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Erschienen in: Experimental Brain Research 2/2010

01.03.2010 | Research Article

Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder

verfasst von: Markus Frings, Kristina Gaertner, Paul Buderath, Marcus Gerwig, Hanna Christiansen, Beate Schoch, Elke R. Gizewski, Johannes Hebebrand, Dagmar Timmann

Erschienen in: Experimental Brain Research | Ausgabe 2/2010

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Abstract

Structural changes of the cerebellum have been reported in several psychiatric diseases like schizophrenia, autism and attention-deficit/hyperactivity disorder (ADHD). Beside behavioral deficits children with ADHD often show slight motor abnormalities. Cerebellar malfunction may contribute. The cerebellum is a structure essential for motor coordination, various forms of motor learning and timing of motor responses. In the present study, eyeblink conditioning was applied to investigate learning and timing of motor responses both in children with ADHD and children with cerebellar lesions. Acquisition, timing and extinction of conditioned eyeblink responses were investigated in children with ADHD, children with chronic surgical cerebellar lesions and controls using a standard delay paradigm with two different interstimulus intervals. Timing of conditioned eyeblink responses was significantly impaired in children with ADHD in the long interstimulus interval condition. Also in children with cerebellar lesions conditioned responses (CR) tended to occur earlier than in controls. Incidences of CRs were significantly reduced in children with cerebellar lesions and tended to be less in children with ADHD than in controls. Extinction of the CRs was impaired in children with cerebellar lesions in both interstimulus interval conditions and in children with ADHD in the long interstimulus interval condition. Cerebellar malfunction may contribute to disordered eyeblink conditioning in ADHD. However, because CR abnormalities differed between ADHD and cerebellar subjects, dysfunction of non-cerebellar structures cannot be excluded.
Literatur
Zurück zum Zitat American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders text revision (DSM-IV-TR), 4th edn. American Psychiatric Press Inc, Washington, DCCrossRef American Psychiatric Association (2000) Diagnostic and Statistical Manual of Mental Disorders text revision (DSM-IV-TR), 4th edn. American Psychiatric Press Inc, Washington, DCCrossRef
Zurück zum Zitat Andreasen NC, Flashman L, Flaum M, Arndt S, Swayze V, O’Leary DS, Ehrhardt JC, Yuh WT (1994) Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. J Am Med Assoc 272:1763–1769CrossRef Andreasen NC, Flashman L, Flaum M, Arndt S, Swayze V, O’Leary DS, Ehrhardt JC, Yuh WT (1994) Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. J Am Med Assoc 272:1763–1769CrossRef
Zurück zum Zitat Andreasen NC, O’Leary DS, Cizadlo T, Arndt S, Rezai K, Boles Ponto LL, Watkins GL, Hichwa RD (1996) Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal–thalamic–cerebellar circuitry. Proc Natl Acad Sci USA 93:9985–9990CrossRefPubMed Andreasen NC, O’Leary DS, Cizadlo T, Arndt S, Rezai K, Boles Ponto LL, Watkins GL, Hichwa RD (1996) Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal–thalamic–cerebellar circuitry. Proc Natl Acad Sci USA 93:9985–9990CrossRefPubMed
Zurück zum Zitat Berquin PC, Giedd JN, Jacobsen LK, Hamburger SD, Krain AL, Rapoport JL, Castellanos FX (1998) Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study. Neurology 50:1087–1093PubMed Berquin PC, Giedd JN, Jacobsen LK, Hamburger SD, Krain AL, Rapoport JL, Castellanos FX (1998) Cerebellum in attention-deficit hyperactivity disorder: a morphometric MRI study. Neurology 50:1087–1093PubMed
Zurück zum Zitat Bloedel JR, Bracha V (1995) On the cerebellum, cutaneomuscular reflexes, movement control and the elusive engrams of memory. Behav Brain Res 68:1–44CrossRefPubMed Bloedel JR, Bracha V (1995) On the cerebellum, cutaneomuscular reflexes, movement control and the elusive engrams of memory. Behav Brain Res 68:1–44CrossRefPubMed
Zurück zum Zitat Braitenberg V (1967) Is the cerebellar cortex a biological clock in the millisecond range. Progr Brain Res 25:334–346CrossRef Braitenberg V (1967) Is the cerebellar cortex a biological clock in the millisecond range. Progr Brain Res 25:334–346CrossRef
Zurück zum Zitat Bush G, Valera EM, Seidman LJ (2005) Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions. Biol Psychiatry 57:1273–1284CrossRefPubMed Bush G, Valera EM, Seidman LJ (2005) Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and suggested future directions. Biol Psychiatry 57:1273–1284CrossRefPubMed
Zurück zum Zitat Castellanos FX, Giedd JN, Berquin PC, Walter JM, Sharp W, Tran T, Vaituzis AC, Blumenthal JD, Nelson J, Bastain TM, Zijdenbos A, Evans AC, Rapoport JL (2001) Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 58:289–295CrossRefPubMed Castellanos FX, Giedd JN, Berquin PC, Walter JM, Sharp W, Tran T, Vaituzis AC, Blumenthal JD, Nelson J, Bastain TM, Zijdenbos A, Evans AC, Rapoport JL (2001) Quantitative brain magnetic resonance imaging in girls with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 58:289–295CrossRefPubMed
Zurück zum Zitat Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM, Zijdenbos A, Evans AC, Giedd JN, Rapoport JL (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 288:1740–1748CrossRefPubMed Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, Blumenthal JD, James RS, Ebens CL, Walter JM, Zijdenbos A, Evans AC, Giedd JN, Rapoport JL (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA 288:1740–1748CrossRefPubMed
Zurück zum Zitat Chess AC, Green JT (2008) Abnormal topography and altered acquisition of conditioned eyeblink responses in a rodent model of attention-deficit/hyperactivity disorder. Behav Neurosci 122:63–74CrossRefPubMed Chess AC, Green JT (2008) Abnormal topography and altered acquisition of conditioned eyeblink responses in a rodent model of attention-deficit/hyperactivity disorder. Behav Neurosci 122:63–74CrossRefPubMed
Zurück zum Zitat Coffin JM, Roody S, Schneider K, O’Neill J (2005) Impaired cerebellar learning in children with prenatal alcohol exposure: a comparative study of eyeblink conditioning in children with ADHD and dyslexia. Cortex 41:389–398CrossRefPubMed Coffin JM, Roody S, Schneider K, O’Neill J (2005) Impaired cerebellar learning in children with prenatal alcohol exposure: a comparative study of eyeblink conditioning in children with ADHD and dyslexia. Cortex 41:389–398CrossRefPubMed
Zurück zum Zitat Conners CK (1997) Conners’ rating scales—revised CRS–R. MHS, North Tonawanda Conners CK (1997) Conners’ rating scales—revised CRS–R. MHS, North Tonawanda
Zurück zum Zitat Courchesne E, Saitoh O, Townsend JP, Yeung-Courchesne R, Press GA, Lincoln AJ, Haas RH, Schriebman L (1994) Cerebellar hypoplasia and hyperplasia in infantile-autism. Lancet 343:60–64CrossRef Courchesne E, Saitoh O, Townsend JP, Yeung-Courchesne R, Press GA, Lincoln AJ, Haas RH, Schriebman L (1994) Cerebellar hypoplasia and hyperplasia in infantile-autism. Lancet 343:60–64CrossRef
Zurück zum Zitat Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb FP, Forsting M, Diener HC, Timmann D (2002) MRI atlas of the human cerebellar nuclei. Neuroimage 17:240–255CrossRefPubMed Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb FP, Forsting M, Diener HC, Timmann D (2002) MRI atlas of the human cerebellar nuclei. Neuroimage 17:240–255CrossRefPubMed
Zurück zum Zitat Dimitrova A, Zeljko D, Schwarze F, Maschke M, Gerwig M, Frings M, Beck A, Aurich V, Forsting M, Timmann D (2006) Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei. Neuroimage 30:12–25CrossRefPubMed Dimitrova A, Zeljko D, Schwarze F, Maschke M, Gerwig M, Frings M, Beck A, Aurich V, Forsting M, Timmann D (2006) Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei. Neuroimage 30:12–25CrossRefPubMed
Zurück zum Zitat Doyon J, Penhune V, Ungerleider LG (2003) Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning. Neuropsychologia 41:252–262CrossRefPubMed Doyon J, Penhune V, Ungerleider LG (2003) Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning. Neuropsychologia 41:252–262CrossRefPubMed
Zurück zum Zitat Gerwig M, Dimitrova A, Kolb FP, Maschke M, Brol B, Kunnel A, Böring D, Thilmann AF, Forsting M, Diener HC, Timmann D (2003) Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions. Brain 126:71–94CrossRefPubMed Gerwig M, Dimitrova A, Kolb FP, Maschke M, Brol B, Kunnel A, Böring D, Thilmann AF, Forsting M, Diener HC, Timmann D (2003) Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions. Brain 126:71–94CrossRefPubMed
Zurück zum Zitat Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb FP, Frings M, Thilmann AF, Forsting M, Diener HC, Timmann D (2005) Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci 25:3919–3931CrossRefPubMed Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb FP, Frings M, Thilmann AF, Forsting M, Diener HC, Timmann D (2005) Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci 25:3919–3931CrossRefPubMed
Zurück zum Zitat Gerwig M, Kolb FP, Timmann D (2007) The involvement of the human cerebellum in eyeblink conditioning. Cerebellum 6:38–57CrossRefPubMed Gerwig M, Kolb FP, Timmann D (2007) The involvement of the human cerebellum in eyeblink conditioning. Cerebellum 6:38–57CrossRefPubMed
Zurück zum Zitat Gormezano I, Kehoe EJ (1975) Classical conditioning: some methodical-conceptual issues. In: Estes WK (ed) Handbook of learning and cognitive processes, vol 2. Lawrence Erlbaum, Hillsdale (NJ), pp 143–179 Gormezano I, Kehoe EJ (1975) Classical conditioning: some methodical-conceptual issues. In: Estes WK (ed) Handbook of learning and cognitive processes, vol 2. Lawrence Erlbaum, Hillsdale (NJ), pp 143–179
Zurück zum Zitat Gowen E, Miall RC (2007) The cerebellum and motor dysfunction in neuropsychiatric disorders. Cerebellum 6:268–279CrossRefPubMed Gowen E, Miall RC (2007) The cerebellum and motor dysfunction in neuropsychiatric disorders. Cerebellum 6:268–279CrossRefPubMed
Zurück zum Zitat Holmes G (1939) The cerebellum of man (Hughlings Jackson memorial lecture). Brain 62:1–30CrossRef Holmes G (1939) The cerebellum of man (Hughlings Jackson memorial lecture). Brain 62:1–30CrossRef
Zurück zum Zitat Ivry RB, Diener HC (1991) Impaired velocity perception in patients with lesions of the cerebellum. J Cogn Neurosci 3:355–366CrossRef Ivry RB, Diener HC (1991) Impaired velocity perception in patients with lesions of the cerebellum. J Cogn Neurosci 3:355–366CrossRef
Zurück zum Zitat Ivry RB, Keele SW (1989) Timing functions of the cerebellum. J Cogn Neurosci 1:136–152CrossRef Ivry RB, Keele SW (1989) Timing functions of the cerebellum. J Cogn Neurosci 1:136–152CrossRef
Zurück zum Zitat Karatekin C, Markiewicz SW, Siegel MA (2003) A preliminary study of motor problems in children with attention-deficit/hyperactivity disorder. Percept Mot Skills 97:1267–1280PubMed Karatekin C, Markiewicz SW, Siegel MA (2003) A preliminary study of motor problems in children with attention-deficit/hyperactivity disorder. Percept Mot Skills 97:1267–1280PubMed
Zurück zum Zitat Koch G, Costa A, Brusa L, Peppe A, Gatto I, Torriero S, Gerfo EL, Salerno S, Oliveri M, Carlesimo GA, Caltagirone C (2008) Impaired reproduction of second but not millisecond time intervals in Parkinson’s disease. Neuropsychologia 46:1305–1313CrossRefPubMed Koch G, Costa A, Brusa L, Peppe A, Gatto I, Torriero S, Gerfo EL, Salerno S, Oliveri M, Carlesimo GA, Caltagirone C (2008) Impaired reproduction of second but not millisecond time intervals in Parkinson’s disease. Neuropsychologia 46:1305–1313CrossRefPubMed
Zurück zum Zitat Koekkoek SK, Hulscher HC, Dortland BR, Hensbroek RA, Elgersma Y, Ruigrok TJ, De Zeeuw CI (2003) Cerebellar LTD and learning dependent timing of conditioned eyelid responses. Science 301:1736–1739CrossRefPubMed Koekkoek SK, Hulscher HC, Dortland BR, Hensbroek RA, Elgersma Y, Ruigrok TJ, De Zeeuw CI (2003) Cerebellar LTD and learning dependent timing of conditioned eyelid responses. Science 301:1736–1739CrossRefPubMed
Zurück zum Zitat Konczak J, Schoch B, Dimitrova A, Gizewski E, Timmann D (2005) Functional recovery of children and adolescents after cerebellar tumour resection. Brain 128:1428–1441CrossRefPubMed Konczak J, Schoch B, Dimitrova A, Gizewski E, Timmann D (2005) Functional recovery of children and adolescents after cerebellar tumour resection. Brain 128:1428–1441CrossRefPubMed
Zurück zum Zitat Leitner Y, Barak R, Giladi N, Peretz C, Eshel R, Gruendlinger L, Hausdorff JM (2007) Gait in attention deficit hyperactivity disorder: effects of methylphenidate and dual tasking. J Neurol 254:1330–1338CrossRefPubMed Leitner Y, Barak R, Giladi N, Peretz C, Eshel R, Gruendlinger L, Hausdorff JM (2007) Gait in attention deficit hyperactivity disorder: effects of methylphenidate and dual tasking. J Neurol 254:1330–1338CrossRefPubMed
Zurück zum Zitat Lerer RJ, Lerer MP, Artner J (1977) The effects of methylphenidate on the handwriting of children with minimal brain dysfunction. J Pediatr 91:127–132CrossRefPubMed Lerer RJ, Lerer MP, Artner J (1977) The effects of methylphenidate on the handwriting of children with minimal brain dysfunction. J Pediatr 91:127–132CrossRefPubMed
Zurück zum Zitat McGlinchey-Berroth R, Brawn C, Disterhoft JF (1999) Temporal discrimination learning in severe amnesic patients reveals an alteration in the timing of eyeblink conditioned responses. Behav Neurosci 113:10–18CrossRefPubMed McGlinchey-Berroth R, Brawn C, Disterhoft JF (1999) Temporal discrimination learning in severe amnesic patients reveals an alteration in the timing of eyeblink conditioned responses. Behav Neurosci 113:10–18CrossRefPubMed
Zurück zum Zitat Mostofsky SH, Reiss AL, Lockhart P, Denckla MB (1998) Evaluation of cerebellar size in attention-deficit hyperactivity disorder. J Child Neurol 13:434–439CrossRefPubMed Mostofsky SH, Reiss AL, Lockhart P, Denckla MB (1998) Evaluation of cerebellar size in attention-deficit hyperactivity disorder. J Child Neurol 13:434–439CrossRefPubMed
Zurück zum Zitat Perrett SP, Ruiz BP, Mauk MD (1993) Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci 13:1708–1718PubMed Perrett SP, Ruiz BP, Mauk MD (1993) Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci 13:1708–1718PubMed
Zurück zum Zitat Radonovich KJ, Mostofsky SH (2004) Duration judgments in children with ADHD suggest deficient utilization of temporal information rather than general impairment in timing. Child Neuropsychol 10:162–172CrossRefPubMed Radonovich KJ, Mostofsky SH (2004) Duration judgments in children with ADHD suggest deficient utilization of temporal information rather than general impairment in timing. Child Neuropsychol 10:162–172CrossRefPubMed
Zurück zum Zitat Rubia K, Noorloos J, Sergeant JA (2003) Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing. J Abnorm Child Psychol 31:301–313CrossRefPubMed Rubia K, Noorloos J, Sergeant JA (2003) Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing. J Abnorm Child Psychol 31:301–313CrossRefPubMed
Zurück zum Zitat Sattler J (1992) Assessment of children: WISC III and WPPSI-R supplement. San Diego, CA Sattler J (1992) Assessment of children: WISC III and WPPSI-R supplement. San Diego, CA
Zurück zum Zitat Schmahmann JD, Dojon J, Toga AW, Petrides M, Evans AC (2000) MRI atlas of the human cerebellum. Academic Press, San Diego Schmahmann JD, Dojon J, Toga AW, Petrides M, Evans AC (2000) MRI atlas of the human cerebellum. Academic Press, San Diego
Zurück zum Zitat Szatmari P, Offord DR, Boyle MH (1989) Ontario Child Health Study: prevalence of attention deficit disorder with hyperactivity. J Child Psychol Psychiatry 30:219–230CrossRefPubMed Szatmari P, Offord DR, Boyle MH (1989) Ontario Child Health Study: prevalence of attention deficit disorder with hyperactivity. J Child Psychol Psychiatry 30:219–230CrossRefPubMed
Zurück zum Zitat Tervo RC, Azuma S, Fogas B, Fiechtner H (2002) Children with ADHD and motor dysfunction compared with children with ADHD only. Dev Med Child Neurol 44:383–390PubMedCrossRef Tervo RC, Azuma S, Fogas B, Fiechtner H (2002) Children with ADHD and motor dysfunction compared with children with ADHD only. Dev Med Child Neurol 44:383–390PubMedCrossRef
Zurück zum Zitat Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B (1997) International Cooperative Rating Scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci 145:205–211CrossRefPubMed Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B (1997) International Cooperative Rating Scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci 145:205–211CrossRefPubMed
Zurück zum Zitat Woodruff-Pak DS, Papka M (1996) Huntington’s disease and eyeblink classical conditioning: normal learning but abnormal timing. J Int Neuropsychol Soc 2:323–334CrossRefPubMed Woodruff-Pak DS, Papka M (1996) Huntington’s disease and eyeblink classical conditioning: normal learning but abnormal timing. J Int Neuropsychol Soc 2:323–334CrossRefPubMed
Zurück zum Zitat Woodruff-Pak DS, Papka M, Ivry RB (1996) Cerebellar involvement in eyeblink classical conditioning in humans. Neuropsychology 10:443–458CrossRef Woodruff-Pak DS, Papka M, Ivry RB (1996) Cerebellar involvement in eyeblink classical conditioning in humans. Neuropsychology 10:443–458CrossRef
Zurück zum Zitat Yang B, Chan RC, Zou X, Jing J, Mai J, Li J (2007) Time perception deficit in children with ADHD. Brain Res 1170:90–96CrossRefPubMed Yang B, Chan RC, Zou X, Jing J, Mai J, Li J (2007) Time perception deficit in children with ADHD. Brain Res 1170:90–96CrossRefPubMed
Metadaten
Titel
Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder
verfasst von
Markus Frings
Kristina Gaertner
Paul Buderath
Marcus Gerwig
Hanna Christiansen
Beate Schoch
Elke R. Gizewski
Johannes Hebebrand
Dagmar Timmann
Publikationsdatum
01.03.2010
Verlag
Springer-Verlag
Erschienen in
Experimental Brain Research / Ausgabe 2/2010
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI
https://doi.org/10.1007/s00221-009-2020-1

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