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Poster #S34 IMPOVERISHED HIGH-FREQUENCY OSCILLATORY ACTIVITY IN FRONTAL CORTEX IN INDIVIDUALS WITH SCHIZOPHRENIA DURING IMPLICIT SEQUENCE LEARNING
S100
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
prefrontal and parietal cortex, and the caudate nucleus in schizophrenia. We predicted that brain activity would positively correlate with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia. Methods: Twenty-five healthy adults and 17 people with schizophrenia or schizoaffective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by ELISA. Results: We found a positive correlation between circulating plasma BDNF levels and brain activity in the right parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant difference. Discussion: This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning suggesting that plasma BDNF levels may reflect brain activity in healthy humans. The lack of relationship between plasma BDNF and task related brain activity in patients demonstrates that circulating blood BDNF is not related to frontal-parietal-striatal activity during learning in schizophrenia.
Poster #S33 REDUCED DEACTIVATION IN MEDIAL PREFRONTAL CORTEX DURING AN INNER SPEECH TASK IN SCHIZOPHRENIA PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS Leonie Bais 1,2 , Ans Vercammen 3 , Henderikus Knegtering 4 , André Aleman 5 NeuroImaging Center, University Medical Center Groningen & University of Groningen, the Netherlands; 2 Lentis, Center for Mental Health Care Groningen, The Netherlands; 3 Australian Catholic University, Strathfield, Australia; 4 Lentis; 5 University Medical Center Groningen 1
Background: Patients with schizophrenia often experience auditory verbal hallucinations, a phenomenon that has been explained as inner speech misattributed to an external source. However, the exact neural correlates of AVH and the relationship to the neural processes of inner speech are still unclear. We investigated brain activation during a performance based inner speech task in hallucinating schizophrenia patients as compared to healthy controls and non-hallucinating schizophrenia patients. We expected an aberrant response in hallucinating patients in brain areas that are involved in speech receptive processes. Methods: Hallucinating patients (N=29), non-hallucinating patients (N=16) and healthy controls (N=39) performed a metrical stress evaluation task during fMRI scanning. In the phonetic condition, bisyllabic words were visually presented and subjects had to indicate which syllable carried the metrical stress by imagining hearing the words. The contrast maps of the phonetic condition > baseline were added in a full-factorial design, and the main effect of task in the three groups was calculated. Post-hoc comparisons were used to determine significant pairwise contrasts. Differences in accuracy and reaction times between the three groups were evaluated with ANOVA and post-hoc tests. Results: The main effect of group for the phonetic > baseline condition shows a large cluster in the rostral part of the left medial frontal gyrus (MFG) extending into the left and right rostral part of the anterior cingulate cortex (ACC) (k=173, pfwe=0.002). The hallucinating patients did not deactivate this area, whereas the non-hallucinating patients and healthy controls demonstrated deactivation. Post-hoc tests between the three groups confirm this result, although the contrast between hallucinating and non-hallucinating patients did not survive FWE correction. The hallucinating patients showed slower reaction times than the healthy controls during metrical stress evaluation (p=0.019), but the three groups were equally accurate. Discussion: The rostral part of the middle frontal gyrus and anterior cingulate gyrus are found to be part of the Default Mode Network (DMN), the most active network in the brain during periods of rest, without external stimulation (Buckner et al. 2008). This state is associated with introspective processes. Garrity et al. (2007) found that hallucinations correlated positively with DMN activation during rest periods, as it is thought that schizophrenia patients with AVH are more focused on internal processes. Possibly, the hallucinating patients in present study showed greater resting state activity during the resting blocks, and thus deactivate less than the
non-hallucinating patients and healthy controls when an external stimulus appeared.
Poster #S34 IMPOVERISHED HIGH-FREQUENCY OSCILLATORY ACTIVITY IN FRONTAL CORTEX IN INDIVIDUALS WITH SCHIZOPHRENIA DURING IMPLICIT SEQUENCE LEARNING Bruno Biagianti 1,2 , Leighton Hinkley 3 , Srikantan Nagarajan 3 , Sophia Vinogradov 4,5 1 San Francisco Veterans Affairs Medical Center; 2 University of California San Francisco; 3 UCSF Department of Radiology; 4 University of California, San Francisco; 5 Associate Chief of Staff for Mental Health, SFVA MEdical Center Background: Schizophrenia-related impairments in implicit and explicit learning undermine goal setting and achievement and are critical factors in determining functional and occupational outcome. These learning impairments that are currently not targeted by psychopharmacological and psychosocial interventions are thought to be driven in part by aberrant oscillatory patterns in key regions. Individuals with schizophrenia have showed impaired performance on most explicit learning tasks. However, studies that have investigated implicit learning in schizophrenia with Serial Reaction Time Tasks (SRTT) have produced inconclusive results. Increasing evidence suggests that schizophrenia-related implicit learning deficits are associated with functional abnormalities of the frontal cortex. Here we use magnetoencephalographic imaging (MEG-I) to test the hypothesis that impoverished frontal oscillatory activity over could impede efficient implicit sequence learning in individuals with schizophrenia. Methods: MEG-I data were collected using a 275-channel biomagnetometer (VSM MedTech) from 10 individuals with schizophrenia and 10 healthy subjects during a modified SRTT. In each block, a train of speech sounds (/e/, /i/, /o/, /u/) was presented in the auditory domain either randomly or in an eight-step movement sequence. For each trial, individuals were instructed to repeat into an optical microphone the speech sound. Individuals were presented with a random block followed by three sequence blocks containing the sequence to learn and ending with a post-training random block. Adaptive spatial filtering and Bayesian algorithms implemented in the Neurodynamic Utility Toolbox for MEG were used to estimate neural sources in the time-frequency domains. Neural oscillatory power changes were computed in four frequency bands (theta (3-7), alpha (8-12), beta (15-25), gamma (30-50), high-gamma (70-160Hz) using overlapping time windows (200 ms/150 ms/100 ms) with a sliding step size of 10ms. Results: Change in reaction time between sequence and random trials was statistically significant in healthy subjects (p= 0.01) but not in individuals with schizophrenia (p=0.3). In healthy subjects, changes in beta-activity during sequence learning progressed from left-hemisphere language regions prior to the response (−70ms) to motor, frontal and temporal regions bilaterally post response (70 ms, 210 ms). In schizophrenia, impoverished beta power was observed over frontal cortices from -70ms to 210 ms, bilaterally. During sequence learning, an increase in high-gamma power localized to bilateral frontal cortex was observed in healthy subjects around the response onset. Changes in gamma activity progressed from frontal and temporal regions (−70ms) to bilateral motor and temporal regions post-response (70 ms, 210 ms). In individuals with schizophrenia, regions of frontal cortices involved in speech reception and production showed reduced changes in high-gamma activity post response (70 ms, 210 ms). Discussion: In this study, we found significant implicit sequence learning impairment among people with schizophrenia consistent with impoverished beta and high gamma frontal activity. Reduced high-frequency neural synchrony in these regions could represent a neuroimaging-based marker that predicts deficits in auditory learning as well as receptiveness to neuroplasticity-based interventions. Further studies are needed to investigate whether neuroplasticity-guided cognitive training interventions that target these key neurophysiological processes have the potential to restore frontal oscillatory activity and hence improve implicit learning and functional outcome in schizophrenia.
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
prefrontal and parietal cortex, and the caudate nucleus in schizophrenia. We predicted that brain activity would positively correlate with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia. Methods: Twenty-five healthy adults and 17 people with schizophrenia or schizoaffective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by ELISA. Results: We found a positive correlation between circulating plasma BDNF levels and brain activity in the right parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant difference. Discussion: This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning suggesting that plasma BDNF levels may reflect brain activity in healthy humans. The lack of relationship between plasma BDNF and task related brain activity in patients demonstrates that circulating blood BDNF is not related to frontal-parietal-striatal activity during learning in schizophrenia.
Poster #S33 REDUCED DEACTIVATION IN MEDIAL PREFRONTAL CORTEX DURING AN INNER SPEECH TASK IN SCHIZOPHRENIA PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS Leonie Bais 1,2 , Ans Vercammen 3 , Henderikus Knegtering 4 , André Aleman 5 NeuroImaging Center, University Medical Center Groningen & University of Groningen, the Netherlands; 2 Lentis, Center for Mental Health Care Groningen, The Netherlands; 3 Australian Catholic University, Strathfield, Australia; 4 Lentis; 5 University Medical Center Groningen 1
Background: Patients with schizophrenia often experience auditory verbal hallucinations, a phenomenon that has been explained as inner speech misattributed to an external source. However, the exact neural correlates of AVH and the relationship to the neural processes of inner speech are still unclear. We investigated brain activation during a performance based inner speech task in hallucinating schizophrenia patients as compared to healthy controls and non-hallucinating schizophrenia patients. We expected an aberrant response in hallucinating patients in brain areas that are involved in speech receptive processes. Methods: Hallucinating patients (N=29), non-hallucinating patients (N=16) and healthy controls (N=39) performed a metrical stress evaluation task during fMRI scanning. In the phonetic condition, bisyllabic words were visually presented and subjects had to indicate which syllable carried the metrical stress by imagining hearing the words. The contrast maps of the phonetic condition > baseline were added in a full-factorial design, and the main effect of task in the three groups was calculated. Post-hoc comparisons were used to determine significant pairwise contrasts. Differences in accuracy and reaction times between the three groups were evaluated with ANOVA and post-hoc tests. Results: The main effect of group for the phonetic > baseline condition shows a large cluster in the rostral part of the left medial frontal gyrus (MFG) extending into the left and right rostral part of the anterior cingulate cortex (ACC) (k=173, pfwe=0.002). The hallucinating patients did not deactivate this area, whereas the non-hallucinating patients and healthy controls demonstrated deactivation. Post-hoc tests between the three groups confirm this result, although the contrast between hallucinating and non-hallucinating patients did not survive FWE correction. The hallucinating patients showed slower reaction times than the healthy controls during metrical stress evaluation (p=0.019), but the three groups were equally accurate. Discussion: The rostral part of the middle frontal gyrus and anterior cingulate gyrus are found to be part of the Default Mode Network (DMN), the most active network in the brain during periods of rest, without external stimulation (Buckner et al. 2008). This state is associated with introspective processes. Garrity et al. (2007) found that hallucinations correlated positively with DMN activation during rest periods, as it is thought that schizophrenia patients with AVH are more focused on internal processes. Possibly, the hallucinating patients in present study showed greater resting state activity during the resting blocks, and thus deactivate less than the
non-hallucinating patients and healthy controls when an external stimulus appeared.
Poster #S34 IMPOVERISHED HIGH-FREQUENCY OSCILLATORY ACTIVITY IN FRONTAL CORTEX IN INDIVIDUALS WITH SCHIZOPHRENIA DURING IMPLICIT SEQUENCE LEARNING Bruno Biagianti 1,2 , Leighton Hinkley 3 , Srikantan Nagarajan 3 , Sophia Vinogradov 4,5 1 San Francisco Veterans Affairs Medical Center; 2 University of California San Francisco; 3 UCSF Department of Radiology; 4 University of California, San Francisco; 5 Associate Chief of Staff for Mental Health, SFVA MEdical Center Background: Schizophrenia-related impairments in implicit and explicit learning undermine goal setting and achievement and are critical factors in determining functional and occupational outcome. These learning impairments that are currently not targeted by psychopharmacological and psychosocial interventions are thought to be driven in part by aberrant oscillatory patterns in key regions. Individuals with schizophrenia have showed impaired performance on most explicit learning tasks. However, studies that have investigated implicit learning in schizophrenia with Serial Reaction Time Tasks (SRTT) have produced inconclusive results. Increasing evidence suggests that schizophrenia-related implicit learning deficits are associated with functional abnormalities of the frontal cortex. Here we use magnetoencephalographic imaging (MEG-I) to test the hypothesis that impoverished frontal oscillatory activity over could impede efficient implicit sequence learning in individuals with schizophrenia. Methods: MEG-I data were collected using a 275-channel biomagnetometer (VSM MedTech) from 10 individuals with schizophrenia and 10 healthy subjects during a modified SRTT. In each block, a train of speech sounds (/e/, /i/, /o/, /u/) was presented in the auditory domain either randomly or in an eight-step movement sequence. For each trial, individuals were instructed to repeat into an optical microphone the speech sound. Individuals were presented with a random block followed by three sequence blocks containing the sequence to learn and ending with a post-training random block. Adaptive spatial filtering and Bayesian algorithms implemented in the Neurodynamic Utility Toolbox for MEG were used to estimate neural sources in the time-frequency domains. Neural oscillatory power changes were computed in four frequency bands (theta (3-7), alpha (8-12), beta (15-25), gamma (30-50), high-gamma (70-160Hz) using overlapping time windows (200 ms/150 ms/100 ms) with a sliding step size of 10ms. Results: Change in reaction time between sequence and random trials was statistically significant in healthy subjects (p= 0.01) but not in individuals with schizophrenia (p=0.3). In healthy subjects, changes in beta-activity during sequence learning progressed from left-hemisphere language regions prior to the response (−70ms) to motor, frontal and temporal regions bilaterally post response (70 ms, 210 ms). In schizophrenia, impoverished beta power was observed over frontal cortices from -70ms to 210 ms, bilaterally. During sequence learning, an increase in high-gamma power localized to bilateral frontal cortex was observed in healthy subjects around the response onset. Changes in gamma activity progressed from frontal and temporal regions (−70ms) to bilateral motor and temporal regions post-response (70 ms, 210 ms). In individuals with schizophrenia, regions of frontal cortices involved in speech reception and production showed reduced changes in high-gamma activity post response (70 ms, 210 ms). Discussion: In this study, we found significant implicit sequence learning impairment among people with schizophrenia consistent with impoverished beta and high gamma frontal activity. Reduced high-frequency neural synchrony in these regions could represent a neuroimaging-based marker that predicts deficits in auditory learning as well as receptiveness to neuroplasticity-based interventions. Further studies are needed to investigate whether neuroplasticity-guided cognitive training interventions that target these key neurophysiological processes have the potential to restore frontal oscillatory activity and hence improve implicit learning and functional outcome in schizophrenia.