Neuroprychologia, Vol. 18, PP. 123 to 132. 0 Pergamon Press Ltd. 1980. Printed in Gnat Britain. NEGLECT FOLLOWING DAMAGE TO FRONTAL LOBE OR BASAL GANGLIA ANTONIO R. DAMASIO,HANNA DAMASIOand HELENA CHANG CHUI Department of Neurology, (Division of Behavioral Neurology and Benton Laboratory of Neuropsychology), University of Iowa College of Medicine (Received 27 September 1979) Abstract-Though neglect is often thought to be a sign of parietal lobe damage, particularly of the non-dominant hemisphere, there is evidence that lesions in the frontal lobes and in the basal ganglia can produce neglect also. We present five patients, with lesions in both the mesial and dorsolateral aspects of the frontal lobe, and in the basal ganglia, as examples of “nonparietal” neglect. It is possible that all of these structures belong to an anatomically interconnected system subserving selective attention and that lesions in each of the components are capable of producing neglect although with slightly different characteristics. THE presence of neglect is usually considered a sign of parietal lobe dysfunction and the finding of left sided neglect is almost synonymous with right parietal damage. Yet HEILMAN and VALENSTEIN[1] have described the presence of neglect in association with frontal lobe lesions, in a report which included six cases with circumscribed lesions of the right frontal lobe, three of which were located in the mesial aspect and the other three in the lateral convexity. All patients had right sided lesions thus leaving unanswered the question of whether left frontal lobe lesions might fail to produce the phenomenon as is generally the case with the parietal lobe. For a number of years we have seen several instances of neglect in association with lesions of the frontal lobe in either hemisphere and, in addition, of the basal ganglia. This report exemplifies the condition and emphasizes the association of left frontal damage with unilateral neglect. MATERIALS AND METHOD Five patients in whom neglect was a prominent manifestation, and in whom a cerebral lesion could be localized by means of CT scan (four cases) or radionuclide scan (one case), were studied. The working concept of unilateral neglect encompassed such manifestations as visual, auditory or tactile inattention, as well as lateralized akinesia (of the hemiface or of limbs of one side of the body). The localization of the lesions seen in CT scans was made according to a method described by DAMASIOand DAMASIO[2,3] in which images of abnormal density are plotted in templates of brain sections corresponding to the planes of cut of CT scan and the results read as a three-dimensional construct. The evaluation of neglect was made by clinical means at the bedside, and completed in a laboratory setting using avisual cancellation task [4]. The patient was instructed to cross 94 lines in various orientations approximately 2 cm in length presented with a 17 x 15 cm area centered on a standard 8f x 11 in. white card. Four lines, one in each corner, served as demonstration items. The remaining 90 lines were distributed in 9 columns of IO lines each with 5 lines of each column appearing above and below the horizontal meridian. There were no other marks on the page. The examiner placed the stimulus page in front of the patient with the long edge of the paper aligned in parallel and centered on the patient’s mid-sagittal plane. A score of one was given for each line crossed. Also, credit was given for any mark which touched a stimulus 123 124 ANTONIO R. DAMASIO, HANNA DAMASIO and HELENA CHANG CHUI Table 1. Location of lesion Case 1 Case 2 Case 3 Case 4 Case 5 Left frontal (dorsolateral) Left frontal (mesial) Left frontal (mesial) Right basal ganglia Left basal ganglia Side neglected Right Right Right Left Left line. Total score was the number of lines crossed. This score was subdivided into left, center and right field scores by counting the number of points in the three left, center and right columns, respectively, making this task similar, though more complex. than the one described by ALBERT [5]. Table I summarizes the data for the cases. Details are elaborated below. Case 1. GG is a 74-yr-old right-handed woman with a high school education. In December 1978 she suffered a stroke which left her fully alert and with good aural comprehension but unable to speak. She retained full use of her limbs, readily produced meaningful gestures with both upper extremities and attempted to write on a pad only to discover she merely produced a scribble. Other than her mute, but not akinetic state, the most remarkable clinical finding was neglect of the right half of her surrounding space manifested by (a) inattention to visual and auditory stimuli presented to her right side, (b) paucity of visual saccades towards the right, (c) defective performance in a visual neglect test (Fig. 1). Neglect improved dramatically over a period of 10 days. During the same period mutism was followed by Broca’s and then transcorticai motor aphasia. The lesion involved the dorsolateral frontal lobe on the left side (Fig. 2). The focus of damage included areas 44 and 45, area 46, area 6 and the associated underlying white matter. The area of edema extended into the basal ganglion region. Prefrontal areas 9 and 10 and the mesial part of area 6 were spared. Case 2. JC is a 35-yr-old right-handed female who suffered an embolic stroke in May 1977. She became mute immediately and markedly akinetic though appearing alert. Her right leg and foot were paralyzed. For the ensuing 3 days, although no spontaneous speech was recorded, it became apparent that the patient could repeat elaborate sentences, and could read and understand complex speech. It also was noted that the initial global akinesia was now more prominent in the face and right upper extremity (both had full strength in hard to elicit voluntary maneuvers) and that the patient was inattentive to visual and auditory stimuli presented from the right. A visual neglect test showed defective performance which subsequently improved. The clinical signs of neglect however, persisted longer and their improvement, around 2 weeks post-onset, paralleled improvement in spontaneous speech. The lesion, located in the territory of the left anterior cerebral artery, in all likelihood involved the supplementary motor area, anterior cingulate gyrus and leg region of the motor cortex. Case 3. MM is a 60&r-old right-handed artist, who in 1978 underwent resection of a single metastasis of adenocarcinoma located in theleft mesial frontal cortex (Fig. 3). As a result, she sustained damage to the supplementary motor area, the leg region of area 4, the superior portion of the anterior cingulate gyrus and to the white matter underlying these areas. Immediately after surgery she was akinetic and mute but during the ensuing weeks her clinical status evolved in much the same manner as that of patient JC (Case 2). Her global akinesia focused on the right side and face and there was clear neglect of visual and auditory stimuli presented to the left side. At a slower place than in patient JC the neglect cleared and some spontaneity of speech and general movement was regained. Case 4. CC is a 60-yr-old right-handed woman who suffered a stroke in September of 1978. For approximately I day she was somnolent though arousable and fully oriented. Speech was linguistically intact but dysprosodic and dysarthric. After the third day comprehensive testing was possible and it was noted that the patient had little spontaneous movement or speech, and, in addition. systematically neglected stimuli presented on her left side. A visual cancellation task revealed defective performance, although this improved over a period of 7 days (Fig. 4). The lesion (see Fig. 5) was located in the right medial basal ganglion region, and involved the right putamen, body of the caudate nucleus, and portions of the internal capsules (anterior and posterior limbs). NEGLECTFOLWWING 0 22 Total: 50/90 Tome: 90 set FIG. 1. Case 1. Performance DAMAGETOFRONTAL 28 LOBEORBASALGANGLIA Total:86/90 09121178 GG Time: 80sec 125 09/28/78 GG in visual cancellation task at time of first exam (left) and on re-evaluation (right). Case 5. BF is a 46-yr-old right-handed woman with a personal and familial history of manic-depressive illness and the history of a stroke event 2 yr prior to admission. Treatment took place in a different institution and though it was not possible to obtain details, the disease rendered her “confused and paralyzed on the right side” for a long period of time with gradual recovery. Admission to our department in 1977 was prompted by the finding of severe left-sided visual neglect in a routine clinic visit. Although examination of the patient was difficult due to her disturbed emotional status (manic phase), it was clear that she systematically failed to attend stimuli presented to her left hemispace (to the extent that she was erroneously thought to have a left hemianopia). In addition she had a tendency for left turning immediately after she initiated walking even though urged to follow a straight line. Additionally, her right upper extremity was relatively less used than the left, though not paralyzed or entirely neglected. A CT scan revealed a circumscribed area of low density in the left basal ganglion region. It involved the head of the left caudate, nucleus as well as the surrounding white matter, including the anterior limb of internal capsule and the anterior part of the putamen. It is likely that this represented the result of resolution of an old infarction (Fig. 6). DISCUSSION In view of experiments in non-human primates, it should not be surprising to find neglect in association with non-parietal lesions. WELCH and STUITEVILLE [6] were able to produce unilateral neglect by placing lesions in area 8 of the frontal lobe in the rhesus monkey. Also in the monkey, WATSON et al. [7] obtained neglect after unilateral damage to the anterior cingulate gyrus but not the supplementary motor area, and they have, in addition, produced neglect with unilateral lesions placed in the mesencephalic reticular formation [8]. Damage to the basal ganglia confined to one hemisphere has also produced neglect associated with turning behavior [9] and finally, unilateral lesions of the lateral hypothalamus in the rat have produced neglect also [ 10, 111. Integrating these various findings HEILMAN [121 has proposed an animal model of neglect encompassing sensory (e.g. visual or auditory inattention) and motor (e.g. akinesia) components ard indicating that the process of attention to each half of the stimulating environment and of the subject’s body, calls for the coordinated participation of neocortical (parietal 126 ANTONIO R. DAMASIO, HANNA DAMASIO and HELENA CHANGCHUI * -- FIG. 2. Case 1. Plotting of CT scan low density images in corresponding templates. FIG. 3. Case 3. Plotting of CT scan low density images in corresponding templates. NEGLECT FOLLOWING DAMAGE TO FRONTAL LOBE OR BASAL GANGLIA 127 . 23 Total 79/ 90 FIG. 4. Case 4. Performance 12/13/76 Total: 90/ 90 Time : 100 see 12/18/70 GG in visual cancellation task at time of first exam (left) and on re-evaluation (right). and frontal), limbic, and reticular activating neural components. In our version of the model we would add the neostriatum to the aforementioned structures. Our findings support the notion that in man, too, similar components are at work in attentional processes and that the disruption of any of them can produce neglect which will be lateralized or global depending on whether the lesion is unilateral or bilateral. The lesions in two of our patients affected the crucial mesial frontal cortex (compromising the supplementary motor area, anterior cingulate and their connectivity), in another the lesion was in the dorsolateral frontal lobe cortex which strongly projects to the SMA/ cingulate complex; and, in the two remaining patients, lesions were in the basal ganglia (striatum), a region strongly connected to the latter two. In short, two of the structural components of the proposed attention subserving anatomical structures are affected in our cases, failure of each being capable by itself of producing neglect. It is interesting to note that the neocortical and limbic-cortical structures damaged in our patients are strongly interconnected with area 7 in the parietal lobe, damage of which produces the classically recognized parietal neglect. In addition, following a recently identified principle of cortico-striatal projections it is quite likely that those reciprocally connected cortical structures strongly project in part to the same regions of the striatum [13, 141. We would suggest that these lesions, which produce neglect in the parietal and frontal cortices as well as in basal ganglia comprise a part of the system subserving attention, with the several components exerting different forms of control depending on their hierarchy and consequently producing different forms of neglect when their function is affected. As an example, unilateral frontal lobe lesions produce neglect for shorter periods than parietal lobe lesions and recovery in both animals [15] and man (cf. our cases) occurs more readily. In man the differences may be particularly pronounced. The longer lasting forms of unilateral neglect are related to lesions of the right parietal lobe while the shorter lasting unilateral neglect following frontal lobe lesions appears after damage to either side. But the 128 ANTONIOR. DAMAXO, HANNA DAMASIOand HELENACHANG CHUI most severe form of neglect is the bilateral akinetic and mute state which follows bilateral mesial frontal lobe damage in man or monkey. Those clinical differences shed some light on the question of the respective roles of parietal and frontal hierarchies in attentional mechanisms. The cortex of area 7 in the parietal lobe is generally considered the crucial structure as far as selective attentional processes are concerned. In regard to processes of lateralized visual attention and lateralized upper extremity movement, there is little doubt that in animals and man neurons in area 7 constitute a high level guidance system [16-181. In fact, MOUNTCASTLE [16, 191 views that region and those neurons as containing a “command” mechanism for selective visual attention and visually guided reaching. However, the concept of “command” can be challenged not only on the basis of specific aspects of the date [20, 211 but also because these “command” cells are themselves commanded, e.g. dependent on the “external” control of the limbic system. At least in the case of man those cells are also dependent on a higher executive decision which takes into account complex internal rules and environmental contingencies. It is possible that the latter executive “commands”, as well as part of the limbic ones, come from the SMA/anterior cingulate complex, which receives inputs from the dorsolateral structures of the frontal lobe and from subcortical components of the limbic system. In our view, classical parietal neglect is principally related to damage of area 7, while neglect such as was seen in cases 1, 2 and 3, is the result of damage in two sectors of the frontal lobe which constitute a higher control for the so-called “parietal command device” (its “will”, as it were) and for other parietal lobe regions (such as areas 39 and 40, in all likelihood reduced or absent in the monkey). The appearance of neglect in relation to lesions of the basal ganglia is seen in man, in moderate form, in disease processes of the striatum such as Parkinson’s disease but, it has an animal counterpart also. Unilateral damage of the striatum in rats produces unilateral neglect [9] while bilateral damage leads to an akinetic state of global neglect [22]. In both instances neglect consists of a motor component (akinesia in the side contralateral to the lesion) and a sensory component. In addition, there may be turning behavior towards the side of the lesion and away from the akinetic side [23-251. Case 5 is an example of this phenomenon which belongs with other interesting manifestations described in Parkinsonism such as postural deviation towards the side of the lesion, in standing or walking [26], or scoliosis with the concavity towards the side of the lesion [27]. The intensity of the phenomenon in patient BF, uncommon in our experience in patients with extrapyramidal disease, was possibly due to the type of lesion, since structures in the head of the caudate nucleus were, in all likelihood, effectively destroyed rather than merely dysfunctional. Finally it is intriguing to find a dissociation between the side neglected for vision and the one neglected for motion. It has been suggested that in some cases of left frontal lobe damage neglect can indeed be ipsilateral to the lesion [28]. Such deviant cases might be related to particular instances of dysfunction, in the basal ganglia rather than in the frontal cortex. REFERENCES 1. HEILMAN,K. M. and VALENSTEIN,E. Auditory neglect in man. Arch. Neural. 22, 660-664, 1972. 2. DAMASIO,H. and DAMASIO,A. “Paradoxic” ear extinction in dichotic listening: Possible anatomic significance. Neurology 29, 644-653, 1979. 3. DAMASIO, H., DAMASIO,A., HAMSHER,K. and VARNEY, N. CT scan correlates of aphasia and allied disorders. Neurology 29, 572, 1979. 129 FIG. 6. Case 5. CT scan cuts and plotting of lesion images in corresponding templates. NEGLECTFOLLOWINGDAMAGETO FRONTALLOBEOR BASALGANGLIA 131 4. HAMSHER,K. 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HANNA DAMASIO and HELENA CHANG CHUI 132 Resum6 : Bien qu'on du lobe pari&tal, des preuves que de la base peuvent cornme exemple frontales attribue souvent particuliSrement les lesions aussi frontales produire de negligence internes 11 est possible que anatomi;uement interconnect6 toutes la n6gligence. 11 est possible auss1 que capables caracteres 16gPrement les lesions de produire Nous prdsentons 5 nalades avec l'attentron de chacune la ndgligence 16slons de la base. appartiennent tendant 11 existe des ganglions et des ganglions ces structures sous aux atteintes drozt, et les lesions I'non pariStale" et dorsolat&rales tes soient la negligence de l'h+misphPre 2 un systeme s6lectlve. de ces composan- bren qu'avec des differents. Zusammenfassuq Neglekt wird besonders oft fiir ein Symptom der nicht Beobachtunpen Stammganglien LBsionen des ganglien als diese da13 such zu Neglekt ftiren Beispiel fur “nicht zu einem schiedlichen Systems konnen. Wir beschreiben Neglekt. vermittelt. Es kijnnte Es sein, mit und in den Stammist mdglich, System wenn such und in den 5 Patienten Frontallappens verbundenen hervorrufen, Es gibt jedoch im Frontallappen anatomisch Neglekt Charakterisbika. parietalen” des Parietallappens. gehalten. LPsionen und dorso-lateralen Aufmerksamkeit dieses tiemisph8re die zeigen, medialen Strukturen selektive Anteil dominanten der SchBdigung da13 alle gehtiren, welches da0 Llsionen in jedem mit geringfiigig unter-