From Wikipedia, the free encyclopedia

Nonmotor functions

Prior to the last decade, it was widely accepted that the cerebellum was purely motor-related. However, findings from as early as 1957 and investigations in the past few decades have brought that view strongly into question. Anatomical analyses of the cerebellum show that, along with its well-characterized associations with the motor cortex, the cerebellum has significant projections to nonmotor cortical areas by way of the ventrolateral thalamus. These nonmotor targets include the frontal, prefrontal and posterior parietal cortices, each of which are involved in higher cognitive functions. Neocortical regions innervated by the cerebellum project back to it via the pons, creating a closed-loop circuit (termed cerebero-cerebellar circuit). [1] Researchers hypothesize that the cerebellum is able to exert significant influence over its targets in the neocortex due the large number of projections to nonmotor areas and the closed-loop structure of the cerebero-cerebellar circuits. [2] In addition to the links to cognitive brain areas, cerebellar projections to limbic areas are also hypothesized to exist. [3] Studies show cerebellar activation in a diverse range of cognitive tasks devised to assess attention, working memory, language, learning, executive function and emotion. [2] Mounting evidence of cerebellar abnormalities is leading to new insights of the cerebellum's previously unknown role in developmental disorders such as autism and attention-deficit hyperactivity disorder (ADHD). [4] [5]

Emotion

Far before research uncovered any anatomical pathways between the cerebellum and nonmotor areas, early electrophysiological evidence suggested that a link between the cerebellum and limbic system exists. Zanchetti and Zoccolini discovered the first hints at a nonmotor role for the cerebellum in 1954. By stimulating portions of the cerebellum, the team was able to elicit outbursts of sham rage, a behavior typically controlled by the hypothalamus. [6] Other teams were able to record altered functioning of the amygdala and the cingulate cortex, [7] [3] areas responsible for emotional learning and processing, after stimulating portions of the fastigial nucleus and associated regions of the vermal cortex. Grooming and eating behaviors, and predatory attack behaviors have also been observed following cerebellar stimulation. [8] [9] Despite these findings, the exact nature of the cerebellum's contributions to emotion and limbic function are still unclear. Moreover, the neural mechanisms behind the cerebello-limbic association are unknown due to a lack of clear evidence for an anatomical substrate.

Schmahmann and Sherman discovered a cerebellar "cognitive affective syndrome" in patients with diseases of the cerebellum. [10] Neurological examinations and bedside mental state tests revealed personality changes involving blunted affect. Their examinations also revealed inappropriate behavior as a result of behavioral inhibition, suggesting a possible role for the cerebellum in executive control.

Attention

Some cerebellar projections innervate portions of the dorsolateral prefrontal cortex (DLPFC), a key area responsible for sustaining attention and for working memory. Studies have shown that autistic and non-autistic patients with cerebellar abnormalities have difficulty directing attention. [11] Cerebellar patients also display distractibility and inattention, [11] and individuals with damage to vermal structures have difficulty directing visual attention. [12] Additionally, reduced cerebellar volume and atypical cerebellar activation have been noted in individuals with ADHD [4] There is some debate over the precise neurobiological mechanisms behind ADHD, but these findings suggest that cerebellar dysfunction could help explain not only the attentional difficulties that characterize ADHD, but also deficits in motor-sequencing, working memory, executive function and emotional regulation. Similarly, corresponding deficits in autism could also be partially explained by cerebellar abnormalities.

Language

Deficits in language related to cerebellar damage have been well documented. An early investigation showed that, following damage to the right side of the cerebellum, patients had difficulty associating appropriate verbs with given nouns (e.g. associating "car" with "drive"). [13] The researchers posited that the lack of input from the damaged areas of the cerebellum to the language centers in the left cerebral hemisphere created issues with word finding. Failed attempts to recreate these results cast doubt on this finding. [14] However, there have been studies of language impairments in autism that may support the theory that the cerebellum contributes to language generation. Data shows that autistic subjects with language impairment have significantly different distribution of cerebellar volume compared to non-language-impaired autistic and non-autistic subjects. On average, subjects with language impairment had reduced right-sided cerebellar volume in conjunction with structural defects of Broca's area. [5]

Imaging studies have recorded fMRI during verbal working memory and single word reading tasks and have found unique cerebellar activation patterns for test. [15] [16] Due to motor-related aspects of language (e.g. planning/coordinating vocal cord movements), it is disputed whether cerebellar activation during language tasks is due to the cognitive aspects of language or due to motor activity. [17] In attempts to avoid language-related motor activation, studies examined cerebellar activation in patients instructed to imagine producing simple speech instead of speaking aloud and still found activation in areas of the cerebellum that are associated with language. [2]

Memory

The cerebellum’s role in working memory has been the subject of much research and its role in verbal working memory is especially well known. Meta-analyses of investigations into this role specifically found cerebellar activation in the lateral cerebellar cortexduring verbal working memory tasks. [2] Additionally, patients with cerebellar damage have a shorter verbal working memory span. [18] One study found that a patient with cerebellar damage had temporary difficulty repeating a series of digits in the forward or reverse order in which the experimenter recited them. [19] Full recovery was achieved in a few months, suggesting that other parts of the cerebellum may have taken over that functionality, or that the patient's memory deficits were unrelated to cerebellar damage. Besides evidence for a cerebellar role in working memory, functional imaging has demonstrated that the cerebellum contributes to encoding of long-term episodic memory. [20] While the physiological mechanism by which the cerebellum aids in encoding long-term memory is unknown, the cerebellum's projections to to the DLPFC and parietal regions may provide an anatomical locus for cerebellar contributions to working memory.

References

  1. ^ Kelly RM, Strick PL (2003). "Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate". The Journal of Neuroscience 23(23): 8432-8444. PMID 12968006.
  2. ^ a b c d Strick PL, Dum RP, Fiez JA (2009). "Cerebellum and Nonmotor Function". Annual Review of Neuroscience 32: 413–434.
  3. ^ a b Anand BK, Malhotra CL, Singh B, Dua S. (1959). "Cerebellar projections to limbic system". Journal of Neurophysiology 22: 451–57. PMID 13673296. doi: 10.1016/0014-4886(74)90118-6
  4. ^ a b Cherkasova MV, Hechtman (2009). "Neuroimaging in Attention-Deficit Hyperactivity Disorder: Beyond the Frontostriatal Circuitry". The Canadian Journal of Psychiatry 54(10): 651–664. PMID 19835672. doi: 10.1016/j.biopsych.2005.02.014
  5. ^ a b Hodge SM, Makris N, Kennedy DN, Caviness VS, Howard J, McGrath L, Steele S, Frazier JA, Tager-Flusberg H, Harris GJ (2010). "Cerebellum, Language, and Cognition in Autism and Specific Language Impairment". Journal of Autism and Developmental Disorders 40: 300–316. PMID 19924522. doi: 10.1007/s10803-009-0872-7
  6. ^ Zanchetti A, Zoccolini A (1954). "Autonomic hypothalamic outbursts elicited by cerebellar stimulation". Journal of Neurophysiology 17: 475–83. PMID 13201979.
  7. ^ Snider RS, Maiti A (1976). "Cerebellar contributions to the Papez circuit". Journal of Neuroscience Research 2: 133–46. PMID 950678. doi: 10.1002/jnr.490020204
  8. ^ Reis DJ, Doba N, Nathan MA (1973). "Predatory attack, grooming, and consummatory behaviors evoked by electrical stimulation of cat cerebellar nuclei". Science 182: 845–47. PMID 4795751. doi: [1]10.1126/science.182.4114.845 10.1126/science.182.4114.845]
  9. ^ Berntson GG, Potolicchio SJ Jr, Miller NE (1973). "Evidence for higher functions of the cerebellum: eating and grooming elicited by cerebellar stimulation in cats". Proceedings of the National Academy of Sciences of the United States of America 70: 2497–99. PMID 4517662
  10. ^ Shmahmann JD, Sherman JC (1998). "The cerebellar cognitive affective syndrome". Brain 121: 561–579. PMID 19776302.
  11. ^ a b Courchesne E (1994). "Impairment in shifting attention in autistic and cerebellar patients". Behavioral neuroscience 108: 848–865. PMID 7826509. doi: 10.1037/0735-7044.108.5.848.
  12. ^ Baier Bernhard, Dieterich M, Stoeter P, Birklein F, Müller NG (2010). "Anatomical Correlate of Impaired Covert Visual Attentional Processes in Patients with Cerebellar Lesions". The Journal of Neuroscience 30(10): 3770–3776. PMID 20220011. doi: 10.1523/JNEUROSCI.0487-09.2010.
  13. ^ Fiez J, Petersen S, Cheney M, and Raichle M (1992). "Impaired non-motor learning and error detection associated with cerebellar damage". Brain 115: 151–178. PMID 1559151.
  14. ^ Richter S, Kaiser O, Hein-Kropp C, Dimitrova A, Gizewski E, Beck A, Aurich V, Ziegler W, Timmann D. (2004). "Preserved verb generation in patients with cerebellar atrophy". Neuropsychologia 42: 1235–1246. PMID 15178175. doi: 10.1016/j.neuropsychologia.2004.01.006.
  15. ^ Chein JM, Fissell K, Jacobs S, Fiez JA (2002). "Functional heterogeneity within Broca’s area during verbal working memory". Physiology & Behavior 77: 635–39. PMID 12527011.
  16. ^ Turkeltaub PE, Eden GF, Jones KM, Zeffiro TA 2002. "Meta-analysis of the functional neuroanatomy ofsingle-word reading: method and validation". Neuroimage 16: 765–80. PMID 12169260.
  17. ^ Glickstein M (2207). Current Biology 17(19): 824–827. doi: 10.1016/j.cub.2007.08.009.
  18. ^ Ravizza SM, McCormick CA, Schlerf JE, Justus T, Ivry RB, Fiez JA (2006). "Cerebellar damage produces selective deficits in verbal working memory". NeuroImage 129(2): 306–320. PMID 16317024. doi: 10.1093/brain/awh685.
  19. ^ Silveri M, DiBetta A, Filippini V, Leggio M, Molinari M (1998). "Verbal short-term store rehearsal system and the cerebellum. Evidence from a patient with a right cerebellar lesion". Brain 121: 2175–2187. PMID 9827776.
  20. ^ Fliessbach K, Trautner P, Quesada CM, Christian E. Elger CE, Weber B (2007). "Cerebellar contributions to episodic memory encoding as revealed by fMRI". NeuroImage 35(3): 1330–1337. PMID 17350289. doi: 10.1016/j.neuroimage.2007.02.004.
From Wikipedia, the free encyclopedia

Nonmotor functions

Prior to the last decade, it was widely accepted that the cerebellum was purely motor-related. However, findings from as early as 1957 and investigations in the past few decades have brought that view strongly into question. Anatomical analyses of the cerebellum show that, along with its well-characterized associations with the motor cortex, the cerebellum has significant projections to nonmotor cortical areas by way of the ventrolateral thalamus. These nonmotor targets include the frontal, prefrontal and posterior parietal cortices, each of which are involved in higher cognitive functions. Neocortical regions innervated by the cerebellum project back to it via the pons, creating a closed-loop circuit (termed cerebero-cerebellar circuit). [1] Researchers hypothesize that the cerebellum is able to exert significant influence over its targets in the neocortex due the large number of projections to nonmotor areas and the closed-loop structure of the cerebero-cerebellar circuits. [2] In addition to the links to cognitive brain areas, cerebellar projections to limbic areas are also hypothesized to exist. [3] Studies show cerebellar activation in a diverse range of cognitive tasks devised to assess attention, working memory, language, learning, executive function and emotion. [2] Mounting evidence of cerebellar abnormalities is leading to new insights of the cerebellum's previously unknown role in developmental disorders such as autism and attention-deficit hyperactivity disorder (ADHD). [4] [5]

Emotion

Far before research uncovered any anatomical pathways between the cerebellum and nonmotor areas, early electrophysiological evidence suggested that a link between the cerebellum and limbic system exists. Zanchetti and Zoccolini discovered the first hints at a nonmotor role for the cerebellum in 1954. By stimulating portions of the cerebellum, the team was able to elicit outbursts of sham rage, a behavior typically controlled by the hypothalamus. [6] Other teams were able to record altered functioning of the amygdala and the cingulate cortex, [7] [3] areas responsible for emotional learning and processing, after stimulating portions of the fastigial nucleus and associated regions of the vermal cortex. Grooming and eating behaviors, and predatory attack behaviors have also been observed following cerebellar stimulation. [8] [9] Despite these findings, the exact nature of the cerebellum's contributions to emotion and limbic function are still unclear. Moreover, the neural mechanisms behind the cerebello-limbic association are unknown due to a lack of clear evidence for an anatomical substrate.

Schmahmann and Sherman discovered a cerebellar "cognitive affective syndrome" in patients with diseases of the cerebellum. [10] Neurological examinations and bedside mental state tests revealed personality changes involving blunted affect. Their examinations also revealed inappropriate behavior as a result of behavioral inhibition, suggesting a possible role for the cerebellum in executive control.

Attention

Some cerebellar projections innervate portions of the dorsolateral prefrontal cortex (DLPFC), a key area responsible for sustaining attention and for working memory. Studies have shown that autistic and non-autistic patients with cerebellar abnormalities have difficulty directing attention. [11] Cerebellar patients also display distractibility and inattention, [11] and individuals with damage to vermal structures have difficulty directing visual attention. [12] Additionally, reduced cerebellar volume and atypical cerebellar activation have been noted in individuals with ADHD [4] There is some debate over the precise neurobiological mechanisms behind ADHD, but these findings suggest that cerebellar dysfunction could help explain not only the attentional difficulties that characterize ADHD, but also deficits in motor-sequencing, working memory, executive function and emotional regulation. Similarly, corresponding deficits in autism could also be partially explained by cerebellar abnormalities.

Language

Deficits in language related to cerebellar damage have been well documented. An early investigation showed that, following damage to the right side of the cerebellum, patients had difficulty associating appropriate verbs with given nouns (e.g. associating "car" with "drive"). [13] The researchers posited that the lack of input from the damaged areas of the cerebellum to the language centers in the left cerebral hemisphere created issues with word finding. Failed attempts to recreate these results cast doubt on this finding. [14] However, there have been studies of language impairments in autism that may support the theory that the cerebellum contributes to language generation. Data shows that autistic subjects with language impairment have significantly different distribution of cerebellar volume compared to non-language-impaired autistic and non-autistic subjects. On average, subjects with language impairment had reduced right-sided cerebellar volume in conjunction with structural defects of Broca's area. [5]

Imaging studies have recorded fMRI during verbal working memory and single word reading tasks and have found unique cerebellar activation patterns for test. [15] [16] Due to motor-related aspects of language (e.g. planning/coordinating vocal cord movements), it is disputed whether cerebellar activation during language tasks is due to the cognitive aspects of language or due to motor activity. [17] In attempts to avoid language-related motor activation, studies examined cerebellar activation in patients instructed to imagine producing simple speech instead of speaking aloud and still found activation in areas of the cerebellum that are associated with language. [2]

Memory

The cerebellum’s role in working memory has been the subject of much research and its role in verbal working memory is especially well known. Meta-analyses of investigations into this role specifically found cerebellar activation in the lateral cerebellar cortexduring verbal working memory tasks. [2] Additionally, patients with cerebellar damage have a shorter verbal working memory span. [18] One study found that a patient with cerebellar damage had temporary difficulty repeating a series of digits in the forward or reverse order in which the experimenter recited them. [19] Full recovery was achieved in a few months, suggesting that other parts of the cerebellum may have taken over that functionality, or that the patient's memory deficits were unrelated to cerebellar damage. Besides evidence for a cerebellar role in working memory, functional imaging has demonstrated that the cerebellum contributes to encoding of long-term episodic memory. [20] While the physiological mechanism by which the cerebellum aids in encoding long-term memory is unknown, the cerebellum's projections to to the DLPFC and parietal regions may provide an anatomical locus for cerebellar contributions to working memory.

References

  1. ^ Kelly RM, Strick PL (2003). "Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate". The Journal of Neuroscience 23(23): 8432-8444. PMID 12968006.
  2. ^ a b c d Strick PL, Dum RP, Fiez JA (2009). "Cerebellum and Nonmotor Function". Annual Review of Neuroscience 32: 413–434.
  3. ^ a b Anand BK, Malhotra CL, Singh B, Dua S. (1959). "Cerebellar projections to limbic system". Journal of Neurophysiology 22: 451–57. PMID 13673296. doi: 10.1016/0014-4886(74)90118-6
  4. ^ a b Cherkasova MV, Hechtman (2009). "Neuroimaging in Attention-Deficit Hyperactivity Disorder: Beyond the Frontostriatal Circuitry". The Canadian Journal of Psychiatry 54(10): 651–664. PMID 19835672. doi: 10.1016/j.biopsych.2005.02.014
  5. ^ a b Hodge SM, Makris N, Kennedy DN, Caviness VS, Howard J, McGrath L, Steele S, Frazier JA, Tager-Flusberg H, Harris GJ (2010). "Cerebellum, Language, and Cognition in Autism and Specific Language Impairment". Journal of Autism and Developmental Disorders 40: 300–316. PMID 19924522. doi: 10.1007/s10803-009-0872-7
  6. ^ Zanchetti A, Zoccolini A (1954). "Autonomic hypothalamic outbursts elicited by cerebellar stimulation". Journal of Neurophysiology 17: 475–83. PMID 13201979.
  7. ^ Snider RS, Maiti A (1976). "Cerebellar contributions to the Papez circuit". Journal of Neuroscience Research 2: 133–46. PMID 950678. doi: 10.1002/jnr.490020204
  8. ^ Reis DJ, Doba N, Nathan MA (1973). "Predatory attack, grooming, and consummatory behaviors evoked by electrical stimulation of cat cerebellar nuclei". Science 182: 845–47. PMID 4795751. doi: [1]10.1126/science.182.4114.845 10.1126/science.182.4114.845]
  9. ^ Berntson GG, Potolicchio SJ Jr, Miller NE (1973). "Evidence for higher functions of the cerebellum: eating and grooming elicited by cerebellar stimulation in cats". Proceedings of the National Academy of Sciences of the United States of America 70: 2497–99. PMID 4517662
  10. ^ Shmahmann JD, Sherman JC (1998). "The cerebellar cognitive affective syndrome". Brain 121: 561–579. PMID 19776302.
  11. ^ a b Courchesne E (1994). "Impairment in shifting attention in autistic and cerebellar patients". Behavioral neuroscience 108: 848–865. PMID 7826509. doi: 10.1037/0735-7044.108.5.848.
  12. ^ Baier Bernhard, Dieterich M, Stoeter P, Birklein F, Müller NG (2010). "Anatomical Correlate of Impaired Covert Visual Attentional Processes in Patients with Cerebellar Lesions". The Journal of Neuroscience 30(10): 3770–3776. PMID 20220011. doi: 10.1523/JNEUROSCI.0487-09.2010.
  13. ^ Fiez J, Petersen S, Cheney M, and Raichle M (1992). "Impaired non-motor learning and error detection associated with cerebellar damage". Brain 115: 151–178. PMID 1559151.
  14. ^ Richter S, Kaiser O, Hein-Kropp C, Dimitrova A, Gizewski E, Beck A, Aurich V, Ziegler W, Timmann D. (2004). "Preserved verb generation in patients with cerebellar atrophy". Neuropsychologia 42: 1235–1246. PMID 15178175. doi: 10.1016/j.neuropsychologia.2004.01.006.
  15. ^ Chein JM, Fissell K, Jacobs S, Fiez JA (2002). "Functional heterogeneity within Broca’s area during verbal working memory". Physiology & Behavior 77: 635–39. PMID 12527011.
  16. ^ Turkeltaub PE, Eden GF, Jones KM, Zeffiro TA 2002. "Meta-analysis of the functional neuroanatomy ofsingle-word reading: method and validation". Neuroimage 16: 765–80. PMID 12169260.
  17. ^ Glickstein M (2207). Current Biology 17(19): 824–827. doi: 10.1016/j.cub.2007.08.009.
  18. ^ Ravizza SM, McCormick CA, Schlerf JE, Justus T, Ivry RB, Fiez JA (2006). "Cerebellar damage produces selective deficits in verbal working memory". NeuroImage 129(2): 306–320. PMID 16317024. doi: 10.1093/brain/awh685.
  19. ^ Silveri M, DiBetta A, Filippini V, Leggio M, Molinari M (1998). "Verbal short-term store rehearsal system and the cerebellum. Evidence from a patient with a right cerebellar lesion". Brain 121: 2175–2187. PMID 9827776.
  20. ^ Fliessbach K, Trautner P, Quesada CM, Christian E. Elger CE, Weber B (2007). "Cerebellar contributions to episodic memory encoding as revealed by fMRI". NeuroImage 35(3): 1330–1337. PMID 17350289. doi: 10.1016/j.neuroimage.2007.02.004.

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