Jean Théberge

Resting state default-mode network connectivity in early depression using a seed region-of-interest analysis : Decreased connectivity with caudate nucleus

Aim:  Reports on resting brain activity in healthy controls have described a default‐mode network (DMN) and important differences in DMN connectivity have emerged for several psychiatric conditions. No study to date, however, has investigated resting‐state DMN in relatively early depression before years of medication treatment. The objective of the present study was, therefore, to investigate the DMN in patients seeking help from specialized mental health services for the first time for symptoms of depression.

Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects

Objective:  The goal of this study was to investigate the relationship between default mode network connectivity and the severity of post‐traumatic stress disorder (PTSD) symptoms in a sample of eleven acutely traumatized subjects.

A 4.0-T fMRI study of brain connectivity during word fluency in first-episode schizophrenia

OBJECTIVE To use functional magnetic resonance imaging (fMRI) to investigate functional connectivity, and hence, underlying neural networks, in never-treated, first-episode patients with schizophrenia using a word fluency paradigm known to activate prefrontal, anterior cingulate, and thalamic regions. Abnormal connectivity between the prefrontal cortex (PFC) and other brain regions has been demonstrated in chronic, medicated patients in previous positron emission tomography (PET) studies, but has not to our knowledge, previously been demonstrated using both first-episode, drug-naïve patients and fMRI technology. METHODS A 4.0-Tesla (T) fMRI was used to examine activation and functional connectivity [psychophysiological interactions (PPIs)] during a word fluency task compared to silent reading in 10 never-treated, first-episode patients with schizophrenia and 10 healthy volunteers of comparable age, sex, handedness, and parental education. RESULTS Compared to healthy volunteers, the schizophrenia patient group exhibited less activation during the word fluency task, mostly in the right anterior cingulate and prefrontal regions. Psychophysiological interactions between right anterior cingulate and other parts of the brain revealed a localized interaction with the left temporal lobe in healthy volunteers during the task and a widespread unfocussed interaction in patients. CONCLUSION These findings suggest anterior cingulate involvement in the neuronal circuitry underlying schizophrenia.

Default mode network connectivity : effects of age, sex, and analytic approach

The ‘default mode network’ is a set of brain regions showing correlated, low-frequency activity during rest. It includes the posterior cingulate/precuneus, medial prefrontal cortex, and bilateral inferior parietal cortex. Earlier studies have characterized this network using either region of interest-based correlation analyses or data-driven techniques; however, there is some disagreement over which method is superior. We conducted both types of analysis on a large (N=40) data set and also investigated age and sex differences in the network. Both region of interest-based analyses and independent component analysis identified the default mode network. Age and sex differences were small and there was less agreement between analytic techniques regarding age and sex effects than regarding default mode network structure.

Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder

Järnum H, Eskildsen SF, Steffensen EG, Lundbye‐Christensen S, Simonsen CW, Thomsen IS, Fründ E‐T, Théberge J, Larsson E‐M. Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder.

Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia

BACKGROUND Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown. AIMS To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis. METHOD Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months. RESULTS The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions. CONCLUSIONS Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

Brain activation to favorite music in healthy controls and depressed patients.

Reward-processing neurocircuitry has been delineated using verbal or visual processing and/or decision-making tasks. We examined more basic processes of listening to enjoyable music in healthy and depressed patients. The paradigm was passive, individualized, and brief. Sixteen depressed and 15 control individuals provided favorite music and identified neutral music from selections provided. In the fMRI scanner, individuals heard their neutral and their favorite music for 3 min each. Favorite versus neutral music-listening contrasts showed greater activation in controls than depressed patients in medial orbital frontal cortex and nucleus accumbens/ventral striatum. Left medial prefrontal cortex activity was positively correlated with pleasure scores, whereas middle temporal cortex and globus pallidus were negatively correlated with pleasure. This paradigm activated neurocircuitry of reward processing and showed clinically meaningful alterations in depression.

The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes

Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared with controls. Here we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD−DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioral symptoms. PTSD patients (n=49) with (n=13) and without (n=36) the dissociative subtype and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared with the PTSD−DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception—implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.

Plastic modulation of PTSD resting‐state networks and subjective wellbeing by EEG neurofeedback

Electroencephalographic (EEG) neurofeedback training has been shown to produce plastic modulations in salience network and default mode network functional connectivity in healthy individuals. In this study, we investigated whether a single session of neurofeedback training aimed at the voluntary reduction of alpha rhythm (8–12 Hz) amplitude would be related to differences in EEG network oscillations, functional MRI (fMRI) connectivity, and subjective measures of state anxiety and arousal in a group of individuals with post‐traumatic stress disorder (PTSD).

Duration of untreated psychosis vs. N-acetylaspartate and choline in first episode schizophrenia: a 1H magnetic resonance spectroscopy study at 4.0 Tesla.

N-acetylaspartate (NAA) has been associated with neuronal integrity and function, and choline-containing compounds have been linked to neuronal membrane integrity. This study examined the influence of the duration of untreated psychosis, duration of prodromal symptoms and total length of untreated illness on these markers of neuronal loss or damage. In vivo 1H magnetic resonance spectroscopy data were acquired from 1.5-cc volumes in the left anterior cingulate and left thalamus of 19 never-treated first episode schizophrenic subjects using STEAM20 at 4.0 Tesla. Duration of untreated psychosis, prodrome and total length of untreated illness were correlated with levels of NAA and choline. No significant correlation was observed between NAA and duration of untreated psychosis and untreated illness in both regions examined. Thalamic NAA negatively correlated with duration of prodromal symptoms. A positive correlation between choline and duration of untreated psychosis was identified in both regions studied. Delays in treatment of psychotic symptoms of schizophrenia were not associated with a reduction in markers of neuronal integrity or function in contrast to longer prodromal periods, which were associated with lower NAA. Neuronal damage, potentially detectable via lower NAA, may be occurring before the onset of psychosis. Increased choline is associated with longer duration of untreated psychosis and could indicate that psychosis-related membrane alterations precede the appearance of NAA reductions observed by studies of chronic schizophrenia.