Eye-blink conditioning deficits indicate temporal processing abnormalities in schizophrenia

Abstract

Theoretical models suggest that symptoms of schizophrenia may be due to a dysfunctional modulatory system associated with the cerebellum. Although it has long been known that the cerebellum plays a critical role in associative learning and motor timing, recent evidence suggests that it also plays a role in nonmotor psychological processes. Indeed, cerebellar anomalies in schizophrenia have been linked to cognitive dysfunction and poor long-term outcome. To test the hypothesis that schizophrenia is associated with cerebellar dysfunction, cerebellar-dependent, delay eye-blink conditioning was examined in 62 individuals with schizophrenia and 62 age-matched nonpsychiatric comparison subjects. The conditioned stimulus was a 400 ms tone, which co-terminated with a 50 ms unconditioned stimulus air puff. A subset of participants (25 with schizophrenia and 29 controls) also completed the Wechsler Abbreviated Scale of Intelligence. Participants with schizophrenia exhibited lower rates of eye-blink conditioning, including earlier (less adaptively timed) conditioned response latencies. Cognitive functioning was correlated with the rate of conditioned responsing in the non-psychiatric comparison subjects but not among those with schizophrenia, and the magnitude of these correlations significantly differed between groups. These findings are consistent with models of schizophrenia in which disruptions within the corticocerebellar-thalamic-cortical (CCTC) brain circuit are postulated to underlie the cognitive fragmentation that characterizes the disorder.

Cerebellar motor learning deficits in medicated and medication-free men with recent-onset schizophrenia

“…In agreement with the only other study directly comparing medicated and medication-free patients, 32 our data indicate that patients with schizophrenia show impaired eyeblink conditioning, irrespective of medication status.…”

“…26 Our results are in agreement with those of Bolbecker and colleagues, 32 who included 13 medication-free patients showing significantly fewer CRs and earlier CR response latencies than controls. The authors also observed no effect of medication in eyeblink conditioning.…”

“…In previous studies no correlation between intelligence and eyeblink conditioning was found in patients with schizophrenia. 32,36,39 In addition, we did not find any correlation between years of education and any of our test results. Moreover, in both eyeblink conditioning and saccade adaptation, reflexive movements are adapted by subconscious processes, which require little or no "higher" cognitive input.…”

A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va Disease

“…Eyeblink conditioning deficits have been reported in patients with nonmotor psychiatric diseases such as schizophrenia (Bolbecker et al, 2009b), bipolar disorder (Bolbecker et al, 2009a), and attention deficit/hyperactivity disorder (Frings et al, 2010), as well as in a large number of human cases with cerebellar lesions Kronenbuerger et al, 2007). Most of these studies demonstrate that progressive memory deficits occur over time.…”

Environmental Factors in the Aetiology of Autism – Lessons from Animals Prenatally Exposed to Valproic Acid

“…One difference between children with autism and the VPA-exposed rats was that the animals did not display a higher rate of acquisition of conditioned responses. Almost all studies using eye-blink conditioning in human disorders (e.g., schizophrenia, (Bolbecker et al, 2009); mental retardation, (Hogg et al, 1979); Huntington disease, (Woodruff-Pak & Papka, 1996); Fragile X Syndrome, (Tobia & Woodruff-Pak, 2009) show impairment in conditioning ability compared to control subjects. It is therefore surprising that children with autism and rats exposed to VPA in utero display an enhancement of eye-blink conditioning, which might actually lead to the first 'autismspecific' test for between species comparisons.…”