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Item does not contain fulltext, Background: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. Objectives: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. Methods: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. Results: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. Conclusions: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

Item does not contain fulltext, Background: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. Objectives: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. Methods: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. Results: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. Conclusions: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

Item does not contain fulltext, Background: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. Objectives: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. Methods: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. Results: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. Conclusions: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

Item does not contain fulltext

Item does not contain fulltext

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.