Progressive supranuclear palsy with predominant frontal presentation exhibiting progressive nonfluent aphasia due to crossed aphasia.

Progressive supranuclear palsy (PSP) with predominant frontal presentation (PSP-F) is a clinical phenotype of PSP that is characterized by frontal cognitive impairment and behavioral changes. Here, we report on a patient with pathologically diagnosed PSP-F in whom we were able to observe temporal changes of the clinical manifestations. A 77-year-old right-handed man developed progressive nonfluent aphasia (PNFA) at the age of 69 years, festinating gait, and clumsiness of his left arm at age 75, disinhibition at age 76, and unprovoked falls at age 77. Neurological examination at age 77 revealed limb-kinetic apraxia of the left upper and lower limbs, rigidity, cortical sensory loss, and vertical supranuclear gaze palsy. According to the Movement Disorder Society clinical diagnostic criteria for PSP, his clinical manifestations shifted from suggestive PSP with predominant speech/language disorder to probable PSP-F over nine years. Cerebral atrophy on brain magnetic resonance imaging and decreased accumulation of 99m Tc-ECD on cerebral blood flow single-photon emission computed tomography were noted with right side predominance. Pathologically, 4-repeat tau-immunoreactive globose-type neurofibrillary tangles, coiled bodies, tufted astrocytes, and neuropil threads were observed predominantly in the frontal cortex. Tau pathology of the substantia nigra, locus coeruleus and subthalamic nucleus was mild. These findings suggested that localized tau pathology involving the pars opercularis extended to the precentral gyrus, prefrontal cortex, and brainstem. This case report demonstrates that PSP-F can present as a PNFA due to crossed aphasia.

[Crossed aphasia in neurosurgical practice: case report and literature review]. / Perekrestnaya afaziya (Crossed aphasia) v neirokhirurgicheskoi praktike: opisanie sluchaev i obzor literatury.

BACKGROUND: Crossed aphasia in dexstral (CAD) is an extremely rare disorder. To date, about 200 cases have been described in the literature. MATERIAL AND METHODS: The authors report 4 cases of CAD. Luria's neuropsychological examination was carried out. Functional asymmetry in the arm was analyzed using the Annett questionnaire. MRI and intraoperative findings confirmed localization of lesion in the right hemisphere in all patients. RESULTS: A 59-year-old right-handed man developed frontotemporal aphasia after previous resection of right-sided glioblastoma of fronto-insular-temporal region. In a 31-year-old right-handed man, crossed aphasia occurred after extensive hemorrhage from arteriovenous malformation into the right frontotemporoparietal region. A 39-year-old right-handed man developed severe combined aphasia after resection of diffuse glioma of the right insular-temporal region. A 10-year-old right-handed boy developed aphasia with word forgetting after resection of a large tumor of the right temporal lobe. All patients had impaired dynamic praxis. Other cognitive functions were intact. CONCLUSION: The authors discuss possible combinations of functions in one hemisphere for both right-handers and left-handers and emphasize diverse types of functional asymmetries described in the literature. Different localizations of functions in right-handers and left-handers indicate that local zones with different methods of information processing (successive or simultaneous) can coexist in one hemisphere. Therefore, the functions requiring different processing of information (for example, speech with praxis or spatial functions) can develop in one hemisphere. Cognitive impairment depends not only on the type of functional asymmetry, but also on localization of lesion. Crossed aphasia in right-handers indicates the rarest normal type of functional brain asymmetry with localization of speech functions in the right hemisphere. Possible aphasia in right-handers following damage to homologues of speech zones in the right hemisphere can require additional examination of these patients.

Recovery of language function in Korean-Japanese crossed bilingual aphasia following right basal ganglia hemorrhage.

Few studies have investigated language recovery patterns and the mechanisms of crossed bilingual aphasia following a subcortical stroke. In particular, Korean-Japanese crossed bilingual aphasia has not been reported. A 47-year-old, right-handed man was diagnosed with an extensive right basal ganglia hemorrhage. He was bilingual, fluent in both Korean and Japanese. After his stroke, the patient presented with crossed aphasia. We investigated changes in the Korean (L1) and Japanese (L2) language recovery patterns. Both Korean and Japanese versions of the Western Aphasia Battery (WAB) were completed one month after the stroke, and functional magnetic resonance imaging (fMRI) was performed using picture-naming tasks. The WAB showed a paradoxical pattern of bilingual aphasia, with an aphasia quotient (AQ) of 32 for Korean and 50.6 for Japanese, with Broca's aphasia. The patient scored better in the Japanese version of all domains of the tests. The fMRI study showed left lateralized activation in both language tasks, especially in the inferior frontal gyrus. After six months of language therapy targeting L1, the Korean-WAB score improved significantly, while the Japanese-WAB score showed slight improvement. In this case, the subcortical lesion contributed to crossed bilingual aphasia more highly affecting L1 due to loss of the cortico-subcortical control mechanism in the dominant hemisphere. The paradoxical pattern of bilingual aphasia disappeared after lengthy language therapy targeting L1, and the therapy effect did not transfer to L2. Language recovery in L1 might have been accomplished by reintegrating language networks, including the contralesional language homologue area in the left hemisphere.

Can Lesions in the Right Basal Ganglia Cause Aphasia? Crossed Aphasia in a Right-Handed Patient.

Background: Aphasia is a common neurocognitive disorder caused by impaired speech and language, with stroke being the most frequent cause. The neuroanatomical mechanism underlying this condition is not yet fully understood. Case description: This case describes a 74-year-old Caucasian woman admitted with a clinical picture of right total anterior circulation infarct (TACI) and aphasia, scoring 17 on the National Institutes of Health Stroke Scale. Neuroimaging showed a large cortico-subcortical frontotemporoparietal and insular infarct involving the basal ganglia of the right hemisphere and bilateral focal atherosclerotic stenosis on the M1 segment of the middle cerebral artery. There was no left hemispheric lesion or abnormal electric activity on the electroencephalogram. A formal evaluation was compatible with transcortical motor aphasia. The aetiological study revealed atrial fibrillation, and the case was admitted as an ischaemic stroke of undetermined aetiology with two possible causes - intracranial atherosclerotic stenosis or atrial fibrillation. Conclusion: Our patient fulfilled all the formal criteria for crossed aphasia in dextral (CAD): aphasia, a lesion in the right hemisphere coupled with the structural integrity of the left hemisphere, an established preference for right-hand use without a familial history of left-handedness individuals, and an absence of brain damage in childhood. Our patient's case adds to the evidence that deep structures - alone or in combination with cortical structures - are primarily affected in CAD. LEARNING POINTS: The diagnostic criteria for crossed aphasia in dextral (CAD) are derived from clinical case studies and include aphasia, a lesion in the right hemisphere, a strong preference for using the right hand, the structural integrity of the left hemisphere and no history of brain damage during childhood.The right lentiform nucleus was found to be the most frequent anatomical substrate involved in CAD patients, consistent with our case description.Our patient experienced transcortical motor aphasia due to a stroke in the right hemisphere, adding to the evidence that in CAD patients, deep structures are primarily affected. In contrast, in left hemispheric lesions, cortical structures seem to be the main culprits.

A Case of Mirror-Image Crossed Thalamic Aphasia With Jargon Agraphia.

In right-handed individuals, aphasia resulting from right hemisphere damage is termed crossed aphasia and has a very low occurrence rate. Additionally, aphasia due to thalamic lesions often involves hemorrhage, with infarction cases less frequently reported. We present the case of an 81-year-old right-handed female who developed aphasia due to a right thalamic infarction. She exhibited characteristics typical of thalamic aphasia observed in left thalamic lesions. Furthermore, jargon agraphia manifested during writing tasks. This may suggest disinhibition of the left hemisphere writing motor memory by the right hemisphere language function.

Neural substrate responsible for crossed aphasia.

Crossed aphasia (CA) refers to language impairment secondary to right hemisphere lesion. Imaging analysis on the lesion location of CA has not yet been reported in the literature. This study was proposed to analyze the most prevalent lesion site related to CA. Brain MRI of 7 stroke patients satisfying the criteria for CA were used to define Region of interest (ROIs) before overlaying the images to visualize the most overlapped area. Talairach coordinates for the most overlapped areas were converted to corresponding anatomical regions. Anatomical lesions where more than 3 patients' images were overlapped were considered significant. The overlayed ROIs of 7 patients revealed the lentiform nucleus as the most frequently involved area, overlapping in 6 patients. Our study first demonstrates the areas involved in CA by lesion mapping using brain MRI, and lentiform nucleus is the responsible neural substrate for crossed aphasia.

Patient With Crossed Aphasia Undergoing Long-Term Speech Therapy: A Case Report.

Crossed aphasia (CA) is a type of aphasia caused by cerebral hemispheric lesions on the same side of the dominant hand. The prevalence of CA is extremely rare. To the best of our knowledge, this is the first case report in Korea to conduct 6 years of long-term speech therapy in a case of a patient with CA. The patient was a 57-year-old right-handed man with aphasia caused by extensive acute infarction in the right middle cerebral artery territory. He presented with global aphasia, right-left disorientation, and agraphia. Language function recovered in the first 6 months and then plateaued.

[A case of crossed aphasia following infarction in the right anterior cerebral artery territory].

We report a patient presenting with crossed aphasia following infarction in the territory of the right anterior cerebral artery (ACA). A right-handed 68-year-old woman without a history of correction had acute disturbance of consciousness, left hemiparesis predominant in the lower extremity, speech disorder and left unilateral spatial neglect during the admission due to hypertensive emergency. No other family member was left-handed. MRI of the head revealed acute phase infarction in the territory of the right ACA: mesial frontal lobe including the supplementary motor area, anterior cingulate gyrus, and the corpus callosum. Language symptoms in the subacute phase included difficulty in initiation, slow speech rate, loss of intonation and phonetic paraphasia, and accompanying errors in comprehension, repetition, reading, and writing letters. These symptoms suggested "anomalous" type crossed aphasia. No limb apraxia, construction disorder or left unilateral spatial neglect was observed in this period. Only a few cases of crossed aphasia due to infarction in the territory of the ACA have been reported so far. However, language and concomitant symptoms differs, depending on each case, suggesting a difference in individual cerebral lateralization.

Crossed aphasia confirmed by fMRI in a case with nonfluent variant of primary progressive aphasia carrying a GRN mutation.

OBJECTIVES: To characterize patterns of language lateralization in a right-handed woman with nonfluent/agrammatic primary progressive aphasia (nfvPPA) clinical picture despite showing a prevalent right-sided brain damage. METHODS: We report a case of a 58-year-old woman with nfvPPA diagnosis (age at onset = 55) previously described as a crossed aphasia case with progranulin mutation. At 2 years from the first visit, patient underwent 3DT1-weighted and a task-based functional MRI (fMRI). During the fMRI task, she was asked to perform a letter fluency test as the task of interest and to count forward as the control condition. Image processing and data analysis were performed using SPM12 and the effect of each task was tested at p < 0.05 FWE corrected. RESULTS: The structural MRI confirmed a widespread right fronto-temporal atrophy mainly involving the right inferior frontal gyrus. During the letter fluency task, we observed an increased activation centered at the right inferior orbitofrontal gyrus and right middle frontal gyrus. By reducing the threshold, the pattern of functional activation was still dramatically prevalent at the right side. CONCLUSIONS: We provided evidence of the right language lateralization in a previously suspected crossed nfvPPA. Despite the long disease duration and the large amount of atrophy at the right side, there was no fMRI evidence of a left-hemisphere contribution to language function. We might speculate that compensatory effects do not appear when the premorbid language lateralization is purely right. The investigation of the underlying functional brain substrates in crossed nfvPPA cases may help understanding disease vulnerability in these neurodegenerative conditions.

High Frequency of Crossed Aphasia in Dextral in an Italian Cohort of Patients with Logopenic Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) has been described as a neurodegenerative language disorder mainly affecting the left hemisphere. Few cases of right hemisphere damage in right-handed PPA subjects have been reported. This condition, named crossed aphasia in dextral (CAD), is relatively rare and probably related to an alteration during neurodevelopment of language networks. OBJECTIVE: To explore the prevalence of CAD in an Italian cohort of 68 PPA patients, in order to evaluate whether right hemisphere language lateralization could be a risk factor for PPA. METHODS: Clinical-demographic and cerebral [18F]-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) scan were analyzed, resulting in 23 logopenic variant (lvPPA) patients, 26 non-fluent variant (nfvPPA) patients, and 19 semantic variant (svPPA) patients. SPM single subject routine was performed for diagnostic purposes in order to identify the hypometabolic pattern of each patient. Based on brain metabolic profile, PPA patients were divided in right and left lvPPA, nfvPPA, and svPPA. [18F]FDG-PET group analyses were performed with SPM two-sample t-test routine. RESULTS: 26% of lvPPA cases were identified as CAD based on right hypometabolic pattern. CAD patients did not differ from left lvPPA regarding demographic features and general cognitive performance; however, they performed better in specific working memory tasks and showed brain hypometabolism limited to the superior, middle, and supramarginal temporal gyri. CONCLUSION: Atypical lateralization of language function could determine a vulnerability of the phonological language loop and in that way could be a risk factor for lvPPA.

A Case of Crossed Logopenic Primary Progressive Aphasia in a Dextral Patient with Underlying Frontotemporal Dementia.

A 61-year-old dextral woman was admitted to the hospital with difficulty finding words. Neurological examinations confirmed that her speech was affected by frequent pauses and occasional phonological paraphasia without cognitive deficits. We detected atrophy, hypoperfusion, and hypometabolism in the right perisylvian and parietal regions, expanding to the right anterior temporal lobes and right inferior frontal gyrus (opercular region) by magnetic resonance imaging, single-photon emission computed tomography, and fluorodexyglucose-positron emission tomography (PET), respectively. Amyloid-PET did not identify the accumulation of amyloid beta (Aß) in the bilateral cerebral cortices. We herein report a case of crossed aphasia with Aß-negative logopenic primary progressive aphasia that was likely the result of frontotemporal lobar degeneration.

Crossed Aphasia as a Manifestation of Glioblastoma.

Language and speech function is commonly accepted to be a heavily lateralized function. Greater than 95% of right-handed individuals have left hemispheric dominance for language, and reports in the literature of crossed aphasia (language deficits in a right-handed individual from right-sided pathology) are scant. We report the case of a 52-year-old woman presenting with crossed aphasia from a right temporal glioblastoma. We then expand on a discussion of crossed aphasia in the setting of brain tumors.

Crossed aphasia following cerebral infarction in a right-handed patient with atypical cerebral language dominance.

OBJECTIVE: Crossed aphasia (CA), usually referred to as an acquired language disturbance, is caused by a lesion in the cerebral hemisphere ipsilateral to the dominant hand, and the exact mechanism is not clear. The development of handedness is influenced by education and training and the impact of habitualization, while language is more susceptible to the impact of speech habits, and it is not absolutely accurate to judge cerebral language dominance by the degree of hand preference. METHODS: We describe a case of CA after right hemispheric stroke in a right-handed patient with atypical language dominance and attempt to analyze the mechanism of CA based on functional imaging methods, including arterial spin labeling (ASL) and positron emission tomography/magnetic resonance imaging (PET-MRI). RESULTS: Brain MRI at 24 h after admission showed a large cerebral infarction in the right cerebral hemisphere, including the posteroinferior part of Broca's area in the right frontal lobe, the right temporal lobe, and the right occipital lobe. The patient exhibited a non-fluent aphasia on a standard language test (the Aphasia Battery of Chinese [ABC]) performed on the 7th day after onset. Thus, atypical language dominance was suspected. One week after admission, ASL imaging showed high perfusion in the infarct core zone and low perfusion in the left cerebellar hemisphere. Two months later, PET/MRI demonstrated low metabolism in the posterior frontal lobe, temporal lobe, temporal occipital junction area, and the right basal ganglia. CONCLUSION: The findings suggest that the patient has right-sided cerebral language dominance, or that both hemispheres have linguistic functions. Not all patients show linguistic capabilities on the side opposite hand preference. The language dominance should be predicted by a combination of clinical manifestations and functional imaging techniques.

Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts.

Donepezil (DP), a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014). Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia). A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day) which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy) during 8 weeks (Endpoint 1). Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR) during 3 months (Endpoint 2). Language evaluations, diffusion weighted imaging (DWI), and voxel-based morphometry (VBM) were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these tracts. In conclusion, cholinergic potentiation alone and combined with a model-based aphasia therapy improved language deficits by promoting structural plastic changes in right white matter tracts.

Unexpected Aphasia following Right Temporal Lobectomy as Treatment of Recurrent Super-Refractory Status Epilepticus.

BACKGROUND: Super-refractory status epilepticus (SRSE) is a critical neurological condition with a high mortality rate. There are only limited data to direct the treatment in SRSE, and surgery has been reported to successfully stop SRSE. We present a case of recurrent SRSE treated with urgent right temporal lobectomy in a right-handed woman which potentially saved her life but resulted in crossed sensory aphasia. CASE DESCRIPTION: A 61-year-old woman with a recent episode of prolonged focal SRSE due to right frontotemporal meningioma and hyperkalemia was admitted for recurrence of seizures that evolved to SRSE despite aggressive treatment with multiple fosphenytoin antiepileptic drugs (AEDs) and anesthetics. The patient underwent a right temporal lobectomy to remove the encephalomalacic and gliotic tissue around the meningioma that had been resected during a previous admission. Postoperatively the patient had a protracted course with modest improvement after stepwise reduction in her AEDs; however, her recovery unveiled a severe crossed aphasia. CONCLUSION: Resective surgery is an effective treatment option in the treatment of SRSE, although the recovery period can be protracted. Crossed aphasia after right temporal lobectomy should be considered in patients where it is not possible to complete a presurgical evaluation of higher cortical functions.

A Dextral Primary Progressive Aphasia Patient with Right Dominant Hypometabolism and Tau Accumulation and Left Dominant Amyloid Accumulation.

BACKGROUND: Primary progressive aphasia (PPA) is a degenerative disease that presents as progressive decline of language ability with preservation of other cognitive functions in the early stages. Three subtypes of PPA are known: progressive nonfluent aphasia, semantic dementia, and logopenic aphasia (LPA). PATIENTS AND METHODS: We report the case of a 77-year-old patient with PPA whose clinical findings did not correspond to the three subtypes but mainly fit LPA. Unlike other LPA patients, however, this patient showed a right hemisphere predominant glucose hypometabolism and tau accumulation and a left hemisphere predominant amyloid deposition. The right-handed patient presented with comprehension difficulty followed by problems naming familiar objects. This isolated language problem had deteriorated rapidly for 2 years, followed by memory difficulties and impairment of daily activities. Using a Korean version of the Western Aphasia Battery, aphasia was consistent with a severe form of Wernicke's aphasia. According to the brain magnetic resonance imaging and (18)F-fludeoxyglucose positron emission tomography results, right hemisphere atrophy and hypometabolism, more predominant on the right hemisphere than the left, were apparent despite the fact that Edinburgh Handedness Questionnaire scores indicated strong right-handedness. On Pittsburgh compound B-PET, amyloid accumulation was asymmetrical with the left hemisphere being more predominant than the right, whereas (18)F-T807-PET showed a right dominant tau accumulation. CONCLUSIONS: This is the first report of atypical PPA, in which the patient exhibited crossed aphasia and asymmetrical amyloid accumulation.

18F-FDG PET/CT and functional MRI in a case of crossed logopenic primary progressive aphasia. / 18F-FDG PET/TC y RM funcional en un caso de afasia progresiva primaria logopénica cruzada.

Primary progressive aphasia is a clinical syndrome caused by a neurodegeneration of areas and neural networks involved in language, usually in the left hemisphere. The term "crossed aphasia" denotes an acquired language dysfunction caused by a lesion in the hemisphere ipsilateral to the dominant hand. A case is presented on a 75-year-old right-handed woman with a logopenic variant of primary progressive aphasia with word-finding difficulties of 2 years onset. The 18F-FDG PET/CT showed right temporoparietal hypometabolism. A functional MRI scan was performed during a verb naming task in order to characterise language lateralisation patterns. A similar activation pattern was observed in both hemispheres, with less activation than expected in bilateral inferior frontal gyrus. These findings support that logopenic variant of primary progressive aphasia should not be considered as a neurodegeneration starting in the left brain hemisphere, but as a syndrome characterised by asymmetric neurodegeneration of brain regions and neural networks involved in language.

A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary progressive aphasia.

Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca's area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype.

Crossed aphasia in a dextral without "minor" hemisphere signs.

A case of severe aphasia after right hemisphere stroke, confirmed by CT, in an unambiguously dextral patient is reported. The patient showed no limb apraxia, and performed well on a test of "closure" (Mooney faces). Extensive testing revealed no signs of visuo-spatial neglect. We conclude that "pure" crossed aphasia can occur in the absence of symptoms normally associated with right hemisphere lesions.

Improvement of white matter and functional connectivity abnormalities by repetitive transcranial magnetic stimulation in crossed aphasia in dextral.

As a special aphasia, the occurrence of crossed aphasia in dextral (CAD) is unusual. This study aims to improve the language ability by applying 1 Hz repetitive transcranial magnetic stimulation (rTMS). We studied multiple modality imaging of structural connectivity (diffusion tensor imaging), functional connectivity (resting fMRI), PET, and neurolinguistic analysis on a patient with CAD. Furthermore, we applied rTMS of 1 Hz for 40 times and observed the language function improvement. The results indicated that a significantly reduced structural and function connectivity was found in DTI and fMRI data compared with the control. The PET imaging showed hypo-metabolism in right hemisphere and left cerebellum. In conclusion, one of the mechanisms of CAD is that right hemisphere is the language dominance. Stimulating left Wernicke area could improve auditory comprehension, stimulating left Broca's area could enhance expression, and the results outlasted 6 months by 1 Hz rTMS balancing the excitability inter-hemisphere in CAD.