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1.
J Exp Psychol Learn Mem Cogn ; 47(6): 968-997, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33252925

ABSTRACT

Misinterpretations during language comprehension are common. The ability to recover from processing difficulties is therefore crucial for successful day-to-day communication. Previous research on the recovery from misinterpretations has focused on sentences containing syntactic ambiguities. The present study instead investigated the outcome of comprehension processes and online reading behavior when misinterpretations occurred due to lexical-semantic ambiguity. Ninety-six adult participants read "garden-path" sentences in which an ambiguous word was disambiguated toward an unexpected meaning (e.g., "The ball was crowded"), while their eye movements were monitored. A meaning coherence judgment task required them to decide whether or not each sentence made sense. Results suggested that readers did not always engage in reinterpretation processes but instead followed a "good enough" processing strategy. Successful detection of a violation of sentence coherence and associated reinterpretation processes also required additional processing time compared to sentences that did not induce a misinterpretation. Although these reinterpretation-related processing costs were relatively stable across individuals, there was some evidence to suggest that readers with greater lexical expertise benefited from greater sensitivity to the disambiguating information, and were able to flexibly adapt their online reading behavior to recover from misinterpretations more efficiently. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Comprehension , Reading , Semantics , Adolescent , Adult , Eye Movements , Female , Humans , Male , Young Adult
2.
Cereb Cortex ; 25(11): 4638-50, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26092220

ABSTRACT

Humans can generate mental auditory images of voices or songs, sometimes perceiving them almost as vividly as perceptual experiences. The functional networks supporting auditory imagery have been described, but less is known about the systems associated with interindividual differences in auditory imagery. Combining voxel-based morphometry and fMRI, we examined the structural basis of interindividual differences in how auditory images are subjectively perceived, and explored associations between auditory imagery, sensory-based processing, and visual imagery. Vividness of auditory imagery correlated with gray matter volume in the supplementary motor area (SMA), parietal cortex, medial superior frontal gyrus, and middle frontal gyrus. An analysis of functional responses to different types of human vocalizations revealed that the SMA and parietal sites that predict imagery are also modulated by sound type. Using representational similarity analysis, we found that higher representational specificity of heard sounds in SMA predicts vividness of imagery, indicating a mechanistic link between sensory- and imagery-based processing in sensorimotor cortex. Vividness of imagery in the visual domain also correlated with SMA structure, and with auditory imagery scores. Altogether, these findings provide evidence for a signature of imagery in brain structure, and highlight a common role of perceptual-motor interactions for processing heard and internally generated auditory information.


Subject(s)
Auditory Perception/physiology , Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Imagination/physiology , Individuality , Noise , Acoustic Stimulation , Adult , Aged , Aged, 80 and over , Brain Mapping , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/blood supply , Neural Pathways/physiology , Oxygen/blood , Regression Analysis , Young Adult
3.
Front Hum Neurosci ; 8: 530, 2014.
Article in English | MEDLINE | ID: mdl-25120445

ABSTRACT

Semantic ambiguity resolution is an essential and frequent part of speech comprehension because many words map onto multiple meanings (e.g., "bark," "bank"). Neuroimaging research highlights the importance of the left inferior frontal gyrus (LIFG) and the left posterior temporal cortex in this process but the roles they serve in ambiguity resolution are uncertain. One possibility is that both regions are engaged in the processes of semantic reinterpretation that follows incorrect interpretation of an ambiguous word. Here we used fMRI to investigate this hypothesis. 20 native British English monolinguals were scanned whilst listening to sentences that contained an ambiguous word. To induce semantic reinterpretation, the disambiguating information was presented after the ambiguous word and delayed until the end of the sentence (e.g., "the teacher explained that the BARK was going to be very damp"). These sentences were compared to well-matched unambiguous sentences. Supporting the reinterpretation hypothesis, these ambiguous sentences produced more activation in both the LIFG and the left posterior inferior temporal cortex. Importantly, all but one subject showed ambiguity-related peaks within both regions, demonstrating that the group-level results were driven by high inter-subject consistency. Further support came from the finding that activation in both regions was modulated by meaning dominance. Specifically, sentences containing biased ambiguous words, which have one more dominant meaning, produced greater activation than those with balanced ambiguous words, which have two equally frequent meanings. Because the context always supported the less frequent meaning, the biased words require reinterpretation more often than balanced words. This is the first evidence of dominance effects in the spoken modality and provides strong support that frontal and temporal regions support the updating of semantic representations during speech comprehension.

4.
Brain ; 137(Pt 1): 242-54, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24163248

ABSTRACT

Aphasic deficits are usually only interpreted in terms of domain-specific language processes. However, effective human communication and tests that probe this complex cognitive skill are also dependent on domain-general processes. In the clinical context, it is a pragmatic observation that impaired attention and executive functions interfere with the rehabilitation of aphasia. One system that is important in cognitive control is the salience network, which includes dorsal anterior cingulate cortex and adjacent cortex in the superior frontal gyrus (midline frontal cortex). This functional imaging study assessed domain-general activity in the midline frontal cortex, which was remote from the infarct, in relation to performance on a standard test of spoken language in 16 chronic aphasic patients both before and after a rehabilitation programme. During scanning, participants heard simple sentences, with each listening trial followed immediately by a trial in which they repeated back the previous sentence. Listening to sentences in the context of a listen-repeat task was expected to activate regions involved in both language-specific processes (speech perception and comprehension, verbal working memory and pre-articulatory rehearsal) and a number of task-specific processes (including attention to utterances and attempts to overcome pre-response conflict and decision uncertainty during impaired speech perception). To visualize the same system in healthy participants, sentences were presented to them as three-channel noise-vocoded speech, thereby impairing speech perception and assessing whether this evokes domain general cognitive systems. As expected, contrasting the more difficult task of perceiving and preparing to repeat noise-vocoded speech with the same task on clear speech demonstrated increased activity in the midline frontal cortex in the healthy participants. The same region was activated in the aphasic patients as they listened to standard (undistorted) sentences. Using a region of interest defined from the data on the healthy participants, data from the midline frontal cortex was obtained from the patients. Across the group and across different scanning sessions, activity correlated significantly with the patients' communicative abilities. This correlation was not influenced by the sizes of the lesion or the patients' chronological ages. This is the first study that has directly correlated activity in a domain general system, specifically the salience network, with residual language performance in post-stroke aphasia. It provides direct evidence in support of the clinical intuition that domain-general cognitive control is an essential factor contributing to the potential for recovery from aphasic stroke.


Subject(s)
Aphasia/psychology , Aphasia/rehabilitation , Cognition/physiology , Recovery of Function/physiology , Stroke Rehabilitation , Stroke/psychology , Adult , Aged , Aged, 80 and over , Analysis of Variance , Aphasia/physiopathology , Behavior/physiology , Discrimination, Psychological/physiology , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Psychomotor Performance/physiology , Regression Analysis , Reproducibility of Results , Speech/physiology , Speech Perception/physiology , Stroke/physiopathology
5.
Ann Neurol ; 73(2): 294-302, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23281111

ABSTRACT

OBJECTIVE: Episodic memory encoding of a verbal message depends upon initial registration, which requires sustained auditory attention followed by deep semantic processing of the message. Motivated by previous data demonstrating modulation of auditory cortical activity during sustained attention to auditory stimuli, we investigated the response of the human auditory cortex during encoding of sentences to episodic memory. Subsequently, we investigated this response in patients with mild cognitive impairment (MCI) and probable Alzheimer's disease (pAD). METHODS: Using functional magnetic resonance imaging, 31 healthy participants were studied. The response in 18 MCI and 18 pAD patients was then determined, and compared to 18 matched healthy controls. Subjects heard factual sentences, and subsequent retrieval performance indicated successful registration and episodic encoding. RESULTS: The healthy subjects demonstrated that suppression of auditory cortical responses was related to greater success in encoding heard sentences; and that this was also associated with greater activity in the semantic system. In contrast, there was reduced auditory cortical suppression in patients with MCI, and absence of suppression in pAD. Administration of a central cholinesterase inhibitor (ChI) partially restored the suppression in patients with pAD, and this was associated with an improvement in verbal memory. INTERPRETATION: Verbal episodic memory impairment in AD is associated with altered auditory cortical function, reversible with a ChI. Although these results may indicate the direct influence of pathology in auditory cortex, they are also likely to indicate a partially reversible impairment of feedback from neocortical systems responsible for sustained attention and semantic processing.


Subject(s)
Alzheimer Disease/physiopathology , Auditory Perceptual Disorders/physiopathology , Indans/therapeutic use , Magnetic Resonance Imaging , Memory, Episodic , Piperidines/therapeutic use , Verbal Learning/physiology , Adult , Aged , Aged, 80 and over , Alzheimer Disease/drug therapy , Attention/physiology , Auditory Cortex/physiology , Auditory Perceptual Disorders/drug therapy , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/physiopathology , Donepezil , Female , Humans , Limbic System/physiology , Male , Memory Disorders/drug therapy , Memory Disorders/physiopathology , Mental Recall/drug effects , Mental Recall/physiology , Middle Aged , Nootropic Agents/therapeutic use , Young Adult
6.
Brain ; 134(Pt 9): 2565-81, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21908872

ABSTRACT

Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately to tissue pathology is a key challenge in the field of neurodegenerative disease and particularly relevant to the heterogeneous disorders that comprise the frontotemporal lobar degeneration spectrum. Here we present a retrospective analysis of clinical, neuropsychological and neuroimaging (volumetric and voxel-based morphometric) features in a pathologically ascertained cohort of 95 cases of frontotemporal lobar degeneration classified according to contemporary neuropathological criteria. Forty-eight cases (51%) had TDP-43 pathology, 42 (44%) had tau pathology and five (5%) had fused-in-sarcoma pathology. Certain relatively specific clinicopathological associations were identified. Semantic dementia was predominantly associated with TDP-43 type C pathology; frontotemporal dementia and motoneuron disease with TDP-43 type B pathology; young-onset behavioural variant frontotemporal dementia with FUS pathology; and the progressive supranuclear palsy syndrome with progressive supranuclear palsy pathology. Progressive non-fluent aphasia was most commonly associated with tau pathology. However, the most common clinical syndrome (behavioural variant frontotemporal dementia) was pathologically heterogeneous; while pathologically proven Pick's disease and corticobasal degeneration were clinically heterogeneous, and TDP-43 type A pathology was associated with similar clinical features in cases with and without progranulin mutations. Volumetric magnetic resonance imaging, voxel-based morphometry and cluster analyses of the pathological groups here suggested a neuroanatomical framework underpinning this clinical and pathological diversity. Frontotemporal lobar degeneration-associated pathologies segregated based on their cerebral atrophy profiles, according to the following scheme: asymmetric, relatively localized (predominantly temporal lobe) atrophy (TDP-43 type C); relatively symmetric, relatively localized (predominantly temporal lobe) atrophy (microtubule-associated protein tau mutations); strongly asymmetric, distributed atrophy (Pick's disease); relatively symmetric, predominantly extratemporal atrophy (corticobasal degeneration, fused-in-sarcoma pathology). TDP-43 type A pathology was associated with substantial individual variation; however, within this group progranulin mutations were associated with strongly asymmetric, distributed hemispheric atrophy. We interpret the findings in terms of emerging network models of neurodegenerative disease: the neuroanatomical specificity of particular frontotemporal lobar degeneration pathologies may depend on an interaction of disease-specific and network-specific factors.


Subject(s)
Frontotemporal Lobar Degeneration/pathology , Frontotemporal Lobar Degeneration/physiopathology , Adult , Aged , Brain/pathology , Brain/physiopathology , Cluster Analysis , Cohort Studies , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Frontotemporal Lobar Degeneration/genetics , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Pick Disease of the Brain/pathology , RNA-Binding Protein FUS/genetics , RNA-Binding Protein FUS/metabolism , Retrospective Studies , tau Proteins/genetics , tau Proteins/metabolism
7.
J Cogn Neurosci ; 23(4): 961-77, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20350182

ABSTRACT

This study investigated links between working memory and speech processing systems. We used delayed pseudoword repetition in fMRI to investigate the neural correlates of sublexical structure in phonological working memory (pWM). We orthogonally varied the number of syllables and consonant clusters in auditory pseudowords and measured the neural responses to these manipulations under conditions of covert rehearsal (Experiment 1). A left-dominant network of temporal and motor cortex showed increased activity for longer items, with motor cortex only showing greater activity concomitant with adding consonant clusters. An individual-differences analysis revealed a significant positive relationship between activity in the angular gyrus and the hippocampus, and accuracy on pseudoword repetition. As models of pWM stipulate that its neural correlates should be activated during both perception and production/rehearsal [Buchsbaum, B. R., & D'Esposito, M. The search for the phonological store: From loop to convolution. Journal of Cognitive Neuroscience, 20, 762-778, 2008; Jacquemot, C., & Scott, S. K. What is the relationship between phonological short-term memory and speech processing? Trends in Cognitive Sciences, 10, 480-486, 2006; Baddeley, A. D., & Hitch, G. Working memory. In G. H. Bower (Ed.), The psychology of learning and motivation: Advances in research and theory (Vol. 8, pp. 47-89). New York: Academic Press, 1974], we further assessed the effects of the two factors in a separate passive listening experiment (Experiment 2). In this experiment, the effect of the number of syllables was concentrated in posterior-medial regions of the supratemporal plane bilaterally, although there was no evidence of a significant response to added clusters. Taken together, the results identify the planum temporale as a key region in pWM; within this region, representations are likely to take the form of auditory or audiomotor "templates" or "chunks" at the level of the syllable [Papoutsi, M., de Zwart, J. A., Jansma, J. M., Pickering, M. J., Bednar, J. A., & Horwitz, B. From phonemes to articulatory codes: an fMRI study of the role of Broca's area in speech production. Cerebral Cortex, 19, 2156-2165, 2009; Warren, J. E., Wise, R. J. S., & Warren, J. D. Sounds do-able: auditory-motor transformations and the posterior temporal plane. Trends in Neurosciences, 28, 636-643, 2005; Griffiths, T. D., & Warren, J. D. The planum temporale as a computational hub. Trends in Neurosciences, 25, 348-353, 2002], whereas more lateral structures on the STG may deal with phonetic analysis of the auditory input [Hickok, G. The functional neuroanatomy of language. Physics of Life Reviews, 6, 121-143, 2009].


Subject(s)
Brain Mapping , Brain/physiology , Memory, Short-Term/physiology , Phonetics , Acoustic Stimulation/methods , Adult , Analysis of Variance , Brain/anatomy & histology , Brain/blood supply , Female , Functional Laterality , Humans , Image Processing, Computer-Assisted/methods , Linguistics , Magnetic Resonance Imaging/methods , Male , Oxygen/blood , Reaction Time/physiology , Young Adult
8.
J Neurosci ; 30(41): 13552-7, 2010 Oct 13.
Article in English | MEDLINE | ID: mdl-20943896

ABSTRACT

Our ability to recognize the emotions of others is a crucial feature of human social cognition. Functional neuroimaging studies indicate that activity in sensorimotor cortices is evoked during the perception of emotion. In the visual domain, right somatosensory cortex activity has been shown to be critical for facial emotion recognition. However, the importance of sensorimotor representations in modalities outside of vision remains unknown. Here we use continuous theta-burst transcranial magnetic stimulation (cTBS) to investigate whether neural activity in the right postcentral gyrus (rPoG) and right lateral premotor cortex (rPM) is involved in nonverbal auditory emotion recognition. Three groups of participants completed same-different tasks on auditory stimuli, discriminating between the emotion expressed and the speakers' identities, before and following cTBS targeted at rPoG, rPM, or the vertex (control site). A task-selective deficit in auditory emotion discrimination was observed. Stimulation to rPoG and rPM resulted in a disruption of participants' abilities to discriminate emotion, but not identity, from vocal signals. These findings suggest that sensorimotor activity may be a modality-independent mechanism which aids emotion discrimination.


Subject(s)
Auditory Perception/physiology , Cerebral Cortex/physiology , Discrimination, Psychological/physiology , Emotions/physiology , Recognition, Psychology/physiology , Acoustic Stimulation , Adult , Analysis of Variance , Brain Mapping , Female , Functional Laterality/physiology , Humans , Image Processing, Computer-Assisted , Male , Time Factors , Transcranial Magnetic Stimulation/methods
9.
Brain ; 133(Pt 4): 1200-13, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20142334

ABSTRACT

Despite much recent interest in the clinical neuroscience of music processing, the cognitive organization of music as a domain of non-verbal knowledge has been little studied. Here we addressed this issue systematically in two expert musicians with clinical diagnoses of semantic dementia and Alzheimer's disease, in comparison with a control group of healthy expert musicians. In a series of neuropsychological experiments, we investigated associative knowledge of musical compositions (musical objects), musical emotions, musical instruments (musical sources) and music notation (musical symbols). These aspects of music knowledge were assessed in relation to musical perceptual abilities and extra-musical neuropsychological functions. The patient with semantic dementia showed relatively preserved recognition of musical compositions and musical symbols despite severely impaired recognition of musical emotions and musical instruments from sound. In contrast, the patient with Alzheimer's disease showed impaired recognition of compositions, with somewhat better recognition of composer and musical era, and impaired comprehension of musical symbols, but normal recognition of musical emotions and musical instruments from sound. The findings suggest that music knowledge is fractionated, and superordinate musical knowledge is relatively more robust than knowledge of particular music. We propose that music constitutes a distinct domain of non-verbal knowledge but shares certain cognitive organizational features with other brain knowledge systems. Within the domain of music knowledge, dissociable cognitive mechanisms process knowledge derived from physical sources and the knowledge of abstract musical entities.


Subject(s)
Alzheimer Disease/psychology , Cognition/physiology , Frontotemporal Lobar Degeneration/psychology , Music/psychology , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/physiopathology , Auditory Perception/physiology , Emotions/physiology , Female , Frontotemporal Lobar Degeneration/diagnosis , Frontotemporal Lobar Degeneration/physiopathology , Humans , Male , Middle Aged
10.
Hum Brain Mapp ; 31(3): 365-77, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19777554

ABSTRACT

Speech comprehension involves processing at different levels of analysis, such as acoustic, phonetic, and lexical. We investigated neural responses to manipulating the difficulty of processing at two of these levels. Twelve subjects underwent positron emission tomographic scanning while making decisions based upon the semantic relatedness between heard nouns. We manipulated perceptual difficulty by presenting either clear or acoustically degraded speech, and semantic difficulty by varying the degree of semantic relatedness between words. Increasing perceptual difficulty was associated with greater activation of the left superior temporal gyrus, an auditory-perceptual region involved in speech processing. Increasing semantic difficulty was associated with reduced activity in both superior temporal gyri and increased activity within the left angular gyrus, a heteromodal region involved in accessing word meaning. Comparing across all the conditions, we also observed increased activation within the left inferior prefrontal cortex as the complexity of language processing increased. These results demonstrate a flexible system for language processing, where activity within distinct parts of the network is modulated as processing demands change.


Subject(s)
Brain/diagnostic imaging , Brain/physiology , Language , Semantics , Speech Perception/physiology , Acoustic Stimulation , Adult , Auditory Perception/physiology , Brain Mapping , Decision Making/physiology , Female , Humans , Language Tests , Male , Middle Aged , Neural Pathways/diagnostic imaging , Neural Pathways/physiology , Neuropsychological Tests , Positron-Emission Tomography , Reaction Time , Speech
11.
Brain ; 132(Pt 12): 3428-42, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19903736

ABSTRACT

Focal brain lesions are assumed to produce language deficits by two basic mechanisms: local cortical dysfunction at the lesion site, and remote cortical dysfunction due to disruption of the transfer and integration of information between connected brain regions. However, functional imaging studies investigating language outcome after aphasic stroke have tended to focus only on the role of local cortical function. In this positron emission tomography functional imaging study, we explored relationships between language comprehension performance after aphasic stroke and the functional connectivity of a key speech-processing region in left anterolateral superior temporal cortex. We compared the organization of left anterolateral superior temporal cortex functional connections during narrative speech comprehension in normal subjects with left anterolateral superior temporal cortex connectivity in a group of chronic aphasic stroke patients. We then evaluated the language deficits associated with altered left anterolateral superior temporal cortex connectivity in aphasic stroke. During normal narrative speech comprehension, left anterolateral superior temporal cortex displayed positive functional connections with left anterior basal temporal cortex, left inferior frontal gyrus and homotopic cortex in right anterolateral superior temporal cortex. As a group, aphasic patients demonstrated a selective disruption of the normal functional connection between left and right anterolateral superior temporal cortices. We observed that deficits in auditory single word and sentence comprehension correlated both with the degree of disruption of left-right anterolateral superior temporal cortical connectivity and with local activation in the anterolateral superior temporal cortex. Subgroup analysis revealed that aphasic patients with preserved positive intertemporal connectivity displayed better receptive language function; these patients also showed greater than normal left inferior frontal gyrus activity, suggesting a possible 'top-down' compensatory mechanism. These results demonstrate that functional connectivity between anterolateral superior temporal cortex and right anterior superior temporal cortex is a marker of receptive language outcome after aphasic stroke, and illustrate that language system organization after focal brain lesions may be marked by complex signatures of altered local and pathway-level function.


Subject(s)
Aphasia/physiopathology , Stroke/physiopathology , Temporal Lobe/physiopathology , Aged , Aphasia/diagnostic imaging , Aphasia/pathology , Auditory Cortex/pathology , Auditory Cortex/physiopathology , Brain Mapping , Dominance, Cerebral/physiology , Female , Frontal Lobe/pathology , Frontal Lobe/physiopathology , Functional Laterality/physiology , Humans , Image Processing, Computer-Assisted , Language , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/pathology , Neural Pathways/physiopathology , Positron-Emission Tomography , Prognosis , Recovery of Function/physiology , Speech/physiology , Speech Perception/physiology , Stroke/diagnostic imaging , Stroke/pathology , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Verbal Behavior/physiology
12.
MAGMA ; 22(3): 187-200, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19238472

ABSTRACT

OBJECT: To develop an efficient, automated method to correct through-slice signal loss in gradient-echo EPI at 3T. MATERIAL AND METHODS: The optimal choice of two z-shim values for signal recovery was determined from simulations and experiments. The specific required z-shim values are determined using a rapid calibration method that combines information about the slice profile with a sparse set of measurements. The proposed correction method was implemented for a language fMRI study which suffers from signal loss near the auditory canals, and tested on 12 volunteers. RESULTS: Using a square root sum of squares combination of two z-shim values full signal restoration (to within 2% of the correct value) was achieved in 96% of all correctable brain pixels for 3 mm slices, and partial correction in pixels outside this range. In all subjects, language processing activation was recovered in the inferior and lateral areas of the left temporal lobe which was not detectable with conventional fMRI. CONCLUSION: The careful choice of two z-shim values by the proposed method achieves through-slice signal loss correction for the majority of pixels in the brain for 3 mm slices at 3T.


Subject(s)
Algorithms , Artifacts , Image Interpretation, Computer-Assisted , Animals , Brain/anatomy & histology , Humans , Image Enhancement , Magnetic Resonance Imaging/methods
14.
Brain ; 131(Pt 1): 8-38, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17947337

ABSTRACT

The patient with word-finding difficulty presents a common and challenging clinical problem. The complaint of 'word-finding difficulty' covers a wide range of clinical phenomena and may signify any of a number of distinct pathophysiological processes. Although it occurs in a variety of clinical contexts, word-finding difficulty generally presents a diagnostic conundrum when it occurs as a leading or apparently isolated symptom, most often as the harbinger of degenerative disease: the progressive aphasias. Recent advances in the neurobiology of the focal, language-based dementias have transformed our understanding of these processes and the ways in which they breakdown in different diseases, but translation of this knowledge to the bedside is far from straightforward. Speech and language disturbances in the dementias present unique diagnostic and conceptual problems that are not fully captured by classical models derived from the study of vascular and other acute focal brain lesions. This has led to a reformulation of our understanding of how language is organized in the brain. In this review we seek to provide the clinical neurologist with a practical and theoretical bridge between the patient presenting with word-finding difficulty in the clinic and the evidence of the brain sciences. We delineate key illustrative speech and language syndromes in the degenerative dementias, compare these syndromes with the syndromes of acute brain damage, and indicate how the clinical syndromes relate to emerging neurolinguistic, neuroanatomical and neurobiological insights. We propose a conceptual framework for the analysis of word-finding difficulty, in order both better to define the patient's complaint and its differential diagnosis for the clinician and to identify unresolved issues as a stimulus to future work.


Subject(s)
Aphasia/diagnosis , Anomia/diagnosis , Anomia/etiology , Aphasia/etiology , Aphasia/pathology , Aphasia/psychology , Brain/pathology , Cognition Disorders/etiology , Dementia/complications , Diagnosis, Differential , Humans , Language Tests , Magnetic Resonance Imaging
15.
J Neurosci ; 27(43): 11455-64, 2007 Oct 24.
Article in English | MEDLINE | ID: mdl-17959788

ABSTRACT

Humans devote much time to the exchange of memories within the context of shared general and personal semantic knowledge. Our hypothesis was that functional imaging in normal subjects would demonstrate the convergence of speech comprehension and production on high-order heteromodal and amodal cortical areas implicated in declarative memory functions. Activity independent of speech phase (that is, comprehension and production) was most evident in the left and right lateral anterior temporal cortex. Significant activity was also observed in the posterior cortex, ventral to the angular gyri. The left and right hippocampus and adjacent inferior temporal cortex were active during speech comprehension, compatible with mnemonic encoding of narrative information, but activity was significantly less during the overt memory retrieval associated with speech production. Therefore, although clinical studies suggest that hippocampal function is necessary for the retrieval as well as the encoding of memories, the former appears to depend on much less net synaptic activity. In contrast, the retrosplenial/posterior cingulate cortex and the parahippocampal area, which are closely associated anatomically with the hippocampus, were equally active during both speech comprehension and production. The results demonstrate why a severe and persistent inability both to understand and produce meaningful speech in the absence of an impairment to process linguistic forms is usually only observed after bilateral, and particularly anterior, destruction of the temporal lobes, and emphasize the importance of retrosplenial/posterior cingulate cortex, an area known to be affected early in the course of Alzheimer's disease, in the processing of memories during communication.


Subject(s)
Comprehension/physiology , Speech/physiology , Adult , Female , Humans , Magnetic Resonance Imaging/methods , Male , Memory/physiology , Middle Aged , Positron-Emission Tomography/methods , Speech Perception/physiology , Temporal Lobe/physiology
16.
Neuroimage ; 35(1): 207-13, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17240166

ABSTRACT

The brain bases of specific human behaviours in health and disease are not well established. In this voxel-based morphometric (VBM) study we demonstrate neuroanatomical signatures of different abnormalities of eating behaviour (pathological sweet tooth and increased food consumption, or hyperphagia) in individuals with frontotemporal lobar degeneration (FTLD). Sixteen male patients with FTLD were assessed using the Manchester and Oxford Universities Scale for the Psychopathological Assessment of Dementia and classified according to the presence or absence of abnormal eating behaviours. Volumetric brain magnetic resonance imaging was performed in all patients and in a group of nine healthy age-matched male controls and grey matter changes were assessed using an optimised VBM protocol. Compared with healthy controls, the FTLD group had a typical pattern of extensive bilateral grey matter loss predominantly involving the frontal and temporal lobes. Within the FTLD group, grey matter changes associated with different abnormal behaviours were assessed independently using a covariate-only model. The development of pathological sweet tooth was associated with grey matter loss in a distributed brain network including bilateral posterolateral orbitofrontal cortex (Brodmann areas 12/47) and right anterior insula. Hyperphagia was associated with more focal grey matter loss in anterolateral OFC bilaterally (Brodmann area 11). In accord with emerging evidence in humans and other species, our findings implicate distinct components of a multi-component brain network in the control of specific aspects of eating behaviour.


Subject(s)
Dementia/pathology , Dementia/psychology , Feeding and Eating Disorders/pathology , Feeding and Eating Disorders/psychology , Aged , Electrophysiology , Feeding Behavior/physiology , Humans , Hyperphagia/pathology , Hyperphagia/psychology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/pathology , Neuropsychological Tests , Psychiatric Status Rating Scales
17.
J Neurosci ; 26(50): 13067-75, 2006 Dec 13.
Article in English | MEDLINE | ID: mdl-17167096

ABSTRACT

Social interaction relies on the ability to react to communication signals. Although cortical sensory-motor "mirror" networks are thought to play a key role in visual aspects of primate communication, evidence for a similar generic role for auditory-motor interaction in primate nonverbal communication is lacking. We demonstrate that a network of human premotor cortical regions activated during facial movement is also involved in auditory processing of affective nonverbal vocalizations. Within this auditory-motor mirror network, distinct functional subsystems respond preferentially to emotional valence and arousal properties of heard vocalizations. Positive emotional valence enhanced activation in a left posterior inferior frontal region involved in representation of prototypic actions, whereas increasing arousal enhanced activation in presupplementary motor area cortex involved in higher-order motor control. Our findings demonstrate that listening to nonverbal vocalizations can automatically engage preparation of responsive orofacial gestures, an effect that is greatest for positive-valence and high-arousal emotions. The automatic engagement of responsive orofacial gestures by emotional vocalizations suggests that auditory-motor interactions provide a fundamental mechanism for mirroring the emotional states of others during primate social behavior. Motor facilitation by positive vocal emotions suggests a basic neural mechanism for establishing cohesive bonds within primate social groups.


Subject(s)
Acoustic Stimulation/methods , Auditory Cortex/physiology , Emotions/physiology , Functional Laterality/physiology , Motor Cortex/physiology , Adult , Arousal/physiology , Female , Humans , Magnetic Resonance Imaging/methods , Male
18.
J Neurosci ; 26(28): 7328-36, 2006 Jul 12.
Article in English | MEDLINE | ID: mdl-16837579

ABSTRACT

There is general agreement that, after initial processing in unimodal sensory cortex, the processing pathways for spoken and written language converge to access verbal meaning. However, the existing literature provides conflicting accounts of the cortical location of this convergence. Most aphasic stroke studies localize verbal comprehension to posterior temporal and inferior parietal cortex (Wernicke's area), whereas evidence from focal cortical neurodegenerative syndromes instead implicates anterior temporal cortex. Previous functional imaging studies in normal subjects have failed to reconcile these opposing positions. Using a functional imaging paradigm in normal subjects that used spoken and written narratives and multiple baselines, we demonstrated common activation during implicit comprehension of spoken and written language in inferior and lateral regions of the left anterior temporal cortex and at the junction of temporal, occipital, and parietal cortex. These results indicate that verbal comprehension uses unimodal processing streams that converge in both anterior and posterior heteromodal cortical regions in the left temporal lobe.


Subject(s)
Auditory Pathways , Language , Speech Perception , Temporal Lobe/physiology , Visual Pathways , Adult , Aged , Aged, 80 and over , Brain Mapping , Female , Humans , Male , Middle Aged , Narration , Occipital Lobe/physiology , Parietal Lobe/physiology , Reading , Semantics , Subtraction Technique , Temporal Lobe/diagnostic imaging , Tomography, Emission-Computed
19.
Trends Neurosci ; 28(12): 636-43, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16216346

ABSTRACT

Accumulating evidence in humans and non-human primates implicates the posterior superior temporal plane (STP) in the processing of both auditory spatial information and vocal sounds. Such evidence is difficult to reconcile with existing accounts of the primate auditory brain. We propose that the posteromedial STP generates sequenced auditory representations by matching incoming auditory information with stored templates. These sequenced auditory representations are subsequently used to constrain motor responses. We argue for a re-assessment of the much-debated dorsal auditory pathway in terms of its generic behavioral role as an auditory "do" pathway.


Subject(s)
Animal Communication , Auditory Cortex/physiology , Auditory Pathways/physiology , Auditory Perception/physiology , Motor Activity/physiology , Nerve Net/physiology , Sound Localization/physiology , Animals , Humans , Models, Neurological , Motor Cortex/physiology , Primates
20.
Neurocase ; 9(2): 140-55, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12925938

ABSTRACT

We describe a 76-year-old man (ADY) with dynamic aphasia in the setting of a degenerative frontal lobe dementia: primary progressive dynamic aphasia. He displayed a striking paucity of propositional speech despite intact speech production, and preserved singing and prosody. Vocal expression in the verbal and musical domains was investigated in a series of neuropsychological experiments based on novel language and musical tasks that were designed to establish the nature and specificity of the verbal output deficit. The features of the language disorder indicated that the speech output pathway was disrupted at the early stage of generation of a new pre-verbal message. In contrast, tests of musical output demonstrated that the generation of new musical ideas was unimpaired. The domain-specificity of dynamic aphasia may result from the disruption of specific cognitive processes necessary for the creation of verbal messages, as well as selective damage of brain regions involved in language production.


Subject(s)
Aphasia, Primary Progressive/psychology , Dementia/complications , Dementia/psychology , Frontal Lobe/pathology , Language Disorders/etiology , Music , Speech Disorders/etiology , Aged , Aphasia, Primary Progressive/pathology , Humans , Male
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