Reduced mediodorsal thalamic volume and prefrontal cortical spindle activity in schizophrenia

Abstract

Background We recently found marked deficits in sleep spindles, non-rapid eye movement (NREM) sleep oscillations that are generated within the thalamus and then amplified and sustained in the cortex, in patients with schizophrenia compared to both healthy and psychiatric controls. Here, we investigated the thalamic and cortical contributions to these sleep spindle deficits. Methods Anatomical Volume of Interest analysis (i.e., thalamic volumes) and electroencephalogram (EEG) source modeling (i.e., spindle-related cortical currents) were performed in patients with schizophrenia and healthy comparison subjects. Findings Schizophrenia patients had reduced mediodorsal (MD) thalamic volumes, especially on the left side, compared to healthy controls, whereas whole thalami and lateral geniculate nuclei did not differ between groups. Furthermore, left MD volumes were strongly correlated with the number of scalp-recorded spindles in an anterior frontal region, and cortical currents underlying these anterior frontal spindles were localized in the prefrontal cortex, in Brodmann Area (BA) 10. Finally, prefrontal currents at the peak of spindle activity were significantly reduced in schizophrenia patients and correlated with their performance in an abstraction/working memory task. Conclusion Altogether, these findings point to deficits in a specific thalamo-cortical circuitry in schizophrenia, which is associated with some cognitive deficits commonly reported in those patients.

Topographic deficits in alpha-range resting EEG activity and steady state visual evoked responses in schizophrenia

“…By contrast, we employed a statistical nonparametric mapping (SnPM) with supra-threshold cluster technique (Nichols and Holmes, 2002). SnPM not only allows investigating the entire scalp without choosing a given ROI, but also accounts for the multiple comparison problems created by the numerous scalp electrodes utilized here, as we have demonstrated in a number of several recent publications from our group in schizophrenia and other clinical and non-clinical samples (Ferrarelli et al, 2007(Ferrarelli et al, , 2010Lustenberger and Huber, 2012;Buchmann et al, 2014). Correlational analyses were conducted with linear regression and contrasted with a Fisher z-transformation, where applicable.…”

“…First, thalamic volume and metabolism are reduced in schizophrenia (Danos et al, 2003;Buchmann et al, 2014). These deficits may in part contribute to thalamo-cortical dysrhythmia (TCD), which has been proposed as an underlying mechanism across multiple psychiatric and neurological conditions that manifests as alterations in theta and alpha band oscillations of EEG and MEG recordings (Schulman et al, 2011).…”

Sleep Spindle Deficit in Schizophrenia: Contextualization of Recent Findings

“…These spindles are exaggerated, which means of higher voltage (200-400 μV) and longer duration, more continuously present than controls, often associated with atypical K-complexes. Similar but not continuous bursts (usually 2-4 s in duration) of high-amplitude sleep spindles in the same frequency range (8)(9)(10)(11)(12)(13)(14)(15) have been reported also in older subjects with intellectual disabilities between 14 and 19 years [92]. Phenylketonuria (PKU), an inborn error of metabolism that leads to sever impairment of intellectual ability if left untreated, has been associated with both enhanced [93] and decreased [94] sleep spindle activity.…”

“…SCZ subjects showed a decreased amplitude of spindles in centroparietal regions and duration in prefrontal regions compared to both control populations, whereas slow wave parameters did not differ across groups. Structural MRI and electrophysiological features were then compared between SCZ and healthy control subjects, yielding a correlation between reduced volume in the mediodorsal thalamic nucleus (MD) and reduced number of scalp-recorded anterior frontal sleep spindles in patients [13]. This reduced sleep spindle activity localized in the prefrontal cortex and predicted an impaired performance in an executive function task in SCZ patients [13].…”

“…Structural MRI and electrophysiological features were then compared between SCZ and healthy control subjects, yielding a correlation between reduced volume in the mediodorsal thalamic nucleus (MD) and reduced number of scalp-recorded anterior frontal sleep spindles in patients [13]. This reduced sleep spindle activity localized in the prefrontal cortex and predicted an impaired performance in an executive function task in SCZ patients [13]. Two studies employing a motor sequence task (MST) before and after a night of sleep reported reduced sleep spindle density [14] and coherence [14,15] in SCZ patients, with lower sleep spindle incidence predicting less overnight improvement in the MST [15].…”