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Shared Cortical Anatomy for Motor Awareness and Motor Control

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Science  15 Jul 2005:
Vol. 309, Issue 5733, pp. 488-491
DOI: 10.1126/science.1110625

Abstract

In everyday life, the successful monitoring of behavior requires continuous updating of the effectiveness of motor acts; one crucial step is becoming aware of the movements one is performing. We studied the anatomical distribution of lesions in right-brain–damaged hemiplegic patients, who obstinately denied their motor impairment, claiming that they could move their paralyzed limbs. Denial was associated with lesions in areas related to the programming of motor acts, particularly Brodmann's premotor areas 6 and 44, motor area 4, and the somatosensory cortex. This association suggests that monitoring systems may be implemented within the same cortical network that is responsible for the primary function that has to be monitored.

Although much of the functioning of the body's motor systems occurs without awareness, humans are aware that they are moving (or not moving) different parts of their body, even when performing automatic movements. They can also predict and be aware of the consequences of an intended motor act, with reference to their goals (1). There are, however, pathological states in which movement awareness is dramatically impaired (2, 3). One instance of this phenomenon can be found in right-brain–damaged patients, affected by left-sided hemiplegia, who may deny their deficit and claim that their paralyzed limbs can still move. This disturbance has been termed anosognosia (4) or denial of motor deficit, and it has often been considered part of a multifaceted disorder of spatial representation and awareness, called unilateral neglect (5). However, because neglect and anosognosia may occur independently (68), their cognitive and possibly neuropathological bases might differ (9).

We compared the distributions of brain lesions in patients showing left spatial neglect, left hemiplegia, and anosognosia for motor deficit, with those of patients showing neglect, left hemiplegia, but not anosognosia. Any significant difference in brain damage between these groups of patients should correspond to the damage specific to anosognosia.

Thirty patients with a complete left motor deficit (hemiplegia) after unilateral right-sided brain lesions were investigated. Patients were grouped according to the presence or absence of anosognosia for left hemiplegia and left unilateral spatial neglect. Seventeen patients had anosognosia and neglect, and 12 had neglect without anosognosia (Table 1) (10). The superimposed lesion plots of the 17 hemiplegic patients with anosognosia (A+) and with neglect (N+) (Fig. 1A) were compared with the 12 hemiplegic patients without anosognosia (A–) and with neglect (N+) (Fig. 1B). Table 2 shows the areas that were most frequently involved in the anosognosic group and the statistical comparison between the two groups. The anatomical chi-square distribution of the comparison of A+N+ versus A–N+ patients is shown in Fig. 2. In anosognosic patients, the maximum overlap of brain lesion was centered on the dorsal premotor cortex (Brodmann's area 6; damaged in 94% of A+N+ patients), followed by area 44 and the somatosensory area (88% of the patients), and by the primary motor cortex (82% of the patients). Other neighboring structures that were differentially involved were area 46 and the insula. In both groups of patients, the inferior parietal lobule, which is traditionally associated with spatial neglect (11), was frequently involved. The reversed chi-square comparison of the distribution of the brain lesion in the A–N+ groups compared with the A+N+ group (Fig. 2 and Table 2) showed one single area of difference: the white matter, where axons of the corticospinal tract are located in the depth of the centrum semiovale. This suggest that A–N+ patients tend to have more subcortical lesions than do A+N+ patients, and less or no involvement of cortical areas, confirming that spared awareness of the motor deficit in patients A–N arises from the sparing of the premotor cerebral + cortex, which is contrarily affected in A+N+ patients.

Fig. 1.

(A) Regional lesion distribution in patients with hemiplegia, spatial neglect, and anosognosia. The regional frequency of brain lesions in each area of the right hemisphere is expressed according to the color scale (for example, areas in red show that a lesion is present in 10 patients). (B) Regional lesion distribution in patients with hemiplegia, spatial neglect, and no anosognosia. Each individual lesion has been superimposed onto a standard brain conforming to stereotactic space.

Fig. 2.

Anatomical comparison between ansognosic and nonansognosic patients. On the left, brain areas more frequently damaged in patients with neglect, left hemiplegia, and anosognosia are shown as identified by a pixelwise chi-square analysis. On the right, brain areas more frequently damaged in patients with neglect, left hemiplegia, and without anosognosia are shown. Methods, stereotactic coordinates, and levels of significance are described in Table 2 (10).

Table 1.

Demographic and clinical data of the right-brain—damaged patients with and without anosognosia for hemiplegia. The ranges are reported in parentheses. The asterisk indicates the number of patients in whom tactile sensation was tested, with somatosensory deficit. n.t., not tested; A, anosognosia; N, neglect; + indicates present; - indicates absent.

Patient group No. Age Education (years) Somatosensory deficit of the contralesional side* Line cancellation Albert test, mean no. of items crossed Letter cancellation Diller test, percentage of items crossed Bell test, mean no. of items crossed
Left Right Left Right Left Right
A+N+ 17 75.2 (36-89) 6.5 (0-13) 13/15 (86.7%) 4/18 12/18 0 14.8 0.6/17 3.2/17
A-N+ 12 75.9 (62-85) 5.7 (4-13) 6/11 (54.5%) 8/18 15/18 8.6 65 1.8/17 7.7/17
A+N- (Patient RMA) 1 56 5 No somatosensory deficit 18/18 18/18 n.t. n.t. 17/17 15/17
Table 2.

Brain lesion analysis. Results of anatomical statistical comparisons of patients with hemiplegia and anosognosia and patients with hemiplegia without anosognosia are shown. Stereotactic coordinates are distances, in millimeters, of the center of mass of a significant lesion, from the anterior commissure (10). The table also reports the results for the supramarginal gyrus [Broadmann's Area (BA) 40], the angular gyrus (BA 39), and the superior temporal gyrus (BA 22/42) associated with spatial neglect (11, 24, 25). These areas were not significantly more affected in either group of patients. DLPC, dorsolateral prefrontal cortex; dPMc, dorsal premotor cortex; IFGop, opercular inferior frontal gyrus; PostCG, post-central gyrus; PreCG, precentral gyrus; SMG, supramarginal gyrus; AG, angular gyrus; STG, superior temporal gyrus. n.a., not available, which indicated that it was technically not reliable to isolate the number of voxels damaged in the insula. ns, not significant.

Brain Region (Brodmann's area) Patients with anosognosia Patients without anosognosia Overall regional chi-square P value Mann-Whitney P value based on lesion voxel count Stereotactic coordinates of voxels of maximal significance for each Brodmann's area Voxel-wise chi-square P value
XYZ
dPMc (6) 16/17 5/12 0.007 0.004 33 -2 43 0.025
IFGop (44) 15/17 4/12 0.007 0.0025 44 5 29 0.05
PostCG (3, 1, 2) 15/17 6/12 0.06 0.03 67 -18 37 0.01
PreCG (4) 14/17 4/12 0.021 0.012 43 -6 33 0.01
DLPC (46) 11/17 1/12 0.008 0.003 32 21 36 0.05
Insula 11/17 2/12 0.03 n.a. 49 4 11 0.05
SMG (40) 12/17 7/12 ns: 0.8 ns: 0.17 - - - -
STG (22) 11/17 4/12 ns: 0.2 ns: 0.17 - - - -
STG (42) 10/17 4/12 ns: 0.3 ns: 0.25 - - - -
AG (39) 9/17 6/12 ns: >0.9 ns: 0.70 - - - -
Deep centrum semiovale 0/17 7/12 0.001 n.a. 18 -20 21 0.05

From the above statistical comparisons, having controlled for the factor “spatial neglect,”we predicted that patients with pure anosognosia (i.e., patients showing the denial symptom without neglect) should present with a brain damage that largely overlaps with the areas that distinguish the A+N+ group from the A–N+ patients. We found such a patient (patient RMA in Table 1) who had a pure form of anosognosia without spatial neglect. Figure 3 shows the overlap between his brain damage and the areas that were significantly more affected in the A+N+ group, as compared with the A–N+ group. The predicted overlap is evident in areas 6, 4, 44, and 3 and in the insula.

Fig. 3.

Brain lesion in patient RMA, who has pure anosognosia for hemiplegia without spatial neglect. Areas in red are in common with the brain areas identified by the pixelwise chi-square comparison of patients with anosognosia, as opposed to those without anosognosia. Areas in green are brain areas damaged in patient RMA that are not identified by the chi-square analysis. Areas in purple are those identified by the chi-square analysis and not damaged in patient RMA.

These findings permit us to tease apart the neural correlates of denial of motor deficit from the parietotemporal network commonly associated with spatial neglect; anosognosia for hemiplegia is best explained by the involvement of motor and premotor areas (particularly area 6) and also, although less frequently, of prefrontal areas, such as area 46, and the insula. Observations in patient RMA, who has a pure form of anosognosia, also indicate that the frontal lesions did not affect prefrontal areas but mainly involved the frontal agranular cortex, including area 4, the dorsolateral portion of area 6, and area 44. These latter areas are fundamental components of circuits related to the programming of motor acts, both in humans and in monkeys (12, 13). Premotor areas, and also the primary motor cortex, activate not only during motor preparation but also during motor imagery (1, 14), and a large body of psychological and neuroimaging experiments have been interpreted as favoring a functional equivalence between action generation, action simulation, action verbalization, and perception of action (15). Moreover, even the interpretation of others' actions is related to the activity of neurons located in the premotor cortex (area 6) (16, 17). Our data expand this knowledge by providing evidence of an involvement of the premotor frontal regions in the conscious monitoring of motor acts. These findings are directly relevant for models of motor control and, more generally, for accounts of consciousness. Indeed, the involvement of premotor areas in self-monitoring of action implies that, at least for motor functions, monitoring is neither the prerogative of some kind of central executive system, hierarchically superimposed on sensory-motor and cognitive functions (18, 19), nor a function that is physiologically and anatomically separated from the primary process that has to be monitored. Instead, the anatomical correlates of anosognosia show that monitoring can be implemented in the same neural network responsible for the process that has to be controlled. This is in keeping with other findings in the domain of altered self-monitoring (20).

Recently, it has been proposed that the denial behavior might be due to the fact that patients may experience the movement they intended to perform, but are not able to distinguish between a purely simulated (imaged) action and the actual status of the motor system (3, 21). Our data show that some parts of the motor system can be spared in anosognosic patients. We may speculate that, although the damage to premotor areas impairs the motor-monitoring process, it is still possible, because of some spared premotor activity, to generate a distorted representation of the intended motor act, which is responsible for the false belief of being able to move. Also in this view, the experience of intention to move does not depend on the functioning of a single cortical region, but instead arises from a dynamic interaction between different premotor areas.

Finally, because movements occur in egocentric space, the close association often observed between left-sided anosognosia with left-sided neglect may reflect the damage to common components of a frontoparietal network, specifically related to spatiomotor integration. The lesion to a single component of this network gives rise to selective and spatially constrained disorders of awareness (22, 23).

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