Exploration of cerebellar-dependent associative learning in schizophrenia: Effects of varying and shifting interstimulus interval on eyeblink conditioning.

Abstract

Eyeblink conditioning abnormalities have been reported in schizophrenia, but the extent to which these anomalies are evident across a range of delay intervals (i.e., ISI intervals) is unknown. In addition, the effects of interstimulus interval (ISI) shifts on learning are unknown, though such manipulations can be informative about the plasticity of cerebellar timing functions. Therefore, the primary purpose of the present study was to investigate the interactions between interstimulus interval (ISI) manipulations and learning in schizophrenia. A standard delay eyeblink conditioning procedure with four different interstimulus intervals (ISIs; 250, 350, 550, 850 ms) was employed. Each eyeblink conditioning experiment was immediately followed by another with a different ISI, thus permitting the characterization of conditioned response (CR) learning at one ISI and the extent to which CRs could be generated at a different latency following an ISI shift. Collapsing across all conditions, the schizophrenia group (n=55) had significantly fewer conditioned responses and longer onset latencies than age-matched controls (n=55). Surprisingly, shifting to a new ISI had negligible effects on conditioned response rates in both groups. These findings contribute to evidence of robust eyeblink conditioning abnormalities in schizophrenia and suggest impaired cerebellar function, but underscore the need for more research to clarify the source of these abnormalities and their relationship to clinical manifestations of schizophrenia.

Eyeblink conditioning in unmedicated schizophrenia patients: A positron emission tomography study

“…Eyeblink conditioning is significantly impaired in the patients, and they exhibit significantly fewer CRs during the latter two phases of acquisition than controls. These data replicate previous studies reporting abnormalities in eyeblink conditioning in schizophrenia patients (Brown et al, 2005; Bolbecker et al, 2009, 2011). However, the onset timing of both the overall eyeblink and the CR was non-significant (Fig.…”

“…Early work examining eyeblink conditioning in schizophrenia using behavioral measures has suggested that patients condition faster than controls and have a higher percentage of CRs (Spain, 1966; Sears et al, 2000). However, more recent studies have reported the opposite result (Hofer et al, 2001; Brown et al, 2005; Edwards et al, 2008; Bolbecker et al, 2009, 2011) indicating eyeblink conditioning deficits in schizophrenia.…”

Consensus paper: Decoding the Contributions of the Cerebellum as a Time Machine. From Neurons to Clinical Applications

“…Compared to controls, patients with schizophrenia showed fewer CR incidences and longer CR onset latencies while shifting of the interstimulus interval did not influence CR rates in both groups [190].…”

Aberrant Middle Prefrontal-Motor Cortex Connectivity Mediates Motor Inhibitory Biomarker in Schizophrenia

“…Since the medial prefrontal cortex has been implicated in the pathophysiology of schizophrenia(20), the top-down regulation to motor regions may play a role in motor circuitry abnormalities in schizophrenia. Besides the prefrontal–motor circuitry, other motor circuitries such as the cerebello-thalamo-motor circuit may also be relevant as it controls motor learning and postural control(21,22). Furthermore, altered sensorimotor and basal ganglia circuit abnormalities and their related motor behavioral problems have also been shown in schizophrenia(23–27).…”