional MRI study of split-brain patient, the functional MRI study of aphasia recovery will also provide opportunities to clarify the right hemisphere language function since the right hemisphere is generally intact in the right-handed aphasic.     

Cortical stimulation mapping and Wada results demonstrate a normal variant of right hemisphere language organization

Purpose: Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed in such patients, as most undergo nondominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathologic process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Furthermore, these data confirm the Wada test findings of atypical dominance. Methods: Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our center between 1974 and 2006. Of 1,209 interpretable Wada procedures, 89 patients (7.4%) had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients. Key Findings: Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus, all of which were common zones where language was identified in the left hemisphere dominant comparison sample. Significance: Results suggest that the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding right hemisphere language sites), and that the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization.     

The contribution of the left and right hemispheres to early recovery from aphasia: a SPECT prospective study

This prospective study examined the relationship between post-stroke recovery of aphasia and changes in cerebral blood flow (CBF). To address the question of right hemisphere (RH) involvement in restitution of language, we tested the hypothesis that the increase in perfusion of the RH is crucial for early recovery from aphasia. Twenty-four right-handed patients with acute aphasia following left hemisphere (LH) ischaemic stroke were examined twice with a six-month interval. At each session CBF and language scores were measured on the same stroke patients. Language was measured by selected tasks derived from the Boston Diagnostic Aphasia Examination (BDAE). The SPECT scans were obtained using (99m)Tc-ECD on a triple-head gamma camera Multispect-3. Although initial CBF measured for the whole group of aphasic patients was not a predictor for future language recovery for either hemisphere, increased perfusion of the RH during a six-month interval was found to parallel the recovery of aphasic disorders. There was a correlation between the change in the right parietal CBF (but not the left) and a change in numerous language abilities. Nevertheless, only CBF values on the left predicted performance on the language tests at initial and follow-up examinations. When the area damaged on structural imaging was excluded from perfusion analysis, only subcortical CBF change on the left showed a positive correlation with language improvement. Thus, the cerebral mechanism associated with early recovery from aphasia is a dynamic and complex process that may involve both hemispheres. Probably this mechanism involves functional reorganisation in the speech-dominant (damaged) hemisphere and regression of haemodynamic disturbances in the non-dominant (structurally intact) hemisphere.     

Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia

As previous functional neuroimaging studies could not settle the controversy regarding the contribution of dominant and subdominant hemisphere to recovery from poststroke aphasia, language performance was related to H2(15)O-positron emission tomographic activation patterns in 23 right-handed aphasic patients 2 and 8 weeks after stroke. In patients classified according to the site of lesion (frontal, n = 7; subcortical, n = 9; temporal, n = 7) and in 11 control subjects, flow changes caused by a word repetition task were calculated in 14 regions representing eloquent and contralateral homotopic areas. These areas were defined on coregistered magnetic resonance imaging scans and tested for significance (Bonferroni corrected t test, alpha = 0.0036). At baseline, differences in test performance were only found between the subcortical and temporal group. The extent of recovery, however, differed and was reflected in the activation. The subcortical and frontal groups improved substantially; they activated the right inferior frontal gyrus and the right superior temporal gyrus (STG) at baseline and regained left STG activation at follow-up. The temporal group improved only in word comprehension; it activated the left Broca area and supplementary motor areas at baseline and the precentral gyrus bilaterally as well as the right STG at follow-up, but could not reactivate the left STG. These differential activation patterns suggest a hierarchy within the language-related network regarding effectiveness for improvement of aphasia; ie, right hemispheric areas contribute, if left hemispheric regions are destroyed. Efficient restoration of language is usually only achieved if left temporal areas are preserved and can be reintegrated into the functional network.     

100例脑卒中患者利手与语言优势半球关系的研究

选择１９８８年５月～１９９６年８月经头颅ＣＴ证实为单侧脑卒中且病灶波及语言相关区的病人１００例，在发病２周内进行失语检查，要求患者接受检查时神志清楚，定向力及记忆力好，无智能障碍，既往无脑病疾病史，其检测结果，左脑病变８０例中，有６６例失语；右脑病变２０例中，仅４例失语。经统计学处理差别有高度显著性，说明中国人左脑和右脑均可能控制语言，语言优势侧多在左侧，同时发现，右利手中，６８例左脑病变者有５８     

低级别胶质瘤患者语言相关脑区神经网络的顺应性

Because functional magnetic resonance imaging can be used for dynamic observation of functional cortical changes after brain injuries,we followed up functional magnetic resonance imaging manifestations of a language-related brain network in a low-grade glioma patient.Disease progression and therapy during a 3-year period were followed up at different time points:before and after reoperation,after radiation therapy,and 1 year after irradiation.During the whole 3-year follow-up period,the patient exhibited no neurological deficits while functional magnetic resonance imaging revealed different topologies of the language-related brain network.During disease progression and after irradiation,the language-related brain network was extended or completely transferred to the nondominant (right) hemisphere.In addition,after reoperation and 1 year after irradiation,language areas were primarily found in the language dominant (left) hemisphere.Our results suggest a high level of adaptability of the language-related cortical network of the bilateral hemispheres in this low-grade glioma patient.