A physiological change in the homotopic cortex following left posterior temporal lobe infarction

We investigated the relationship between cerebral activity (measured with positron emission tomography) and word rate in normal subjects and aphasic patients listening to monosyllabic words at rates up to those encountered in normal speech. By measuring the slope of the regression of the individual activity-word rate responses in the temporal cortex in normal subjects, we identified a functional asymmetry in the posterior superior temporal sulcus. The response was greater (steeper) on the left. Using the same study design, we identified a steeper activity-word rate response in the right posterior superior temporal sulcus of patients who had recovered single-word auditory comprehension after infarction of the left posterior temporal cortex. This response was significantly different from that observed in both normal subjects and a group of patients with left hemisphere infarcts that spared the posterior temporal cortex. The results demonstrated a change in physiological responsiveness in the contralateral homotopic cortex after posterior temporal infarction.     

Retrieving meaning after temporal lobe infarction: the role of the basal language area

During speech comprehension the auditory association cortex in the superior temporal cortex is involved in perceptual analysis of the speech signal, whereas the basal language area in the inferior temporal cortex mediates access to word meaning. Disruption of the interaction between the superior and inferior temporal cortices is one factor that may determine recovery from aphasic stroke. We used positron emission tomography to investigate semantic processing within inferior temporal cortex in control subjects and after infarction involving the superior temporal cortex. In the control group, semantic decision making on clear speech activated both anterior fusiform gyri. Chronic aphasic patients were impaired at the task and demonstrated reduced activation within the left anterior fusiform gyrus. A similar pattern of impaired performance and reduced left anterior fusiform gyrus activation was observed when control subjects heard perceptually degraded speech. Performance in both groups predicted activity in the right anterior fusiform gyrus and the temporal poles, where accuracy linearly correlated with activity. These results demonstrate that the function of the basal language area is sensitive to changes in the quality of perceptual input. In addition, different profiles of response observed in each hemisphere suggest distinct contributions of both left and right inferior temporal cortices to the semantic processing of speech.     

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.     

Processing the spatial configuration of complex actions involves right posterior parietal cortex: An fMRI study with clinical implications

The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object-related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage.     

Blunted prefrontal cortical 18fluorodeoxyglucose positron emission tomography response to meta-chlorophenylpiperazine in impulsive aggression

BACKGROUND: Impulsive aggression is a prevalent problem and yet little is known about its neurobiology. Preclinical and human studies suggest that the orbital frontal cortex and anterior cingulate cortex play an inhibitory role in the regulation of aggression. METHODS: Using positron emission tomography, regional metabolic activity in response to a serotonergic stimulus, meta-chlorophenylpiperazine (m-CPP), was examined in 13 subjects with impulsive aggression and 13 normal controls. The anterior cingulate and medial orbitofrontal regions were hypothesized to respond differentially to m-CPP in patients and controls. In the frontal cortex, regional metabolic glucose response to m-CPP was entered into a group (impulsive aggressive, control) x slice (dorsal, middle, orbital) x position (medial, lateral) x location (anterior, posterior) x hemisphere (right, left) mixed-factorial analysis of variance design. A separate group (impulsive aggressive, controls) x anteroposterior location (Brodmann areas 25, 24, 31, 29) x hemisphere (right, left) analysis of variance was used to examine regional glucose metabolism in the cingulate gyrus. RESULTS: Unlike normal subjects, patients with impulsive aggression did not show activation specifically in the left anteromedial orbital cortex in response to m-CPP. The anterior cingulate, normally activated by m-CPP, was deactivated in patients; in contrast, the posterior cingulate gyrus was activated in patients and deactivated in controls. CONCLUSIONS: The decreased activation of inhibitory regions in patients with impulsive aggression in response to a serotonergic stimulus may contribute to their difficulty in modulating aggressive impulses.     

EEG delta band as a marker of brain damage in aphasic patients after recovery of language

In this study spectral delta percentage was used to assess both brain dysfunction/inhibition and functional linguistic impairment during different phases of word processing. To this aim, EEG delta amplitude was measured in 17 chronic non-fluent aphasic patients while engaged in three linguistic tasks: Orthographic, Phonological and Semantic. Average mapping of aphasics’ structural lesion showed core damage in the left cortical-subcortical perisylvian areas. Delta amplitude was overall significantly higher in aphasics with respect to matched controls, a result in line with the view that diaschisis/cortical inhibition persists to some extent also in the chronic phase. Analysis of regions of interest revealed a peak of delta activity in left perilesional EEG sites, posterior to the core damage where residual suffering tissue probably projects its dysfunctional activity. Time course of word processing showed in patients greater delta percentage/inhibition in the first interval after word offset in correspondence of which verbal working memory is engaged. The significant interaction including group and task factors points to greater left posterior inhibition in aphasics across all tasks and left vs. right anterior relative disinhibition only during the Phonological task, whereas controls showed greater left vs. right disinhibition at anterior sites in all tasks. Delta band, in addition to its ability to reflect structural damage, was effective in the assessment of functional impairment as well as of linguistic reorganization of aphasics at hemispheric level with a spatial scalp distribution consistent with lesion map.     

Delineating necessary and sufficient neural systems with functional imaging studies of neuropsychological patients.

This paper demonstrates how functional imaging studies of neuropsychological patients can provide a way of determining which areas in a cognitive network are jointly necessary and sufficient. The approach is illustrated with an investigation of the neural system underlying semantic similarity judgments. Functional neuroimaging demonstrates that normal subjects activate left temporal, parietal, and inferior frontal cortices during this task relative to physical size judgments. Neuropsychology demonstrates that damage to the temporal and parietal regions results in semantic deficits, indicating that these areas are necessary for task performance. In contrast, damage to the inferior frontal cortex does not impair task performance, indicating that the inferior frontal cortex might not be necessary. However, there are two other possible accounts of intact performance following frontal lobe damage: (1) there is functional reorganization involving the right frontal cortex and (2) there is peri-infarct activity around the damaged left-hemisphere tissue. Functional imaging of the patient is required to discount these possibilities. We investigated a patient (SW), who was able to associate words and pictures on the basis of semantic relationships despite extensive damage to the left frontal, inferior parietal, and superior temporal cortices. Although SW showed peri-infarct activation in left extrasylvian temporal cortices, no activity was observed in either left or right inferior frontal cortices. These findings demonstrate that activity in extrasylvian temporo-parietal and medial superior frontal regions is sufficient to perform semantic similarity judgments. In contrast, the left inferior frontal activations detected in each control subject appear not to be necessary for task performance. In conclusion, necessary and sufficient brain systems can be delineated by functional imaging or brain-damaged patients who are not functionally impaired.     

Brain SPECT imaging in transcortical aphasias: the functional status of the left perisylvian language cortex*

Single photon emission computerized tomography (SPECT) with 99mTc-HMPAO was used to examine the functional status of the left perisylvian language cortex (PLC) in eight patients with transcortical aphasias (TAs) due to cerebrovascular accidents. According to the lesion location within the left hemisphere, the aphasic patients were divided into two groups: (a) patients with corticosubcortical lesions involving portions or the whole PLC (perisylvian group, n = 4); (b) patients with corticosubcortical lesions sparing the PLC (extraperisylvian group, n = 4). Results showed that, as expected, the perisylvian group had significant decrements in regional cerebral blood flow (rCBF) in structurally damaged regions of the left PLC, although some morphologically spared regions of the left PLC (Wernicke's area) also had perfusion defects in one patient. Among the extraperisylvian group, there was structural and functional damage to the posterior association areas, but two patients additionally had significant decrements of rCBF in morphologically spared regions of the PLC (Wernicke's area, sensorimotor cortex, Broca's area). These findings demonstrate not only that the left PLC may be structurally and functionally damaged among patients with TAs, but additionally suggest a major contribution of the right hemisphere in the mediation of residual language repetition.     

Language-related brain function during word repetition in post-stroke aphasics

We compared fMRI findings (using SPM99) obtained with repetition task in normal subjects with those of two patients with Broca's and Wernicke's aphasia who received speech therapy and showed complete recovery. Both aphasic patients with left hemisphere damage who showed complete recovery exhibited activation of only the compensatory area in the right hemisphere during the repetition task. Recovery from Broca's aphasia involves reorganization and neuromodulation between the external temporopolar area and the anterior superior temporal area of the superior temporal gyrus, putamen and the inferior frontal gyrus, while that from Wernicke's aphasia involves reorganization and neuromodulation between the superior temporal gyrus of the temporal region, the posterior supramarginal gyrus and inferior parietal lobule of the parietal region.     

Recovery of semantic word processing in global aphasia: a functional MRI study

One important issue concerning the recovery of higher cognitive functions-such as word comprehension in aphasia-is to what extent impairments can be compensated for by intact parts of the network of areas normally involved in a closely related function ("redundancy recovery"). In a previous functional MRI investigation, we were able to show that left hemispheric redundancy recovery within a distributed system of related lexical-semantic functions was the most probable basis of recovery of comprehension from transcortical sensory aphasia. The question remained, however, whether redundancy recovery may play a more general role in the recovery of comprehension after large left hemispheric lesions and severe aphasia. We had the possibility, using the same fMRI paradigm, to study seven cases with left middle cerebral artery (MCA) infarction and partial recovery of comprehension > or =6 months after presentation with global aphasia on acute assessment. Lateralization of activation did not differ significantly between patients and controls. The most consistent regions of activation included the left extrasylvian posterior temporal and the right posterior parietal cortex. Recovery of language comprehension was associated predominantly with activations in regions, which were also activated in several normal subjects. We suggest that a redundancy recovery mechanism within multiple representations of closely related functions was more important than take-over of function by previously unrelated areas (vicariation) as the basis of recovery of word comprehension in our patients in spite of extensive left hemispheric damage. We conclude that redundancy within the lexical-semantic system seems to make an important contribution to recovery of comprehension even in severe aphasia.     

Compensatory recombination phenomena of neurological functions in central dysphagia patients

We speculate that cortical reactions evoked by swallowing activity may be abnormal in patients with central infarction with dysphagia. The present study aimed to detect functional imaging features of cerebral cortex in central dysphagia patients by using blood oxygen level-dependent functional magnetic resonance imaging techniques. The results showed that when normal controls swallowed, primary motor cortex(BA4), insula(BA13), premotor cortex(BA6/8), supramarginal gyrus(BA40), and anterior cingulate cortex(BA24/32) were activated, and that the size of the activated areas were larger in the left hemisphere compared with the right. In recurrent cerebral infarction patients with central dysphagia, BA4, BA13, BA40 and BA6/8 areas were activated, while the degree of activation in BA24/32 was decreased. Additionally, more areas were activated, including posterior cingulate cortex(BA23/31), visual association cortex(BA18/19), primary auditory cortex(BA41) and parahippocampal cortex(BA36). Somatosensory association cortex(BA7) and left cerebellum in patients with recurrent cerebral infarction with central dysphagia were also activated. Experimental findings suggest that the cerebral cortex has obvious hemisphere lateralization in response to swallowing, and patients with recurrent cerebral infarction with central dysphagia show compensatory recombination phenomena of neurological functions. In rehabilitative treatment, using the favorite food of patients can stimulate swallowing through visual, auditory, and other nerve conduction pathways, thus promoting compensatory recombination of the central cortex functions.     

Facial recognition in patients with focal brain lesions

The performances of patients with radiologically or surgically verified focal lesions on a test requiring the identification of unfamiliar faces were investigated. Nonaphasic patients with posterior right hemisphere lesions and aphasic patients with substantial impairment in language comprehension showed a notably high frequency of defect. The frequency of defective performance in nonaphasic patients with right anterior lesions was higher than normal but less than that of the previously mentioned groups. Nonaphasic patients with left hemisphere lesions and aphasic patients without substantial impairment in language comprehension performed on a level comparable with that of control subjects. It is concluded that the identification of unfamiliar faces is a bihemispheric process, possibly involving linguistic as well as visuoperceptive components.     

Functional neuroanatomy of speech processing within the temporal cortex

The phonemic structure of the maternal language determines the way of perceiving speech signals. A typical example is that native Japanese listeners map two English phonemes, /r/ and /l/, onto the same /R/. This perceptual assimilation of speech sounds has been associated with the left and/or right posterior perisylvian region, but the precise functional anatomy is unknown. Using functional magnetic resonance imaging and a repetition priming paradigm, we identified three subregions in the left temporal cortex: an anterior division sensitive to language-specific phonological knowledge, and a midlateral and a posterior division related to other vocal stimuli features. Dynamic causal modeling supports the scheme by which the anterior pathway processes perceptual assimilation; the posterior pathway processes lexico-semantic information.     

Words in melody: an H(2)15O PET study of brain activation during singing and speaking

We used H(2)15O PET to characterize the interaction of words and melody by comparing brain activity measured while subjects spoke or sang the words to a familiar song. Relative increases in activity during speaking vs singing were observed in the left hemisphere, in classical perisylvian language areas including the posterior superior temporal gyrus, supramarginal gyrus, and frontal operculum, as well as in Rolandic cortices and putamen. Relative increases in activity during singing were observed in the right hemisphere: these were maximal in the right anterior superior temporal gyrus and contiguous portions of the insula; relative increases associated with singing were also detected in the right anterior middle temporal gyrus and superior temporal sulcus, medial and dorsolateral prefrontal cortices, mesial temporal cortices and cerebellum, as well as in Rolandic cortices and nucleus accumbens. These results indicate that the production of words in song is associated with activation of regions within right hemisphere areas that are not mirror-image homologues of left hemisphere perisylvian language areas, and suggest that multiple neural networks may be involved in different aspects of singing. Right hemisphere mechanisms may support the fluency-evoking effects of singing in neurological disorders such as stuttering or aphasia.     

Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions

Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.     

Cortical activation studies in aphasia

Positron emission tomography and functional magnetic resonance imaging are the major techniques of functional brain imaging. Both techniques have been used successfully in studies of the speech-relevant cortex in normal individuals and in aphasic patients with brain lesions. The activation studies basically agree with the classic model of language organization in that the left inferior frontal and superior temporal cortex (Broca’s and Wernicke’s area, respectively) are the pivotal areas of speech processing. Activation studies additionally emphasize that the speech-relevant cortex is a rather widespread network. It also encompasses contributions from other left hemispheric regions and, to some degree, from the contralateral right hemisphere. The studies of aphasic patients point out that the functional preponderance of the left over the right cerebral hemisphere varies between individuals, and that language recovery after stroke depends on the restitution of the speech-relevant network in both brain hemispheres.     

Altered hemispheric asymmetry of auditory N100m in adults with developmental dyslexia

The current study aimed at determining whether the deviance of hemispheric asymmetry in the auditory cortex of children with dyslexia is also evident in dyslexic adults. Ten adult dyslexic subjects and 10 normally literate controls were presented with the syllable [ba:] while event-related brain activity was recorded from both hemispheres using whole-head magnetoencephalography. In control subjects, the auditory N100m source was found to be asymmetrical with a more anterior localization in the right than in the left perisylvian cortex (difference = 0.78 cm). The N100 m dipoles in dyslexic adults did not exhibit the same interhemispheric asymmetry (difference = -0.06 cm). The results indicate that reduced hemispheric laterality of perisylvian regions in dyslexia persists into adulthood.     

Left hemisphere contribution to motor programming of aphasic speech: a reaction time experiment in aphasic patients

Simple reaction time to lateralized visual dot stimuli was studied in 10 fluent and 10 nonfluent right-handed chronic aphasics with left hemisphere lesions. As well as the standard simple reaction time condition, the patients were given a concomitant verbal task, requiring overt articulation while reacting to the visual stimuli. Compared with the control condition, in both aphasic groups the verbal task produced an overall lengthening of latencies, with a significant slowing down of responses to the stimuli located in the right visual half-field. According to these results the verbal concurrent activity appears to involve the left hemisphere as in normal subjects, suggesting that the undamaged regions of the left hemisphere have a role to play in the motor programming of aphasic speech. As a collateral finding, the difference between latencies to stimuli ipsilateral and contralateral to the responding hand--a measure of interhemispheric transmission time--is greatly increased in patients with motor deficits. This is consistent with the view that, in simple visuo-motor reaction time, interhemispheric transfer takes place between anterior regions of the brain.     

Parallel systems in the control of speech

Modern neuroimaging techniques have advanced our understanding of the distributed anatomy of speech production, beyond that inferred from clinico‐pathological correlations. However, much remains unknown about functional interactions between anatomically distinct components of this speech production network. One reason for this is the need to separate spatially overlapping neural signals supporting diverse cortical functions. We took three separate human functional magnetic resonance imaging (fMRI) datasets (two speech production, one “rest”). In each we decomposed the neural activity within the left posterior perisylvian speech region into discrete components. This decomposition robustly identified two overlapping spatio‐temporal components, one centered on the left posterior superior temporal gyrus (pSTG), the other on the adjacent ventral anterior parietal lobe (vAPL). The pSTG was functionally connected with bilateral superior temporal and inferior frontal regions, whereas the vAPL was connected with other parietal regions, lateral and medial. Surprisingly, the components displayed spatial anti‐correlation, in which the negative functional connectivity of each component overlapped with the other component's positive functional connectivity, suggesting that these two systems operate separately and possibly in competition. The speech tasks reliably modulated activity in both pSTG and vAPL suggesting they are involved in speech production, but their activity patterns dissociate in response to different speech demands. These components were also identified in subjects at “rest” and not engaged in overt speech production. These findings indicate that the neural architecture underlying speech production involve s parallel distinct components that converge within posterior peri‐sylvian cortex, explaining, in part, why this region is so important for speech production. Hum Brain Mapp 35:1930–1943, 2014. © 2013 Wiley Periodicals, Inc.     

A case of aphasia with speech disorders by infarction of the left caudate nucleus and putamen

An infarction involving the left putamen, caudate nucleus and the anterior limb of the internal capsule, resulted in aphasia with semantic paraphasias, verbal incoherence and verbal memory impairment. Cerebral blood flow (CBF) studies with 133Xe inhalation at 20 days post onset showed, on one hand, a bilateral lowering of cortical blood flow and on the other hand a left frontal-parietal hypoperfusion area. Spontaneous recovery occurred within 2 months. While the mean CBF became normal at 14 months post onset, a relative hypoperfusion area persisted on the anterior left hemispheric cortex. On the basis of these findings and current CBF and metabolic studies carried out in patients with subcortical lesions, the authors discuss the role of cortical and subcortical structures in subcortical aphasic syndromes. The importance of reciprocal connections between cortex, striatum and thalamus is stressed.