Richard W. J. Neufeld

Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation

BACKGROUND The goal of this study was to examine the neuronal circuitry underlying dissociative responses to traumatic script-driven imagery in sexual-abuse-related posttraumatic stress disorder (PTSD). Pilot studies in our laboratory have shown that PTSD patients had very different responses to traumatic script-driven imagery. Approximately 70% of patients relived their traumatic experience and showed an increase in heart rate while recalling the traumatic memory. The other 30% of patients had a dissociative response with no concomitant increase in heart rate. This article focuses on the latter group. METHODS The neuronal circuitry underlying dissociative responses in PTSD was studied using the traumatic script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength in 7 subjects with sexual-abuse-related PTSD and 10 control subjects. RESULTS Compared with control subjects, PTSD patients in a dissociative state showed more activation in the superior and middle temporal gyri (BA 38), the inferior frontal gyrus (BA 47), the occipital lobe (BA 19), the parietal lobe (BA 7), the medial frontal gyrus (BA 10), the medial cortex (BA 9), and the anterior cingulate gyrus (BA 24 and 32). CONCLUSIONS These findings suggest that prefrontal and limbic structures underlie dissociative responses in PTSD. Differences observed clinically, psychophysiologically, and neurobiologically between patients who respond to traumatic script-driven imagery with dissociative versus nondissociative responses may suggest different neuronal mechanisms underlying these two distinct reactions.

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.

Meta-analysis of alexithymia in posttraumatic stress disorder.

The authors present a meta-analysis investigating the prevalence of alexithymia in 12 studies encompassing 1,095 individuals with posttraumatic stress disorder (PTSD). A large effect size was found associating PTSD with alexithymia. Effect sizes were higher in studies of male combat PTSD samples in comparison with studies of other PTSD samples. Clinical and research directions are discussed.

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.

Clinical and Neural Correlates of Alexithymia in Posttraumatic Stress Disorder

Individuals with posttraumatic stress disorder (PTSD) often exhibit deficits in emotional experience and expression, which suggests that certain individuals with PTSD may be alexithymic. In this study, in a sample of 105 individuals with PTSD, clinical correlates of alexithymia included reexperiencing, hyperarousal, numbing, dissociative symptoms, and retrospectively reported experiences of childhood emotional neglect. In a subsample of 26 individuals with PTSD related to a motor vehicle accident, functional neural responses to trauma-script imagery were associated with severity of alexithymia, including increased right posterior-insula and ventral posterior-cingulate activation and decreased bilateral ventral anterior-cingulate, ventromedial prefrontal, anterior-insula, and right inferior frontal cortex activation. Clinical and theoretical implications and future research directions are discussed.

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.

Evidence for Cortical Dysfunction in Autism: A Proton Magnetic Resonance Spectroscopic Imaging Study

BACKGROUND Although brain imaging studies have reported neurobiological abnormalities in autism, the nature and distribution of the underlying neurochemical irregularities are unknown. The purpose of this study was to examine cerebral gray and white matter cellular neurochemistry in autism with proton magnetic resonance spectroscopic imaging (MRSI). METHODS Proton MRSI examinations were conducted in 26 males with autism (age 9.8 +/- 3.2 years) and 29 male comparison subjects (age 11.1 +/- 2.4 years). Estimates of cerebral gray and white matter concentrations of N-acetylaspartate (NAA), creatine + phosphocreatine, choline-containing compounds, myo-inositol, and glutamate + glutamine (Glx) were made by linear regression analysis of multi-slice MRSI data and compared between groups. Regional estimates of metabolite concentration were also made with multivariate linear regression, allowing for comparisons of frontal, temporal, and occipital gray matter, cerebral white matter, and the cerebellum. RESULTS Patients with autism exhibited significantly lower levels of gray matter NAA and Glx than control subjects. Deficits were widespread, affecting most cerebral lobes and the cerebellum. No significant differences were detected in cerebral white matter or cerebellar metabolite levels. CONCLUSIONS These results suggest widespread reductions in gray matter neuronal integrity and dysfunction of cortical and cerebellar glutamatergic neurons in patients with autism.

Neural correlates of trauma script-imagery in posttraumatic stress disorder with and without comorbid major depression: A functional MRI investigation

The goal of this study was to compare neural activation patterns in patients with PTSD with and without current comorbid major depression. Traumatized subjects with PTSD (n=11), PTSD+major depression (MDD, n=15), and subjects (n=16) who met criterion A for PTSD but never developed the disorder were studied using the script-driven symptom-provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4-Tesla field strength. Both the PTSD+MDD and PTSD-MDD groups revealed decreased brain activation in the anterior cingulate gyrus (BA 24) and the right ventrolateral prefrontal cortex (BA 47). After covariation for differences in PTSD severity between these groups, the left insula (BA 13) remained more significantly activated in the PTSD-MDD group than in the PTSD+MDD group. In contrast, the PTSD+MDD group showed greater activation than the PTSD-MDD group in the bilateral anterior cingulate gyrus (BA 24) and posterior cingulate cortices (BA 23, 31). These results suggest different patterns of brain activation related to comorbid major depression occurring in the context of PTSD.

A short echo proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients

BACKGROUND Past 1H magnetic resonance spectroscopy (MRS) studies of the temporal lobe in schizophrenic patients have shown decreased levels of N-acetylaspartate (NAA) suggesting reduced neuronal density in this region. However, the measured volumes have been large and included contributions from mostly white matter. METHODS Short echo 1H MRS was used to measure levels of NAA and other metabolites (i.e., glutamate and glutamine) from a 6 cm3 volume in the left mesial-temporal lobe of 11 first-episode schizophrenic patients and 11 healthy control subjects of comparable age, gender, handedness, education, and parental education levels. Spectra were quantified without operator interaction using automated software developed in our laboratory. Metabolite levels were normalized to the internal water concentration of each volume studied. Images were also obtained to determine temporal lobe gray and white matter volumes. RESULTS No significant differences were found between levels of NAA or other metabolites, or gray and white matter volumes, in first-episode schizophrenic patients and comparison subjects. CONCLUSIONS Since the volume studied was small compared to previous studies and contained mostly gray matter, this result suggests consequential NAA decreases may be restricted to regions of white matter.

Neural Correlates of Levels of Emotional Awareness During Trauma Script-Imagery in Posttraumatic Stress Disorder

Objective: To examine individual differences in levels of emotional awareness as a predictor of the blood oxygenation level dependent (BOLD) response to trauma script-driven imagery in trauma-exposed individuals with (n = 25) and without (n = 16) posttraumatic stress disorder (PTSD). Methods: Participants completed the Levels of Emotional Awareness Scale (LEAS) and a functional magnetic resonance imaging trauma script-driven imagery paradigm. Results: Patients with PTSD exhibited lower LEAS scores in comparison with the control group. LEAS scores correlated positively with BOLD activity during trauma script-imagery in the ventral anterior cingulate cortex (vACC) in healthy controls, whereas LEAS scores correlated negatively with activation of vACC in individuals with PTSD. Conclusion: Patients with PTSD exhibit lower than average levels of emotional awareness. Levels of emotional awareness are differentially associated with vACC response during trauma script-driven imagery in healthy controls versus individuals with PTSD. PTSD = posttraumatic stress disorder; LEAS = Levels of Emotional Awareness Scale; vACC = ventral anterior cingulate cortex; dACC = dorsal anterior cingulate cortex; mPFC = medial prefrontal cortex; BA = Brodmann Area; DSM-IV = Diagnostic and Statistical Manual—4th Edition; BOLD = blood oxygenation level dependent; SVC = small volume corrected; fMRI = functional magnetic resonance imaging.