• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jnnpsycJournal of Neurology, Neurosurgery and PsychiatryVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Neurol Neurosurg Psychiatry. Feb 1995; 58(2): 192–200.
PMCID: PMC1073317

Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease.

Abstract

The corpus striatum serves a critical function in inhibiting involuntary, intrusive movements. Striatal degeneration in Huntington's disease results in a loss of motor inhibition, manifested by abnormal involuntary choreiform movements. Sensorimotor inhibition, or "gating", can be measured in humans using the startle reflex: the startle reflex is normally inhibited when the startling stimulus is preceded 30-500 ms earlier by a weak prepulse. In the present study, prepulse inhibition (PPI) was measured in patients with Huntington's disease to quantify and characterise sensorimotor gating. Compared with age matched controls, patients with Huntington's disease exhibit less PPI. Startle gating deficits are evident in patients with Huntington's disease when startle is elicited by either acoustic or tactile stimuli. Even with stimuli that elicit maximal PPI in normal subjects, patients with Huntington's disease exhibit little or no PPI, and their pattern of startle gating does not show the normal modulatory effects usually elicited by changing the prepulse interval or intensity. Startle amplitude and habituation and latency facilitation are largely intact in these patients, although reflex latency is significantly slowed. In patients with Huntington's disease, startle reflex slowing correlates with cognitive impairment measured by the dementia rating scale, and with the performance disruptive effects of interference measured by the Stroop test. These findings document a profound disruption of sensorimotor gating in patients with Huntington's disease and are consistent with preclinical findings that identify the striatum and striatopallidal GABAergic efferent circuitry as critical substrates for sensorimotor gating of the startle reflex.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Groves PM. A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement. Brain Res. 1983 Mar;286(2):109–132. [PubMed]
  • Penney JB, Jr, Young AB. Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci. 1983;6:73–94. [PubMed]
  • Ison JR, McAdam DW, Hammond GR. Latency and amplitude changes in the acoustic startle reflex of the rat produced by variation in auditory prestimulation. Physiol Behav. 1973 Jun;10(6):1035–1039. [PubMed]
  • Davis M, Gendelman DS, Tischler MD, Gendelman PM. A primary acoustic startle circuit: lesion and stimulation studies. J Neurosci. 1982 Jun;2(6):791–805. [PubMed]
  • Caine SB, Geyer MA, Swerdlow NR. Hippocampal modulation of acoustic startle and prepulse inhibition in the rat. Pharmacol Biochem Behav. 1992 Dec;43(4):1201–1208. [PubMed]
  • Caine SB, Geyer MA, Swerdlow NR. Carbachol infusion into the dentate gyrus disrupts sensorimotor gating of startle in the rat. Psychopharmacology (Berl) 1991;105(3):347–354. [PubMed]
  • Swerdlow NR, Braff DL, Geyer MA. GABAergic projection from nucleus accumbens to ventral pallidum mediates dopamine-induced sensorimotor gating deficits of acoustic startle in rats. Brain Res. 1990 Nov 5;532(1-2):146–150. [PubMed]
  • Swerdlow NR, Braff DL, Masten VL, Geyer MA. Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens. Psychopharmacology (Berl) 1990;101(3):414–420. [PubMed]
  • Swerdlow NR, Geyer MA. Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine tegmental nucleus. Behav Neurosci. 1993 Feb;107(1):104–117. [PubMed]
  • Swerdlow NR, Geyer MA. Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia. Pharmacol Biochem Behav. 1993 Mar;44(3):741–744. [PubMed]
  • Butler RW, Jenkins MA, Braff DL. The abnormality of normal comparison groups: the identification of psychosis proneness and substance abuse in putatively normal research subjects. Am J Psychiatry. 1993 Sep;150(9):1386–1391. [PubMed]
  • Braff DL, Grillon C, Geyer MA. Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry. 1992 Mar;49(3):206–215. [PubMed]
  • Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L. Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology. 1978 Jul;15(4):339–343. [PubMed]
  • Wan FJ, Swerdlow NR. Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats. Psychopharmacology (Berl) 1993;113(1):103–109. [PubMed]
  • Swerdlow NR, Auerbach P, Monroe SM, Hartston H, Geyer MA, Braff DL. Men are more inhibited than women by weak prepulses. Biol Psychiatry. 1993 Aug 15;34(4):253–260. [PubMed]
  • Shoulson I, Fahn S. Huntington disease: clinical care and evaluation. Neurology. 1979 Jan;29(1):1–3. [PubMed]
  • Folstein SE, Jensen B, Leigh RJ, Folstein MF. The measurement of abnormal movement: methods developed for Huntington's disease. Neurobehav Toxicol Teratol. 1983 Nov-Dec;5(6):605–609. [PubMed]
  • Butters N, Sax D, Montgomery K, Tarlow S. Comparison of the neuropsychological deficits associated with early and advanced Huntington's disease. Arch Neurol. 1978 Sep;35(9):585–589. [PubMed]
  • Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL. A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry. 1993 Feb 15;33(4):298–301. [PubMed]
  • Braff DL, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry. 1990 Feb;47(2):181–188. [PubMed]
  • Ferguson IT, Lenman JA, Johnston BB. Habituation of the orbicularis oculi reflex in dementia and dyskinetic states. J Neurol Neurosurg Psychiatry. 1978 Sep;41(9):824–828. [PMC free article] [PubMed]
  • Kuwert T, Lange HW, Langen KJ, Herzog H, Aulich A, Feinendegen LE. Cortical and subcortical glucose consumption measured by PET in patients with Huntington's disease. Brain. 1990 Oct;113(Pt 5):1405–1423. [PubMed]
  • Groves PM, Boyle RD, Welker RL, Miller SW. On the mechanism of prepulse inhibition. Physiol Behav. 1974 Mar;12(3):367–375. [PubMed]
  • Kemble ED, Ison JR. Limbic lesions and the inhibition of startle reactions in the rat by conditions of preliminary stimulation. Physiol Behav. 1971 Dec;7(6):925–928. [PubMed]
  • Schwarcz R, Tamminga CA, Kurlan R, Shoulson I. Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia. Ann Neurol. 1988 Oct;24(4):580–582. [PubMed]
  • Schwarcz R, Whetsell WO, Jr, Mangano RM. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science. 1983 Jan 21;219(4582):316–318. [PubMed]
  • Smith SJ, Lees AJ. Abnormalities of the blink reflex in Gilles de la Tourette syndrome. J Neurol Neurosurg Psychiatry. 1989 Jul;52(7):895–898. [PMC free article] [PubMed]
  • Coon H, Plaetke R, Holik J, Hoff M, Myles-Worsley M, Waldo M, Freedman R, Byerley W. Use of a neurophysiological trait in linkage analysis of schizophrenia. Biol Psychiatry. 1993 Sep 1;34(5):277–289. [PubMed]
  • Graham FK. Presidential Address, 1974. The more or less startling effects of weak prestimulation. Psychophysiology. 1975 May;12(3):238–248. [PubMed]
  • Hackley SA, Graham FK. Effects of attending selectively to the spatial position of reflex-eliciting and reflex-modulating stimuli. J Exp Psychol Hum Percept Perform. 1987 Aug;13(3):411–424. [PubMed]
  • Blumenthal TD, Gescheider GA. Modification of the acoustic startle reflex by a tactile prepulse: the effects of stimulus onset asynchrony and prepulse intensity. Psychophysiology. 1987 May;24(3):320–327. [PubMed]
  • Blumenthal TD, Levey BJ. Prepulse rise time and startle reflex modification: different effects for discrete and continuous prepulses. Psychophysiology. 1989 Mar;26(2):158–165. [PubMed]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...