Medial Frontal Cortex Infarction and the Alien Hand Sign Gary Goldberg, MD; Nathaniel H. Mayer, MD; Joseph U. Toglia, MD \s=b\ Two right-handed patients with infarction involving the left medial frontal cortex are described. Both patients exhibited a form of transcortical motor aphasia and a psychomotor disturbance involving the right arm characterized by forced grasping, motor perseveration, and the presence of apparently purposeful movements that appeared to be dissociated from conscious volition. The latter feature is noted to be identical to the alien hand sign as described in the left arm of commissurotomized patients and patients with callosal neoplasm or infarction. It is suggested that the observed dissociation of conscious intention from purposeful movement may be related to dysfunction of the medial frontal cortex contralateral to the impaired extremity as much as to hemispheric disconnection. (Arch Neurol 1981;38:683-686) stress the non-unity of the personality in patients with callosal section and its possible psychiatric effects."3 He then quoted Goldstein's description of a patient who complained "of a feel¬ ing of strangeness in relation to the movements of the left hand which she described with such curious expres¬ sions (she would say that someone was moving her hand and that she wasn't doing it herself) that she was regarded at first as a paranoiac."3·4 In this article, we describe two patients who, in addition to other findings, exhibited the alien hand sign in the right arm in association with infarction involving the left medial frontal cortex as documented by radionuclide scan and computed tomography (CT). REPORT OF CASES Case 1.—A 63-year-old, right-handed rPhe concept of the "alien hand" was introduced by Brion and Jedynak1 based on their observations of three patients with tumors of the corpus callosum. In reviewing the syndrome following cerebral commissurotomy, Bogen described the alien hand sign as "a circumstance in which one of the patient's hands behaves in a way which the patient finds 'foreign,' 'alien,' or at least uncooperative."2 Geschwind indicated that Kurt Goldstein "was perhaps the first to woman was first observed to have difficul¬ Accepted for publication Feb 26, 1981. From the Departments of Rehabilitation Medicine (Drs Goldberg and Mayer) and Neurology (Dr Toglia), Temple University Faculty of Medicine, Philadelphia. Reprint requests to Department of Rehabilitation Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, M5G 1\m=x\5, Ontario, Canada (Dr Goldberg). Three weeks after onset, she still did not initiate conversation but rather remained silent until spoken to. Her verbal output was characterized by difficulty in initiat¬ ing responses, struggle, and hesitation. In repetition of phrases, her speech was entirely intact. Her verbal comprehension was quite good. The movement in the arm ... ty in speaking and weakness of the right leg. She appeared alert but did not initiate conversation. She spoke very haltingly in reply to questions. Her comprehension of speech was good, as was her ability to repeat complex phrases and sentences. She had a mild right facial weakness, a moder¬ ate paresis of the right arm, and a total paralysis of the right leg. A strong grasp reflex was noted in the right hand. Com¬ puted tomography demonstrated an area of decreased density in the left frontal medial cortex (Fig 1), and a subsequent isotope scan showed increased uptake in this same area (Fig 2). Downloaded From: http://archneur.jamanetwork.com/ by a University of Manitoba User on 06/18/2015 had recovered to the point where she had good strength and was not bound to syner¬ gies. The right leg remained impaired and she was not yet ambulatory. The right arm was noted to display the following motor behavior: 1. There was a strong grasp reflex in the right hand. 2. The patient would reach out sponta¬ neously with the right hand and then would not be able to release her grip voluntarily. She was unable consciously to inhibit this behavior although she was quite aware of it and was obviously frustrated by her inabil¬ ity to prevent it. She tended to restrain the movement of the right arm by holding it by her side with the more "obedient" left arm. At times, the right arm was noted to interfere with tasks being performed by the left arm. This "intermanual conflict"2·5 was observed at one point when it was noted that her right hand came up to keep her glasses on after she had begun to remove them with the left hand. She was aware of these conflicts but was, again, Fig 1.—Case 1, computed tomograms demonstrate area of decreased density in left medial frontal cortex (arrows). Fig 2.—Case 1, radionuclide brain scan showing area of increased uptake along posteromedial aspect of left frontal lobe. Above, anterior view; below, left lateral view. frustrated by being unable to prevent them consciously. 3. Motor perseveration was evident. The patient would begin to perform a task with her right arm but it would begin to persev¬ erate uncontrollably. The left arm would then interrupt the perseveration by re¬ straining the right arm and then complete the task. This was noted, for example, on several occasions when she was attempting to apply the brakes on her wheelchair. Later, a slowly improving ability devel¬ oped to inhibit to some extent the unwanted behavior of the right arm through concentrated effort. When these unwanted activities of the right arm began to interfere with performance of some task, they could be interrupted by the examiner through the issuance of a simple motor command, such as "place your right arm across your lap." The patient would then be able to obey this command and, in the process of doing so, override the aber¬ rant motor behavior. In the fifth week after onset, the patient Fig 3—Case 2, radionuclide brain scan demonstrates zone of increased uptake extending along medial aspect of left frontal lobe. Above, anterior view; below, left lateral view. began to walk alone. The right arm would, however, tend spontaneously to reach out and grasp objects (eg, door knobs) that she passed, thus interfering greatly with her progression. This was minimized by having her repetitively tap on her thigh with the right hand as she walked or walk with a cane held in the right hand. Case 2.—A 76-year-old, right-handed woman was first observed after having collapsed with sudden muteness and rightsided weakness. A brain scan done one week following admission showed in¬ creased uptake in the left medial frontal cortex (Fig 3). A lesion in this area was confirmed by CT scan (Fig 4). On examination three weeks after onset, she was fully alert and able to respond to questions with single-word replies al¬ though she did not initiate conversation spontaneously. Her responses were charac¬ terized by a great deal of difficulty in initiation. She could repeat complex phrases without difficulty. Her verbal com¬ prehension was good. She tended compul- Downloaded From: http://archneur.jamanetwork.com/ by a University of Manitoba User on 06/18/2015 sively to repeat parts of questions asked of her before struggling to initiate a response and tended to whisper her reply. When she spoke on the telephone as opposed to faceto-face, her conversational speech was sig¬ nificantly improved. A strong grasp reflex was noted in the hand. Spontaneous goal-directed movements of the right arm were noted to right that, judging by the patient's them, did not seem to be consciously intended. For example, at one point it was noted that the patient had picked up a pencil and had begun scribbling with the right hand. When her attention was directed to this activity, she reacted with dismay, immediately withdrew the pencil, and pulled the right hand to her side using the left hand. She then indicated that she had not herself initiated the original action of the right arm. She often reacted occur response to with dismay and frustration at her inabili¬ ty to prevent these unintended movements of the right arm. She experienced a feeling of dissociation from the actions of the right speech disturbance would be expected to appear with damage to the "supple¬ mentary motor area and related para- Fig 4.—Case 2, computed tomograms demonstrate area of decreased density in¬ volving left medial frontal cortex (ar¬ rows). arm, stating on several occasions that "it will not do what I want it to do." She also displayed motor perseveration of the right arm when she attempted to use it. Often, she would attempt to restrain these unwanted actions of the right arm by holding it by her side with the left arm. The aberrant behavior of the right arm could be interrupted when the examiner issued a simple verbal command. COMMENT Our two patients both displayed a strong grasp reflex in the right hand. They were both noted to have motor perseveration, ie, inappropriate repe¬ tition of a simple movement of the right hand and arm usually triggered by an attempt at voluntary activity. Both patients additionally exhibited a speech disorder consisting of a lack of spontaneous speech production with preserved ability to repeat. This pattern is often designated transcor¬ tical motor aphasia, although some authors have argued that it is not indeed an aphasia.6 Goldstein has attributed this form of speech impair¬ ment to either a "heightening of the speech threshold" or, more typically, an attenuation or loss of the "speech impulse."7 This type of speech distur¬ bance has been described in patients who have sustained damage to the left medial frontal cortex.8 u Brown12 has suggested that this form of "partial mutism" observed in such patients may be a disturbance intermediate between the total mutism associated with bilateral damage of the cingulate gyrus and the "selective speech loss" seen in left-sided neocortical damage of the classic motor areas for speech. He has further postulated that such a limbic structures derived from, and possibly including, the cingulate por¬ tion of the limbic system."12 Shahani et al presented the case of a right-handed patient who had suf¬ fered infarction of the medial frontal cortex due to occlusion of the left pericallosal artery.13 He had trouble¬ some spontaneous grasping and motor perseveration in the right arm, of which he was fully aware but could not consciously inhibit. He tended to re¬ strain these movements of the right arm using his left arm. The authors found, as we did in our patients, that the ability to execute a new movement with resulting inhibition of the aber¬ rant movement was retained. They speculated that the association of the grasp reflex with motor perseveration was significant and that the problem common to both behaviors may be a deficiency in the mechanism that pro¬ duces the voluntary inhibition of movement. The medial frontal cortex, they believed, was somehow involved with this mechanism.13 In our patients, apparently purpose¬ ful (ie, goal-directed) movements that appeared to be occurring independent of conscious volitional control were noted in the right arm. In patient 1, there was also some evidence of con¬ flict between the motor behaviors of the two arms, with the right arm being the identified offender. Both patients exhibited the adaptive action of controlling the unwanted activity by restraining the right arm physi¬ cally with the left arm. Bogen has recently described sev¬ eral dissociative psychomotor phe¬ nomena observed in an "acute discon¬ nection syndrome," a transient state seen in patients in the first few weeks following section of the corpus callosum for intractable epilepsy.2 These include "intermanual conflict," the "alien hand sign" as defined previous¬ ly, and "autocriticism," another phe¬ nomenon observed in both presented cases, in which the patient expresses astonishment and frustration fre¬ quently in reaction to "the capacity of the hand to behave independently of conscious volition." Similar phe¬ nomena have been described by other investigators following commissurotomy5 and in association with midline tumors.1 These dissociative phenom¬ ena can be distinguished from those classically associated with parietal lobe damage, such as autotopagnosia, in that the latter seem to be related to impaired interpretation of body per... Downloaded From: http://archneur.jamanetwork.com/ by a University of Manitoba User on 06/18/2015 ception, whereas the former would appear to be a misinterpretation of body action. Are these behaviors due to damage to the corpus callosum alone and do they result from deficits in only interhemispheric transfer? Damage to the corpus callosum cannot be ruled out in the two cases reported. However, in the right-handed, split-brain patients, the alien hand sign was invariably observed with respect to the behavior of the left hand.2 5 Why, then, should the identical problem have been observed in the right hand of the right-handed patients with left me¬ dial frontal cortex infarctions? It is possible that these peculiar dissocia¬ tive psychomotor behaviors result in part from damage to medial frontal cortex contralateral to the involved extremity. In the commissurotomized patients, their transient occurrence could have resulted from retraction of the medial surface of the nondominant right hemisphere intraoperative- ly in the course of exposing the corpus callosum for section.14 Two functional zones on the medial surface of the frontal lobes, damage to which may be implicated in the ap¬ pearance of this psychomotor distur¬ bance, as well as the speech disorder, are the supplementary motor area (SMA) and the cingulate cortex. These two areas are reciprocally intercon¬ nected.6 Electrical stimulation in con¬ scious human subjects seems to elicit similar forms of behavior from both the SMA and anterior cingulate cor¬ tex.1516 Penfield and Jasper reported that stimulation of the SMA produced vocalizations, speech arrest, complex coordinated or repetitive movements usually appearing in the contralateral arm, and arrest or slowing of volun¬ tary action following which it was noted that the patient was "usually puzzled by his inability to execute" the action he had intended.15 Talairach et al found that continuous electrical stimulation of anterior cingulate cor¬ tex in epileptic patients produced complex, highly integrated forms of motor behavior that resulted from compounding of various simple "prim¬ itive" movements that appeared most often in the contralateral arm.16 Sanides17 has shown that, in the primate brain, the SMA is a paralimbic expan¬ sion zone of encephalized limbic (cin¬ gulate) cortex and that it is of cytoarchitectural form intermediate in type between limbic cortex and neocortex. In primate studies, Mountcastle et al18 have attributed voluntary motor command functions to cells in posteri¬ or parietal cortex (area 7), but in a recent study, Robinson et al19 found that cells in this area were consistently activated by specific stimuli and that their activity was enhanced when a subsequent motor response occurred. Whether or not the enhancement of the neuronal activity and the associated overt motor re¬ sponse would appear following a sen¬ sory trigger was believed to depend on the coupling of a motivational-behav¬ ioral influence. The authors suggested that such an influence could arrive via afférents to posterior parietal cortex from the cingulate gyrus.20·21 Damasio and Van Hoesen have described four patients with lesions involving the left SMA as localized by CT scan. These patients were noted to have initially exhibited a global akinesia that eventually became circum¬ scribed to the right side of the body. The authors concluded that damage to the SMA decreased the "drive" to execute both spontaneous and voli¬ tional movement.6 Recently, regional cerebral blood more flow studies in man have demon¬ strated bilateral activation of the SMA in association with various com¬ plex movements of the extremities as well as with speech, and it has been hypothesized that the SMA functions in the "programming" of these motor acts, ie, the SMA was believed to be involved in the assembly and execu¬ tion of time-ordered sequences of motor instructions in algorithmic form.2224 On the basis of these region¬ al cerebral blood flow studies as well as additional evidence in man and animals, Orgogozo and Larsen25 have suggested that the SMA may act in a "supramotor" capacity in the cortical organization of voluntary movements. They postulated that the SMA may contribute to the establish¬ ment of new motor programs and probably controls the execution of established sub¬ routines according to external and internal inputs. Its anatomical connections and the available physiological data suggest that the SMA could be the place where external inputs and commands are matched with internal needs and drives to enable the formulation of a strategy of voluntary movements.24 The alien hand sign and the accom¬ panying dissociative psychomotor dis¬ turbances, as well as the speech disor¬ der associated with left medial frontal cortex damage, could be interpreted as faulty initiation, execution, and inhibition of preexisting essentially intact motor subroutines. These pro¬ gram controls may no longer be cou¬ pled normally to "external and inter¬ nal inputs." The appearance of these dissociative phenomena may thus be related to damage to the SMA, its connecting fibers, or associated struc¬ tures located on the medial frontal surface of the hemisphere contralater¬ al to the involved extremity. Meeta Peer, MD, assisted with case 1; Ida Bracht and Ron Kalstein provided technical assistance; and Judith Ottervik, Paula Sobel, MA, CCC, Deborah Minden, MA, Carson Schneck, MD, PhD, and Richard Herman, MD, provided helpful discussion and comments during the preparation of this article. References 1. Brion S, Jedynak C-P: Trouble du transfert interh\l=e'\misph\l=e'\rique\l=a`\propos de trois observations de tumeurs du corps calleux: Le signe de la main \l=e'\trang\l=e'\re.Rev Neurol 1972;126:257-266. 2. Bogen JE: The callosal syndrome, in Heilman KM, Valenstein E (eds): Clinical Neuropsychology. New York, Oxford University Press, 1979, pp 308-359. 3. Geschwind N: Disconnexion syndromes in animals and man. Brain 1965;88:237-294, 585\x=req-\ 644. 4. Goldstein K, cited by Geschwind N: Disconnexion syndromes in animals and man. Brain 1965;88:237-294, 585-644. 5. Wilson DH, Reeves A, Gazzaniga M, et al: Cerebral commissurotomy for control of intractable seizures. Neurology 1977;27:708-715. 6. Damasio AR, Van Hoesen GW: Structure and function of the supplementary motor area. Neurology 1980;30:359. 7. Goldstein K: Language and Language Disturbances. New York, Grune & Stratton Inc, 1948. 8. Masdeu JC, Schoene WC, Funkenstein H: Aphasia following infarction of the left supple- mentary motor area. Neurology 1978;28:1220\x=req-\ 1223. 9. Alexander MP, Schmitt MA: The aphasia syndrome of stroke in the left anterior cerebral artery territory. Arch Neurol 1980;37:97-100. 10. Rubens AB: Aphasia with infarction in the territory of the anterior cerebral artery. Cortex 1975;11:239-250. 11. K\l=o"\rnyeyE: Aphasie transcorticale et \l=e'\cholalie: Le probl\l=e'\mede l'initiative de la par\l=o^\le.Rev Neurol 1975;131:347-363. 12. Brown J: Mind, Brain and Consciousness: The Neuropsychology of Cognition. New York, Academic Press Inc, 1977. 13. Shahani B, Burrows P, Whitty CWM: The reflex and perseveration. Brain grasp 1970;93:181-192. 14. Wilson DH, Reeves A, Gazzaniga M: Divi- sion of the corpus callosum for uncontrollable epilepsy. Neurology 1978;28:649-653. 15. Penfield W, Jasper H: Epilepsy and the Functional Anatomy of the Human Brain. Boston, Little Brown & Co, 1954, pp 88-108. 16. Talairach J, Bancaud J, Geier S, et al: The cingulate gyrus and human behavior. Electroencephalogr Clin Neurophysiol 1973;34:45-52. 17. Sanides F: Functional architecture of motor and sensory cortices in primates in the light of a new concept of neocortex evolution, in Noback C, Montagna W (eds): The Primate Brain. New York, Appleton-Century-Crofts, 1970, pp 137-208. 18. Mountcastle VB, Lynch JC, Georgopoulos A, et al: Posterior parietal association cortex of the monkey: Command functions for operations within extrapersonal space. J Neurophysiol 1975;38:871-908. Downloaded From: http://archneur.jamanetwork.com/ by a University of Manitoba User on 06/18/2015 19. Robinson DL, Goldberg ME, Stanton GB: Parietal association cortex in the primate: Sensory mechanisms and behavioral modulations. J Neurophysiol 1978;41:910-932. 20. Mesulam M-M, Van Hoesen GW, Pandya DN, et al: Limbic and sensory connections of the inferior parietal lobule (area PG) in the rhesus monkey: A study with a new method for horseradish peroxidase histochemistry. Brain Res 1977;136:393-414. 21. Baleydier C, Mauguiere F: The duality of the cingulate gyrus in the monkey: Neuroanatomical study and functional hypothesis. Brain 1980;103:525-554. 22. Roland PE, Larsen B, Lassen NA, et al: Supplementary motor area and other cortical areas in organization of voluntary movements in man. J Neurophysiol 1980;43:118-136. 23. Roland PE, Skinh\l=o/\jE, Lassen NA, et al: Different cortical areas in man in organization of voluntary movements in extrapersonal space. J Neurophysiol 1980;43:137-150. 24. Larsen B, Skinh\l=o/\j E, Lassen NA: Variations in regional cortical blood flow in the right and left hemispheres during automatic speech. Brain 1978;101:193-209. 25. Orgogozo JM, Larsen B: Activation of the supplementary motor area during voluntary movement in man suggests it works as a supramotor area. Science 1979;206:847-850.