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Working Memory Goal Maintenance
Task NameDescriptionCognitive Construct ValidityNeural Construct ValiditySensitivity to ManipulationRelationships to Behavior and SchizophreniaPsychometricsStage of ResearchMONSTER TASK
ERPThis paradigm is called the MONSTER approach (Manipulation of Orthogonal Neural Systems Together in Electrophysiological Recordings). It is not a single paradigm, but rather a general approach for efficiently measuring multiple ERP components that reflect different neural/cognitive systems. The general idea is to have multiple factors that are manipulated orthogonally in a single block of trials, such that the same set of trials can be recombined in different orthogonal ways to extract different components. This is much more efficient than running a separate block of trials to measure the effect of each manipulation. For example, the N2pc and the P3 can be measured in the same paradigm by combining a factor of attended stimulus side (left vs. right) with a factor of stimulus probability (rare vs. frequent). On each trial, a black character appears on the left side of the fixation point and a right character appears on the right side. Subjects are instructed to press one of two buttons to indicate whether the black character is a consonant or a vowel (this is actually counterbalanced, with attention directed to the black character in some trial blocks and to the white character in others). The side containing the black item varies unpredictably from one stimulus to the next. The N2pc is isolated with a contralateral-minus-ipsilateral difference waveform (contra vs. ipsi hemisphere relative to the location of the stimulus). The black character would be a consonant on most trials (e.g., 80%) and a vowel on the remaining trials (e.g., 20%; this would also be counterbalanced). The P3 is isolated with a rare-minus-frequent difference wave (irrespective of which side contained the black character). All of the trials are used for both the N2pc subtraction (contra minus ipsi, collapsed across rare and frequent) and the P3 subtraction (rare minus frequent, collapsed across contra and ipsi), dramatically increasing the amount of information that can be obtained in a given amount of recording time. It is possible to isolate 3 or even 4 different components simultaneously with this approach. For example, we have combined the P3 and N2pc manipulations with an upper vs. lower field manipulation that isolates the C1 wave (reflecting primarily activity in area V1).
ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_34" \o "Hackley, 2007 #10557" Hackley, Schankin, Wohlschlaeger, & Wascher, 2007; HYPERLINK \l "_ENREF_42" \o "Luck, 2009 #10547" Luck et al., 2009)
MANUSCRIPTS ON THE WEBSITE:
ADDIN EN.REFLIST Hackley, S. A., Schankin, A., Wohlschlaeger, A., & Wascher, E. (2007). Localization of temporal preparation effects via trisected reaction time. Psychophysiology, 44(2), 334-338.
Luck, S. J., Kappenman, E. S., Fuller, R. L., Robinson, B., Summerfelt, A., & Gold, J. M. (2009). Impaired response selection in schizophrenia: evidence from the P3 wave and the lateralized readiness potential. Psychophysiology, 46(4), 776-786.
Depends on which manipulations are usedDepends on which manipualtions are used. UnknownSome aspects have been studied in schizophrenia, such as impaired response selection and impaired P3 waves in a response selection task.
ADDIN EN.CITE Luck200910547(Luck et al., 2009)105471054717Luck, S. J.Kappenman, E. S.Fuller, R. L.Robinson, B.Summerfelt, A.Gold, J. M.University of California, Davis, California, USA. sjluck@ucdavis.eduImpaired response selection in schizophrenia: evidence from the P3 wave and the lateralized readiness potentialPsychophysiologyPsychophysiology776-864642009/04/24AdultContingent Negative Variation/*physiology*ElectroencephalographyFemaleFunctional Laterality/physiologyHumansMaleMiddle AgedPhotic StimulationPsychiatric Status Rating ScalesPsychomotor Performance/physiologyReaction Time/physiologySchizophrenia/*physiopathologySchizophrenic Psychology2009Jul1540-5958 (Electronic)
0048-5772 (Linking)19386044http://www.ncbi.nlm.nih.gov/pubmed/193860442706937PSYP817 [pii]
10.1111/j.1469-8986.2009.00817.xeng( HYPERLINK \l "_ENREF_42" \o "Luck, 2009 #10547" Luck et al., 2009)UnknownThere is evidence that this specific task elicits deficits in schizophrenia at the behavioral level. Unknown at the neural level.
We need to assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for the imaging and behavioral data.
We need to study whether or not performance on this task changes in response to psychological or pharmacological intervention.Sternberg Item Recognition Test
fMRIThe SIRP is a continuous performance, choice reaction time task that requires working memory. Subjects memorize a set of targets (e.g., digits). They are then presented with multiple probes (single digits) and respond by indicating whether the probe is a target (a member of the memorized set) or a foil (not a member of the memorized set). Correct responses are predicated on an accurate representation of the targets in WM for the duration of the block, despite interference from non-target probes. A linear relationship exists between set size (the number of targets) and reaction time (RT), the time needed to indicate whether a presented digit is a target or a foil (Sternberg 1966). When RTs are plotted against the number of targets (set size), the slope of the linear function provides a measure of working memory efficiency (the speed of mental scanning). The intercept provides a measure of the perceptual, motor and cognitive functions (e.g., binary decision) that do not depend on working memory and do not vary as a function of set size. This allows working memory and non-working memory components of RT to be dissociated. Additional advantages of the SIRP include that it is relatively free from practice effects (Kristofferson 1972), it constrains strategy and requires working memory. And groups with different performance levels can be matched for performance by comparing across different levels of working memory load.
ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_15" \o "Brown, 2010 #10568" Brown et al., 2010; HYPERLINK \l "_ENREF_48" \o "Manoach, 2003 #7180" Manoach, 2003; HYPERLINK \l "_ENREF_61" \o "Potkin, 2009 #10563" Potkin, Turner, Brown, et al., 2009)
MANUSCRIPTS ON THE WEBSITE:
ADDIN EN.REFLIST Brown, G. G., Mathalon, D. H., Stern, H., Ford, J., Mueller, B., Greve, D. N., et al. (2010). Multisite reliability of cognitive BOLD data. Neuroimage.
Manoach, D. S. (2003). Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophrenia Research, 60(2-3), 285-298.
Potkin, S. G., Turner, J. A., Brown, G. G., McCarthy, G., Greve, D. N., Glover, G. H., et al. (2009). Working memory and DLPFC inefficiency in schizophrenia: the FBIRN study. Schizophr Bull, 35(1), 19-31.
Specific manipulations of the items in the SIRP memory set across trials elicits interference control, as validated by relationships to other measures of interference control and activation of key brain regions thought to be involved in responding to conflict and managing conflict.
ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_35" \o "Jonides, 2000 #4421" Jonides et al., 2000; HYPERLINK \l "_ENREF_36" \o "Jonides, 2006 #8025" Jonides & Nee, 2006; HYPERLINK \l "_ENREF_65" \o "Thompson-Schill, 2002 #8027" Thompson-Schill et al., 2002)Indirect evidence from monkey neurophysiology that DLPFC is essential to WM maintenance. In healthy individuals DLPFC recruitment is associated with WM load. In schizophrenia, DLPFC recruitment is inversely related to error rate. There may be more direct evidence but I am not aware of it.UnknownWM is consistently impaired in schizophrenia as well as healthy first degree relatives. Patients with schizophrenia reliably show 'inefficient' recruitment of the DLPFC during the SIRP. Inefficiency has been associated with a putative risk gene for schizophrenia MTHFR 667C>T, the effects of which are mediated by COMT 158ValMet. Several other genes associated with forebrain development and the stress response also predict DLPFC activation during the SIRP ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_62" \o "Potkin, 2009 #10562" Potkin, Turner, Fallon, et al., 2009)There is a recent comprehensive paper on test-retest (across site reliability). Good reliability was achieved with the averaging of a large number of runs (e.g., 8), but lower reliability with fewer runs. The activation examined was not specific to interference trials ADDIN EN.CITE Brown201010568(Brown et al., 2010)105681056817Brown, G. G.Mathalon, D. H.Stern, H.Ford, J.Mueller, B.Greve, D. N.McCarthy, G.Voyvodic, J.Glover, G.Diaz, M.Yetter, E.Ozyurt, I. B.Jorgensen, K. W.Wible, C. G.Turner, J. A.Thompson, W. K.Potkin, S. G.VA San Diego Healthcare System and University of California San Diego, Department of Psychiatry, San Diego, CA 92161, USA.Multisite reliability of cognitive BOLD dataNeuroimageNeuroimage2010/10/122010Oct 121095-9572 (Electronic)
1053-8119 (Linking)20932915http://www.ncbi.nlm.nih.gov/pubmed/20932915S1053-8119(10)01278-4 [pii]
10.1016/j.neuroimage.2010.09.076Eng( HYPERLINK \l "_ENREF_15" \o "Brown, 2010 #10568" Brown et al., 2010).
The WM-related response properties are relatively free from practice effects (Kristofferson 1972). Analysis of the data from 7 healthy subjects who performed approximately 1645 trials of the SIRP at three levels of WM load during 30 consecutive daily sessions indicated that although the intercepts decreased with practice, the slopes did not change. Errors were maintained at a low level with a gradual decline over days. These findings suggest that the SIRP is readily adaptable to repeat studies of WM using fMRI and MEG. We conducted a test-retest reliability study of the SIRP in controls and patients with schizophrenia. While the magnitude of activation in key regions of the WM network were highly reliable in controls, patients showed poor reliability, which was interpreted to reflect greater variability of network recruitment due to a failure to hone the optimal pattern of neural activation for task performance.
ADDIN EN.CITE Manoach20015293(Manoach et al., 2001)5293529317Manoach, D. S.Halpern, E. F.Kramer, T. S.Chang, Y.Goff, D. C.Rauch, S. L.Kennedy, D. N.Gollub, R. L.Test-retest reliabilty of a functional MRI working memory paradigm in normal and schizophrenic subjectsAmerican Journal of PsychiatryAmerican Journal of Psychiatry955-95815862001( HYPERLINK \l "_ENREF_49" \o "Manoach, 2001 #5293" Manoach et al., 2001)There is evidence that this specific task elicits deficits in schizophrenia at the behavioral and neural levels.
There is some evidence on the psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for the imaging and behavioral data.
We need to study whether or not performance on this task changes in response to psychological or pharmacological intervention.Switching Stroop Task
fMRI or ERPSubjects respond verbally or by button press to the color of a word which is itself the name of a color. Stimuli may be congruent (word and color are the same), or incongruent (word and color differ). Subjects are slower and lees accurate when the word and color conflict on incongruent trials (the Stroop effect). Conflict adaptation is computed by comparing performance on incongruent trials following another incongruent trial (II faster and more accurate) vs. that of incongruent trials following a congruent trial (CI, slower and less accurate) as well as IC trials (slower, less accurate) compared to CC (faster, more accurate) trials. Post error adjustments also measured using this paradigm.
MANUSCRIPTS ON THE WEBSITE:
Alain, C., McNeely, H. E., He, Y., Christensen, B. K., & West, R. (2002). Neurophysiological evidence of error-monitoring deficits in patients with schizophrenia. Cereb Cortex, 12(8), 840-846.
Egner, T., Delano, M., & Hirsch, J. (2007). Separate conflict-specific cognitive control mechanisms in the human brain. Neuroimage, 35(2), 940-948.
West, R., & Travers, S. (2008). Tracking the temporal dynamics of updating cognitive control: an examination of error processing. Cereb Cortex, 18(5), 1112-1124.
Task widely used as measure of goal maintenance and response inhibition, more recently used to measure conflict adaptation. Strong links to neural systems, ACC activity greatest during CI trials and errors, predicts subsequent performance adjustments, DLPFC greatest on trials with large adjustments, predicted by previous trial ACC activity ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_28" \o "Egner, 2007 #8594" Egner, Delano, & Hirsch, 2007; HYPERLINK \l "_ENREF_29" \o "Egner, 2005 #8595" Egner & Hirsch, 2005; HYPERLINK \l "_ENREF_38" \o "Kerns, 2004 #7320" Kerns, Cohen, Stenger, & Carter, 2004).
By varying the nature of the cues that are presented and the demands to perform a single task over time or to switch between trials one can isolate neural activity related to a number of different constructs. For instance: 1) Using multiple cues mapped to each task in pure and mixed blocks one could distinguish between activity related to encoding the cue, retrieving the task rule from memory, and configuring the task set ( ADDIN EN.CITE West200810721(West & Travers, 2008)107211072117West, R.Travers, S.Department of Psychology, Iowa State University, Ames, IA 50011, USA. rwest@iastate.eduTracking the temporal dynamics of updating cognitive control: an examination of error processingCereb CortexCereb Cortex1112-241852007/08/25AdolescentAdultAffect/*physiologyCognition/*physiologyElectroencephalographyEvoked Potentials/*physiologyFemaleGyrus Cinguli/*physiologyHappinessHumansMalePrefrontal Cortex/*physiologyReaction Time/physiology2008May1460-2199 (Electronic)
1047-3211 (Linking)17716989http://www.ncbi.nlm.nih.gov/pubmed/17716989bhm142 [pii]
10.1093/cercor/bhm142eng( HYPERLINK \l "_ENREF_67" \o "West, 2008 #10721" West & Travers, 2008). 2) Comparing task cues (cue that indicate the task to perform) and transition cues (cues that indicate that a switch is required but do not indicate which task is required) one can distinguish activity related to "task switching" (alternations differ from repetitions and effects are similar for different types of cues) from activity related to "retrieving from the focus of attention" that is likely required with transition cues but not task cues (West et al., in press).
Has been used in schizophrenia to measure changes in conflict adaptation and neural correlates in schizophrenia as well as error related adjustments and neural correlates (fMRI and ERPs) ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_1" \o "Alain, 2002 #8593" Alain, McNeely, He, Christensen, & West, 2002; HYPERLINK \l "_ENREF_10" \o "Becker, 2008 #8596" Becker, Kerns, Macdonald, & Carter, 2008; HYPERLINK \l "_ENREF_37" \o "Kerns, 2005 #7109" Kerns et al., 2005; HYPERLINK \l "_ENREF_54" \o "McNeely, 2003 #8592" McNeely, West, Christensen, & Alain, 2003; HYPERLINK \l "_ENREF_57" \o "Nordahl, 2001 #8591" Nordahl et al., 2001).
Individuals with schizophrenia showed impaired behavioral performance on a switching version of the Stroop task. Also show impairments on both ERP and fMRI measures of brain systems associated with dynamic adjustments of control (fMRI and ERPs) ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_1" \o "Alain, 2002 #8593" Alain et al., 2002; HYPERLINK \l "_ENREF_10" \o "Becker, 2008 #8596" Becker et al., 2008; HYPERLINK \l "_ENREF_37" \o "Kerns, 2005 #7109" Kerns et al., 2005; HYPERLINK \l "_ENREF_54" \o "McNeely, 2003 #8592" McNeely et al., 2003; HYPERLINK \l "_ENREF_57" \o "Nordahl, 2001 #8591" Nordahl et al., 2001).
Little to nothing known about psychometric properties of conflict adaptation and post error adjustment measures using this task.
The Stroop effect is clearly sensitive to practice effects with the magnitude of the interference effect and number of errors decreasing over time. The primary behavioral dependent measure for the task switching version of the task has typically been response time so floor and ceiling effects are not as great of an issue. In some cases we have observed floor effects in older adults in terms of accuracy for switch incongruent trials and this could extend to patients. An additional issue that becomes relevant when using ERPs is that using a longer cue-to-stimulus interval to get good ERP data can sometime results in weaker behavioral effects than might be expected. This may be less of a concern if neural measures are of primary concern, however, it is a limitation of the task that we have encountered.
There is evidence that this specific task elicits deficits in schizophrenia at both the behavioral and neural level.
We need to assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for this task.
We need to study whether or not performance on this task changes in response to psychological or pharmacological intervention
Spatial Delayed Response Task
fMRI
PET
In this task, participants are cued to one or more spatial locations, and after some delay must indicate memory for that spatial location ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_25" \o "Driesen, 2008 #10631" Driesen et al., 2008; HYPERLINK \l "_ENREF_64" \o "Srimal, 2008 #10614" Srimal & Curtis, 2008).
MANUSCRIPTS ON THE WEBSITE:
ADDIN EN.REFLIST Driesen, N. R., Leung, H. C., Calhoun, V. D., Constable, R. T., Gueorguieva, R., Hoffman, R., et al. (2008). Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence. Biol Psychiatry, 64(12), 1026-1034.
Srimal, R., & Curtis, C. E. (2008). Persistent neural activity during the maintenance of spatial position in working memory. Neuroimage, 39(1), 455-468.
Unclear as a specific measure of attention control. Good evidence as a measure of maintenance of information in short term memory stores. Degree to which control of attention is assessed may depend on interference presented during the delay period.Numerous studies have shown activation of various frontal and parietal memory related regions in this task ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_23" \o "Curtis, 2003 #10623" Curtis & D'Esposito, 2003; HYPERLINK \l "_ENREF_24" \o "Curtis, 2004 #6814" Curtis, Rao, & D'Esposito, 2004; HYPERLINK \l "_ENREF_64" \o "Srimal, 2008 #10614" Srimal & Curtis, 2008).
Ketamine-disruption of spatial working memory combined with PET F18-[FGD]-imaging of hyper-frontality (Castner lab). This paradigm combines behavior with a PET imaging sessions conducted immediately after. In this design I am highlighting the manual-spatial delayed response task of spatial working memory is employed. Performance is impaired by pre-treatment with ketamine. Accordingly, In the same subjects ketamine treatment causes a correlative increase in structures Elevations in metabolism were significant in the anterior cingulate cortex and posterior parietal cortex and approached significance in the in caudal dorsolateral prefrontal cortex (dlPFC) and head of caudate nucleus (details of poster follow). This paradigm can be modified to different acute (amphetamine) and sub-chronic (PCP) approaches as well as paradigm selection (including touch screen tasks) to provide a more solid neurobiological understanding of drug-disruption and reversal of novel anti-psychotic and cognitive normalizing therapies for schizophrenia. In my company we have had similar success at replicating the imaging end-points but we have yet to combine the behavior and imaging together.
Since there is a direct correlation between poor and pharmacological reversed ketamine induce-changes in activation in frontal and fronto-quasi-straial/striatal structure and these are mapped by behavioral performance in task known to be substrates of the preceding behavior we can build a strong hypothesis around the overall paradigm. It could potentially guide dose selection but more importantly identify novel therapeutic approaches. If the approach can be combined with awake PET then the power of the approach will be greater (currently the animals need to be sedated for the imaging portion).Behavioral impairments in schizophrenia have been shown in numerous studies ADDIN EN.CITE Park19928064(Park & Holtzman, 1992)8064806417Park, S.Holtzman, P.S.Schizophrenics show spatial working memory deficitsArchives of General PsychiatryArch Gen PsychiatryArchives of General PsychiatryArch Gen Psychiatry975-982491992( HYPERLINK \l "_ENREF_59" \o "Park, 1992 #8064" Park & Holtzman, 1992). Imaging studies also show evidence of altered activation in dorsal frontal-parietal systems ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_25" \o "Driesen, 2008 #10631" Driesen et al., 2008).
UnknownThere is evidence that this specific task elicits deficits in schizophrenia at the behavioral and neural level.
We need to assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for the imaging and behavioral data.
We need to study whether or not performance on this task changes in response to psychological or pharmacological intervention.AX CPT
(letter and dot versions)
fMRIThe letter and dot versions of this task are adaptations of the expectancy AX task created by Cohen and colleagues (Servan-Schreiber et al., 1996), which is in turn a variant of the traditional AX-CPT ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_46" \o "MacDonald, 2005 #7106" A. W. MacDonald, 3rd et al., 2005). The DPX uses pairs of simple dot patterns rather than letter pairs as stimuli. The basic structure of both tasks are that there are four types of trials: AX, AY, BX and BY. AX trials are target trials; in these types of trials a valid cue is followed by a valid probe. The 3 other trial types are Non-target trials in which either a valid cue is followed by an invalid probe (AY type trials) or an invalid cue is followed by either a valid or invalid probe (BX or BY probes, respectively). Participants are required to make one response for target trials, and another response for non-target trials.
MANUSCRIPTS ON THE WEBSITE:
Edwards, B. G., Barch, D. M., & Braver, T. S. (2010). Improving prefrontal cortex function in schizophrenia through focused training of cognitive control. Front Hum Neurosci, 4, 32.
MacDonald, A. W., 3rd, Goghari, V. M., Hicks, B. M., Flory, J. D., Carter, C. S., & Manuck, S. B. (2005). A convergent-divergent approach to context processing, general intellectual functioning, and the genetic liability to schizophrenia. Neuropsychology, 19(6), 814-821.
The nature of the cue (valid or invalid) provides the context for responding on given trial. The majority of trials are target trials (AX trials). This feature is intended to encourage participants to expect a valid probe to follow a valid cue. A consequence of this manipulation is that participants develop a prepotency to respond with target responses on trials for which valid cues are presented, regardless of whether the trials were of the target (AX) or non-target (AY) type. Non-target cues provide the context that a non-target response will be required, regardless of the nature of the probe (valid or invalid). A consequence of the expectancy manipulation is that AY error rates will be higher. On BX trials participants with normal context processing must maintain the cue in order to inhibit the prepotency to respond to valid probes with a target response. Compared with controls, persons with impaired context processing would be expected to make fewer AY errors but more BX errors. One advantage of the DPX over the AX is that dot patterns used are more amenable to parametrical manipulations than are letters. By manipulating the similarity between valid probes (Xs) and invalid ones (Yes), the proportion of errors in the AY difficulty control condition can be manipulated. This, in turn, increased the likelihood of an interpretable BX versus AY interaction.
Original model demonstrating framework for context processing: ADDIN EN.CITE Cohen199266666617Cohen, J. D.Servan-Schreiber, D.Context, cortex and dopamine: A connectionist approach to behavior and biology in schizophreniaPsychological ReviewPsychological Review45-779911992( HYPERLINK \l "_ENREF_22" \o "Cohen, 1992 #66" Cohen & Servan-Schreiber, 1992)
Formal model of AX task linking performance to DA gating: ADDIN EN.CITE Braver199930653065306517Braver, T. S.Barch, D. M.Cohen, J. D.Cognition and control in schizophrenia: A computational model of dopamine and prefrontal functionBiological PsychiatryBiological Psychiatry312-328461999( HYPERLINK \l "_ENREF_12" \o "Braver, 1999 #3065" Braver, Barch, & Cohen, 1999)
Demonstration of convergence of context processing performance, and deficits in patients, across three tasks: ADDIN EN.CITE Cohen19994290(J. D. Cohen, D. M. Barch, C. Carter, & D. Servan-Schreiber, 1999)4290429017Cohen, J. D.Barch, D. M.Carter, C.Servan-Schreiber, D.Context-processing deficits in schizophrenia: Converging evidence from three theoretically motivated cognitive tasksJournal of Abnormal PsychologyJournal of Abnormal Psychology120-1331081999( HYPERLINK \l "_ENREF_20" \o "Cohen, 1999 #4290" J. D. Cohen, D. M. Barch, C. Carter, & D. Servan-Schreiber, 1999)
Greater B-related activity following the cue in dorsolateral prefrontal cortex and other components of the executive control network, including frontopolar cortex and inferior parietal cortex ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_14" \o "Braver, 2009 #9092" Braver, Paxton, Locke, & Barch, 2009; HYPERLINK \l "_ENREF_44" \o "MacDonald, 2006 #7414" A. W. MacDonald, 3rd, Becker, & Carter, 2006; HYPERLINK \l "_ENREF_45" \o "MacDonald, 2003 #6684" A. W. MacDonald, 3rd & Carter, 2003).Performance and brain activity on the AX version improves in individuals with schizophrenia response to cognitive training ADDIN EN.CITE Edwards201010722(Edwards, Barch, & Braver, 2010)107221072217Edwards, B. G.Barch, D. M.Braver, T. S.Departments of Psychology, Washington University St. Louis, MO, USA.Improving prefrontal cortex function in schizophrenia through focused training of cognitive controlFront Hum NeurosciFront Hum Neurosci3242010/05/1320101662-5161 (Electronic)
1662-5161 (Linking)20461148http://www.ncbi.nlm.nih.gov/pubmed/20461148286656610.3389/fnhum.2010.00032eng( HYPERLINK \l "_ENREF_27" \o "Edwards, 2010 #10722" Edwards, Barch, & Braver, 2010).
Performance on the AX-CPT improves in response to amphetamine administration in both individuals with schizophrenia ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_5" \o "Barch, 2005 #7022" Barch & Carter, 2005) and healthy controls ADDIN EN.CITE Barch20077418741874185Barch, D. M.Braver, T. S.Engle, R. W.Sedek, G.von Hecker, U.McIntosh, A. M.Cognitive control in schizophrenia: Psychological and neural mechanismsCognitive limitations in aging and psychopathology2007( HYPERLINK \l "_ENREF_4" \o "Barch, 2007 #7418" Barch & Braver, 2007).
Some evidence of improvement in response to gabergic modulation ADDIN EN.CITE Lewis20088988(Lewis et al., 2008)8988898817Lewis, D. A.Cho, R. Y.Carter, C. S.Eklund, K.Forster, S.Kelly, M. A.Montrose, D.Department of Psychiatry, W1651 Biomedical Science Tower, 3511 O'Hara St., Pittsburgh, PA 15213, USA. lewisda@upmc.eduSubunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophreniaAm J PsychiatryAm J Psychiatry1585-9316512AdolescentAdultAntipsychotic Agents/therapeutic useBrief Psychiatric Rating ScaleCognition Disorders/diagnosis/*epidemiologyDiagnostic and Statistical Manual of Mental DisordersDouble-Blind MethodElectrocardiographyHumansMaleMiddle AgedNeuropsychological TestsReceptors, GABA-A/*metabolismSchizophrenia/drug therapy/*epidemiology/*metabolismSeverity of Illness IndexSynaptic Transmission/*physiology2008Dec18923067http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18923067( HYPERLINK \l "_ENREF_41" \o "Lewis, 2008 #8988" Lewis et al., 2008).Evidence of trait-like impairment in schizophrenia patients: ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_46" \o "MacDonald, 2005 #7106" A. W. MacDonald, 3rd et al., 2005)
Evidence of specificity of impairment and relation to PFC dysfunction: ADDIN EN.CITE Barch200361306130613017Barch, D. M.Sheline, Y. I.Csernansky, J. G.Snyder, A. Z.Working memory and prefrontal cortex dysfunction: Specificity to schizophrenia as compared to major depressionBiological PsychiatryBiological Psychiatry376-384532003( HYPERLINK \l "_ENREF_8" \o "Barch, 2003 #6130" Barch, Sheline, Csernansky, & Snyder, 2003)
Link to PFC impairment in unmedicated patients, specificity of impairments to schizophrenia, and further demonstrating link to disorganization symptoms of schizophrenia: ADDIN EN.CITE MacDonald200564786478647817MacDonald, A.Carter, C. S.Kerns, J. G.Ursu, S.Barch, D. M.Holmes, A. J.Stenger, V. A.Cohen, J. DSpecificity of prefrontal dysfunction and context processing deficts to schizophrenia in a never medicated first-episode psychotic sampleAmerican Journal of PsychiatryAmerican Journal of Psychiatry475-4841622005( HYPERLINK \l "_ENREF_43" \o "MacDonald, 2005 #6478" A. MacDonald et al., 2005)
ADDIN EN.CITE Cohen199266666617Cohen, J. D.Servan-Schreiber, D.Context, cortex and dopamine: A connectionist approach to behavior and biology in schizophreniaPsychological ReviewPsychological Review45-779911992( HYPERLINK \l "_ENREF_22" \o "Cohen, 1992 #66" Cohen & Servan-Schreiber, 1992)
ADDIN EN.CITE Braver199930653065306517Braver, T. S.Barch, D. M.Cohen, J. D.Cognition and control in schizophrenia: A computational model of dopamine and prefrontal functionBiological PsychiatryBiological Psychiatry312-328461999( HYPERLINK \l "_ENREF_12" \o "Braver, 1999 #3065" Braver et al., 1999)
ADDIN EN.CITE Cohen19994290(J. D. Cohen et al., 1999)4290429017Cohen, J. D.Barch, D. M.Carter, C.Servan-Schreiber, D.Context-processing deficits in schizophrenia: Converging evidence from three theoretically motivated cognitive tasksJournal of Abnormal PsychologyJournal of Abnormal Psychology120-1331081999( HYPERLINK \l "_ENREF_20" \o "Cohen, 1999 #4290" J. D. Cohen et al., 1999)
ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_46" \o "MacDonald, 2005 #7106" A. W. MacDonald, 3rd et al., 2005)
ADDIN EN.CITE Barch20036131(Barch, Carter, & Cohen, 2003)6131613117Barch, D. M.Carter, C. S.Cohen, J. D.Context processing deficit in schizophrenia: Diagnostic specificity, 4-week course, and relationships to clinical symptomsJournal of Abnormal PsychologyJournal of Abnormal Psychology132-143112132-1432003( HYPERLINK \l "_ENREF_6" \o "Barch, 2003 #6131" Barch, Carter, & Cohen, 2003)
ADDIN EN.CITE Barch20036130(Barch, Sheline, et al., 2003)6130613017Barch, D. M.Sheline, Y. I.Csernansky, J. G.Snyder, A. Z.Working memory and prefrontal cortex dysfunction: Specificity to schizophrenia as compared to major depressionBiological PsychiatryBiological Psychiatry376-384532003( HYPERLINK \l "_ENREF_8" \o "Barch, 2003 #6130" Barch, Sheline, et al., 2003)
ADDIN EN.CITE MacDonald200564786478647817MacDonald, A.Carter, C. S.Kerns, J. G.Ursu, S.Barch, D. M.Holmes, A. J.Stenger, V. A.Cohen, J. DSpecificity of prefrontal dysfunction and context processing deficts to schizophrenia in a never medicated first-episode psychotic sampleAmerican Journal of PsychiatryAmerican Journal of Psychiatry475-4841622005( HYPERLINK \l "_ENREF_43" \o "MacDonald, 2005 #6478" A. MacDonald et al., 2005)
ADDIN EN.CITE MacDonald20036121(A. W. MacDonald, Pogue-Geile, Johnson, & Carter, 2003)6121612117MacDonald, A. W.Pogue-Geile, M. F.Johnson, M. K.Carter, C. S.A specific deficit in context processing in the unaffected siblings of patients with schizophreniaArchives of General PsychiatryArchives of General Psychiatry57-65602003( HYPERLINK \l "_ENREF_47" \o "MacDonald, 2003 #6121" A. W. MacDonald, Pogue-Geile, Johnson, & Carter, 2003)
BX errors had an alpha of .88 ADDIN EN.CITE Cohen199980908090809017Cohen, J.D.Barch, D.M.Carter, C.S.Servan-Schreiber, D.Context-processing deficits in schizophrenia: Converging evidence from three theoretically motivated cognitive tasksJournal of Abnormal PsychologyJournal of Abnormal Psychology120-133108119991999( HYPERLINK \l "_ENREF_21" \o "Cohen, 1999 #8090" J. D. Cohen, D. M. Barch, C. S. Carter, & D. Servan-Schreiber, 1999).
Currently under investigation for both behavioral and imaging versions.There is evidence that this specific task elicits deficits in schizophrenia at the both the behavioral and neural level.
We need to further assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for this task.
There is evidence that performance on this task changes in response to psychological or pharmacological intervention.P300 Oddball Task
ERPIn the typical paradigm, subjects hear a sequence of low and high pitched tones, with one of these occurring frequently (e.g., 90%) and the other occurring infrequently (e.g., 10%). Subjects either press a button when they detect the infrequent pitch or count occurrences of the infrequent pitch. The amplitude and latency of the P300 peak can be measured from the waveform elicited by the infrequent pitch or from the infrequent-minus-frequent difference wave.
ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_26" \o "Duncan-Johnson, 1977 #4301" Duncan-Johnson & Donchin, 1977; HYPERLINK \l "_ENREF_33" \o "Gonsalvez, 2007 #10943" Gonsalvez, Barry, Rushby, & Polich, 2007; HYPERLINK \l "_ENREF_60" \o "Polich, in press #10942" Polich, in press)
MANUSCRIPTS ON THE WEBSITE:
Gonsalvez, C. J., Barry, R. J., Rushby, J. A., & Polich, J. (2007). Target-to-target interval, intensity, and P300 from an auditory single-stimulus task. Psychophysiology, 44(2), 245-250.
Mathalon, D. H., Ford, J. M., Rosenbloom, M., & Pfefferbaum, A. (2000). P300 reduction and prolongation with illness duration in schizophrenia. Biol Psychiatry, 47(5), 413-427.
--P300 (P3b) generation depends on an intact temporal-parietal junction, and it also appears to involve the operation of the locus coeruleus norepinephrine system ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_39" \o "Knight, 1989 #10949" Knight, Scabini, Woods, & Clayworth, 1989; HYPERLINK \l "_ENREF_56" \o "Nieuwenhuis, 2005 #10944" Nieuwenhuis, Aston-Jones, & Cohen, 2005).P300 is exquisitely sensitive to factors related to attention and working memory, and substantial evidence links it to the LC-NE transmitter system. However, relatively little evidence directly demonstrates that individual differences in P300 can be used to assess these cognitive and neural systems (reverse inference).Hundreds of studies have shown reduced P300 amplitude in schizophrenia, but the link between these effects and specific neural/cognitive systems has not been firmly established ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_30" \o "Ford, 2001 #10951" Ford, Mathalon, Kalba, Marsh, & Pfefferbaum, 2001; HYPERLINK \l "_ENREF_31" \o "Ford, 1999 #10955" Ford et al., 1999; HYPERLINK \l "_ENREF_32" \o "Ford, 2000 #10952" Ford, Mathalon, White, & Pfefferbaum, 2000; HYPERLINK \l "_ENREF_50" \o "Mathalon, 2000 #10953" Mathalon, Ford, & Pfefferbaum, 2000; HYPERLINK \l "_ENREF_51" \o "Mathalon, 2000 #10954" Mathalon, Ford, Rosenbloom, & Pfefferbaum, 2000).P300 shows excellent test-retest reliability (> .8 in some studies) ADDIN EN.CITE Sinha199210957(Sinha, Bernardy, & Parsons, 1992)109571095717Sinha, R.Bernardy, N.Parsons, O. A.Department of Psychiatry and Behavioral Science, University of Oklahoma Sciences Center, Oklahoma City.Long-term test-retest reliability of event-related potentials in normals and alcoholicsBiol PsychiatryBiol Psychiatry992-100332111992/12/01AdultAlcoholism/*physiopathology/psychology/rehabilitationAttention/physiologyCerebral Cortex/physiopathologyElectroencephalography/*instrumentation/statistics & numerical dataEvoked Potentials, Auditory/*physiologyEvoked Potentials, Visual/*physiologyFemaleFollow-Up StudiesHumansMaleMiddle AgedPattern Recognition, Visual/physiologyPitch Discrimination/physiologyReproducibility of ResultsSignal Processing, Computer-Assisted/*instrumentation1992Dec 10006-3223 (Print)
0006-3223 (Linking)1467390http://www.ncbi.nlm.nih.gov/pubmed/1467390eng( HYPERLINK \l "_ENREF_63" \o "Sinha, 1992 #10957" Sinha, Bernardy, & Parsons, 1992).There is evidence that this specific task elicits deficits in schizophrenia at the both the behavioral and neural level.
We need to further assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for this task.
There is evidence that performance on this task changes in response to psychological or pharmacological intervention.NBack
fMRIParticipants are presented with a series of stimuli and asked to either: respond on the current trial with the stimulus presented N back (e.g., 1 back, 2 back, etc), which is the NIH version; or respond target if the current item is either a prespecified target (e.g., X; 0-back), the same as the immediately preceding item (1-back), same as the item 2-back, etc.
MANUSCRIPTS ON THE WEBSITE:
Brahmbhatt, S. B., Haut, K., Csernansky, J. G., & Barch, D. M. (2006). Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings. Schizophrenia Research, 87(1-3), 191-204.
Mattay, V. S., Goldberg, T. E., Fera, F., Hariri, A. R., Tessitore, A., Egan, M. F., et al. (2003). Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proceedings of the National Academy of Sciences, 100(10), 6186-6191.
Examination of lure trials, which are repeated in the wrong nback condition allows some insight into goal maintenance specifically ADDIN EN.CITE Brahmbhatt20067430(Brahmbhatt, Haut, Csernansky, & Barch, 2006)7430743017Brahmbhatt, S. B.Haut, K.Csernansky, J. G.Barch, D. M.Washington University, Department of Psychology, One Brookings Drive, Box 1125, St. Louis, MO 63130, USA. sbbrahmb@wustl.eduNeural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblingsSchizophrenia ResearchSchizophrenia Research191-204871-3AdultCerebellum/physiopathologyDiagnostic and Statistical Manual of Mental DisordersFemaleFunctional Laterality/physiologyHumansMagnetic Resonance ImagingMaleMemory Disorders/diagnosis/*epidemiology*Nonverbal CommunicationPrefrontal Cortex/physiopathologyRisk Factors*Schizophrenia/diagnosis/epidemiology/physiopathologySeverity of Illness Index*Siblings*Verbal Behavior2006Oct16842976http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16842976( HYPERLINK \l "_ENREF_11" \o "Brahmbhatt, 2006 #7430" Brahmbhatt, Haut, Csernansky, & Barch, 2006).Numerous studies have shown activation of dorsal frontal parietal system and subcortical regions ADDIN EN.CITE Braver19971524(Braver et al., 1997)1524152417Braver, T. S.Cohen, J. D.Nystrom, L. E.Jonides, J.Smith, E. E.Noll, D. C.A parametric study of prefrontal cortex involvement in human working memoryNeuroimageNeuroimage49-6251fMRI, PFC, WM, nback1997( HYPERLINK \l "_ENREF_13" \o "Braver, 1997 #1524" Braver et al., 1997).There are several studies showing change as a function of both pharmacological challenge and cognitive remediation ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_2" \o "Apud, 2007 #10970" Apud et al., 2007; HYPERLINK \l "_ENREF_52" \o "Mattay, 2000 #6515" Mattay et al., 2000; HYPERLINK \l "_ENREF_53" \o "Mattay, 2002 #6549" Mattay et al., 2002; HYPERLINK \l "_ENREF_69" \o "Wykes, 2002 #6825" Wykes et al., 2002)Many studies have shown both behavioral and functional activation deficits in schizophrenia ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_7" \o "Barch, 2002 #5579" Barch, Csernansky, Conturo, Snyder, & Ollinger, 2002; HYPERLINK \l "_ENREF_11" \o "Brahmbhatt, 2006 #7430" Brahmbhatt et al., 2006; HYPERLINK \l "_ENREF_16" \o "Callicott, 2000 #5286" Callicott et al., 2000; HYPERLINK \l "_ENREF_17" \o "Callicott, 2003 #6487" Callicott, Egan, et al., 2003; HYPERLINK \l "_ENREF_18" \o "Callicott, 1999 #3432" Callicott et al., 1999; HYPERLINK \l "_ENREF_19" \o "Callicott, 2003 #6652" Callicott, Mattay, et al., 2003).Little is known about test-retest reliability or other psychometric characteristicsThere is evidence that this specific task elicits deficits in schizophrenia at the both the behavioral and neural level.
We need to further assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for this task.
There is evidence that performance on this task changes in response to psychological or pharmacological intervention.Tower of London Planning
fMRIDescription taken from ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_68" \o "Williams-Gray, 2007 #10989" Williams-Gray, Hampshire, Robbins, Owen, & Barker, 2007)
The TOL requires subjects to rearrange three colored balls, which are distributed between three pockets displayed in the lower half of a computer screen to match a template array displayed in the upper half of the screen (Owen et al., 1990). In this one-touch version of the test, subjects were asked to indicate the correct number of moves required to complete the problem by selecting from one of four numbers (14) presented at the bottom of the screen [adapted from Owen et al. (1995) and Baker et al. (1996)]
MANUSCRIPTS ON THE WEBSITE:
Barnett, J. H., Robbins, T. W., Leeson, V. C., Sahakian, B. J., Joyce, E. M., & Blackwell, A. D. (2010). Assessing cognitive function in clinical trials of schizophrenia. Neurosci Biobehav Rev, 34(8), 1161-1177.
Newman, S. D., Greco, J. A., & Lee, D. (2009). An fMRI study of the Tower of London: a look at problem structure differences. Brain Res, 1286, 123-132.
The task requires maintaining the goal of moving the balls while performing other computation necessary to achieve the goalThere is evidence that this task engages frontal striatal circuitry relevant for goal maintenance ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_3" \o "Baker, 1996 #11009" Baker et al., 1996; HYPERLINK \l "_ENREF_55" \o "Newman, 2009 #11027" Newman, Greco, & Lee, 2009).Lopa withdrawal impairs TOL performance in parkinsons patients ADDIN EN.CITE Lange199211016(Lange et al., 1992)110161101617Lange, K. W.Robbins, T. W.Marsden, C. D.James, M.Owen, A. M.Paul, G. M.Department of Clinical Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunctionPsychopharmacology (Berl)Psychopharmacology (Berl)394-4041072-31992/01/01Brain Diseases/*physiopathologyCognition Disorders/*chemically induced/psychologyDiscrimination (Psychology)/drug effectsFemaleFrontal Lobe/*physiopathologyHumansLearning/drug effectsLevodopa/*adverse effects/therapeutic useMaleMemory/drug effectsMiddle AgedParkinson Disease/*complications/drug therapyPsychomotor Performance/drug effectsSubstance Withdrawal Syndrome/*physiopathology19920033-3158 (Print)
0033-3158 (Linking)1615139http://www.ncbi.nlm.nih.gov/pubmed/1615139eng( HYPERLINK \l "_ENREF_40" \o "Lange, 1992 #11016" Lange et al., 1992). Modafinal improves TOL performance ADDIN EN.CITE Turner200311025(Turner et al., 2003)110251102517Turner, D. C.Robbins, T. W.Clark, L.Aron, A. R.Dowson, J.Sahakian, B. J.Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.Cognitive enhancing effects of modafinil in healthy volunteersPsychopharmacology (Berl)Psychopharmacology (Berl)260-916532002/11/06AdultBenzhydryl Compounds/*pharmacologyBlood Pressure/drug effectsCognition/*drug effectsDecision Making/drug effectsDose-Response Relationship, DrugDouble-Blind MethodHeart Rate/drug effectsHumansMaleMemory/drug effectsNeuroprotective Agents/*pharmacologyPain MeasurementPattern Recognition, Visual/drug effectsPsychological Tests2003Jan0033-3158 (Print)
0033-3158 (Linking)12417966http://www.ncbi.nlm.nih.gov/pubmed/1241796610.1007/s00213-002-1250-8eng( HYPERLINK \l "_ENREF_66" \o "Turner, 2003 #11025" Turner et al., 2003).There is evidence that individuals with schizophrenia show deficits on this task ADDIN EN.CITE ADDIN EN.CITE.DATA ( HYPERLINK \l "_ENREF_58" \o "Pantelis, 1997 #10998" Pantelis et al., 1997)Evidence regarding psychometrics is reviewed in ADDIN EN.CITE Barnett201011010(Barnett et al., 2010)110101101017Barnett, J. H.Robbins, T. W.Leeson, V. C.Sahakian, B. J.Joyce, E. M.Blackwell, A. D.Department of Psychiatry, University of Cambridge, Cambridge, UK. jhb32@cam.ac.ukAssessing cognitive function in clinical trials of schizophreniaNeurosci Biobehav RevNeurosci Biobehav Rev1161-773482010/01/292010Jul1873-7528 (Electronic)
0149-7634 (Linking)20105440http://www.ncbi.nlm.nih.gov/pubmed/20105440S0149-7634(10)00013-8 [pii]
10.1016/j.neubiorev.2010.01.012eng( HYPERLINK \l "_ENREF_9" \o "Barnett, 2010 #11010" Barnett et al., 2010)There is evidence that this specific task elicits deficits in schizophrenia at the both the behavioral and neural level.
We have some information, but we need to further assess psychometric characteristics such as test-retest reliability, practice effects, and ceiling/floor effects for this task.
There is evidence that performance on this task changes in response to psychological or pharmacological intervention.
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Gonsalvez, C. J., Barry, R. J., Rushby, J. A., & Polich, J. (2007). Target-to-target interval, intensity, and P300 from an auditory single-stimulus task. Psychophysiology, 44(2), 245-250.
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MacDonald, A., Carter, C. S., Kerns, J. G., Ursu, S., Barch, D. M., Holmes, A. J., et al. (2005). Specificity of prefrontal dysfunction and context processing deficts to schizophrenia in a never medicated first-episode psychotic sample. American Journal of Psychiatry, 162, 475-484.
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MacDonald, A. W., Pogue-Geile, M. F., Johnson, M. K., & Carter, C. S. (2003). A specific deficit in context processing in the unaffected siblings of patients with schizophrenia. Archives of General Psychiatry, 60, 57-65.
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