Abstract
Background: Prepulse inhibition (PPI) of the startle reflex reflects early stages
of information processing and is modulated by selective attention. Animal models indicate
medial frontal-thalamic circuitry is important in PPI modulation. We report data from
the first functional magnetic resonance imaging (fMRI) study examining whether attending
to or ignoring a prepulse differentially activates brain areas within this circuitry.
Methods: Ten healthy subjects received structural and functional MRI. During fMRI
acquisition, subjects heard intermixed attended and ignored tones serving as prepulses
to the startle stimulus. Regions of interest were traced on structural MRI and coregistered
to fMRI images.
Results: Greater amplitude fMRI blood-oxygen-level-dependent response to attended
than ignored PPI conditions occurred in the right thalamus, and bilaterally in the
anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed
deactivation. In transitional medial cortex (Brodmann Area 32), which is involved
in affective processing of noxious stimuli, the startle-alone condition elicited the
greatest response, the attended-PPI condition showed the smallest response, and the
ignored-PPI condition was intermediate.
Conclusions: These findings extend animal models to humans by indicating thalamic
involvement in the modulation of PPI. Further fMRI investigations may elucidate other
key structures in the circuitry underlying normal and disordered modulation of PPI.
Keywords
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References
- Thalamic abnormalities in schizophrenia visualized though magnetic resonance image averaging.Science. 1994; 266: 294-298
- The Comprehensive Assessment of Symptoms and History (CASH).Arch Gen Psychiatry. 1992; 49: 615-623
- Tests for comparing images based on randomization and permutation methods.J Cereb Blood Flow Metab. 1996; 16: 1261-1279
- Short lead interval startle modification.in: Dawson M.E. Schell A.M. Böehmelt A.H. Startle Modification Implications for Neuroscience, Cognitive Science, and Clinical Science. Cambridge University Press, New York1999: 51-71
- Prestimulus effects on human startle reflex in normals and schizophrenics.Psychophysiology. 1978; 15: 339-343
- Gating and habituation of the startle reflex in schizophrenic patients.Arch Gen Psychiatry. 1992; 49: 206-215
- Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex.Psychopharmacology. 1994; 113: 487-492
- A method of basal forebrain anatomical standardization for functional image analysis.Psychiatry Res Neuroimaging. 1998; 84: 113-125
- PET and MRI of the thalamus in never-medicated patients with schizophrenia.Am J Psychiatry. 1996; 153: 191-199
- Magnetic resonance imaging assessment of thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder.Arch Gen Psychiatry. 2001; 58: 133-140
- Human Neuroanatomy. Williams & Wilkins, Baltimore1983
- Schizophrenia and anteroventral thalamic nucleus.Psychiatry Res Neuroimaging. 1998; 82: 1-10
- A primary acoustic startle circuit.J Neurosci. 1982; 2: 791-805
- Attention and schizophrenia.J Abnorm Psychology. 1993; 102: 633-641
- Cognitive, clinical, and neurophysiological implications of startle modification.in: Lang P.J. Simons R.F. Balaban M.T. Attention and Orienting Sensory and Motivational Processes. Lawrence Erlbaum, Hillsdale, NJ1997: 257-275
- Modification of the acoustic startle-reflex eyeblink.Biol Psychol. 1993; 35: 185-200
- Probing the orienting response with startle modification and secondary reaction time.Psychophysiology. 1994; 31: 68-78
- The psychological significance of human startle eyeblink modification.Biol Psychology. 1998; 47: 1-43
- Mediodorsal nucleus.J Comp Neurol. 1988; 277: 195-213
- The more or less startling effects of weak prestimulation.Psychophysiology. 1975; 12: 238-248
- Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.Am J Psychiatry. 1999; 156: 1190-1199
- Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients.Psychophysiology. 1998; 35: 186-198
- Age-related shift in brain region activity during successful memory performance.Neurobiol Aging. 1998; 19: 437-445
- Anterior cingulate gyrus volume and glucose metabolism in autistic disorder.Am J Psychiatry. 1997; 154: 1047-1050
- Reflex modification in the domain of startle.Psychol Rev. 1980; 87: 175-189
- Tracking early and late stages of information processing.Psychophysiology. 1996; 33: 148-155
- Cortical development and thalamic pathology in schizophrenia.Schizophr Bull. 1997; 23: 483-501
- The neurobiology of startle.Prog Neurobiol. 1999; 59: 107-128
- Deficient sensorimotor gating after 6-hydroxydopamine lesion of the rat medial prefrontal cortex is reversed by haloperidol.Eur J Neurosci. 1994; 6: 1837-1845
- Regulation of prepulse inhibition by ventral pallidal projections.Brain Res Bull. 1997; 43: 219-228
- Dopaminergic stimulation disrupts sensorimotor gating in the rat.Psychopharmacology. 1988; 94: 507-514
- An Atlas of the Human Brain for Computerized Tomography. Igaku-Shoin, Tokyo1978
- Neuroleptic treatment is an unlikely cause of elevated dopamine in thalamus of schizophrenic subjects.Psychiatry Res. 1992; 45: 203-208
- PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and 11CFLB 457.Neuroimage. 1999; 10: 666-674
- Accurate three-dimensional registration of CT, PET, and/or MR images of the brain.J Comp Assist Tomogr. 1989; 13: 20-26
- Analysis of individual positron emission tomography activation maps by detection of high signal-to-noise-ratio pixel clusters.J Cereb Blood Flow Metab. 1993; 13: 425-437
- The dopamine D2, but not D3 or D4, receptor subtype is essential for the disruption of prepulse inhibition produced by amphetamine in mice.J Neurosci. 1999; 19: 4627-4633
- Thalamic deactivation during early implicit sequence learning.Neuroreport. 1998; 9: 865-870
- Three-dimensional analysis of clustered voxels in 15O-butanol brain activation images.Hum Brain Mapp. 1993; 1: 3-19
- Pharmacology of sensory gating in the ascending auditory system of the pigeon.Psychopharmacology. 1999; 145 (Columba livia): 273-282
- Attentional modulation of startle in psychosis-prone college students.Psychophysiology. 1995; 32: 266-273
- Automatic and controlled attentional processes in startle eyeblink modification.Psychophysiology. 2000; 37: 409-417
- Dorsal striatal size, shape, and metabolic rate in never-medicated and previously medicated schizophrenics performing a verbal learning task.Arch Gen Psychiatry. 1998; 55: 235-243
- Neurophysiology and neuropharmacology of short lead interval startle modification.in: Dawson M.E. Schell A.M. Böehmelt A.H. Startle Modification Implications for Neuroscience, Cognitive Science, and Clinical Science. Cambridge University Press, New York1999: 114-133
- Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine nucleus.Behav Neurosci. 1993; 107: 104-117
- Neural substrates of sensorimotor gating of the startle reflex.J Psychopharmacology. 1992; 6: 176-190
- The effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine-inhibition of sensorimotor gating of the startle response in the rat.J Pharmacol Exp Ther. 1991; 256: 530-536
- Increased sensitivity to the sensorimotor gating-disruptive effects of apomorphine-after lesions of medial prefrontal cortex or ventral hippocampus in adult rats.Psychopharmacology. 1995; 122: 27-34
- Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging.Eur J Neurosci. 1996; 8: 1461-1473
- Rapid automated algorithm for aligning and reslicing PET images.J Comput Assist Tomogr. 1992; 16: 620-633
- Startle and sensorimotor correlates of ventral thalamic dopamine and GABA in rodents.Neuroreport. 1995; 6: 2495-2499
- Characterization of D2 receptors and dopamine levels in the thalamus of the rat.Life Sci. 1991; 48: 1845-1852
- Magnetic resonance in schizophrenia.Semin Clin Neuropsychiatry. 1996; 1: 4-19
Article info
Publication history
Accepted:
January 16,
2001
Received in revised form:
January 5,
2001
Received:
October 5,
2000
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
