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J J Kew

Publications and source records attributed to J J Kew.

8 recordsLinked to original sources

Abnormal access of axial vibrotactile input to deafferented somatosensory cortex in human upper limb amputees.

We studied two human subjects with total deafferentation of one upper limb secondary to traumatic multiple cervical root avulsions. Both subjects developed a phantom limb and underwent elective amputation of the paralyzed, deafferentated limb. Psychophysical study revealed in each subject an area of skin in the pectoral region ipsilateral to the amputation where vibrotactile stimulation (VS) elicited referred sensations (RS) in the phantom limb. Positron emission tomography was then used to measure regional cerebral blood flow changes during VS of the pectoral region ipsilateral to the amputation with RS and during VS of a homologous part of the pectoral region adjacent to the intact arm without RS. A voxel-based correlation analysis was subsequently used to study functional connectivity. VS of the pectoral region adjacent to the intact arm was associated with activation of the dorsal part of the contralateral primary somatosensory cortex (S1) in a position consistent with the S1 trunk area. In contrast, VS of the pectoral region ipsilateral to the amputation with RS was associated with activation of the contralateral S1 that extended from the level of the trunk representation ventrally over distances of 20 and 12 mm, respectively, in the two subjects. The area of S1 activated during VS of the digits in a normal control subject was coextensive with the ventral S1 region abnormally activated during VS of the ectopic phantom representation in the two amputees, suggesting that the deafferented digit or hand/arm area had been activated by sensory input from the pectoral region. Correlation analysis showed an abnormal pattern of intrinsic connectivity within the deafferented S1 hand/arm area of both amputees. In one subject, the deafferented S1 was functionally connected with 3 times as many S1 voxels as the normally afferented S1. This abnormal functional connectivity extended in both the rostrocaudal and ventrodorsal dimensions. The results demonstrate that sensory input delivered to the axial body surface may gain access to the S1 hand/arm area in some humans who have suffered extensive deafferentation of this area. The findings are consistent with the hypothesis that deafferentation of an area of S1 may result in activation of previously dormant inputs from body surfaces represented in immediately adjacent parts of S1. The results also provide evidence that changes in functional connectivity between these adjacent areas of the cortex play a role in the somatotopic reorganization.

Adult↗

Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.

PET measurements of regional cerebral blood flow (rCBF) were used to explore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation paradigm of executive frontal lobe function (verbal fluency), which contrasted rCBF during word generation and word repetition, was used. Two groups of ALS patients, defined by the presence or absence of cognitive impairment (ALSi) (impaired, n = 6: ALSu unimpaired, n = 6) were compared with healthy age-matched controls (n = 6). Patient selection was based on prior performance on a written test of verbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi group only, with marked deficits in tests of intrinsic generation. The ALSi patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46 and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic nuclear complex. Although the three groups showed matched word generation performance on the scanning paradigm, the ALSu group displayed a relatively unimpaired pattern of activation. These results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study suggests dysfunction of DLPFC in some ALS patients with associated cognitive impairments.

Aged↗

A positron emission tomography study of frontal lobe function (verbal fluency) in amyotrophic lateral sclerosis.

Positron emission tomography (PET) was used to investigate the location of cerebral cortical and subcortical abnormalities in non-demented patients with amyotrophic lateral sclerosis (ALS). Involvement of the frontal lobes was investigated with a task of executive frontal lobe function (verbal fluency/word generation), using a PET activation paradigm. Two groups of ALS patients defined by the presence or absence of cognitive impairment were tested. ALS patients who had cognitive impairments showed a region of cortical and subcortical dysfunction which extended across a wide area of the frontal lobes, and included the insular cortex and thalamic nuclear complex. These findings support the notion that extra-motor involvement is relatively common in ALS and broadens concepts of selective vulnerability in ALS.

Amyotrophic Lateral Sclerosis↗

Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation.

1. Two complimentary techniques were used to study cortical function in six human upper limb amputees: positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) were made in subjects during limb movements to study activation of the primary motor (M1), primary somatosensory (S1), and association cortices; and electromyographic responses to transcranial magnetic stimulation (TMS) were measured in proximal upper limb muscles to assess the excitability of corticospinal neurons in subjects at rest. 2. To explore possible cortical mechanisms governing the phantom limb phenomenon, PET and TMS findings were compared between subjects with acquired, traumatic upper limb amputations (n = 3), in whom phantom limb symptoms were prominent, and congenital upper limb amputees (n = 3) without phantom limbs. 3. Paced shoulder movements were associated with significant blood flow increases in the contralateral M1/S1 cortex of both groups of amputees. In traumatic amputees, these increases were present over a wider area and were of significantly greater magnitude in the partially deafferented cortex contralateral to the amputation. In congenital amputees blood flow increases were also present over a wider area in the partially deafferented M1/S1 cortex, but their magnitude was not significantly different from that in the normally afferented M1/S1 cortex. 4. Abnormal blood flow increases also were present in the partially deafferented M1/S1 cortex of traumatic amputees during movement of the ipsilateral, intact arm. Abnormal ipsilateral M1/S1 responses were not present during movement of the intact arm in the congenital group. 5. TMS studies showed that the abnormal blood flow increases in the partially deafferented M1 cortex of traumatic amputees were associated with increased corticospinal excitability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cortical function in progressive lower motor neuron disorders and amyotrophic lateral sclerosis: a comparative PET study.

OBJECTIVE: To compare cortical function at rest and during limb movement in patients with progressive lower motor neuron degeneration (LMND) and amyotrophic lateral sclerosis (ALS). METHODS: PET was used to measure regional cerebral blood flow (rCBF) in five patients with progressive LMND, six patients with classic ALS with a similar degree of motor impairment, and six age-matched control subjects; measurements were taken in the resting state and while subjects moved a joystick with their right hand. RESULTS: rCBF at rest in the primary sensorimotor cortex (SMC) was significantly (p < 0.001) lower in ALS patients than in control subjects or LMND patients. rCBF at rest did not differ significantly between LMND patients and controls. During joystick movement, ALS patients showed significantly (p < 0.001) greater rCBF increases than controls or LMND patients in the hand/arm area of the SMC bilaterally, the face area of the contralateral SMC, the second somatic sensory (SII) cortex bilaterally, and the contralateral premotor and supplementary motor cortices. LMND patients showed significantly (p < 0.001) greater rCBF increases than controls and ALS patients only in the anterior insular cortex bilaterally. CONCLUSIONS: The finding of reduced rCBF at rest, together with abnormal bilateral activation and altered somatotopy during movement, in the sensorimotor cortex of ALS but not LMND patients suggests that these abnormalities reflect loss of pyramidal neurons. Abnormal activation of perisylvian areas (insular and SII cortices) during limb movement in both LMND and ALS patients suggests that these may be accessory sensorimotor areas that are recruited nonspecifically in response to limb weakness.

Adult↗

Cortical function in amyotrophic lateral sclerosis. A positron emission tomography study.

Positron emission tomography was used to measure regional cerebral blood flow (rCBF) in 12 patients with amyotrophic lateral sclerosis (ALS) and six age-matched controls. Scans were performed at rest, and while subjects performed stereotyped and freely selected movements of a joystick with their right hand. Statistical parametric mapping was used to determine significant differences in rCBF between the two groups at rest and during activation. The ALS group showed no significant difference in global cerebral blood flow at rest compared with controls. However, rCBF at rest was significantly (P < 0.01) reduced in the ALS group in the primary sensorimotor cortex, the lateral premotor cortex, the supplementary motor area, the anterior cingulate cortex, the paracentral lobule and the superior and inferior parietal cortex. Comparison of the increase in rCBF caused by freely selected joystick movements over the resting state between the two groups of subjects showed significantly (P < 0.001) greater activation in ALS patients in the ventral third (face area) of the contralateral primary sensorimotor cortex and in the adjacent contralateral ventral premotor and parietal association cortices; significantly (P < 0.01) greater activation of the contralateral anterior insula and the ipsilateral anterior cingulate cortex (dorso-caudal area 24) was also present in ALS patients. When a comparison of the rCBF response to the free selection task with that to the stereotyped task was performed between the two groups of subjects, ALS patients showed significantly impaired (P < 0.01) activation of the rostral anterior cingulate cortex (area 32), medial prefrontal cortex (area 10), left parahippocampal gyrus and retrosplenial cortex. The pattern of reduced rCBF at rest in ALS patients probably reflects a combination of neuronal loss in all areas of cortex projecting through the pyramidal tract together with loss of projections from the sensorimotor cortex to the motor association areas. The expansion of the upper limb output zone of the sensorimotor cortex in ALS patients during contralateral upper limb movement may represent cortical reorganization in response to Betz cell loss or corticospinal tract disruption. Abnormal recruitment of non-primary motor areas may also represent functional adaptation to a corticospinal tract lesion. Focally impaired activation of the medial prefrontal cortex and parahippocampal gyrus in ALS patients during the process of internal generation of movement could underlie the frontal lobe cognitive deficits reported in previous neuropsychological studies of ALS.

Adult↗

The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study.

Neuropsychological assessment of 16 clinically non-demented patients with amyotrophic lateral sclerosis (ALS) and 16 age-matched controls revealed significantly (P < 0.05) impaired verbal fluency and picture recall in the ALS patients. On the basis of their verbal fluency scores, two subgroups of the ALS patients (five high, five low scores) and a different group of five age-matched controls then underwent positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Scans were performed in the resting state and while subjects performed stereotyped or freely selected movements of a joystick with their right hand. The pattern of cerebral activation associated with self-generated activity was determined by comparing the profile of rCBF during freely selected and stereotyped joystick movements. Statistical parametric mapping was used to determine significant differences in rCBF between the groups at rest and during activation. Regional cerebral blood flow at rest was significantly (P < 0.01) reduced in the anterior cingulate cortex of both ALS subgroups in comparison with controls. The profile of cortical and subcortical activation during performance of freely selected joystick movements relative to stereotyped movements was abnormal in ALS patients: (i) ALS patients with a normal fluency score showed significantly (P < 0.01) attenuated rCBF responses in comparison with controls in the left medial prefrontal cortex (Brodmann area 10) and the right and left parahippocampal gyri; (ii) ALS patients with impaired verbal fluency showed significantly (P < 0.01) attenuated rCBF responses in comparison with controls in the right and left medial prefrontal cortex (areas 9 and 10), the rostral aspects of the right anterior cingulate cortex (areas 24 and 32), the right parahippocampal gyrus and the anterior thalamic nuclear complex; (iii) ALS patients with impaired verbal fluency showed significantly (P < 0.01) attenuated rCBF responses in comparison with patients with normal verbal fluency in the right parahippocampal gyrus, the anterior thalamic nuclear complex and the rostral anterior cingulate cortex (area 24). Regional cerebral blood flow at rest in the right parahippocampal gyrus of ALS patients was significantly correlated with verbal fluency score (P = 0.01) and picture recall score (P = 0.01). Activation of the anterior thalamic nuclear complex in ALS patients was also significantly correlated with verbal fluency score (P = 0.001) and picture recall score (P = 0.01). The results show that abnormalities of function are present in regions along a limbo-thalamo-cortical pathway in some ALS patients during performance of a self-generated motor task.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗