NOTE BEHAVIORAL EFFECTS OF DAMAG ETO THE RIGHT INSULA AND SURROU NDING REGIONS 1 Marcelo Berthier, Sergio Starkstein 2 and Ramon Leiguarda (Dr. Raul Carrea Institute for Neurological Research - FLENI) Since Broca's (1863) description of a case of aphasia following a localized brain lesion, great efforts have been devoted to the study of cortical areas specialized in different neuropsychological functions (Damasio and Geschwind, 1985). Nevertheless, the literature on behavioral .deficits produced by insular lesions is scanty. We report the case of a right-handed patient who after an ischemic infarction that involved the entir~ insular cortex and adjacent white matter on the right hemisphere developed multimodal neglect, mutism, oral apraxia and ideomotor apraxia for the right hand. CASE REPORT A 55-year-old male college graduate, with a history of rheumatic mitral valve disease, valvular surgery at 50, and on oral anticoagulants since then, abruptly developed on December 7, 1984loss of articulate language with preservation of comprehension (aphemia) and left-sided weakness. He was strongly right-handed and there was no history of familial sinistrality or early brain damage. On examination the patient was alert, oriented in space and person but not to time. He could communicate only by writing. He wrote compulsively with a wide left margin, extra strokes and a noticeable upward slant. He was unable to read aloud or repeat simple words. Comprehension of written language and denom­ ination by writing were preserved. Mental as well as written calculation were impaired. The patient was aware of his condition and worried about his future. He tended to turn his head and eyes to the right and failed to orient to stimuli presented on the left. The patient did not respond to either somesthetic or nociceptive stimuli on the left side, where proprioception was also abolished. He did not move his left limbs either spontaneously or in reaction to painful stimuli. 1 This work has been presented in part at the Thirty-eighth Annual Meeting of the American Academy of Neurology. New Orleans, USA, April 1986, and was published in abstract form in Neurology, 36 (Supp I), pp. 318, April 1986. Present address: Depart. of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Meyer Building 4-119, Baltimore, USA. 2 Cortex (1987) 23, 673-678 674 Marcelo Berthier, Sergio Starkstein and Ramon Leiguarda Fig. I -Patient's draw­ ing showing left hemispatial neglect and constructional apraxia.· However, on being ordered to look at his left limbs and urged strongly to move them, he was able to do so, disclosing only a mild hemiparesis. Left hyperreflexia with clonus and an extensor plantar response were also present. Neither on command nor to imitation could the patient imitate the gallop of a horse, blow out a match or throw a kiss. He could not perform transitive movements on command with his right hand, but showed a mild improvement when given the actual object or shown how to perform the movement. His left arm was impos­ sible to assess because of his severe motor neglect. Visual fields were full but he invariably extinguished left visual and auditive stimuli on double simultaneous stimulation. When he performed the Line-Crossing-Out-Task (Albert, 1973), he omitted cancelling many of the left lines. He also omitted the left details on Fig. 2 - CT-scan showing an ischemic infarction involving the right insula. Insular infarction 675 TABLE I A Summary of the Most Relevant Neuropsychological Deficiencies Neuropsychological testing Normal scpre Three dimensional block construction 29 formA Motor impersistence 0-2 errors (24-32) Visual form discrimination (41-54) Facial recognition 8/10 Tactile form perception * Judgement of line orientation (21-30) * Assessed for the right hand only. Patient score 10 5 errors 15­ 34 4/10 20 (severely defective) (severely defective) (severely defective) (severely defective) (defective) (borderline) drawing figures (Figure 1). These clinical findings persisted unchanged until death, one month later. An EEG·showed right fronto-temporal slowing. ACT­ scan demonstrated a right ischemic infarction that destroyed the entire insula and the inner cortical surface of the adjacent fronto-temporo-parietal operculum (Figure 2). The patient was assessed using a comprehensive neuropsychological battery (Table 1), which showed severe impairment on the following tasks: Three­ Dimensional Block Construction, Motor lmpersistence, Facial Recognition, Visual Form Discrimination and Tactile Form Perception (Benton, Hamsher, Varney and Spreen, 1983). He performed flawlessly on a Phoneme Discrimina­ tion Task (Benton et al., 1983) and also showed adequate comprehension of intoned speech and facial emotions. On the Edinburgh Inventory of Handedness (Oldfield, 1971) his laterality quotient was+ 100 (extreme right-handed). Following his stroke, the patient developed nocturnal anxiety, agitation and initial insomnia. Although he denied being depressed, a Dexamethasone Supres­ sion Test (DST) showed non-supression (basal plasmatic cortisol: 13.6 ug/ dl, 8 AM: 9.8 ug/dl, 4 PM: 7.8 ug/dl, 11 PM: 5.1 ug/dl). Treatment for depression unfortunately could not be initiated since he suffered a cardiac arrest on January 3, 1985. He responded to resuscitation maneuvres but remained unconscious. A repeat CT-scan disclosed a new low-density lesion in the right corona radiata. Some hours later he died after a second cardiac arrest. Fig. 3 -Drawn coronal sections of the right hemisphere showing the lesion involving the entire insula and the inner cortical surface on the fronto-temporo-parietal operculum. 676 Marcelo Berthier, Sergio Starkstein and Ramon Leiguarda On anatomo-pathological examination, an ischemic infarction involving the whole right insular cortex, adjacent white matter, extreme capsule and the inner cortical surface of the right fronto-temporo-parietal operculum was observed (Figure 3). There was no damage on the left hemisphere. Small infarcts (less than 1 em in diameter) and diffuse demyelinization were also observed in the right corona radiata, both attributable to agonal events. DISCUSSION , A severe neglect syndrome, oral apraxia, mutism and ideomotor apraxia for the right hand developed in our patient following infarction of the right insular cortex and adjacent white matter. On clinical examination the salient features of his neglect were a tendency to tum eyes and head towards the side of the lesion, contralateral lack of sponta­ neous movement, tactile inattention and difficulty in performing tasks that require adequate scanning of external space to the left. Taken together, these findings resemble a predominantly "frontal-type" neglect (Mesulam, 1981). Although clinical descriptions of cases with restricted insular lesions are indeed rare, insular anatomy, connectivity and physiology have been extensively studied in monkeys and man (Mesulam and Mufson, 1985). The insula consti­ tutes a polymodal convergence area (Pandya and Kuypers, 1969; Jones and Powell, 1970; Guldin and Markowitsch, 1984; Mesulam and Mufson, 1985), whose anterior portion has main connections with orbitofrontal, temporopolar and olfactory cortices, anterior cingulate and parahippocampal gyri, thalamus and amygdala (Mesulam and Mufson, 1985; Mufson and Mesulam, 1984) and participates in olfactory, gustatory, autonomic and limbic functions (Penfield and Faulk, 1955; Benjamin and Burton, 1968; MesulamandMufson, 1985). The posterior insula has main connections with frontal, temporal and parietal cortices as well as the thalamus (Mufson and Mes~am, 1984; Mesulam and Mufson, 1985). It functions in relation to external space, participating in somesthetic, auditory and skeletomotor behavior (Showers and Laver, 1961; Fallon, Beneven­ to and Loe, 1978; Robinson and Burton, 1980; Mesulam and Mufson, 1985). Given its strategic location, it relays sensory information into the limbic system after receiving data from all sensory modalities (Mesulam and Mufson, 1985). In our patient, the insular lesion probably disrupted connections with impor­ tant areas normally involved in arousal, attention and activation, such as the cingulate gyrus, prefrontal cortex, area 6 and centromedian, parafascicular, reticular and medial pulvinar thalamic nuclei. There also was damage to the white matter adjacent to the insular cortex and subjacent to the inferior parietal lobe, so that the neglect syndrome might also be contingent on the interruption of the attentionalloop as parietal level. It was significant that the patient exhibited a total loss of pain perception on the left side. Although this finding may be interpreted as a component of a severe neglect syndrome, there is·an alternative explanation. Biemond ( 1956) described the case of a patient who suffered a right hemispheric stroke involving the insula, rolandic operculum and the adjacent centrum semiovale, exhibiting as the salient feature a complete analgesia on the left side of the body. Biemond speculated that the absence of pain perception may be attributable to the involvement of the second somatosensory area (SII). However, since in our patient damage on SII Insular infarction 677 was only minor and limited to the inner portion of the parietal opercular cortex, we would rather agree with Mesulam and Mufson's (1985) hypothesis in that the loss of pain perception should be ascribed to a somesthetic-limbic (posterior insula-amygdala) disconnection. Geschwind (1965) advanced a similar explana­ tion for the lack of appropriate response to painful stimulation in patients presenting asymbolia for pain, pointing out that an insular lesion is crucial for disconnecting SII from the limbic system. In our patient, language as well as oral and limb praxis (all typical left hemisphere functions) were lateralized to the right side, his "crossed" aphemia coexisting with the neglect syndrome. Previous reports (Henderson, 1983; Basso, Capitani, Laiacona and Zanobio, 1985) are coincident with our finding, suggest­ ing that right side language representation in some crossed aphasics may fail to modify right hemisphere dominance for attention and visuospatial skills. Finally, our right-handed patient also showed oral and ideomotor apraxia for the right hand, suggesting a dissociation between dominance for handedness (left hemisphere) and dominance for kinesthetic motor engrams (right hemisphere). A similar case showing dissociation of handedness and motor skills has been recently reported by Rapcsak, Gonzalez Rothi and Heilman ( 1986), and Kramer, Delis and N akada (1985) recently reported the case of a right-handed patient who developed a buccofacial apraxia following a right parietal lesion ("crossed apraxia"). These findings suggest that handedness does not always determine location for kinesthetic motor engrams, and that there may be a subgroup of right handed individuals who, like our patient, have their motor engrams stored in the right hemisphere (Rapcsak et al., 1986). ABSTRACT A severe multimodal neglect syndrome, mutism, oral apraxia and ideomotor apraxia for the right hand suddenly developed in a right-handed male following a right hemisphere (central) stroke. Neuropathologic examination showed an ischemic infarction involving the whole right insula, adjacent white matter, and the inner cortical surface of the right fronto-temporo-parietal operculum. The left hemisphere was spared. It is suggested that damage to the right insula (a poly­ modal convergence area), and the adjacent white matter may lead to severe neglect. Our case also demonstrates a clear dissociation between dominance for handedness and dominance for kinesthetic motor engrams. Acknowledgements. The authors are indebted to Dr. Elliot D. Ross and Dr. Robert G. Robinson for their valuable advice while preparing the manus­ cript. Dr. Enrique Faccio performed the neuropathological study. This research has been supported by a grant from Instituto Di Tella, Buenos Aires, Argentina. REFERENCES ALBERT, M.A. A simple test of visual neglect. Neurology, 23: 658-664, 1973. BASSO, A., CAPITAN!, E., LAIACONA, M., and ZANOBIO, M. Crossed aphasia: one or more syndromes? Cortex, 21: 25-46, 1985. 678 Marcelo Berthier, Sergio Starkstein and Ramon Leiguarda BENJAMIN, R.M, and BURTON, H. Projection of taste nerve afferents to anterior opercular­ insular cortex in squirrel monkey (Saimiri sciureus). Brain Research, 7: 221-231, 1968. BENTON, A.L., HAMSHER, K., VARNEY, N.R., and SPREEN, 0. Contributions to Neuro­ psychological Assessment. New York: Oxford University Press, 1983. BIEMOND, A. The conduction of pain above the level of the thalamus opticus. Archives of Neurology and Psychiatry, 75: 231-244, 1956. BROCA, P. Localisation des fonctions cerebrales: siege du langage articule. Bulletin de Ia Societe d'Anthropologie de Paris, 4: 200-203, 1863. DAMASIO, A.R. and GESCHWIND, N. Anatomical localization in clinical neuropsychology. In P.J. Vinken, G.W. Bruyn and H.L. Klawans, (Eds), Handbook ofClinical Neurology. Clinical Neuropsychology. North Holland, Amsterdam Elsevier, Vol. 45, Ch. 2, pp 7-22, 1985. FALLON, J.H., BENEVENTO, L.A., and LOE, P.R. (Frequency~dependentto.tonesinneu• rons of cat insular cortex (AIV). Brain Research, 145: 161-167, 1978. GESCHWIND, N. Disconnexion syndromes in animals and man. Part. I Brain, 88: 237-294, 1965. GULDIN, W.O., and MARKOWITSCH; H.J. Cortical and thalamic afferent connections of the insular and adjacent cortex of the rat. Journal of Comparative Neurology; 229: 393-418, 1984. HENDERSON; V.W. Speech fluency in crossed aphasia. Brain,106:. 837-858, 1983. JONES, E.G., and PowELL, T.P.S. An anatomical study of conveying sensory pathways within the cerebral cortex of the monkey. Brain, 93: 793-820, 1970. KRAMER, J.H., DELIS, D.C., and NAKADA, T. Buccofacial apraxia without aphasia due to a right parietal lesion. Annals of Neurology,-18: 512-514, 1985. MESULAM, M.M. A cortical network for directed attention and unilateral neglect. Annals of Neurology, 10: 309-325, 1981. · MESULAM, M.M., and MUFSON, E.F. The insula of Reil in man and monkey. Architec­ tonics, connectivity and function. In A Peters and E.G. Jones (Eds.), Cerebral Cortex. New York: Plenum Press, Vol. 4, Ch. 5, pp. 179-226, 1985. MUFSON, E.F., and MESULAM, M.M. Thalamic connections of the insula in the rhesus monkey and comments of the paralimbic connectivity of the medial pulvinar nucleus. Journal of Comparative Neurology, 227: 109-120, 1984. OLDFIELD, R.C. The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia, 9: 97-113, 1971. PANDYA, D.N., and KUYPERS, H.G.J.M. Cortico-cortical connections in the rhesus mon­ key. Brain Research, 13: 13-36, 1969. PENFIELD, W., and FAULK, M.E. The insula. Brain, 78: 445-470, 1955. RAPCSAK, S.Z., GONZALES ROTHI, L.J., and HEILMAN, K.M. Apraxia in a patient with atypical cerebral dominance. Neurology, 36 (supp/.1): 345, 1986. ROBINSON, C.L., and BURTON, H. Somatic submodality distribution within the second somatosensory (SII), 7 b, retroinsular, post-auditory and granular insular cortical areas of M. fascicularis. Journal of Comparative Neurology, 192: 93-108, 1980. SHOWERS, M.J.C., and LAVER, E.W. Somatovisceral motor patterns in the insula. Journal of Comparative Neurology, 109: 261-315, 1961. Dr. Marcelo Berthier, Institute de Investigaciones Neurol6gicas Dr. R..Carrea- FLENI, Ayacucho 2166, 1112, Buenos Aires, Argentina.