Thalamocortical connectivity and its relationship with symptoms and cognition across the psychosis continuum.

BACKGROUND: Coordination between the thalamus and cortex is necessary for efficient processing of sensory information and appears disrupted in schizophrenia. The significance of this disrupted coordination (i.e. thalamocortical dysconnectivity) to the symptoms and cognitive deficits of schizophrenia is unclear. It is also unknown whether similar dysconnectivity is observed in other forms of psychotic psychopathology and associated with familial risk for psychosis. Here we examine the relevance of thalamocortical connectivity to the clinical symptoms and cognition of patients with psychotic psychopathology, their first-degree biological relatives, and a group of healthy controls. METHOD: Patients with a schizophrenia-spectrum diagnosis (N = 100) or bipolar disorder with a history of psychosis (N = 33), their first-degree relatives (N = 73), and a group of healthy controls (N = 43) underwent resting functional MRI in addition to clinical and cognitive assessments as part of the Psychosis Human Connectome Project. A bilateral mediodorsal thalamus seed-based analysis was used to measure thalamocortical connectivity and test for group differences, as well as associations with symptomatology and cognition. RESULTS: Reduced connectivity from mediodorsal thalamus to insular, orbitofrontal, and cerebellar regions was seen in schizophrenia. Across groups, greater symptomatology was related to less thalamocortical connectivity to the left middle frontal gyrus, anterior cingulate, right insula, and cerebellum. Poorer cognition was related to less thalamocortical connectivity to bilateral insula. Analyses revealed similar patterns of dysconnectivity across patient groups and their relatives. CONCLUSIONS: Reduced thalamo-prefrontal-cerebellar and thalamo-insular connectivity may contribute to clinical symptomatology and cognitive deficits in patients with psychosis as well as individuals with familial risk for psychotic psychopathology.

Interoception Underlies Therapeutic Effects of Mindfulness Meditation for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

BACKGROUND: Mindfulness-based interventions have proven efficacy in treating posttraumatic stress disorder (PTSD), but the neurobiological mechanism underlying the therapeutic effects is unknown. As mindfulness meditation cultivates attention to the present moment and bodily sensations, neural functions related to interoception (i.e., central processes of bodily signals) might be such a mechanism. METHODS: We conducted a clinical trial in which veterans with PTSD were randomly assigned to receive an 8-week mindfulness-based stress reduction (MBSR) intervention (n = 47) or an active control intervention (present-centered group therapy; n = 51). We assessed pre- and postintervention PTSD symptoms and electroencephalography measures of neural outcomes, including spontaneous brain activity, cognitive task-related brain responses, and interoceptive brain responses (heartbeat-evoked brain responses). We conducted statistical causal mediation analyses using treatment type as a predictor, pre- and postintervention measures of symptom severity as treatment response, and the neural outcomes as mediators. RESULTS: Compared with the control group, the MBSR group had greater improvements in PTSD symptoms and increases in spontaneous alpha power (8-13 Hz), task-related frontal theta power (4-7 Hz in 140-220 ms after stimulus), and frontal theta heartbeat-evoked brain responses (3-5 Hz and 265-336 ms after R peak). The mediation analysis using latent difference score modeling revealed that only changes in frontal theta heartbeat-evoked brain responses mediated the MBSR treatment effect. CONCLUSIONS: Mindfulness meditation improves brain functions of attentional control and resting brain states reflective of internally oriented relaxation. However, interoceptive neural functions enhanced by MBSR seem to be a primary cerebral mechanism that improves symptoms of PTSD.

Transcendental meditation for veterans with post-traumatic stress disorder.

OBJECTIVE: Transcendental Meditation (TM) is a mental technique using a mantra to facilitate meditation. TM has a potential for treating symptoms of posttraumatic stress disorder (PTSD), but its clinical efficacy remains to be clarified. This pilot study evaluated the acceptability, preliminary effectiveness, and neurophysiology of TM for veterans with PTSD. METHOD: Twenty-nine veterans (20.7% female) were recruited from a major medical center and enrolled in the study. TM instruction was provided by certified TM teachers from the Maharishi Foundation and consisted of 8 weeks of individual and group-based meditation instruction and practice. Outcomes were assessed at baseline, during treatment, posttreatment, and at 2-month follow-up, and included clinical interviews, self-report questionnaires, and electroencephalography (EEG) recorded during resting and meditation states. RESULTS: From baseline to posttreatment, participants reported reductions in PTSD symptoms, experiential avoidance, and depressive and somatic symptoms, as well as increases on measures of mindfulness and quality of life. Gains were either maintained or continued to improve through the 2-month follow-up. Compared to baseline, EEG spectral power increased in low-frequency bands (1-7 Hz) at posttreatment and follow-up and only during meditation states suggesting TM-specific changes in brain state associated with the intervention. CONCLUSIONS: TM appears to be an acceptable and effective treatment for veterans with PTSD that warrants further study regarding specific outcomes and beneficial changes in brain function. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Frequency-specific disruptions of neuronal oscillations reveal aberrant auditory processing in schizophrenia.

Individuals with schizophrenia exhibit abnormalities in evoked brain responses in oddball paradigms. These could result from (a) insufficient salience-related cortical signaling (P300), (b) insufficient suppression of irrelevant aspects of the auditory environment, or (c) excessive neural noise. We tested whether disruption of ongoing auditory steady-state responses at predetermined frequencies informed which of these issues contribute to auditory stimulus relevance processing abnormalities in schizophrenia. Magnetoencephalography data were collected for 15 schizophrenia and 15 healthy subjects during an auditory oddball paradigm (25% targets; 1-s interstimulus interval). Auditory stimuli (pure tones: 1 kHz standards, 2 kHz targets) were administered during four continuous background (auditory steady-state) stimulation conditions: (1) no stimulation, (2) 24 Hz, (3) 40 Hz, and (4) 88 Hz. The modulation of the auditory steady-state response (aSSR) and the evoked responses to the transient stimuli were quantified and compared across groups. In comparison to healthy participants, the schizophrenia group showed greater disruption of the ongoing aSSR by targets regardless of steady-state frequency, and reduced amplitude of both M100 and M300 event-related field components. During the no-stimulation condition, schizophrenia patients showed accentuation of left hemisphere 40 Hz response to both standard and target stimuli, indicating an effort to enhance local stimulus processing. Together, these findings suggest abnormalities in auditory stimulus relevance processing in schizophrenia patients stem from insufficient amplification of salient stimuli.

Abnormalities of neuronal oscillations and temporal integration to low- and high-frequency auditory stimulation in schizophrenia.

BACKGROUND: Electroencephalography and magnetoencephalography studies indicate among schizophrenia patients (SZ) abnormal, often reduced, entrained steady-state (aSSR) and transient (N100/M100) neural responses to auditory stimuli. We complement this literature by focusing analyses on auditory cortices, assessing a wide range of stimulation frequencies with long driving periods and evaluating relationships between aSSR and M100 reductions in SZ. METHODS: Seventeen SZ and 17 healthy subjects (H) participated. Stimuli were 1500 msec binaural broadband noise sequences modulated at 5, 20, 40, 80, or 160 Hz. Magnetoencephalography data were collected and co-registered with structural magnetic resonance images. The aSSRs and M100s projected into brain space were analyzed as a function of hemisphere, stimulus density, and time. RESULTS: For aSSR, SZ displayed weaker entrainment bilaterally at low (5-Hz) and high (80-Hz) modulation frequencies. To 40-Hz stimuli, SZ showed weaker entrainment only in right auditory cortex. For M100, while responses for H increased linearly with stimulus density, this effect was weaker or absent in SZ. A principal components analysis of SZ deficits identified low (5-Hz entrainment and M100) and high (40- to 80-Hz entrainment) frequency components. Discriminant analysis indicated that the low-frequency component uniquely differentiated SZ from H. The high-frequency component correlated with negative symptoms among SZ. CONCLUSIONS: The SZ auditory cortices were unable to 1) generate healthy levels of theta and high gamma band (80-Hz) entrainment (aSSR), and 2) augment transient responses (M100s) to rapidly presented auditory information (an index of temporal integration). Only the latter was most apparent in left hemisphere and may reflect a prominent neurophysiological deficit in schizophrenia.