Prepulse inhibition

Last updated
Prepulse inhibition: preceding stimulus attenuates the startle response. Prepulse Inhibition schematically.png
Prepulse inhibition: preceding stimulus attenuates the startle response.

Prepulse inhibition (PPI) is a neurological phenomenon in which a weaker prestimulus (prepulse) inhibits the reaction of an organism to a subsequent strong reflex-eliciting stimulus (pulse), often using the startle reflex. The stimuli are usually acoustic, but tactile stimuli (e.g. via air puffs onto the skin) [1] and light stimuli [2] are also used. When prepulse inhibition is high, the corresponding one-time startle response is reduced.

Contents

The reduction of the amplitude of startle reflects the ability of the nervous system to temporarily adapt to a strong sensory stimulus when a preceding weaker signal is given to warn the organism. PPI is detected in numerous species including mice and humans. Although the extent of the adaptation affects numerous systems, the most comfortable to measure are the muscular reactions, which are normally diminished as a result of the nervous inhibition.

Deficits of prepulse inhibition manifest in the inability to filter out the unnecessary information; they have been linked to abnormalities of sensorimotor gating. Such deficits are noted in patients with conditions like schizophrenia and Alzheimer's disease, and in people under the influence of drugs, surgical manipulations, or mutations. Human studies of PPI have been summarised in reviews by Braff et al. (2001) [3] and Swerdlow et al. (2008). [4]

PPI and startle reflex apparatus for mice Startle Imetronic.jpg
PPI and startle reflex apparatus for mice

Procedure

PPI measurement in human. Matt's PhD Study.jpg
PPI measurement in human.

The main three parts of the procedure are prepulse, startle stimulus, and startle reflex. Different prepulse-to-pulse intervals, or lead intervals, are used: 30, 60, 120, 240 and 480 ms. Lead interval counts from the start of prepulse to the start of the pulse. With the interval exceeding 500 ms, prepulse facilitation – increased response – is most likely to follow. [5]

A burst of white noise is usually used as the acoustic startle stimulus. Typical durations are 20 ms for prepulse and 40 ms for pulse. Background noise with 65-70 dB is used in human studies, and 30–40 dB in rodent experiments. Prepulse is typically set 3–12 dB louder than background. Startle response is measured in rodents using the so-called automated "startle chambers" or "stabilimeter chambers", with detectors recording whole-body reaction. [5]

In humans, the movements of oculomotor muscles ("eye-blink reflex" or "eye-blink response" assessed using electromyographic recording of orbicularis oculi muscle and by oculography) could be used as a measure. Pulse-alone results are compared to prepulse-plus-pulse, and the percentage of the reduction in the startle reflex represents prepulse inhibition. Possible hearing impairment must be taken into account, as, for example, several strains of mice develop high frequency hearing loss when they mature. [5]

The recorded signal needs to be passband filtered between 28 Hz and 500 Hz. By this step, artifacts from eye movements and muscle activity independent of blink responses are removed. To avoid aliasing artifacts the sampling rate of the signal should be at least 1024 Hz which is larger than twice the upper bound of the bandpass filter (twice the Nyquist frequency). After filtering, the resulting signal is rectified and smoothed. [6]

Reporting the signal deflection evoked by the startle stimulus, the term mean amplitude (mA) refers to the average startle response excluding nonresponse trials. However, to calculate the mean magnitude (mM), nonresponse trials are set to zero before averaging. Dividing the number detected responses (number of trials used to compute amplitude) by the total number of eliciting stimuli yields the response probability (P). Thus, increasing response probability shifts average response magnitude towards average response amplitude. [6] [7]

[8]

It is recommend to use the computed mean magnitude to report the average startle response. Since this metric includes also nonresponse measures, it exhibits increased validity compared to mean amplitude. [6]

Major features

The magnitude of PPI is often significant, reaching as much as 65% in healthy subjects, with maximum inhibition is typically observed at 120 ms interval. [9] The baseline startle response does not affect overall PPI levels – this finding was first discovered in rat studies [10] and later duplicated in the studies of mice. [11] The opposite reaction, Prepulse Facilitation (PPF)-- the tendency for a subject to have an increased startle response following a lower-intensity prepulse stimulus—is typically noted when the interval between stimuli lasts longer than 500 ms. PPF is thought to reflect, at least partially, sustained attention: the prepulse, if not followed within less than half a second by the pulse, will tend to make the subject more likely to have a startle response rather than less.

Another moderating variable in prepulse inhibition and facilitation is sex difference, with men having higher PPI (i.e., when a prepulse is quickly followed by a pulse, all subjects tend to experience a reduced startle response, with men often experiencing lesser startle responses compared to women) and women having higher PPF (i.e., when the prepulse occurs more than half a second before the pulse, all subjects tend to experience heightened startle responses, with women tending to experience greater startle responses than men). [12] For acoustic stimuli, monaural PPI is higher than binaural—the startle response is reduced when the stimulus (noise) is only experienced in one ear rather than both ears. [13] [14] Even the very first prepulse of a test session induces inhibition, which indicates that conditioning and learning are not necessary for this effect to occur. However, the lack of conditionality has been questioned. [15] However a thousandth prepulse also induces inhibition; the phenomenon is highly robust [16]

Response and reaction are affected by interval duration and attention. It is thought that the short intervals used in PPI task do not give enough time for the activation of a volitional response: the reaction to pulses and prepulses separated by short time frames is believed to be involuntary. Prepulses could be attended or ignored, and attention affects the outcome. In one study, normal college students were instructed to attend to one of the kind of prepulses, high- or low-pitched, and ignore the other. Attended prepulse caused significantly greater inhibition at the 120 ms interval compared to the ignored one, and significantly greater facilitation at the 2000 ms interval. This reflects the tendency of subjects to expect to hear a particular frequency of pulsed sound, an effect that is highly pronounced when the prepulse occurs two seconds before the pulse and when there are other pulses being heard which are being consciously "ignored". [17] Increased prepulse duration leads to increase in PPI: the longer the prepulse, the greater the reduction in subsequent startle responses. Steady background noise facilitates the startle response, while pulsed background produces inhibition. [18]

History of scientific work

Prepulse inhibition was first described in 1862 by Sechenov and was rediscovered at least twice before Howard S. Hoffman discovered it again in 1963. Hoffman was the first to use the term prepulse. He continued his work on startle into the 1980s. His many papers on the reflex and its modification laid the groundwork for the widespread use of prepulse inhibition today in studies of schizophrenia and other disorders. [19]

One possible reason it was discovered and rediscovered is that it got confused with Pavlovian conditioning. Another is that it didn't fit nicely into theories of the times. [20]

Disruption

Disruptions of PPI are studied in humans and many other species. The most studied are deficits of PPI in schizophrenia, although this disease is not the only one to be associated with such deficits. They have been noted in panic disorder (Ludewig, et al., 2005), schizotypal personality disorder, [21] obsessive-compulsive disorder (Swerdlow et al., 1993), Huntington's disease, [22] nocturnal enuresis and attention deficit disorder (Ornitz et al. 1992), and Tourette's syndrome (Swerdlow et al. 1994; Castellanos et al. 1996). According to one study, people who have temporal lobe epilepsy with psychosis also show decreases in PPI, unlike those who have TLE without psychosis. [23] Therefore, PPI deficits are not typical to specific disease, but rather tell of disruptions in a specific brain circuit.

PPI deficit in schizophrenia

PPI deficits represent a well-described finding in schizophrenia, with the first report dating back to 1978. [24] The abnormalities are also noted in unaffected relatives of the patients. [25] [26] In one study, patients failed to show increased PPI to attended prepulses. [27] Dopamine, which plays a major role in schizophrenia, had been shown to regulate sensorimotor gating in rodent models. [28] [29] These findings fit to the dopamine hypothesis of schizophrenia. In theory, PPI disruption in schizophrenia may be related to the processes of sensory flooding and cognitive fragmentation. This makes disrupted PPI potentially useful as an endophenotype in the diagnosis of schizophrenia.

Antipsychotic medication have been shown to increase PPI in patients, with atypical antipsychotics having more effect. Patients display the same gender difference in PPI as healthy people: males have higher PPI compared to females. One notable finding is that patients are specifically deficient in PPI with 60 ms prepulse intervals relative to intervals of other lengths; this remains so even under antipsychotic treatment. [30]

The other fact is the influence of cigarette smoking: the research suggests that smoking does indeed "calm the nerves". Non-smoking patients have lower PPI compared to smokers, and heavy smokers have the highest PPI. [30] [31] This finding runs in accord with the high rates of smoking among schizophrenic patients, estimated at 70%, [32] with many patients smoking more than 30 cigarettes a day. [33] Some studies show association of schizophrenia with the CHRNA7 and CHRFAM7A genes, which code for alpha7 subunit of nicotinic receptors, but other studies are negative. [34] [35] Contrary to the predictions, nicotine receptor alpha7 subunit knockout mice do not show disruptions in PPI. [36]

In rodents

Murine models are widely used to test hypotheses linking genetic components of various diseases with sensorimotor gating. While some of the hypotheses stand to the test, others are not, as some mice models show unchanged or increased PPI contrary to the expectations, as in the tests of COMT-deficient mice. [37]

Certain surgical procedures also disrupt PPI in animals, helping to unravel the underlying circuitry.

Many animal studies of PPI are undertaken in order to understand and model the pathology of schizophrenia. [38] Schizophrenia-like PPI disruption techniques in rodents have been classified in one review [39] into four models:

Diverse chemical compounds are tested on animals with such deficits. Compounds that are able to restore PPI could be further investigated for their potential antipsychotic role.

A review of the genetic underpinnings of prepulse inhibition can be found in a meta-analysis conducted by Quednow et al. (2017). [40] Additionally an updated summary of both preclinical and clinical findings with PPI can be found in a recent comprehensive review. [4]

See also

Related Research Articles

Schizotypal personality disorder, also known as schizotypal disorder, is a cluster A personality disorder. The Diagnostic and Statistical Manual of Mental Disorders (DSM) classification describes the disorder specifically as a personality disorder characterized by thought disorder, paranoia, a characteristic form of social anxiety, derealization, transient psychosis, and unconventional beliefs. People with this disorder feel pronounced discomfort in forming and maintaining social connections with other people, primarily due to the belief that other people harbor negative thoughts and views about them. Peculiar speech mannerisms and socially unexpected modes of dress are also characteristic. Schizotypal people may react oddly in conversations, not respond, or talk to themselves. They frequently interpret situations as being strange or having unusual meanings for them; paranormal and superstitious beliefs are common. Schizotypal people usually disagree with the suggestion that their thoughts and behaviors are a 'disorder' and seek medical attention for depression or anxiety instead. Schizotypal personality disorder occurs in approximately 3% of the general population and is more commonly diagnosed in males.

In animals, including humans, the startle response is a largely unconscious defensive response to sudden or threatening stimuli, such as sudden noise or sharp movement, and is associated with negative affect. Usually the onset of the startle response is a startle reflex reaction. The startle reflex is a brainstem reflectory reaction (reflex) that serves to protect vulnerable parts, such as the back of the neck and the eyes (eyeblink) and facilitates escape from sudden stimuli. It is found across many different species, throughout all stages of life. A variety of responses may occur depending on the affected individual's emotional state, body posture, preparation for execution of a motor task, or other activities. The startle response is implicated in the formation of specific phobias.

Sensory gating describes neural processes of filtering out redundant or irrelevant stimuli from all possible environmental stimuli reaching the brain. Also referred to as gating or filtering, sensory gating prevents an overload of information in the higher cortical centers of the brain. Sensory gating can also occur in different forms through changes in both perception and sensation, affected by various factors such as "arousal, recent stimulus exposure, and selective attention."

Latent inhibition (LI) is a technical term in classical conditioning, where a familiar stimulus takes longer to acquire meaning than a new stimulus. The term originated with Lubow and Moore in 1973. The LI effect is latent in that it is not exhibited in the stimulus pre-exposure phase, but rather in the subsequent test phase. "Inhibition", here, simply connotes that the effect is expressed in terms of relatively poor learning. The LI effect is extremely robust, appearing in both invertebrate and mammalian species that have been tested and across many different learning paradigms, thereby suggesting some adaptive advantages, such as protecting the organism from associating irrelevant stimuli with other, more important, events.

<span class="mw-page-title-main">Neurotensin</span> Chemical compound

Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of bovine hypothalamus based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats.

The mismatch negativity (MMN) or mismatch field (MMF) is a component of the event-related potential (ERP) to an odd stimulus in a sequence of stimuli. It arises from electrical activity in the brain and is studied within the field of cognitive neuroscience and psychology. It can occur in any sensory system, but has most frequently been studied for hearing and for vision, in which case it is abbreviated to vMMN. The (v)MMN occurs after an infrequent change in a repetitive sequence of stimuli For example, a rare deviant (d) stimulus can be interspersed among a series of frequent standard (s) stimuli. In hearing, a deviant sound can differ from the standards in one or more perceptual features such as pitch, duration, loudness, or location. The MMN can be elicited regardless of whether someone is paying attention to the sequence. During auditory sequences, a person can be reading or watching a silent subtitled movie, yet still show a clear MMN. In the case of visual stimuli, the MMN occurs after an infrequent change in a repetitive sequence of images.

Chakragati mouse (ckr) is an insertional transgenic mouse mutant displaying hyperactive behaviour and circling. It is also deficient in prepulse inhibition, latent inhibition and has brain abnormalities such as lateral ventricular enlargement that are typical to endophenotypic models of schizophrenia, which make it useful in screening for antipsychotic drug candidates. The mouse is currently licensed by Chakra Biotech.

In genetic epidemiology, endophenotype is a term used to separate behavioral symptoms into more stable phenotypes with a clear genetic connection. By seeing the EP notion as a special case of a larger collection of multivariate genetic models, which may be fitted using currently accessible methodology, it is possible to maximize its valuable potential lessons for etiological study in psychiatric disorders. The concept was coined by Bernard John and Kenneth R. Lewis in a 1966 paper attempting to explain the geographic distribution of grasshoppers. They claimed that the particular geographic distribution could not be explained by the obvious and external "exophenotype" of the grasshoppers, but instead must be explained by their microscopic and internal "endophenotype". The endophenotype idea represents the influence of two important conceptual currents in biology and psychology research. An adequate technology would be required to perceive the endophenotype, which represents an unobservable latent entity that cannot be directly observed with the unaided naked eye. In the investigation of anxiety and affective disorders, the endophenotype idea has gained popularity.

Dopamine receptor D<sub>3</sub> Subtype of Dopamine Receptor

Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.

In cognitive psychology, the Eriksen flanker task is a set of response inhibition tests used to assess the ability to suppress responses that are inappropriate in a particular context. The target is flanked by non-target stimuli which correspond either to the same directional response as the target, to the opposite response, or to neither. The task is named for American psychologists Barbara. A. Eriksen & Charles W. Eriksen, who first published the task in 1974, and for the flanker stimuli that surround the target. In the tests, a directional response is assigned to a central target stimulus. Various forms of the task are used to measure information processing and selective attention.

In neuroscience, the N100 or N1 is a large, negative-going evoked potential measured by electroencephalography ; it peaks in adults between 80 and 120 milliseconds after the onset of a stimulus, and is distributed mostly over the fronto-central region of the scalp. It is elicited by any unpredictable stimulus in the absence of task demands. It is often referred to with the following P200 evoked potential as the "N100-P200" or "N1-P2" complex. While most research focuses on auditory stimuli, the N100 also occurs for visual, olfactory, heat, pain, balance, respiration blocking, and somatosensory stimuli.

A depolarizing prepulse (DPP) is an electrical stimulus that causes the potential difference measured across a neuronal membrane to become more positive or less negative, and precedes another electrical stimulus. DPPs may be of either the voltage or current stimulus variety and have been used to inhibit neural activity, selectively excite neurons, and increase the pain threshold associated with electrocutaneous stimulation.

<span class="mw-page-title-main">Sumanirole</span> Chemical compound

Sumanirole (PNU-95,666) is a highly selective D2 receptor full agonist, the first of its kind to be discovered. It was developed for the treatment of Parkinson's disease and restless leg syndrome. While it has never been approved for medical use it is a highly valuable tool compound for basic research to identify neurobiological mechanisms that are based on a dopamine D2-linked (vs. D1-, D3-, D4-, and D5-linked) mechanism of action.

<span class="mw-page-title-main">Sonepiprazole</span> Chemical compound

Sonepiprazole (U-101,387, PNU-101,387-G) is a drug of the phenylpiperazine class which acts as a highly selective D4 receptor antagonist. In animals, unlike D2 receptor antagonists like haloperidol, sonepiprazole does not block the behavioral effects of amphetamine or apomorphine, does not alter spontaneous locomotor activity on its own, and lacks extrapyramidal and neuroendocrine effects. However, it does reverse the prepulse inhibition deficits induced by apomorphine, and has also been shown to enhance cortical activity and inhibit stress-induced cognitive impairment. As a result, it was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to its comparator olanzapine no benefits were found and it was not researched further for this indication.

Error-related negativity (ERN), sometimes referred to as the Ne, is a component of an event-related potential (ERP). ERPs are electrical activity in the brain as measured through electroencephalography (EEG) and time-locked to an external event or a response. A robust ERN component is observed after errors are committed during various choice tasks, even when the participant is not explicitly aware of making the error; however, in the case of unconscious errors the ERN is reduced. An ERN is also observed when non-human primates commit errors.

Fear-potentiated startle (FPS) is a reflexive physiological reaction to a presented stimulus, and is an indicator of the fear reaction in an organism. The FPS response can be elicited in the face of any threatening stimulus, but it can also be elicited by a neutral stimulus as a result of fear conditioning, a process that occurs when a benign stimulus comes to evoke fear and anxiety upon being paired with a traumatic or fear-provoking event. The stimulus in question is usually of auditory or visual nature, and startle response measures include eyeblink rates and pulse/heart rate. The negative impact of heightened FPS in the face of neutral stimuli can be treated pharmacologically, using psychotropic medications that are typically used to reduce anxiety in humans. Recent literature, moreover, has implicated increased FPS responses as a correlate in posttraumatic stress disorder (PTSD) and other anxiety disorders.

Sensory-motor coupling is the coupling or integration of the sensory system and motor system. Sensorimotor integration is not a static process. For a given stimulus, there is no one single motor command. "Neural responses at almost every stage of a sensorimotor pathway are modified at short and long timescales by biophysical and synaptic processes, recurrent and feedback connections, and learning, as well as many other internal and external variables".

<span class="mw-page-title-main">Animal model of schizophrenia</span>

Research into the mental disorder of schizophrenia, involves multiple animal models as a tool, including in the preclinical stage of drug development.

In electroencephalography, the P50 is an event related potential occurring approximately 50 ms after the presentation of a stimulus, usually an auditory click. The P50 response is used to measure sensory gating, or the reduced neurophysiological response to redundant stimuli.

<span class="mw-page-title-main">Conditioned avoidance response test</span> Test of antipsychotic-like activity

The conditioned avoidance response (CAR) test, also known as the active avoidance test, is an animal test used to identify drugs with antipsychotic-like effects. It is most commonly employed as a two-way active avoidance test with rodents. The test assesses the conditioned ability of an animal to avoid an unpleasant stimulus. Drugs that selectively suppress conditioned avoidance responses without affecting escape behavior are considered to have antipsychotic-like activity. Variations of the test, like testing for enhancement of avoidance and escape responses, have also been used to assess other drug effects, like pro-motivational and antidepressant-like effects.

References

  1. ↑ Braff DL, Grillon C, Geyer MA (March 1992). "Gating and habituation of the startle reflex in schizophrenic patients". Archives of General Psychiatry. 49 (3): 206–15. doi:10.1001/archpsyc.1992.01820030038005. PMID   1567275.
  2. ↑ Weber M, Swerdlow NR (January 2008). "Rat strain differences in startle gating-disruptive effects of apomorphine occur with both acoustic and visual prepulses". Pharmacology Biochemistry and Behavior. 88 (3): 306–11. doi:10.1016/j.pbb.2007.08.014. PMC   2266874 . PMID   17900675.
  3. ↑ Braff DL, Geyer MA, Swerdlow NR (July 2001). "Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies". Psychopharmacology. 156 (2–3): 234–58. doi:10.1007/s002130100810. PMID   11549226. S2CID   37231909.
  4. 1 2 Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL (August 2008). "Realistic expectations of prepulse inhibition in translational models for schizophrenia research". Psychopharmacology. 199 (3): 331–88. doi:10.1007/s00213-008-1072-4. PMC   2771731 . PMID   18568339.
  5. 1 2 3 Geyer MA, McIlwain KL, Paylor R (2002). "Mouse genetic models for prepulse inhibition: an early review". Molecular Psychiatry. 7 (10): 1039–53. doi: 10.1038/sj.mp.4001159 . PMID   12476318.
  6. 1 2 3 Blumenthal, Terry D.; Cuthbert, Bruce N.; Filion, Diane L.; Hackley, Steven; Lipp, Ottmar V.; Van Boxtel, Anton (2005). "Committee report: Guidelines for human startle eyeblink electromyographic studies". Psychophysiology. 42 (1): 1–15. doi: 10.1111/j.1469-8986.2005.00271.x . ISSN   0048-5772. PMID   15720576.
  7. ↑ Blumenthal, Terry D.; Elden, Aake; Flaten, Magne Arve (2004). "A comparison of several methods used to quantify prepulse inhibition of eyeblink responding". Psychophysiology. 41 (2): 326–332. doi:10.1111/j.1469-8986.2003.00144.x. ISSN   0048-5772. PMID   15032998.
  8. ↑ Blumenthal, Terry D.; Keith Berg, W. (1986). "Stimulus Rise Time, Intensity, and Bandwidth Effects on Acoustic Startle Amplitude and Probability". Psychophysiology. 23 (6): 635–641. doi:10.1111/j.1469-8986.1986.tb00682.x. ISSN   0048-5772. PMID   3823338.
  9. ↑ Graham FK (May 1975). "Presidential Address, 1974. The more or less startling effects of weak prestimulation". Psychophysiology. 12 (3): 238–48. doi: 10.1111/j.1469-8986.1975.tb01284.x . PMID   1153628.
  10. ↑ Swerdlow NR, Geyer MA, Braff DL (July 2001). "Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges". Psychopharmacology. 156 (2–3): 194–215. doi:10.1007/s002130100799. PMID   11549223. S2CID   20001872.
  11. ↑ Paylor R, Crawley JN (July 1997). "Inbred strain differences in prepulse inhibition of the mouse startle response". Psychopharmacology. 132 (2): 169–80. doi:10.1007/s002130050333. PMID   9266614. S2CID   31381584.
  12. ↑ Aasen I, Kolli L, Kumari V (January 2005). "Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies". Journal of Psychopharmacology. 19 (1): 39–45. doi:10.1177/0269881105048890. PMID   15671127. S2CID   25689769.
  13. ↑ Hoffman HS, Stitt CL (November 1980). "Inhibition of the glabella reflex by monaural and binaural stimulation". Journal of Experimental Psychology. Human Perception and Performance. 6 (4): 769–76. doi:10.1037/0096-1523.6.4.769. PMID   6449543.
  14. ↑ Kumari V, Fannon D, Sumich AL, Sharma T (May 2007). "Startle gating in antipsychotic-naïve first episode schizophrenia patients: one ear is better than two". Psychiatry Research. 151 (1–2): 21–8. doi:10.1016/j.psychres.2006.09.013. PMID   17382404. S2CID   28141508.
  15. ↑ Folk CL, Gibson BS (2001). Attraction, Distraction and Action: multiple perspectives on attentional capture. Amsterdam; New York: Elsevier. ISBN   978-0-444-50676-4.
  16. ↑ Wu MF, Krueger J, Ison JR, Gerrard RL (April 1984). "Startle reflex inhibition in the rat: its persistence after extended repetition of the inhibitory stimulus". Journal of Experimental Psychology: Animal Behavior Processes. 10 (2): 221–8. doi:10.1037/0097-7403.10.2.221. PMID   6716052.
  17. ↑ Filion DL, Dawson ME, Schell AM (July 1993). "Modification of the acoustic startle-reflex eyeblink: a tool for investigating early and late attentional processes". Biological Psychology. 35 (3): 185–200. doi:10.1016/0301-0511(93)90001-O. PMID   8218613. S2CID   20468822.
  18. ↑ Hoffman HS, Fleshler M (September 1963). "Startle Reaction: Modification by Background Acoustic Stimulation". Science. 141 (3584): 928–30. Bibcode:1963Sci...141..928H. doi:10.1126/science.141.3584.928. PMID   14043340. S2CID   35906761.
  19. ↑ Powers AS, Leitner D (2007). "Obituary: Howard S. Hoffman (1925-2006)". American Psychologist. 62 (4): 320. doi:10.1037/0003-066X.62.4.320.
  20. ↑ Ison JR, Hoffman HS (July 1983). "Reflex modification in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon". Psychological Bulletin. 94 (1): 3–17. doi:10.1037/0033-2909.94.1.3. PMID   6353464.
  21. ↑ Cadenhead KS, Geyer MA, Braff DL (December 1993). "Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder". The American Journal of Psychiatry. 150 (12): 1862–7. doi:10.1176/ajp.150.12.1862. PMID   8238643.
  22. ↑ Swerdlow NR, Paulsen J, Braff DL, Butters N, Geyer MA, Swenson MR (February 1995). "Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease". Journal of Neurology, Neurosurgery, and Psychiatry. 58 (2): 192–200. doi:10.1136/jnnp.58.2.192. PMC   1073317 . PMID   7876851.
  23. ↑ Morton, N., Gray, N.S., Mellers, J., Toone, B., Lishman, W.A., & Gray, J.A. (1994). Prepulse inhibition in temporal lobe epilepsy. Schizophrenic Research, 15, 191.
  24. ↑ Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (July 1978). "Prestimulus effects on human startle reflex in normals and schizophrenics". Psychophysiology. 15 (4): 339–43. doi:10.1111/j.1469-8986.1978.tb01390.x. PMID   693742.
  25. ↑ Kumari V, Das M, Zachariah E, Ettinger U, Sharma T (September 2005). "Reduced prepulse inhibition in unaffected siblings of schizophrenia patients". Psychophysiology. 42 (5): 588–94. doi:10.1111/j.1469-8986.2005.00346.x. PMID   16176381.
  26. ↑ Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL (October 2000). "Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits". The American Journal of Psychiatry. 157 (10): 1660–8. doi:10.1176/appi.ajp.157.10.1660. PMID   11007721.
  27. ↑ Hazlett EA, Romero MJ, Haznedar MM, New AS, Goldstein KE, Newmark RE, Siever LJ, Buchsbaum MS (July 2007). "Deficient attentional modulation of startle eyeblink is associated with symptom severity in the schizophrenia spectrum". Schizophrenia Research. 93 (1–3): 288–95. doi:10.1016/j.schres.2007.03.012. PMID   17478083. S2CID   29638347.
  28. ↑ Mansbach RS, Geyer MA, Braff DL (1988). "Dopaminergic stimulation disrupts sensorimotor gating in the rat". Psychopharmacology. 94 (4): 507–14. doi:10.1007/BF00212846. PMID   3131796. S2CID   23317079.
  29. ↑ Swerdlow NR, Keith VA, Braff DL, Geyer MA (February 1991). "Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat". The Journal of Pharmacology and Experimental Therapeutics. 256 (2): 530–6. PMID   1825226.
  30. 1 2 Swerdlow NR, Light GA, Cadenhead KS, Sprock J, Hsieh MH, Braff DL (December 2006). "Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function". Archives of General Psychiatry. 63 (12): 1325–35. doi: 10.1001/archpsyc.63.12.1325 . PMID   17146007.
  31. ↑ Kumari V, Soni W, Sharma T (June 2001). "Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia". Human Psychopharmacology. 16 (4): 321–326. doi:10.1002/hup.286. PMID   12404567. S2CID   46185396.
  32. ↑ Leonard S, Adler LE, Benhammou K, Berger R, Breese CR, Drebing C, et al. (December 2001). "Smoking and mental illness". Pharmacology Biochemistry and Behavior. 70 (4): 561–70. doi:10.1016/S0091-3057(01)00677-3. PMID   11796154. S2CID   25912660.
  33. ↑ de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ (July 2002). "Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital". Schizophrenia Research. 56 (1–2): 55–65. doi:10.1016/S0920-9964(01)00192-X. PMID   12084420. S2CID   23890132.
  34. ↑ Gene Overview of All Published Schizophrenia-Association Studies for CHRFAM7A Archived 2007-09-27 at the Wayback Machine – Schizophrenia Gene Database.
  35. ↑ Gene Overview of All Published Schizophrenia-Association Studies for CHRNA7 Archived 2007-09-27 at the Wayback Machine – Schizophrenia Gene Database
  36. ↑ Paylor R, Nguyen M, Crawley JN, Patrick J, Beaudet A, Orr-Urtreger A (1998). "Alpha7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice". Learning & Memory. 5 (4–5): 302–16. doi:10.1101/lm.5.4.302. PMC   311270 . PMID   10454356.
  37. ↑ Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M (August 1998). "Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior". Proceedings of the National Academy of Sciences of the United States of America. 95 (17): 9991–6. Bibcode:1998PNAS...95.9991G. doi: 10.1073/pnas.95.17.9991 . PMC   21449 . PMID   9707588.
  38. ↑ Swerdlow NR, Geyer MA (1998). "Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia". Schizophrenia Bulletin. 24 (2): 285–301. doi: 10.1093/oxfordjournals.schbul.a033326 . PMID   9613626.
  39. ↑ Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (July 2001). "Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review". Psychopharmacology. 156 (2–3): 117–54. doi:10.1007/s002130100811. PMID   11549216. S2CID   12941254.
  40. ↑ Quednow BB, Ejebe K, Wagner M, Giakoumaki SG, Bitsios P, Kumari V, Roussos P (December 2017). "Meta-analysis on the association between genetic polymorphisms and prepulse inhibition of the acoustic startle response". Schizophrenia Research. 198: 52–59. doi:10.1016/j.schres.2017.12.011. PMID   29287625. S2CID   22852105.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.