Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia.

BACKGROUND: Prepulse inhibition (PPI) is the normal suppression of the startle reflex when an intense startling stimulus is preceded by a barely detectable prepulse. Habituation of the acoustic startle reflex is decrement in response when the same stimulus is presented repeatedly. These factors have been proposed as neurophysiologic measures of sensorimotor gating or filtering and discussed as trait-linked markers for information-processing deficits in schizophrenia-spectrum disorders. The aim of this study was to examine whether first-episode schizophrenia patients also exhibit deficits in PPI and habituation. METHODS: Never-medicated male schizophrenic and schizophreniform patients in their first psychotic episode (n=24) were compared with age-matched healthy men (n=21) in an acoustic startle paradigm assessing PPI (30-, 60-, 120-, 240-, and 2000-msec interstimulus intervals) and habituation. RESULTS: Compared with control subjects, first-episode patients exhibited significant deficits in both PPI in the 60-msec prepulse condition and startle habituation. Patients also exhibited less facilitation in the 2000-msec prepulse condition. CONCLUSIONS: In combination with other studies, these findings indicate that PPI and habituation may be sensitive intermediate phenotypic markers for information-processing deficits in schizophrenic patients.     

Measuring P50 suppression and prepulse inhibition in a single recording session.

OBJECTIVE: Two distinct measures have been used to assess inhibitory gating deficits in schizophrenia patients: P50 suppression and prepulse inhibition of the startle response. It remains unclear whether both measures can be assessed in a single testing session. METHOD: Twelve normal subjects underwent testing in a carefully designed combined P50/prepulse inhibition session using stimulus characteristics similar to those described in the existing literature. RESULTS: The levels of both P50 suppression and prepulse inhibition obtained in the combined session were highly similar to those obtained in independent testing of previous cohorts of normal subjects. As in previous experiments, P50 suppression and prepulse inhibition were not significantly correlated. CONCLUSIONS: Measuring P50 suppression and prepulse inhibition in a single session is feasible and offers a unique opportunity to assess these two distinct gating measures contemporaneously in cohorts of normal comparison subjects and schizophrenia patients, so that temporal shifts in one or both measures are minimized.     

Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype?

OBJECTIVE: Subjects with schizotypal personality disorder demonstrate deficits in inhibition when assessed on prepulse inhibition, P50 suppression, and antisaccade paradigms. This study determined if distinct subgroups of subjects with schizotypal personality disorder could be identified on the basis of performance on these measures and whether endophenotypes could be defined for future genetic study by using measures of inhibitory function. METHOD: Prepulse inhibition, P50 suppression, and antisaccade paradigms were assessed in 21 subjects with schizotypal personality disorder. RESULTS: Seven subjects with schizotypal personality disorder had deficits on each paradigm; seven had no deficits on any paradigm. P50 and antisaccade deficits were present in five of the same subjects and significantly correlated. CONCLUSIONS: These results suggest that P50 and antisaccade performance reflects a common endophenotype and that prepulse inhibition identifies a separate endophenotype reflecting different neurobiological substrate(s) in subjects with schizotypal personality disorder. This pattern may generalize to schizophrenia spectrum disorder patients.     

Sensorimotor gating deficits in adults with autism.

BACKGROUND: Prepulse inhibition (PPI) is an operational measure of sensorimotor gating and is impaired in a family of neuropsychiatric disorders characterized by abnormalities of inhibitory function. Adults with autistic disorder (AD) exhibit clinical features of inhibitory deficits, such as restrictive and repetitive behaviors, that may be explained by deficits in sensorimotor gating. METHODS: Acoustic startle reactivity, habituation, and PPI (30-, 60-, 120-msec interstimulus intervals) were assessed in 14 adult men diagnosed with AD and 16 typically developing normal comparison (NC) participants. All participants were administered measures of intelligence and frontal-executive functioning. RESULTS: Adults with AD exhibited significantly less PPI in the 60-msec condition than NC participants, which was correlated with increased ratings of restricted and repetitive behaviors. The groups did not differ on measures of startle amplitude or overall habituation. There was, however, a significant group-by-block habituation effect. Furthermore, PPI was not related to intelligence but was moderately associated with performance on a measure of frontal-executive functioning. CONCLUSIONS: Adults with AD have sensorimotor gating deficits similar to other neurodevelopmental disorders, implicating a failure of normal inhibitory regulation of sensory, motor, and attentional mechanisms. Thus, PPI deficits may be indirectly linked to one of the hallmark features of AD.     

Prepulse inhibition and P50 suppression: commonalities and dissociations

Patients with schizophrenia exhibit reduced levels of both prepulse inhibition of the startle reflex (PPI) and condition-test suppression of the P50 event-related potential. This study investigated the extent to which PPI and P50 suppression, which exhibit similar parametric sensitivities, are intrinsically auditory phenomena or can be induced cross-modally, and reflect common or distinct neural mechanisms of inhibition. PPI, N100, and P50 were assessed in 20 healthy male volunteers, using auditory test probes and both visual and auditory lead stimuli, separated by 100- or 500-ms interstimulus intervals (ISIs). PPI was found in the auditory-lead condition across the complete group, and with visual-lead stimuli in approximately half of the subjects. Intra-modal auditory PPI was significantly higher with the 100-ms ISI than with the 500-ms ISI. P50 suppression was found only with the 500-ms ISI, with no difference between the auditory and visual conditions. Source analyses revealed that suppression was associated with frontal cortical activity. N100 suppression was found only in the auditory condition, with no difference between 100- and 500-ms ISIs. Although both phenomena are considered to provide operational measures of gating, PPI and P50 suppression are differentially sensitive to ISI and therefore reflect partly different neural mechanisms. They are not intrinsically auditory phenomena, and both appear to involve frontal cortical activity. In contrast, N100 suppression is most likely based on refractory mechanisms intrinsic to the auditory system.     

Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication

BACKGROUND: Prepulse inhibition of the startle reflex response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect represents an operational index of sensorimotor gating and is found to be deficient in schizophrenia. Prepulse inhibition deficits in schizophrenia seem to be partially normalized by typical antipsychotics and more fully by some atypical antipsychotics. Early onset of schizophrenia, particularly in men, has been associated with abnormal brain maturation, profound neuropsychological deficits, and less responsiveness to antipsychotic medication. We evaluated the effects of the age of onset of illness, current positive and negative symptoms, and the type of medication (typical vs atypical) on prepulse inhibition of the startle response in schizophrenia. METHODS: Thirty-eight male schizophrenic patients and 20 healthy male controls underwent testing for prepulse inhibition of the acoustic startle response. RESULTS: Earlier onset of illness was associated with reduced prepulse inhibition, while adult onset of illness was not. No significant relationships occurred between current symptoms and prepulse inhibition. Patients given typical, but not atypical, antipsychotics exhibited less prepulse inhibition compared with healthy controls. CONCLUSION: Early onset of illness is associated with profound deficits in prepulse inhibition of the startle response in men with schizophrenia.     

Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania.

BACKGROUND: Deficits in sensorimotor gating as assessed by prepulse inhibition (PPI) and habituation of the human startle response have been noted in schizophrenia and other patients with known dysfunction in the brain substrates that regulate PPI. During acute mania, bipolar disorder (BD) and schizophrenia patients present with symptoms that are similar. To determine if these clinical similarities extend to neurophysiologic domains, PPI and startle habituation were assessed in BD patients with acute psychotic mania and compared with a sample of acutely psychotic schizophrenia patients and a normal comparison group. METHODS: Fifteen BD patients, 16 schizophrenia patients, and 17 control subjects were assessed on PPI and startle habituation. RESULTS: The BD patients had significantly lower PPI than did the control subjects in two of the three PPI conditions (60- and 120-msec interstimulus intervals) as well as less startle habituation. The BD patients did not statistically differ from the schizophrenia patients in PPI or habituation. CONCLUSIONS: These findings of sensorimotor gating deficits among bipolar disorder patients are consistent with other findings using different measures of information processing and suggest that the neurobiological substrates underlying sensorimotor gating may be dysregulated during acute manic and psychotic states.     

Symptom correlates of prepulse inhibition deficits in male schizophrenic patients

OBJECTIVE: Information processing, inhibitory, and gating deficits in human and animal model studies of schizophrenia are demonstrated by using prepulse inhibition of the startle reflex. Prepulse inhibition deficits in schizophrenic patients correlate with core cognitive symptoms, such as thought disorder and distractibility, but their relationship to positive and negative symptoms of schizophrenia is less clear. METHOD: Fifty-one male schizophrenic patients and 26 male normal comparison subjects were tested for prepulse inhibition of the eyeblink component of the startle reflex measured by electromyogram recording. Startling stimuli (118 dB) were presented alone (pulse only) or were preceded 60 msec by discrete prepulse stimuli of 2, 4, 8, or 16 dB above the background 70-dB noise level. In addition, patients were assessed for demographic variables, generalized symptoms (Brief Psychiatric Rating Scale), and positive and negative symptoms. RESULTS: Schizophrenic and comparison groups differed significantly in the amount of prepulse inhibition produced by the 16-dB prepulse, with schizophrenic patients showing the expected deficient prepulse inhibition. Latency of the eyeblink response was generally slower for the schizophrenic patients, but the prepulse-induced latency facilitation for schizophrenic patients and comparison subjects did not differ significantly. The pattern of prepulse inhibition deficits in schizophrenic patients remained, with age and education controlled, in an analysis of covariance and subgroup matching. Deficient prepulse inhibition correlated with both positive and negative symptoms of schizophrenia. CONCLUSIONS: Under these experimental conditions, schizophrenia-linked deficits in prepulse inhibition detected with a relatively strong prepulse are correlated with both positive and negative symptoms of schizophrenia. The level of correlation, while significant in this cohort, is not as robust as that in previous reports linking prepulse inhibition deficits with other measures, such as thought disorder. Future work should probably focus on the relationship of prepulse inhibition deficits to measures such as thought disorder rather than positive and negative symptoms.     

Sensory gating in schizophrenics and normal controls: effects of changing stimulation interval

Auditory evoked potentials were recorded using a paired click, conditioning-testing paradigm in 10 schizophrenics and in 10 normal subjects with no family history of psychotic disorder. The paradigm is used to demonstrate central nervous system gating of responsiveness to auditory stimuli by examining the extent to which the response to the conditioning stimulus diminishes the response to a test stimulus occurring a short time later. Recordings were made at conditioning-testing intervals of 500 msec, 150 msec, and 75 msec to determine subjects' gating of responsiveness to stimuli repeated at various intervals. The schizophrenics had conditioning-testing ratios indicative of poor gating of the auditory P50 wave at the 500-msec and 150-msec intervals, but most patients had good sensory gating at the 75-msec interval. Normal subjects showed good sensory gating at all three intervals. Results suggest that although sensory gating mechanisms responsible for changes in neuronal response at longer intervals are chronically defective in schizophrenics, other gating mechanisms functioning at shorter intervals appear to be intact and function well in most patients. The results may lead to increased specification of the neurobiological basis of sensory abnormalities in schizophrenia.     

Gating of the vertex somatosensory and auditory evoked potential P50 and the correlation to skin conductance orienting response in healthy men

A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schizophrenia, we might expect the processing deficits to act on multiple modalities. We have examined the gating of median nerve somatosensory EP (SEP) following paired stimulation identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of 500, 750 and 1000 ms and the correlation of gating to the skin conductance orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and 0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45 in N80 in the AEP. Repetition effects in the two modalities were not correlated. AEP P50 gating was correlated to skin conductance level (SCL). The combination of recording repetition effects on the mid-latency EP in two modalities could provide a method for investigating if deficits of information processing in schizophrenia are cross-modal.     

Prepulse inhibition and P50 suppression are both deficient but not correlated in schizophrenia patients.

BACKGROUND: Inhibitory measures such as prepulse inhibition of the acoustic startle reflex (PPI) and event related potential P50 suppression have been widely reported to show deficits in schizophrenia patients. The relationship between PPI and P50 suppression in schizophrenia patients has remained unclear. METHODS: One hundred fifty-six schizophrenia patients and 104 normal comparison subjects (NCS) were tested on PPI and P50 suppression. RESULTS: Eighty-one patients and 70 NCS had valid and scorable data on both PPI and P50 suppression paradigms. As in the larger groups, these cohorts had deficits on both PPI (p < .05) and P50 suppression (p < .05). Analyses revealed a weak, but significant correlation between PPI and P50 suppression in the NCS group (r = .33, p < .05) but not in the patient group (r = .03, ns). CONCLUSIONS: Although PPI and P50 suppression were both reduced in the patients, they were not correlated. This divergence suggests that these gating functions are complementary or redundant levels of "protection" against processes that may lead to cognitive fragmentation.     

Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients.

BACKGROUND: The magnitude of the startle eyeblink response is reduced if the startle eliciting stimulus is shortly preceded by another stimulus. There is evidence that schizophrenia patients exhibit impairments in this so-called prepulse inhibition. Our study investigated whether prepulse inhibition is affected by neuroleptic drug treatment as is suggested by animal research. METHODS: Prepulse inhibition was tested in five unmedicated and 20 medicated inpatients with schizophrenia, and 12 normal controls. RESULTS: The unmedicated schizophrenia patients showed a strong impairment of sensorimotor gating as indexed by the absence of prepulse inhibition. By contrast, the medicated patients showed a pronounced prepulse inhibition that did not differ from that of the normal controls. There was a substantial covariation between the rated severity of the positive syndrome and the amount of prepulse inhibition--i.e., the patients whose positive symptoms were rated as more severe showed less prepulse inhibition. CONCLUSIONS: These data suggest that the impaired sensorimotor gating of schizophrenia patients is not a stable vulnerability indicator, but may rather be related to the positive syndrome and may be improved by treatments with neuroleptic medication.     

Disrupted sensory gating in pathological gambling.

BACKGROUND: Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. METHODS: The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. RESULTS: Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. CONCLUSIONS: In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.     

Sensory gating of the P13 midlatency auditory evoked potential and the startle response in the rat

The human P1/P50 midlatency auditory evoked potential and the startle response (SR) have been used as measures of sensory and sensorimotor gating, respectively. In the present study, both prepulse and paired stimulus paradigms were used in order to investigate the relationship between sensory gating mechanisms of the P13 potential, the putative rodent equivalent of the P1 potential, and those of the SR. In addition, these were compared to the properties of the N40 potential, another measure of sensory gating. Simultaneous recordings from the vertex (P13 potential and N40 potential) and neck musculature (SR) showed that (1) in a prepulse paradigm, increasing the intensity of the prepulse or decreasing the interstimulus interval resulted in increased inhibition of the P13 potential, N40 potential (to a lesser degree) and the SR (to a greater degree), (2) when using a low signal-to-noise ratio between the prepulse intensity and the background level, prepulse inhibition of the SR was reduced or absent while that of the P13 potential was present, (3) the amplitude of the 'prepulse evoked' P13 potential was significantly correlated with prepulse inhibition of the P13 potential, the N40 potential and the SR, (4) in a paired identical stimulus paradigm, decreasing the interstimulus interval resulted in increased habituation of the P13 potential, N40 potential (to a lesser degree) and the SR, and (5) increasing the intensity of the paired stimulation resulted in increased habituation of the P13 potential and the N40 potential (to a lesser degree), but not of the SR. These results demonstrate the presence of prepulse inhibition of the P13 potential, the N40 potential and the SR in a parallel manner, but show certain specific differences in their responses to parametric changes.     

Sensory gating in rats: lack of correlation between auditory evoked potential gating and prepulse inhibition

This study was designed to evaluate the possible similarities between two paradigms designed to measure sensory gating: (1) an auditory evoked potential (AEP), called the P50 gating paradigm; and (2) an acoustic startle (ASR), called the prepulse inhibition paradigm. These paradigms show a number of methodological, pharmacological, and neurobiological similarities, and they are both disturbed in patients with schizophrenia. In the first of three experiments, the AEP gating and the ASR gating were measured in rats. Although both AEP and ASR gating could readily be obtained, there appeared to be no correlation between the performance in these two paradigms. This lack of correlation was confirmed using a factor analytical approach, where the AEP gating and the ASR gating parameters were found to load on different factors. In the second experiment, the interstimulus interval in the ASR paradigm was increased to 500 ms (identical to the interstimulus interval of the AEP gating paradigm). This increase reduced the degree of ASR gating, although some gating could still be obtained. Again no correlation was found between AEP and ASR gating, and this was again confirmed by the factorial analysis. In the final experiment, the effects of the dopamine D2/3 agonist 7-OHDPAT were evaluated in both paradigms. This selective agonist dose dependently reduced ASR gating but had no effect on AEP gating. Together, these data strongly suggest that AEP and ASR gating measure two different aspects of information processing and indicate that both paradigms may be important for investigating the neurobiological disturbances observed in patients with psychoses.     

Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia

Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp 35:3578–3587, 2014. © 2013 Wiley Periodicals, Inc .     

Reduced P50 auditory gating response in psychiatrically normal chronic marihuana users: a pilot study.

BACKGROUND: Neurophysiological studies of marihuana (THC) often contain uncontrolled confounds [psychiatric diagnoses, polydrug use, central nervous system (CNS)-relevant injury, etc.] that can alter electrophysiological measures. This P50 sensory gating report is part of a larger neurophysiological and neurocognitive investigation of chronic THC exposure using rigorously screened medically and psychiatrically normal individuals without concurrent use of non-THC substances. METHODS: Following medical and psychiatric screening, including serial urine drug screens, technically adequate P50 paired auditory recovery tests were obtained on 19 chronic THC users and 14 control subjects. Fifty pairs of 80-dB auditory clicks (1 pair per 10 sec, 500-msec interclick separation) were delivered through earphones. The sensory gating measure was the ratio between the P50 amplitudes at the vertex elicited by the conditioning (first) and test (second) click. RESULTS: THC subjects had significantly higher sensory gating ratios (i.e., reduced suppression) than did control subjects. Among THC users, sensory gating ratios did not correlate with duration or frequency of THC use, although subjects with ratios above 40 had nearly twice the number of "joint-years" of THC exposure than did those with lower ratios. CONCLUSIONS: Reduced P50 suppression in the sensory gating paradigm may be a possible neurophysiological CNS sequela of long-term cumulative exposure to THC.     

Prepulse inhibition and habituation of the startle response are stable neurobiological measures in a normal male population.

Prepulse inhibition (PPI) and habituation of the startle response are operational measures of sensorimotor gating and information processing. Changes in the normal inhibition and habituation of the startle response may provide trait markers for illnesses such as schizophrenia that have altered neurotransmitter control of the neural circuitry that modulates these measures. The stability of PPI and habituation was assessed in 10 normal male subjects. Prepulse inhibition was found to be most stable in the more intense prepulse conditions, and habituation was most stable in the early portion of the test session. These data support the hypothesis that PPI and habituation are relatively stable neurobiological markers.     

Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder

OBJECTIVE: The schizophrenia spectrum includes individuals with schizophrenia, their relatives, and individuals with schizotypal personality disorder. Subjects in the schizophrenia spectrum have disorders of attention, cognition, and information processing. Attention and information processing can be assessed by testing suppression of the P50 event-related potential; the amplitude of the P50 wave is measured in response to each of two auditory clicks. In normal subjects, the P50 wave following the second click is suppressed, or "gated." Schizophrenic patients and their relatives show less suppression of the second P50 wave. Deficits in P50 suppression have high heritability and show linkage to the alpha-7 subunit of the nicotinic cholinergic receptor gene in families with schizophrenia, suggesting that deficits in P50 suppression are trait markers for gating abnormalities in schizophrenia spectrum subjects. Although schizotypal subjects have been shown to have deficits in sensorimotor gating as measured by prepulse inhibition, to the authors' knowledge P50 sensory gating in schizotypal personality disorder has yet to be reported. METHOD: P50 suppression in 26 subjects with schizotypal personality disorder and 23 normal subjects was assessed through auditory conditioning and testing. RESULTS: The subjects with schizotypal personality had significantly less P50 suppression than did the normal subjects. CONCLUSIONS: Subjects with schizotypal personality disorder may have trait-linked sensory gating deficits similar to those in patients with schizophrenia and their relatives. Because these subjects may manifest sensory gating deficits without overt psychotic symptoms, it is likely that these deficits represent a core cognitive dysfunction of the schizophrenia spectrum.     

Sensory and sensorimotor gating deficits after neonatal ventral hippocampal lesions in rats

Neonatal ventral hippocampal lesions (NVHLs) in rats lead to reduced prepulse inhibition (PPI) of startle and other behavioral deficits in adulthood that model abnormalities in schizophrenia patients. A neurophysiological deficit in schizophrenia patients and their first-degree relatives is reduced gating of the P50 event-related potential (ERP). N40 ERP gating in rats may be a cross-species analog of P50 gating, and is disrupted in experimental manipulations related to schizophrenia. Here, we tested whether N40 gating as well as PPI is disrupted after NVHLs, using contemporaneous measures of these two conceptually related phenomena. Male rat pups received sham or ibotenic acid NVHLs on postnatal day 7. PPI was tested on days 35 and 56, after which rats were equipped with cortical surface electrodes for ERP measurements. One week later, PPI and N40 gating were measured in a single test, using paired S1-S2 clicks spaced 500 ms apart to elicit N40 gating. Compared to sham-lesioned rats, those with NVHLs exhibited PPI deficits on days 35 and 56. NVHL rats also exhibited reduced N40 gating and reduced PPI, when measured contemporaneously at day 65. Deficits in PPI and N40 gating appeared most pronounced in rats with larger lesions, focused within the ventral hippocampus. In this first report of contemporaneous measures of two important schizophrenia-related phenotypes in NVHL rats, NVHLs reproduce both sensory (N40) and sensorimotor (PPI) gating deficits exhibited in schizophrenia. In this study, lesion effects were detected prior to pubertal onset, and were sustained well into adulthood.