The TCT (targeted cognitive training) group showed an increase in Ba-Pa Quiet M100 response amplitude to each syllable after training, while Computer Games (CG) control condition subjects did not and Healthy Comparison subjects did not (Session x Group: F[2,44]=4.3, p=.019; TCT Session p=.008, CG Session ns, HC Session ns. No significant Syllable interactions). Method for M100 response= MEG-derived activity in BA41 using CTF’s SAM beamformer virtual channel localization over time and represents the broadband activity response. Baseline contrasts of SZ and HC at this location produce a nice theta/alpha band difference between the two groups, although the whole-head analysis of TCT is underpowered to produce similar auditory enhancement as reported here. Only the first syllable presentation in the task is presented here. TCT subjects that showed greater auditory M100 enhancement also showed increased scores on measures associated with Speed of Processing (LH: .530, p=.024) and Executive Function (Tower of London – LH: .659, p=.003; RH: .603, p=.008*). Correlation was performed across syllable, Tower of london is graphed here. CG subjects did not show significant correlation.
Sophia Vinogradov Webinar SRF
Neuroplasticity-based cognitive training in schizophrenia Sophia Vinogradov, M.D. University of California, San Francisco; SFVA Medical CenterThe brain adapts to salient experiences by representing the relevant sensorystimuli and action outputs with disproportionately larger and more coordinatedpopulations of neurons.Merzenich & Jenkins,1993; Buomomano & Merzenich, 1998; Merzenich & DeCharms, 1996; Merzenich, 2001
In schizophrenia…• Neurons within the brain are not networking together (mapping together) to support normal cognitive processes.• Abnormal signal detection Abnormal networking Abnormal brain functionsHaig et al, 2000Goldman-Rakic, 1999Taylor 2002, 2005
We know from basic science that…• The accuracy, fidelity, and efficiency of brain networks can be improved through intensive, progressive, heavily rewarded, perceptual and cognitive training. Temple et al, 2000 Temple et al, 2003 Merzenich et al, 1999
In the impaired brain…• Training must focus both on relevant lower level perceptual processes as well as higher-order cognitions in order to maximize plastic changes. Vinogradov, Fisher, de Villers-Sidani, in press
Interacting feed-forward and feed-back processescontribute to cognitive operations
Improvements in neural system functionshould translate to improved quality of life Life Function Work Social Leisure Cognitive Function Attention Language Problem Solving Learning and Memory Speed of Information Processing Brain Function Accuracy of Information Processing Neuromodulatory Function 6
Neuroplasticity-based cognitive training contains several active ingredients• Training of relevant perceptual processes• Use of implicit learning mechanisms• Highly intensive training schedules• Carefully controlled and constrained learning tasks• Individualized adaptation of task difficulty• Frequent and repetitive engagement of attention and reward systems
Why auditory systems? Why verbal learning/memory?• Schizophrenia = Widespread disturbances in neural systems subserving verbal memory operations• Abnormalities in frontotemporal cortical networks during auditory and verbal working memory, word encoding, and recognition1• Disturbances also present at earliest stages of auditory processing2 1. Weiss and Heckers 2001 Ragland et al 2002 2. Kasai K, et al 2002 Light et al 2007 Kawakubo et al 2006
Cognitive change after Targeted Cognitive Training (TCT) vs. Computer Games (CG) TCT (N=40) CG (N=32) *p<.05, **p<.01 0.8 0.6 0.4 Z-Score Change 0.2 0 -0.2 -0.4 -0.6 -0.8 Global Speed of Working Verbal Visual Problem Cognition** Processing* Memory Learning and Learning and Solving Memory** Memory Results of Repeated Measures ANOVA: Relative to the CG group, the TCT group show significant gains in Global Cognition , Speed of Processing, and Verbal Learning and Memory. The CG group show a significant decline in Verbal Learning and Memory.
Global Cognition at baseline, post-training,and 6-Months in TCT (N=27) and CG (N=24) Baseline Post-BFP 6-Months 0.0 -0.2 -0.4 -0.6Z-Score -0.8 -1.0 -1.2 -1.4 -1.6 TCT Global Cognition CG Global CognitionResults of Repeated Measures ANOVA: Relative to the CG group, the TCT group showsignificant gains in Global Cognition from Baseline to Post-BFP (p < .01), and significant gainsfrom baseline to 6-Months Post Training at trend level (p=.08).
Association between change in cognition and change in Quality of Life Targeted Cognitive Computer Games Training (TCT) Control Group (CG) r (p) r (p) Global Cognition .39 (.05) .02 (.93) Speed of Processing .50 (.01) .28 (.18) Working Memory .45 (.02) -.10 (.65) Verbal Learning and -.09 (.67) -.01 (.97) Memory Visual Learning and .15 (.47) -.17 (.44) Memory Problem Solving .20 (.51) .29 (.41) Change scores = 6-Months Post-Training minus Baseline.
Serum anticholinergic activity is negatively correlated with cognitive improvement 2 R = 0.20, p = .02 7 (Square Root Transformed) 6 5 Baseline SAA 4 3 2 1 0 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Global Cognition (Z-Score Change)SAA uniquely accounted for 20% of the variance in change in Global Cognition, independentof the effects of IQ, age, and symptom severity (N=25). Vinogradov, Fisher, Holland, Kirshner, Pollock, AJP, 2009
After training, SZ subjects show enhanced M100 response Left hemisphere Right hemisphereAverage Z-amplitude Brodmann Area 41 50-150ms LH: -47.14 -26.90 10.10 Session One Session Two The enhanced M100 response correlates with improved executive function Change: Executive Function Left hemisphere Right hemisphere Change: M100 amplitude
Frontal cortical activation after trainingpredicts enhanced social functioning 6months later 6 rs = .61, p = .05 Social functioning 6 months after 5 computerized training 4 3 2 1 0 -1 -4 -2 0 2 4 6 Mean mPFC signal for self-generated minus externally-presented items after 80 hours vs baseline
Conclusions• “Neuroplasticity-based” targeted cognitive training in schizophrenia appears to result in improved cognitive performance and “restoration” of neural correlates of both elemental and complex operations.• Training-induced increases in frontal cortical activation patterns predict real-world functional improvement 6 months later.
• Open questions: – What are the necessary and sufficient elements of training? What neural mechanisms support the response to training? How can we develop the most efficient and robust training approaches possible? – What forms of training result in robust, enduring, and adaptive changes in neural system functioning