International Journal of Pediatrics 2.3. Neural Mechanism 2.3.1. Spinal Reﬂex Center and Higher Brain Mechanism. Because anencephalic infants demonstrate a positive grasp reﬂex in both the hands and feet, the cerebral hemispheres are apparently not necessary for the reﬂexes [37–39]. Shahani et al. [40] reported that the latency of the palmar grasp reﬂex was 40 msec on direct electrical stimulation of the aﬀerent ﬁbers in the median and ulnar nerves at the level of the wrist in an adult patient who showed the palmar grasp reﬂex following a vascular lesion in the cerebral hemisphere. This short latency excludes the long cerebral reﬂex arcs and puts this grasp reﬂex in the category of segmental reﬂexes mediated at the level of the spinal cord. The spinal reﬂex center, however, is controlled by a higher brain mechanism. The grasp reﬂexes can be elicited in neonates and early infants as a result of insuﬃcient control of the spinal mechanism by the immature brain, but the reﬂexes gradually disappear with age, due to the increased inhibition accompanying brain maturation [23, 41]. Adult patients with lesions in the frontal lobes sometimes exhibit a grasp reﬂex of the hands and feet [23, 33, 37, 41–45]. Such reappearance of these reﬂexes in adults is attributed to the release of the spinal reﬂex center from the disturbed higher brain mechanism, suggesting that these reﬂexes are only inhibited, and not lost, after the infantile period. Many attempts have been made to determine the pathological site of the grasp reﬂexes by means of clinical observation or animal experiments [37, 46–48]. In 1927, Adie and Critchley [37] analyzed 13 patients with a tumor or vascular lesion in a frontal lobe who exhibited a palmar grasp reﬂex on the side opposite to that of the diseased frontal lobe. They conﬁrmed that the palmar grasp reﬂex was most evident when pyramidal signs were absent, and thus they concluded that the lesion responsible for the reﬂex was extrapyramidal. In 1938, Goldstein [41] described that a lesion involving the medial aspect of a frontal lobe seemed to be especially prone to produce the plantar grasp reﬂex on the opposite side. More recent studies have implicated lesions of the medial or lateral frontal cortex anterior to the primary motor area, that is, the supplementary motor area (SMA), premotor cortex, and cingulate motor cortex, as the etiology of the palmar grasp reﬂex [23, 45, 48, 49]. These ﬁndings indicate that nonprimary motor areas comprise substantial portions of the brain that exert inhibitory control over the spinal reﬂex mechanism underlying the grasp reﬂexes and that the destruction of these structures will release the inhibitory control and thus lead to the reappearance of the reﬂexes. 2.3.2. Descending Control of the Spinal Circuit by the Non- primary Motor Cortex. Nonprimary motor areas play im- portant roles in the planning, preparation, initiation, and execution of motor behavior [50–55]. These areas con- tain corticospinal neurons and thereby a somatotopically arranged map of the body [54, 56–58]. However, the cortical projections from these areas to the spinal cord do not necessarily have a direct inﬂuence on spinal motor neurons. The majority of the neurons terminate in the intermediate 3 zone in the spinal cord and connect with interneurons [53, 56, 59, 60]. The essential roles of nonprimary motor areas in the spinal cord are thought to be in the preparation and modulation of the spinal circuitry through interneurons rather than the generation of movements that require a direct command to the spinal motor neurons [52, 53, 60, 61]. On the other hand, because interneurons are substantially related to the modulation of spinal reﬂexes [52, 57], the descending inhibitory control of the grasp reﬂexes by nonpri- mary motor areas may also occur through spinal interneu- rons. As brain maturation proceeds, increasing control of the spinal circuit by the nonprimary motor areas will replace the simple reﬂex grasping during early infancy, with more regulatory and adaptive voluntary grasping in older infants. However, the proportion of patients with a lesion of a nonprimary motor area in whom a grasp reﬂex can be elicited is not necessarily high. In the series of De Renzi and Barbieri [44], the palmar grasp reﬂex was elicited in 21 of 32 (66%) patients with a medial frontal lesion and in 8 of 30 (26%) with a lateral frontal lesion. On the other hand, a minority of patients with a deep lesion including the basal ganglia without frontal cortical damage were reported to exhibit a positive palmar grasp reﬂex [44], and the extension of an SMA lesion into more lateral regions of area 6 may increase the strength of the grasp reﬂex [48]. These observations seem to indicate that the inhibitory stimuli from upper brain structures travel via multiple routes [44], and the extent of the release of control depends not only on the speciﬁcity of the location but also on the extent and severity of the lesions. Clinical studies have revealed that some patients with a frontal lesion exhibit a grasp reﬂex of the hands or feet, or both [33, 41, 43]. This ﬁnding suggests that diﬀerent sites are speciﬁc to each of the grasp reﬂexes of the hands and feet within the nonprimary motor cortex. As demonstrated, each nonprimary motor area retains some degree of a somatotopically arranged map of the body that represents peripheral innervation, which is dominated by descending pathways from the area through connections to diﬀerent levels of the spinal cord [54, 56–58]. We speculate that the grasp reﬂexes of the hands and feet may be elicited according to the speciﬁc location of each lesion corresponding to the ﬁngers or toes on the map in nonprimary motor areas. 2.3.3. Factors Aﬀecting Responses in Infants. In normal cir- cumstances, higher brain centers control the spinal mech- anism that regulates the coordination among agonists, antagonists, and synergists in an adaptable manner by means of reciprocal innervation. In children with spastic type CP, however, deviation in terms of reciprocal innervation caused by damage to the pyramidal tract leads to excess cocontrac- tion at proximal joints, whereas deviation leads to excess reciprocal inhibition through spastic antagonists at distal joints, inducing weakness of the agonists [62]. A diminished or negative plantar grasp reﬂex may be caused by weak toe ﬂexors, as induced by excessive reciprocal inhibition of the ﬂexors through the predominance of extensors over ﬂexors in tonus in a lower limb in these children. They also exhibit the