Hippocampal Non-Theta-Contingent Eyeblink Classical Conditioning: A Model System for Neurobiological Dysfunction

Abstract

Typical information processing is thought to depend on the integrity of neurobiological oscillations that may underlie coordination and timing of cells and assemblies within and between structures. The 3–7 Hz bandwidth of hippocampal theta rhythm is associated with cognitive processes essential to learning and depends on the integrity of cholinergic, GABAergic, and glutamatergic forebrain systems. Since several significant psychiatric disorders appear to result from dysfunction of medial temporal lobe (MTL) neurochemical systems, preclinical studies on animal models may be an important step in defining and treating such syndromes. Many studies have shown that the amount of hippocampal theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning and attainment of asymptotic performance. Our lab has developed a brain–computer interface that makes eyeblink training trials contingent upon the explicit presence or absence of hippocampal theta. The behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to fourfold increase in learning speed over non-theta states. The non-theta behavioral impairment is accompanied by disruption of the amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns dependent on theta state. Our findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta. Here, we focus on the impairments in the non-theta state, integrate them into current models of psychiatric disorders, and suggest how improvement in our understanding of neurobiological oscillations is critical for theories and treatment of psychiatric pathology.

Diminished auditory sensory gating during active auditory verbal hallucinations

“…This would suggest that there has been a collapse of the top-down modulatory networks controlling gating more generally. As such, the present neurophysiological analysis is consistent with that of our recent fMRI network analysis (Thoma et al, 2016), the results of which suggested that as one moves into the AVH-on state, pre-frontally mediated networks, presumably associated with executive control, go off-line, and a predominant temporal lobe AVH network emerges supporting the experience of AVH.…”

“…Questions regarding the extent to which patients are able to successfully indicate the onset or offset of AVH may bear on the present conclusions, but data presented elsewhere demonstrated a high test-retest reliability of our button press protocol in an overlapping sample of schizophrenia patients (Thoma et al, 2016). Lastly, these findings emphasize the importance of using the temporal sensitivity of neurophysiological measures to better understand the state-related changes in neural functioning underlying schizophrenia symptoms.…”

“…Hence, a more severe AVH experience results in a greater attempt to reduce the processing of invasive voices perceived to be incoming from the environment. A second possibility is that greater suppression of S2 is one consequence of AVH network formation (Thoma et al, 2016), resulting in reduced processing of stimuli from the external environment and increased processing of internally generated data, ultimately resulting in more severe AVH. Of course, it is possible that both mechanisms are operating simultaneously resulting in a vicious circle in which greater S2 suppression leads to increasing AVH severity and greater suppression of S2.…”

Transgenerational aspects of former Swiss child laborers: do second generations suffer from their parents’ adverse early-life experiences?

“…Within a project on biological consequences of childhood experiences and trauma, a subsample of former child laborers provided further information (Küffer et al, 2016). Data collection for the parental control sample was done within the context of the current study between 2013 and 2014.…”

Protocol for a between-group experimental study examining cultural differences in emotion processing between Malay and Caucasian adults with and without major depressive disorder

“…6 7 These differences affect MDD in terms of the factors involved in the development and maintenance of MDD, the way in which MDD symptoms are manifested, and how MDD is expressed, discussed and managed. [8][9][10][11][12][13][14][15][16] Studies have also found that culture influences physical health and medical conditions. 17 18 In terms of reporting the symptoms of MDD, Chinese and Malaysian Chinese patients tend to focus on the somatic symptoms, while patients from American, European Canadian and European Australian cultural backgrounds tend to focus on the psychological symptoms.…”