See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/12236576
Combined semantic dementia and apraxia in a patient with frontotemporal lobar degeneration. ARTICLE in PSYCHIATRY RESEARCH · DECEMBER 2000 Impact Factor: 2.68 · DOI: 10.1016/S0925-4927(00)00065-2 · Source: PubMed
CITATIONS
DOWNLOADS
VIEWS
7
54
73
7 AUTHORS, INCLUDING: Ulrike Halsband
Jan Kassubek
University of Freiburg
Universität Ulm
71 PUBLICATIONS 2,856 CITATIONS
381 PUBLICATIONS 4,861 CITATIONS
SEE PROFILE
SEE PROFILE
Sylvia M Gustin
Freimut Juengling
University of New South Wales
PET/CT-Center Northwest-Switzerland…
31 PUBLICATIONS 540 CITATIONS
122 PUBLICATIONS 1,824 CITATIONS
SEE PROFILE
SEE PROFILE
Available from: Freimut Juengling Retrieved on: 03 August 2015
Psychiatry Research: Neuroimaging Section 100 Ž2000. 21᎐29
Combined semantic dementia and apraxia in a patient with frontotemporal lobar degeneration Gunter Schumanna , Ulrike Halsband b, Jan Kassubek c , Sylvia Gustin b, Theda Heinks b, Freimut D. Juengling d,U , Michael Hull ¨ a a
Department of Psychiatry, Uni¨ ersity of Freiburg, Freiburg, Germany Department of Psychology, Uni¨ ersity of Freiburg, Freiburg, Germany c Department of Neurology, Uni¨ ersity of Freiburg, Freiburg, Germany d Department of Nuclear Medicine, Uni¨ ersity of Freiburg, Freiburg, Germany b
Received 21 December 1999; received in revised form 10 March 2000; accepted 6 April 2000
Abstract In this study we report neuropsychological and brain-imaging findings in a patient with frontotemporal lobar degeneration. Brain imaging using registration of 18 fluorodeoxyglucose ŽFDG.-PET data to three-dimensional Ž3-D. magnetic resonance imaging showed atrophy and highly significant hypometabolism of the left temporal lobe and both frontal lobes. Volumetric measurements of the hippocampiramygdala showed a reduction in volume of 25% on the left compared to right within cortical areas. Neuropsychological testing revealed semantic dementia with severe anomia as well as apraxia with impairment of both recognition and production of motor acts. The implications of this case of early manifestation of frontotemporal lobar degeneration for our knowledge of dementia are discussed. 䊚 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Frontotemporal lobar degeneration; Semantic dementia; Apraxia; 3-D MRI; FDG-PET
1. Introduction Semantic dementia is a manifestation of frontotemporal lobar degeneration which is characU
Corresponding author. Department of Nuclear Medicine, University Hospital Freiburg, Hugstetterstrasse 55, D-79106 Freiburg, Germany. Tel.: q49-761-270-3916; fax: q49-761270-3930. E-mail address:
[email protected] ŽF.D. Juengling..
terised by selective neuropsychological disturbances. The disease often presents with progressive semantic aphasia ŽMesulam, 1982; GraffRadford et al., 1990; Kertesz et al., 1998.. Its core features include language disorder, perceptual disorder, insidious onset and a preservation of single word repetition, reading and writing as well as perceptual matching and drawing reproduction ŽNeary et al., 1998.. Significant overlap of syndromes presenting
0925-4927r00r$ - see front matter 䊚 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 9 2 5 - 4 9 2 7 Ž 0 0 . 0 0 0 6 5 - 2
22
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
with progressive aphasia as well as apraxia similar to corticobasal degeneration, behavioural changes similar to those in frontal lobe dementia, extrapyramidal manifestations and motor neuron disease have been reported on both a neuropsychological ŽKertesz and Munoz, 1997. and a neuropathological level ŽRossor et al., 2000.. However, few studies have correlated neuropsychological deficits and brain imaging using registration of position emission tomography ŽPET. data to 3-D magnetic resonance imaging ŽMRI..
2. Methods
Calculation was preserved. Concentration was relatively unimpaired. He achieved a score of 28 on the Mini-Mental State Examination ŽMMSE.. 2.1.3. Laboratory tests Laboratory tests including complete blood count, blood chemistry, thyroid function, serology for treponema pallidum and borrelia burgdorferi as well as CSF diagnostics were within normal limits. EEG was normal. 2.1.4. Rele¨ ant physical history and examination There was no history or risk factor for vascular disease. Neurological examination was uneventful.
2.1. Patient 2.2. Procedures 2.1.1. Present medical history Mr B, a 59-year-old, right-handed previously psychiatrically healthy motor mechanic, noted increasing difficulties in remembering names of people and problems with naming tools and spare parts at work 4 years prior to the present investigation. After retirement due to multiple disk prolapses, he spent his days at home where he used to walk in the neighbourhood looking for coins on his way and trying to memorise words from illustrated word lists which he had written and drawn himself. He experienced difficulties in recognising familiar faces. Psychiatric family history and drugralcohol history were uneventful. 2.1.2. Mental status examination Mr B presented as a well-groomed and cooperative man. He was alert and fully oriented. Psychomotor activity was normal. His mood was moderately expansive while his affect was blunted and inappropriate to the content of the interview. Fluctuations in affect with sudden angry outbursts were reported by his wife. His speech was pressed, meaningful, generally fluent with normal articulation, phonology and syntactic structure. It was occasionally interrupted by word-finding difficulties. He frequently used stereotypical characterisations which appeared empty in content and emotion. Paraphrases and misnomers were noted. Single word comprehension was severely impaired. No perceptual disturbances were observed.
2.2.1. Neuropsychological e¨ aluation The patient was administered a series of neuropsychological tests, as outlined in Table 1. For an analysis of gesture comprehension and imitation, the patient was shown 136 meaningful pantomimed motor acts on a videoscreen and asked to identify the movements and to imitate the motor acts from memory. The patient’s results were compared to results of individual subjects with parietal lobe lesions Ž6 patients with lesions in the right parietal cortex and 4 patients with lesions in the left parietal cortex; mean age 62 years, range 55᎐71 years. ŽHalsband, 1999; Halsband et al., 2000.. 2.2.2. Image acquisition 18 Fluordeoxyglucose ŽFDG. PET and three-dimensional Ž3-D. MRI data were acquired according to previously described standards ŽFriston et al., 1994; Juengling et al., 1999, 2000.. In detail, the patient was placed in an acoustically isolated and dimmed room for 20 min before injection. Image acquisition was started 40 min after application. Attenuation correction was performed mathematically using the standard algorithm implemented in ECAT 6.5 software. Initially, the patient’s head was aligned parallel to the orbitomeatal line to centre the brain within the acquisition volume. A short position scan was acquired to confirm the volume covered, and the
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
23
Table 1 Function
Testa
Score
Performance
Intellectual
WAIS-R
Picture Arrangement ŽPA.: RS 2; SS 3 Object Assembly ŽOA.: RS 30; SS 11 Block Design ŽBD.: RS 27; SS 10 Digit Span ŽDS.: RS 14; SS 11 IQ s 119
Within the average range on OA, BD DS. Severely impaired on PA Above average
Categories completed: RS 3; PR 6᎐10 Total number correct: RS 66 Total number of errors: RS 62; SS 77; PS 6 Perseverative errors: RS 33; SS 81; PS 10 Failure to maintain set: RS 4; PR - 1 142 s
Impaired
Digit Span Corsi Block Tapping Rey᎐Osterrieth Figure
RS 14; SS 11 Span forward: 6 Span backward: 6 Copy: RS 71; SS 12 I-Recall: RS 51; SS 13 D-Recall: RS 51; SS 13
Average Average
Token-Test
Errors: RS Žage-corr.. 14; PR 75
Mild aphasic impairment Severely impaired Preserved Moderately impaired Average
RSPM Cognitive flexibility
WCST
TMT-B Memory
Speechrlanguage
Naming Fluency Comprehension Repetition Spelling
Attentionr concentration
Visuo-spatial
2-Step commands corr.: 7r10 Single wordsrshort sentences: Corr.: 13r14 Corr.: Reg.: 10r10 Irreg.: 4r10 Non-words: 7r10
SKT
Impaired range
Upper average
Difficulty spelling irregular words
Within average range Impaired range
TMT-A
43 s
Rey-Figure Topography
Well organised; upper average range Good geographical orientation when provided with maps of Germany
Preserved
a WAIS-R, Wechsler Adult Intelligence Scale-Revised; RSPM, Raven’s Standard Progressive Matrices; WCST, Wisconsin Card Sorting Test; TMT-ArB, Trail Making Test ArB; SKT ŽSyndrom-Kurztest zur Erfassung von Aufmerksamkeits- und ., German memory and attention test battery; RS, raw score; SS, standard score; PR, percentile range; PS, Gedachtnisstorungen ¨ ¨ percentile score.
patient was repositioned to ensure covering the complete temporal lobes. For coregistration of the PET data set to the 3-D MRI, the scans of the different modalities were first registered onto each other using the automated image registration algorithm ŽAIR. ŽWoods et al., 1998.. Then, spatial normalisation to stereotaxic Talairach
space was performed on the 3-D MRI data set using SPM96 ŽFriston et al., 1994., and the parameters were transferred to PET data. The normalised FDG-PET data were compared to a normal database by computing pixelwise t-statistics for detection of hypometabolic areas. The normal database used for this comparison con-
24
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
sisted of 11 males, mean age 56 years, age range 50᎐66 years. All of them had no history of neurological or psychiatric disease, their clinical neuropsychological status was normal as tested by non-standardised interview. The MMSE score was 30 points in all patients. The resulting t-statistic was transformed to a normal statistic yielding a Z-score for each pixel. The Z-score voxel clusters were projected onto the realigned MRI data set using the SPM projection routine, which additionally displays the Talairach coordinates, thus allowing anatomic identification. Additional volumetric measurement studies of 3-D MRI were performed using the software package ANALYZE ŽCNSoftware, Essex, GB..
3. Results 3.1. Neuropsychological e¨ aluation (cf. Table 1) Mr B was administered the Raven’s Standard Progressive Matrices and he obtained an IQ of 119, indicating well-preserved non-verbal problem-solving abilities. He was impaired on the Wisconsin Card Sorting Test, but he showed normal cognitive flexibility in a German screening test battery, the SKT ŽErzigkeit, 1992.. His non-verbal memory was well preserved. On the complex Rey Osterreith-Figure, his performance was in the superior range for both the immediate and the delayed recall. Furthermore, the results of the Digit Span Test of the Wechsler Adult Intelligence Scale ᎏ revised ŽWAIS-R. and Corsi’s Block Tapping Task were above average. Visual memory, as assessed by the SKT and the Wechsler Memory Scale, was unimpaired. The patient had no obvious difficulties in topographical orientation. The patient presented with a pronounced form of anomia, as determined by the Aachen Aphasia Test ŽAAT. ŽHuber et al., 1984.. He was severely impaired in finding names of animate and inanimate objects. For instance, when shown a picture of a cow, the patient uttered the words horse or sheep. Interestingly, the naming difficulties occurred in the absence of problems in identifying
its distinguishing characteristics. The patient could draw a complex technical chart of the engine compartment, but he was unable to name its components, a problem he had been confronted with during his daily activities at work. He was, however, able to write to dictation the appropriate names with occasional orthographical errors. A standardised assessment ŽAAT. revealed an impairment in spelling irregular words Ž4r10. and non-words Ž7r10., while spelling of regular words was preserved Ž10r10.. Due to limited compliance of the patient, it was not possible to perform full range testing for aphasia. We could, however, show preserved fluency, average repetition, and moderately impaired comprehension. In the Token-Test, the patient showed mild aphasic impairment. Whereas he had difficulties in understanding the more complex instructions in this test, he gave no evidence of confusing colours and shapes. Both gesture comprehension and production were significantly impaired. While our patient had a predominantly left-temporal lesion, apraxic patients with dorsally located lesions of the left parietal lobe barely involving temporal lobe structures showed pronounced disturbances in the production of movements, but the comprehension of the symbolic and representational content of motor acts was less severely disturbed ŽFig. 1.. Mr B had difficulties in indicating the context in which the actions appear Že.g. to put one’s hand up at school.. Furthermore, the patient was impaired in the usage of tools. No problems occurred in action discrimination when evaluating whether a complex motor sequence was correctly performed. When provided with selected pictures of faces expressing basic emotions like happiness, sadness, fear, disgust or surprise, Mr B. was neither able to describe the feeling of the person Žexcept for happiness., nor could he imitate the facial expressions. He also had problems finding the context in which the emotions could appear. 3.2. FDG-PET and MRI Statistical analysis of the FDG-PET data revealed bihemispheric regions of significant hy-
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
25
Fig. 1. Distribution of errors in the recognition and production of pantomimed motor acts Žin %. made by the patient as compared to individual subjects with parietal lobe lesions Ž1᎐6: patients with lesions in the right parietal cortex; 7᎐10: patients with lesions in the left parietal cortex..
pometabolism Ž P- 0.001. when compared to the normal database within the temporal and frontal lobes: Reduced glucose metabolism within the temporal lobes was more pronounced and of a larger extent in the left hemisphere, where temporomesial structures as well as hippocampus, amygdala and neocortical areas were affected. The hypometabolic areas within the left temporal lobe included the middle temporal gyrus ŽMTG., inferior temporal gyrus ŽITG. and parahippocampal gyrus ŽGH.. For the hippocampus and the amygdala, reduced metabolism could be shown throughout each whole structure. The maximum Z-score value Ž Z s 4.25. was localised in the left amygdala ŽTalairach coordinates x s y30; y s y14; z s y24. ŽFig. 2A.. In the right hemisphere, only small hypometabolic areas within the MTG and ITG were found, whereas, both the hippocampal formation and amygdala showed no abnormalities in metabolism. Additionally, several disseminated focal areas of reduced FDG uptake were detected in frontal lobe areas bihemispherically. Morphological MR imaging re-
vealed marked temporal atrophy on the left side and mild atrophy on the right. Volumetric measurements of the amygdalae showed a reduction in volume of 29% on the left compared to the right, while left hippocampal volume was reduced by 25%. Covariate analysis suggested partial volume effects due to atrophy to be negligible Žobserved effect f 8%.. Image registration to 3-D MRI additionally confirmed that the hypometabolic regions projected onto grey matter areas ŽFig. 2B..
4. Discussion In this study we report neuropsychological and brain-imaging findings in a 59-year-old patient who presented with symptoms of semantic dementia Žin the absence of general cognitive decline. and apraxia characterised by difficulties in gesture comprehension and imitation. The patient suffered from pronounced anomia, manifested by severely impaired naming and im-
26
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
Fig. 2.
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
paired comprehension. Neuropsychological and clinical assessment revealed additional core diagnostic features of semantic dementia ŽNeary et al., 1998.. Preserved fluency, intact grammatical organisation, average repetition capacity, and preserved spelling of regular words could be demonstrated. Impairment in spelling irregular words and non-words can be interpreted as a mild surface dysgraphia or simply as a function of the educational level of Mr B. The performance of our patient in non-verbal memory tasks was preserved. Specifically, his performance in the Rey᎐Osterrieth Figure Test was in the upper average range, suggesting unimpaired perceptual matching and drawing reproduction capabilities, another core diagnostic feature of semantic dementia. The results of the Token Test ᎏ namely the absence of problems confusing colours and shapes ᎏ suggest that the anomia observed in this patient was not predominantly due to problems in auditory comprehension and encoding ŽLezak, 1995., but a consequence of an impairment of semantic processing or retrieval. While we cannot formally distinguish between semantic anomia and a pure retrieval deficit, our diagnosis of semantic dementia is in keeping with previous cases with a comparable cognitive profile and comparable morphological alterations ŽGraffRadford et al., 1990; Sakurai et al., 1998.. Anamnestic evidence provided by the patient and his wife points towards additional core features, such as prosopagnosia and an insidious onset with gradual progression of the disease. Brain imaging using registration of FDG-PET data to 3-D MRI showed marked left temporal atrophy as well as highly significant hypo-
27
metabolism localised within the cortical areas of the left middle temporal gyrus ŽMTG., left interior temporal gyrus ŽITG. and left parahippocampal gyrus ŽGH.. These findings are consistent with previous results showing atrophy of the inferior temporal lobe in patients with semantic dementia ŽHodges et al., 1992.. Recent PET studies demonstrated activation of the left temporal cortex upon retrieval of semantic memory in healthy subjects ŽWiggs et al., 1999. and substantially reduced activity, particularly in the left posterior inferior temporal gyrus, in patients with semantic dementia ŽMummery et al., 1999.. It is, therefore, reasonable to propose that the symptomatology observed in our patient correlates with the finding of both atrophy and hypometabolism in MTG, ITG and GH. Whereas the cognitive profile of our patient includes typical aspects of semantic dementia, the parallel occurrence of apraxia at an early stage of the disease is a less frequent finding. Anatomically, apraxias appear as a possible consequence following damage to the memory andror motor association areas, primarily in the posterior parietal lobe of the language-dominant hemisphere ŽHalsband and Freund, 1993; Heilman, 1979.. The disturbance of conceptual planning movement results in error-prone control of the primary motor areas, which appears as a temporal and spatial disintegration up to a total blocking of movements. In contrast to classical apraxia, we could not show anatomical lesions or alterations of metabolism in the posterior parietal lobe of our patient. However, both recognition and production of motor acts were impaired. While revealing the intricate interdependency between sensory
Fig. 2. ŽA. Distribution of hypometabolic areas. Upper row: maximum intensity projection of Z-scores onto the standard SPM glass brain. The red arrowhead marks maximum Z-value within the hippocampus ŽTalairach coordinates x s y30; y s y14; z s y24.. Lower row: fusion image of parametric maps with the individual 3-D MRI in axial, coronal and sagittal view. Z-score is indexed by the colour bar, maximum value localization marked by red cross-hair. ŽB. Representative corresponding slices Žrealigned to the stereotaxic coordinate grid by Talairach. of 3-D MRI Žrow 1., fusion images of coregistered MRI and PET Žrow 2. and FDG-PET Žrow 3.. For anatomic orientation, the Talairach z-coordinates are given at the bottom of each column. Colour encoding in percentages of global maximum activity ŽECAT countsrpixelrs. is indexed by the colour bar. In the 3-D MRI Žrow 1., note the asymmetry of the temporal lobes due to atrophy of the left side. The red arrows in the fusion images Žrow 2. point to hypometabolic areas in the hypotrophic left hippocampus. The white arrows mark the hypometabolic and hypotrophic left middle temporal gyrus ŽMTG..
28
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29
and motor processes this combined deficit points toward the need for further clarification of the relationship between disturbances of symbol formation, the meaningfulness and contextual usefulness of gestural content and motor output ŽJeannerod and Decety, 1995; Rizzolatti et al., 1996; Merians et al., 1997; Halsband, 1998.. Although our patient had major difficulties in recognition and production of pantomimed motor acts, he had no problems in driving his familiar car and in everyday actions, such as dressing himself or walking. This contextual dependence offers an interesting mode of access for the investigation of different levels of disturbance and suggests a context-specific interaction between cognitive representation and production ŽJeannerod and Decety, 1995.. Amygdala function has been suggested to play an important role for the ability to recognise emotional expression of human faces ŽMorris et al., 1996, 1998.. Mr B was not able to describe emotions, like sadness, fear, disgust or surprise, presented in selected pictures of human faces. We found a 25% reduction in volume as well as a highly significant hypometabolism Ž Z s 4.25, P0.001. in the left hippocampusramygdala complex, excluding partial volume effects due to atrophy. Amygdala function has been shown to be involved in the ability to recognise the emotional expression of human faces ŽMorris et al., 1998.. Clinically, Mr B presented with moderately expansive mood, blunted and inappropriate affect as well as sudden angry outbursts, suggesting frontal lobe pathology. Hypometabolism in several disseminated bihemispheric focal areas of the frontal lobe correlated with the clinical presentation. In contrast to some of the patients with semantic dementia described before ŽGraff-Radford et al., 1990; Edwards-Lee et al., 1997., our patient attained an MMSE score of 28, suggesting an early state of the disease. Nevertheless, we found extensive brain damage in our patient, resulting in anomia as well as marked apraxia. This combined deficit shows that early manifestations of seemingly highly selective deficits reveal a complex pattern of neuropsychological, metabolic and anatomical defects.
References Edwards-Lee, T., Miller, B.L., Benson, D.F., Cummings, J.L., Russell, G.L., Boone, K., Mena, I., 1997. The temporal variant of frontotemporal dementia. Brain 120, 1027᎐1040. Erzigkeit, H., 1992. Kurztest zur Erfassung von Gedachtnis¨ und Aufmerksamkeitsstorungen SKT. Weinheim. ¨ Friston, K.J., Holmes, A.P., Worsley, K.J., Poline, J.P., Frith, C.C., Frackowiak, R.S.J., 1994. Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping 2, 189᎐210. Graff-Radford, N.R., Damasio, A.R., Hyman, B.T., Hart, M.N., Tranel, D., Damasio, H., Van Hoesen, G.W., Rezai, K. et al., 1990. Progressive aphasia in a patient with Pick’s disease. Neurology 40, 620᎐626. Halsband, U., 1998. Brain mechanisms of apraxia. In: Milner, A.D. ŽEd.., Comparative Neuropsychology. Oxford University Press, New York. Halsband, U., 1999. Neuropsychologische und neurophysiologische Studien zum motorischen Lernen. Pabst Science Publishers, Lengerich, Berlin. Halsband, U., Freund, H.J., 1993. Motor learning. Current Opinion in Neurobiology 3, 940᎐949. Halsband, U., Weyers, H.M., Schmitt, J., Binkowski, F., Grutzner, G., Freund, H.J., 2000. Recognition and imita¨ tion of pantomimed motor acts after unilateral lesions to the parietal cortex as compared to premotor areas: a perspective on apraxia. Neuropsychologia, in press. Heilman, K.M., 1979. Apraxia. In: Heilman, K.M., Valenstein, E. ŽEds.., Clinical Neuropsychology. Oxford University Press, New York. Hodges, J.R., Patterson, K., Oxbury, S., Funnel, F., 1992. Semantic dementia. Progressive fluent aphasia with temporal lobe atrophy. Brain 115, 1783᎐1806. Huber, W., Poeck, K., Willmes, K., 1984. The Aachen Aphasia Test. Advances in Neurology 42, 291᎐303. Jeannerod, M., Decety, J., 1995. Mental motor imagery: a window into the representational stages of action. Current Opinion in Neurobiology. 5, 727᎐732. Juengling, F.D., Kassubek, J., Moser, E., Nitzsche, E.U., 1999. Precise localization of dysfunctional areas in vertebro-basilar infarction by FDG- and H 2 15 O-PET using standardized image analysis and image registration to 3-D MR. Nuklearmedizin 38, 341᎐344. Juengling, F.D., Kassubek, J., Otte, A., 2000. Standardization of cerebral PET imaging in clinical neurological diagnostics. European Journal of Nuclear Medicine 27 Ž1., 98. Lezak, M.D., 1995. Neuropsychological Assessment, 3d ed. Oxford University Press, OxfordrNew York. Kertesz, A., Munoz, D.G., 1997. Primary progressive aphasia. Clinical Neurosciences 4, 95᎐102. Kertesz, A., Davidson, W., McCabe, P., 1998. Primary progressive aphasia: a case study. Journal of the International Neuropsychological Society 4, 388᎐398. Merians, A.S., Clark, M., Poizner, H., Macauley, B., Gonzalez Rothi, L.J., Heilman, K., 1997. Visual-imitative dissociation apraxia. Neuropsychologia 35, 1483᎐1490.
G. Schumann et al. r Psychiatry Research: Neuroimaging 100 (2000) 21᎐29 Mesulam, M.M., 1982. Slowly progressive aphasia without generalized dementia. Annals of Neurology 11, 592᎐598. Morris, J.S., Frith, C.D., Perrett, D.I. et al., 1996. A differential neural response in the human amygdala to fearful and happy facial expressions. Nature 383, 812᎐815. Morris, J.S., Friston, K.J., Buchel, C., Frith, C.D., Young, ¨ A.W., Calder, A.J., Dolan, R.J., 1998. A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain 121, 47᎐57. Mummery, C.J., Patterson, K., Wise, R.J., Vandenbergh, R., Price, C.J., Hodges, J.R., 1999. Disrupted temporal lobe connections in semantic dementia. Brain 122, 61᎐73. Neary, D., Snowden, J.S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P.H., Albert, M., Boone, K., Miller, B.L., Cummings, J., Benson, D.F., 1998. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51, 1546᎐1554.
29
Rizzolatti, G., Fadiga, L., Gallese, V., Fogassi, L., 1996. Premotor cortex and the recognition of action. Cognitive Brain Research. 3, 131᎐141. Rossor, M.N., Revesz, T., Lantos, P.L., Warringtom, E.K., 2000. Semantic dementia with ubiquitin-positive tau-negative inclusion bodies. Brain 123, 267᎐276. Sakurai, Y., Murayama, S., Fukusako, Y., Bando, M., Iwata, M., Inoue, K., 1998. Progressive aphemia in a patient with Pick’s disease: a neuropsychological and anatomic study. Journal of the Neurological Sciences 159, 156᎐161. Wiggs, C.L., Weisberg, J., Martin, A., 1999. Neural correlates of semantic and episodic memory retrieval. Neuropsychologia 37, 103᎐118. Woods, R.P., Grafton, S.T., Holmes, C.J., Cherry, S.R., Mazziotta, J.C., 1998. Automated image registration. General methods and intrasubject intramodality validation. Journal of Computer Assisted Tomography 22, 141᎐154.
