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.     

Mixed language dominance: insights from a case of unexpected fluent aphasia with semantic jargon resulting from massive left perisylvian lesion

We report a right-handed patient with a massive lesion in left perisylvian language cortex, who unexpectedly presented with fluent aphasia with semantic jargon. Language deficits were assessed with a comprehensive battery of language tests. Comprehension, naming, reading, and writing were severely impaired, and verbal expression was moderately fluent with semantic jargon. Although the patient’s lesion included brain areas typically essential for motor speech coordination, he was neither nonfluent nor apraxic. He exhibited strikingly unexpected aphasia with semantic jargon and prominent comprehension deficits, suggesting that this is a case of mixed dominance: the right hemisphere likely controls motor speech and basic syntactic skills, while the severely damaged left hemisphere controls semantic processing, predictably severely impaired.     

The right hemisphere is not unitary in its role in aphasia recovery

Neurologists and aphasiologists have debated for over a century whether right hemisphere recruitment facilitates or impedes recovery from aphasia. Here we present a well-characterized patient with sequential left and right hemisphere strokes whose case substantially informs this debate. A 72-year-old woman with chronic nonfluent aphasia was enrolled in a trial of transcranial magnetic stimulation (TMS). She underwent 10 daily sessions of inhibitory TMS to the right pars triangularis. Brain activity was measured during picture naming using functional magnetic resonance imaging (fMRI) prior to TMS exposure and before and after TMS on the first day of treatment. Language and cognition were tested behaviorally three times prior to treatment, and at 2 and 6 months afterward. Inhibitory TMS to the right pars triangularis induced immediate improvement in naming, which was sustained 2 months later. fMRI confirmed a local reduction in activity at the TMS target, without expected increased activity in corresponding left hemisphere areas. Three months after TMS, the patient suffered a right hemisphere ischemic stroke, resulting in worsening of aphasia without other clinical deficits. Behavioral testing 3 months later confirmed that language function was impacted more than other cognitive domains. The paradoxical effects of inhibitory TMS and the stroke to the right hemisphere demonstrate that even within a single patient, involvement of some right hemisphere areas may support recovery, while others interfere. The behavioral evidence confirms that compensatory reorganization occurred within the right hemisphere after the original stroke. No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based.     

Neural correlates of phonological and semantic-based anomia treatment in aphasia

Most naming treatments in aphasia either assume a phonological or semantic emphasis or a combination thereof. However, it is unclear whether semantic or phonological treatments recruit the same or different cortical areas in chronic aphasia. Employing three persons with aphasia, two of whom were non-fluent, the present study compared changes in neural recruitment associated with phonologic and semantic-based naming treatments. The participants with non-fluent aphasia were able to name more items following both treatment approaches. Although this was not the case for the participant who had fluent aphasia, her naming errors decreased considerably following treatment. Post-treatment fMRI revealed similar changes in neural activity bilaterally in the precuneus among the two non-fluent participants--increased activity was noted in the right entorhinal cortex and posterior thalamus on post-treatment scans for the third participant. These findings imply that cortical areas not traditionally related to language processing may support anomia recovery in some patients with chronic aphasia.     

Task-dependent changes in brain activation following therapy for nonfluent aphasia: discussion of two individual cases.

The complex process of cortical reorganization of language-related brain regions during recovery from aphasia and the effects of therapeutic interventions on brain systems are poorly understood. We studied two patients with chronic aphasia and compared their functional neuroanatomical responses to a younger control group on two tasks, an oral-reading task involving overt speech and a "passive" audiovisual story-comprehension task. Following identical therapy, we re-examined behavioral (language) and functional neuroanatomical changes using the same functional magnetic resonance imaging (fMRI) tasks. We hypothesized that better recovery would be associated with brain activation patterns more closely resembling healthy controls, whereas positive responses to language treatment would be associated with increased activity in undamaged left perisylvian areas and/or right-hemisphere areas homologous to the damaged regions. For the participant with a frontal lesion who was most responsive to therapy, brain activation increased in the right hemisphere during oral-reading, but decreased bilaterally in most regions on story-comprehension. The other participant with a temporal-parietal lesion showed decreased activation, particularly in the right hemisphere, during oral-reading but increased activation bilaterally on story-comprehension. Results highlight individual variability following language therapy, with brain activation changes depending on lesion site and size, language skill, type of intervention, and the nature of the fMRI task.     

Functional activation independently contributes to naming ability and relates to lesion site in post‐stroke aphasia

Language network reorganization in aphasia may depend on the degree of damage in critical language areas, making it difficult to determine how reorganization impacts performance. Prior studies on remapping of function in aphasia have not accounted for the location of the lesion relative to critical language areas. They rectified this problem by using a multimodal approach, combining multivariate lesion‐symptom mapping and fMRI in chronic aphasia to understand the independent contributions to naming performance of the lesion and the activity in both hemispheres. Activity was examined during two stages of naming: covert retrieval, and overt articulation. Regions of interest were drawn based on over‐ and under‐activation, and in areas where activity had a bivariate relationship with naming. Regressions then tested whether activation of these regions predicted naming ability, while controlling for lesion size and damage in critical left hemisphere naming areas, as determined by lesion‐symptom mapping. Engagement of the right superior temporal sulcus (STS) and disengagement of the left dorsal pars opercularis (dPOp) during overt naming was associated with better than predicted naming performance. Lesions in the left STS prevented right STS engagement and resulted in persistent left dPOp activation. In summary, changes in activity during overt articulation independently relate to naming outcomes, controlling for stroke severity. Successful remapping relates to network disruptions that depend on the location of the lesion in the left hemisphere. Hum Brain Mapp 38:2051–2066, 2017. © 2017 Wiley Periodicals, Inc.     

Diagnostic criteria for fronto-temporal lobe degeneration

Circumscribed atrophy of the frontal and temporal lobes (frontotemporal lobar degeneration) accounts for about one fifth of cases of primary degenerative dementia occurring before the age of 65. It produces three prototypical clinical syndromes. The most common is frontotemporal dementia, characterized by personality change and profound alteration in social conduct and associated with bilateral atrophy of the frontal and anterior temporal lobes. Progressive non-fluent aphasia is characterized by difficulty in verbal expression, anomia and phonemic errors in the presence of relative preservation of comprehension and associated with atrophy predominantly of the left hemisphere. In semantic dementia there is fluent speech with semantic errors and severely impaired comprehension and naming, together with a visual associative agnosia, resulting from bilateral atrophy of the inferior and middle temporal gyri. The clinical syndromes occur with either of two main histological types: prominent microvacuolar change, without specific histological features (frontal lobe degeneration-type), severe astrocytic gliosis with or without ballooned cells and inclusion bodies (Pick-type). To improve clinical recognition and advance understanding of this relatively common form of cerebral degeneration, members of an international workshop on Frontotemporal Lobar Degeneration developed consensus criteria, building upon earlier published clinical diagnostic guidelines for frontotemporal dementia. The consensus criteria reported here specify core and supportive features for each of the prototypical clinical syndromes: frontotemporal dementia, progressive aphasia and semantic dementia, as well as providing broad inclusion and exclusion criteria for the generic entity of frontotemporal lobar degeneration.     

命名性失语与命名障碍16例分析

本文对１６例首发单灶脑病变患者进行了一般命名、颜色命名和失语检查，发现失语患者１０例，另外６例无明显失语。分析结果表明：命名性失语与其它类型失语的命名障碍各有特点，两者为两种不同的概念。一般命名和颜色命名各自有其独立的脑部解剖联系和发生机制，大脑半球不同部位的损害，可产生具有相应特点的命名障碍。     

Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients

Summary Twenty-six aphasic patients who had an ischaemic infarct in the territory of the left middle cerebral artery (MCA) were investigated. Cranial computed tomography (CT) showed various lesion sites: infarcts restricted to cortical structures in 12 patients, combined cortical and subcortical infarcts in 7 and isolated subcortical infarcts sparing the left cortex in another 7 cases. ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography revealed remote hypometabolism of the left convexity cortex and of the left basal ganglia, which was extended further than the morphological infarct zone in all cases. Types and degrees of aphasia were classified using the Aachener Aphasie Test (AAT): 10 patients had global aphasia, 2 Broca's, 5 Wernicke's, and 5 amnesic aphasia. Four patients suffered from minimal or residual aphasic symptoms. The AAT results were compared with the regional cerebral metabolic rates of glucose of the left hemisphere. Irrespective of the infarct location all five AAT subtests (Token test, repetition, written language, confrontation naming, auditory and reading comprehension) were closely correlated among each other and with left parieto-temporal metabolic rates, whereas left frontal and left basal ganglia metabolism showed no significant correlation. The close relation between left temporo-parietal functional activity and all five AAT subtests suggests that the different aspects of aphasia tested by AAT can be related to a common disorder of language processing in those areas.     

Therapy-induced neuroplasticity in chronic aphasia

Research on the neural substrate of aphasia recovery has consistently increased since the advent of functional neuroimaging. The evidence from therapy-induced aphasia recovery studies shows that better recovery results from the reactivation of left hemisphere function; still, the specific left hemisphere key areas that sign successful outcome with a specific therapy approach remain to be identified. Nine participants suffering from aphasia received brief and intensive therapy with Semantic Feature Analysis (SFA). Behavioural and neuroimaging data during overt picture naming were obtained prior to and after therapy. This paper reports on a group of participants having benefited from SFA, and two distinct patterns of improvement. Correlational analysis showed that differences in outcome were not related to lesion size, but were negatively correlated with damage to Broca's area (BA45). Moreover, a group analysis showed that therapy-induced recovery following SFA was characterized by (a) a significant correlation between improvement and activation in the left precentral gyrus (BA4/6) before therapy, and (b) the recruitment of the left inferior parietal lobule, an area known for its role in semantic integration, following therapy with SFA. Individual fMRI analyses showed that although adaptive brain plasticity appeared to operate differently in each patient, best responders to SFA therapy recruited less areas after training compared to participants having shown less recovery who showed a larger number of activated areas sustaining recovery. The results of the present study suggest that a significant activation of BA4/6 could indicate the use of SFA to achieve successful outcome. Also our results suggest that greater SFA improvement in chronic aphasia is associated with recruitment of areas in the left hemisphere.     

Motor speech disorder after removal of a glioblastoma in the left hemisphere: Cortical disorder or apraxia?

A 38-year-old male patient with a deep central parietal lesion in the left hemisphere reveals a motor speech disorder but no aphasia as evidenced by linguistic testing with the Aachener Aphasietest. Nuclear magnetic resonance tomography of the brain shows no lesion of the brainstem. Whether the speech disorder can be termed cortical dysarthria or apraxia of speech is left open to discussion.     

Intensive semantic intervention in fluent aphasia: A pilot study with fMRI

Background : This pilot study presents a method of rehabilitation based on the assumption that there is a widely distributed neural network that supports semantic processing and that can be used to improve word retrieval without explicit naming. It employs functional imaging to help understand the neural basis of response to treatment. Aims : There are both behavioural and neural questions. First, this study investigates whether intensive therapy designed to reduce production errors by eliminating oral responses can yield improved naming of trained items. Second, it investigates whether changes in naming will be associated with changes in fMRI activation and whether the changes in activation pattern associated with recovery are primarily in the right hemisphere lpar;RH) or in perilesional tissue. Methods & Procedures : Four weeks of intensive semantic therapy designed to activate the semantic network and minimise errors was administered to AT, an individual with Wernicke's aphasia. Pre- and post-therapy behavioural testing included standard tests of aphasia, naming of pictures from training sets, and a narrative speech sample. Functional imaging of experimental and control tasks was completed pre- and post-therapy. Outcomes & Results : After 4 weeks of training, AT demonstrated improved naming and showed increased use of nouns in narrative speech. FMRI demonstrated increased activation of the left inferior frontal cortex during verb generation as well as increased inferior posterior temporal RH activation. Conclusions : These results support the effectiveness of intensive intervention methods that require semantic judgements rather than naming and the use of fMRI to understand the neural basis of the response.     

Repetitive transcranial magnetic stimulation of the dominant hemisphere can disrupt visual naming in temporal lobe epilepsy patients.

We used repetitive transcranial magnetic stimulation (rTMS) to study visual naming in 14 patients with temporal lobe epilepsy. Ten had left hemisphere language by Wada testing and all experienced speech arrest with rTMS of the motor speech area in the left frontal lobe. One left-hander had speech arrest with stimulation of sites on both sides. Subjects were asked to name pictures or read words presented on a computer monitor. rTMS was delivered on half of the trials. Stimulation sites were the motor speech area in the left frontal lobe, the mirror site on the right, and the left and right mid superior and posterior temporal lobes. rTMS at left hemisphere sites caused more naming errors than did right hemisphere rTMS. All individual subjects, except two who had temporal lobe resections and the one with bilateral speech arrest, produced more naming errors with rTMS of left hemisphere sites. There was no significant effect on word reading. rTMS at the left hemisphere and right frontal sites produced reductions in reaction time for picture naming, but not for word reading. This was observed for both correct and incorrect responses. This study shows that left hemisphere rTMS can disrupt visual naming selectively.     

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.     

Model-oriented naming therapy in semantic dementia: A single-case fMRI study

Background: Studies on anomia treatment in semantic dementia demonstrate that re-learning is possible, but maintenance and generalisation of improvements are limited. Changes in cortical activation associated with anomia treatment have already been demonstrated in aphasic patients after stroke. Recovery of brain functions under the impact of deficit-specific treatment in semantic dementia has not been explored yet. Nevertheless, recent activation studies using language tasks in patients with neurodegenerative diseases report altered activation patterns, involving diverse brain regions ipsi- or contralateral to the primarily affected left hemisphere.

Aims: The purpose of the present study was to investigate if phonological and semantic cueing hierarchies established for naming therapy in aphasia were also effective in a patient with semantic dementia. Moreover, we aimed to examine changes of brain activity associated with anomia treatment.

Methods & Procedures: One individual with semantic dementia participated in the present study. Over a period of 4 weeks the participant received an intensive model-oriented treatment with phonological and semantic cueing hierarchies. Two pre-tests and two post-tests (one immediately after training and one 2 months later) were administered. The second pre-test and both follow-ups were registered inside the scanner.

Outcomes & Results: Behaviourally, both treatments resulted in specific training effects, which subsequently decreased over time. Concerning functional magnetic resonance imaging data, improved naming following therapy was mirrored by changes in cortical activity, predominantly located in right superior and inferior temporal gyrus.

Conclusions: Cueing hierarchies were successful, resulting in specific and immediate treatment effects, corroborating previous treatment studies in semantic dementia. Treatment-induced changes in cortical activity were mainly concentrated in right temporal cortex. Since right-sided modulation of cortical activity was associated with training-induced improvements in task performance, it may reflect right hemispheric compensatory mechanisms in this participant.     

Left-hemispheric brain activity reflects formant transitions in speech sounds

Connected speech is characterized by formant transitions whereby formant frequencies change over time. Here, using magneto-encephalography, we investigated the cortical activity in 10 participants in response to constant-formant vowels and diphthongs with formant transitions. All the stimuli elicited prominent auditory N100m responses, but the formant transitions resulted in latency modulations specific to the left hemisphere. Following the elicitation of the N100m, cortical activity shifted some 10 mm towards anterior brain areas. This late activity resembled the N400m, typically obtained with more complex utterances such as words and/or sentences. Thus, the present study demonstrates how magnetoencephalography can be used to investigate the spatiotemporal evolution in cortical activity related to the various stages of the processing of speech.     

Clinical-anatomical correlation in a selective phonemic speech production impairment

Although phonemic paraphasias are common in aphasic disorders, including Broca's aphasia, conduction aphasia and transcortical motor aphasia, selective phonemic speech production impairment, or phonemic disintegration, is unusual. A patient with a selective phonemic speech production disorder underwent clinical, neuropsychological and structural neuroradiological assessment over a period of 6 years. The disorder was characterised by phonemic paraphasias (phonemic disintegration) with preserved comprehension and naming. Imaging showed a focal lesion in the white matter of the left precentral gyrus and, to a lesser extent, the posterior part of the left middle frontal gyrus, with overlying cortical atrophy. Biopsy of the lesion, after several years of observation, showed a calcified haemangioma. Clinical-anatomical correlation in this case suggests the importance of primary motor cortex of the inferior precentral (pre-Rolandic) gyrus and subjacent white matter in phoneme production, with sparing of the posterior inferior frontal gyrus (Broca's area).