FD was supported by a Young Investigator Award from the National Alliance for Research on Schizophrenia and Depression and a CPRF Award from the Canadian Psychiatric Research Foundation.

1. Experimental Design, Methodological Issues, &amp; Stimuli
The SMP consist of two tasks, an encoding task and a retrieval task, and recording of brain activity may occur during the encoding task or during 
both encoding and retrieval tasks (see Figure 1 for a diagram illustrating the design of the SMP).
<img src="/files/ftp_upload/2433/2433fig1.jpg" alt="Figure 1" /> 
Figure 1. General Diagram of the SMP design. Brain regions whose activity dur...

<ol>
	<li>Bradley, M. M., Greenwald, M. K., Petry, M. C., Lang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remembering+pictures:+pleasure+and+arousal+in+memory.">Remembering pictures: pleasure and arousal in memory.</a> J Exp Psychol Learn Mem Cogn. 18, 379-390 (1992).</li><li>Christianson, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emotional+stress+and+eyewitness+memory:+a+critical+review.">Emotional stress and eyewitness memory: a critical review.</a> Psychol Bull. 112, 284-309 (1992).</li><li>Paller, K. A., Wagner, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Observing+the+transformation+of+experience+into+memory.">Observing the transformation of experience into memory.</a> Trends Cogn Sci. 6, 93-102 (2002).</li><li>Dolcos, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Impact of Emotion on Memory: Evidence from Brain Imaging Studies. , (2009).</li><li>Dolcos, F., Denkova, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+encoding+emotional+memories:+a+review+of+functional+neuroimaging+evidence.">Neural correlates of encoding emotional memories: a review of functional neuroimaging evidence.</a> Cell Science Reviews. 5, 78-122 (2008).</li><li>Dolcos, F., LaBar, K. S., Cabeza, R., Uttl, B., Ohta, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+memory-enhancing+effect+of+emotion:+Functional+neuroimaging+evidence.">The memory-enhancing effect of emotion: Functional neuroimaging evidence.</a> Memory and Emotion: Interdisciplinary Perspectives. , 107-134 (2006).</li><li>LaBar, K. S., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+neuroscience+of+emotional+memory.">Cognitive neuroscience of emotional memory.</a> Nat Rev Neurosci. 7, 54-64 (2006).</li><li>Dolcos, F., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Event-related+potentials+of+emotional+memory:+encoding+pleasant,+unpleasant,+and+neutral+pictures.">Event-related potentials of emotional memory: encoding pleasant, unpleasant, and neutral pictures.</a> Cogn Affect Behav Neurosci. 2, 252-263 (2002).</li><li>Dolcos, F., Graham, R., LaBar, K. S., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coactiviation+of+the+amygdala+and+hippocampus+predicts+better+recall+for+emotional+than+for+neutral+pictures.">Coactiviation of the amygdala and hippocampus predicts better recall for emotional than for neutral pictures.</a> Brain &#38; Cognition. 51, 221-223 (2003).</li><li>Dolcos, F., LaBar, K. S., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dissociable+effects+of+arousal+and+valence+on+prefrontal+activity+indexing+emotional+evaluation+and+subsequent+memory:+an+event-related+fMRI+study.">Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related fMRI study.</a> Neuroimage. 23, 64-74 (2004).</li><li>Dolcos, F., LaBar, K. S., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interaction+between+the+amygdala+and+the+medial+temporal+lobe+memory+system+predicts+better+memory+for+emotional+events.">Interaction between the amygdala and the medial temporal lobe memory system predicts better memory for emotional events.</a> Neuron. 42, 855-863 (2004).</li><li>Dolcos, F., LaBar, K. S., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remembering+one+year+later:+role+of+the+amygdala+and+the+medial+temporal+lobe+memory+system+in+retrieving+emotional+memories.">Remembering one year later: role of the amygdala and the medial temporal lobe memory system in retrieving emotional memories.</a> Proc Natl Acad Sci U S A. 102, 2626-2631 (2005).</li><li>Ritchey, M., Dolcos, F., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+amygdala+connectivity+in+the+persistence+of+emotional+memories+over+time:+an+event-related+FMRI+investigation.">Role of amygdala connectivity in the persistence of emotional memories over time: an event-related FMRI investigation.</a> Cereb Cortex. 18, 2494-2504 (2008).</li><li>Jacques, S. t., Dolcos, P. L., Cabeza, F., R, . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+aging+on+functional+connectivity+of+the+amygdala+for+subsequent+memory+of+negative+pictures:+a+network+analysis+of+functional+magnetic+resonance+imaging+data.">Effects of aging on functional connectivity of the amygdala for subsequent memory of negative pictures: a network analysis of functional magnetic resonance imaging data.</a> Psychol Sci. 20, 74-84 (2009).</li><li>Jacques, S. t., Dolcos, P., Cabeza, F., R, . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+aging+on+functional+connectivity+of+the+amygdala+during+negative+evaluation:+a+network+analysis+of+fMRI+data.">Effects of aging on functional connectivity of the amygdala during negative evaluation: a network analysis of fMRI data.</a> Neurobiol Aging. 31, 315-327 (2010).</li><li>Hayes, J. P., LaBar, K. S., McCarthy, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduced+hippocampal+and+amygdala+activity+predicts+memory+distrotions+for+trauma+reminders+in+combat-related+PTSD.">Reduced hippocampal and amygdala activity predicts memory distrotions for trauma reminders in combat-related PTSD.</a> J Psychiatr Res. , (2011).</li><li>Ritchey, M., Dolcos, F., Eddington, K. M., Strauman, T. J., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+correlates+of+emotional+processing+in+depression:+Changes+with+cognitive+behavioral+therapy+and+predictors+of+treatment+response.">Neural correlates of emotional processing in depression: Changes with cognitive behavioral therapy and predictors of treatment response.</a> Journal of Psychiatric Research. , (2010).</li><li>Kleinsmith, L. J., Kaplan, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Paired-associate+learning+as+a+function+of+arousal+and+interpolated+interval.">Paired-associate learning as a function of arousal and interpolated interval.</a> J Exp Psychol. 65, 190-193 (1963).</li><li>Kensinger, E. A., Schacter, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amygdala+activity+is+associated+with+the+successful+encoding+of+item,+but+not+source,+information+for+positive+and+negative+stimuli.">Amygdala activity is associated with the successful encoding of item, but not source, information for positive and negative stimuli.</a> J Neurosci. 26, 2564-2570 (2006).</li><li>Kensinger, E. A., Corkin, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Two+routes+to+emotional+memory:+distinct+neural+processes+for+valence+and+arousal.">Two routes to emotional memory: distinct neural processes for valence and arousal.</a> Proc Natl Acad Sci U S A. 101, 3310-3315 (2004).</li><li>Kensinger, E. A., Garoff-Eaton, R. J., Schacter, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Memory+for+specific+visual+details+can+be+enhanced+by+negative+arousing+content.">Memory for specific visual details can be enhanced by negative arousing content.</a> Journal of Memory and Language. 54, 99-112 (2006).</li><li>Bradley, M. M., Cuthbert, B. N., Lang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Picture+media+and+emotion:+effects+of+a+sustained+affective+context.">Picture media and emotion: effects of a sustained affective context.</a> Psychophysiology. 33, 662-670 (1996).</li><li>Lang, P. J., Bradley, M. M., Cuthbert, B. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technical+Report+A-8.">Technical Report A-8.</a> International affective picture system (IAPS): Affective ratings of pictures and instruction manual. , (2008).</li><li>Lang, P. J., Bradley, M. M., Cuthbert, B. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Technical+report+C-1.">Technical report C-1.</a> Affective norms for English workds (ANEW): Stimuli, instruction manual and affective ratings. , (2008).</li><li>Bradley, M. M., Lang, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measuring+emotion:+the+Self-Assessment+Manikin+and+the+Semantic+Differential.">Measuring emotion: the Self-Assessment Manikin and the Semantic Differential.</a> J Behav Ther Exp Psychiatry. 25, 49-59 (1994).</li><li>Kensinger, E. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remembering+emotional+experiences:+the+contribution+of+valence+and+arousal.">Remembering emotional experiences: the contribution of valence and arousal.</a> Rev Neurosci. 15, 241-251 (2004).</li><li>Hamann, S. B., Ely, T. D., Grafton, S. T., Kilts, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amygdala+activity+related+to+enhanced+memory+for+pleasant+and+aversive+stimuli.">Amygdala activity related to enhanced memory for pleasant and aversive stimuli.</a> Nat Neurosci. 2, 289-293 (1999).</li><li>Watson, D., Clark, L. A., Tellegen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+validation+of+brief+measures+of+positive+and+negative+affect:+the+PANAS+scales.">Development and validation of brief measures of positive and negative affect: the PANAS scales.</a> J Pers Soc Psychol. 54, 1063-1070 (1988).</li><li>Spielberger, C. D., Gorsuch, R. L., Lushene, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Manual for the State-Trait Anxiety Inventory. , (1970).</li><li>Voyvodic, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-Time+fMRI+Paradigm+Control,+Physiology,+and+Behavior+Combined+with+Near+Real-Time+Statistical+Analysis.">Real-Time fMRI Paradigm Control, Physiology, and Behavior Combined with Near Real-Time Statistical Analysis.</a> NeuroImage. 10, 91-106 (1999).</li><li>Tulving, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Memory+and+consciousness.">Memory and consciousness.</a> Canadian Psychology. 26, 1-12 (1985).</li><li>Eldridge, L. L., Knowlton, B. J., Furmanski, C. S., Bookheimer, S. Y., Engel, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Remembering+episodes:+a+selective+role+for+the+hippocampus+during+retrieval.">Remembering episodes: a selective role for the hippocampus during retrieval.</a> Nat Neurosci. 3, 1149-1152 (2000).</li><li>Kirwan, C. B., Jones, C. K., Miller, M. I., Stark, C. E. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-resolution+fMRI+investigation+of+the+medial+temporal+lobe.">High-resolution fMRI investigation of the medial temporal lobe.</a> Human Brain Mapping. 28, 959-966 (2007).</li><li>Preston, A. R., Bornstein, A. M., Hutchinson, J. B., Gaare, M. E., Glover, G. H., Wagner, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-resolution+fMRI+of+Content-sensitive+Subsequent+Memory+Responses+in+Human+Medial+Temporal+Lobe.">High-resolution fMRI of Content-sensitive Subsequent Memory Responses in Human Medial Temporal Lobe.</a> Journal of Cognitive Neuroscience. 22, 156-173 (2010).</li><li>Robinson, S., Pripfl, J., Bauer, H., Moser, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+EPI+voxel+size+on+SNR+and+BOLD+sensitivity+in+the+anterior+medio-temporal+lobe:+a+comparative+group+study+of+deactivation+of+the+Default+Mode.">The impact of EPI voxel size on SNR and BOLD sensitivity in the anterior medio-temporal lobe: a comparative group study of deactivation of the Default Mode.</a> Magnetic Resonance Materials in Physics, Biology and Medicine. 21, 279-290 (2008).</li><li>Daselaar, S. M., Fleck, M. S., Cabeza, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Triple+Dissociation+in+the+Medial+Temporal+Lobes:+Recollection,+Familiarity,+and+Novelty.">Triple Dissociation in the Medial Temporal Lobes: Recollection, Familiarity, and Novelty.</a> Journal of Neurophysiology. 96, 1902-1911 (2006).</li><li>McGaugh, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Memory--a+century+of+consolidation.">Memory--a century of consolidation.</a> Science. 287, 248-251 (2000).</li><li>McGaugh, J. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+amygdala+modulates+the+consolidation+of+memories+of+emotionally+arousing+experiences.">The amygdala modulates the consolidation of memories of emotionally arousing experiences.</a> Annu Rev Neurosci. 27, 1-28 (2004).</li></ol>

This experimental protocol allows investigation of the neural correlates of the memory-enhancing effect of emotion, by specifically separating 
the memory-related brain activity that is susceptible to modulation by emotion from activity in brain regions susceptible to emotion modulation during 
general/perceptual processing. This design has been instrumental in advancing our understanding of the neural mechanisms underlying the impact of emotion on 
memory, and given its versatility it is expected that SMP will remain cr...

brain imaging investigation of the memory-enhancing effect of emotion

Emotional events tend to be better remembered than non-emotional events1,2. One goal of cognitive and affective neuroscientists is 
to understand the neural mechanisms underlying this enhancing effect of emotion on memory. A method that has proven particularly influential in the 
investigation of the memory-enhancing effect of emotion is the so-called subsequent memory paradigm (SMP). This method was originally used to investigate the 
neural correlates of non-emotional memories3, and more recently we and others also applied it successfully to studies of emotional memory (reviewed in4, 5-7). 
Here, we describe a protocol that allows investigation of the neural correlates of the memory-enhancing effect of emotion using the SMP in conjunction with 
event-related functional magnetic resonance imaging (fMRI). An important feature of the SMP is that it allows separation of brain activity specifically 
associated with memory from more general activity associated with perception. Moreover, in the context of investigating the impact of emotional stimuli, 
SMP allows identification of brain regions whose activity is susceptible to emotional modulation of both general/perceptual and memory-specific processing. 
This protocol can be used in healthy subjects8-15, as well as in clinical patients where there are alterations in the neural correlates of emotion perception 
and biases in remembering emotional events, such as those suffering from depression and post-traumatic stress disorder (PTSD)16, 17.

Watch this Scientific Journal Video about Brain Imaging Investigation of the Memory-Enhancing Effect of Emotion at JoVE.com

Brain Imaging Investigation of the Memory-Enhancing Effect of Emotion

We present a protocol that uses functional magnetic resonance imaging to investigate the neural correlates of the memory-enhancing effect of emotion. This protocol allows identification of brain activity specifically linked to memory-related processing, contrary to more general perceptual processing, and can be used with healthy and clinical populations.

Emotional events tend to be better remembered than non-emotional events1,2. One goal of cognitive and affective neuroscientists is 
to understand the ...

brain-imaging-investigation-of-the-memory-enhancing-effect-of-emotion

Research

JoVE Journal

Neuroscience

Brain Imaging Investigation of the Neural Correlates of Observing Virtual Social Interactions

The ability to gauge social interactions is crucial in the assessment of others&#x2019; intentions. Factors such as facial expressions and body language affect our decisions in personal and professional life alike 1. These "friend or foe" judgements are often based on first impressions, which in turn may affect our decisions to "approach or avoid". Previous studies investigating the neural correlates of social cognition tended to use static facial stimuli 2. Here, we illustrate an experimental design in which whole-body animated characters were used in conjunction with functional magnetic resonance imaging (fMRI) recordings. Fifteen participants were presented with short movie-clips of guest-host interactions in a business setting, while fMRI data were recorded; at the end of each movie, participants also provided ratings of the host behaviour. This design mimics more closely real-life situations, and hence may contribute to better understanding of the neural mechanisms of social interactions in healthy behaviour, and to gaining insight into possible causes of deficits in social behaviour in such clinical conditions as social anxiety and autism 3.

This article demonstrates an experimental design in which whole-body animated characters are used in conjunction with functional magnetic resonance imaging (fMRI) to investigate the neural correlates of observing virtual social interactions.

The ability to gauge social interactions is crucial in the assessment of others&#x2019; intentions. Factors such as facial expressions and body language ...

Brain Imaging Investigation of the Neural Correlates of Emotional Autobiographical Recollection

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning 1 - remembering positive AMs is associated with increased personal well-being and self-esteem 2, whereas remembering and ruminating on negative AMs may lead to affective disorders 3. Although significant progress has been made in understanding the brain mechanisms underlying AM retrieval in general (reviewed in 4, 5), less is known about the effect of emotion on the subjective re-experience of AMs and the associated neural correlates. This is in part due to the fact that, unlike the investigations of the emotion effect on memory for laboratory-based microevents (reviewed in 6, 7-9), often times AM studies do not have a clear focus on the emotional aspects of remembering personal events (but see 10). Here, we present a protocol that allows investigation of the neural correlates of recollecting emotional AMs using functional magnetic resonance imaging (fMRI). Cues for these memories are collected prior to scanning by means of an autobiographical memory questionnaire (AMQ), therefore allowing for proper selection of emotional AMs based on their phenomenological properties (i.e., intensity, vividness, personal significance). This protocol can be used in healthy and clinical populations alike.

We present a protocol that allows investigation of the neural correlates of recollecting emotional autobiographical memories, using functional magnetic resonance imaging. This protocol can be used with both healthy and clinical participants.

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning 1 - remembering positive AMs is ...

Brain Imaging Investigation of the Neural Correlates of Emotion Regulation

The ability to control/regulate emotions is an important coping mechanism in the face of emotionally stressful situations. Although significant progress has been made in understanding conscious/deliberate emotion regulation (ER), less is known about non-conscious/automatic ER and the associated neural correlates. This is in part due to the problems inherent in the unitary concepts of automatic and conscious processing1. Here, we present a protocol that allows investigation of the neural correlates of both deliberate and automatic ER using functional magnetic resonance imaging (fMRI). This protocol allows new avenues of inquiry into various aspects of ER. For instance, the experimental design allows manipulation of the goal to regulate emotion (conscious vs. non-conscious), as well as the intensity of the emotional challenge (high vs. low). Moreover, it allows investigation of both immediate (emotion perception) and long-term effects (emotional memory) of ER strategies on emotion processing. Therefore, this protocol may contribute to better understanding of the neural mechanisms of emotion regulation in healthy behaviour, and to gaining insight into possible causes of deficits in depression and anxiety disorders in which emotion dysregulation is often among the core debilitating features.

We present a protocol that allows investigation of the neural correlates of deliberate and automatic emotion regulation, using functional magnetic resonance imaging. This protocol can be used in healthy participants, both young and older, as well as in clinical patients.

The ability to control/regulate emotions is an important coping mechanism in the face of emotionally stressful situations. Although significant progress ...

Brain Imaging Investigation of the Impairing Effect of Emotion on Cognition

Emotions can impact cognition by exerting both enhancing (e.g., better memory for emotional events) and impairing (e.g., increased emotional distractibility) effects (reviewed in 1). Complementing our recent protocol 2 describing a method that allows investigation of the neural correlates of the memory-enhancing effect of emotion (see also 1, 3-5), here we present a protocol that allows investigation of the neural correlates of the detrimental impact of emotion on cognition. The main feature of this method is that it allows identification of reciprocal modulations between activity in a ventral neural system, involved in 'hot' emotion processing (HotEmo system), and a dorsal system, involved in higher-level 'cold' cognitive/executive processing (ColdEx system), which are linked to cognitive performance and to individual variations in behavior (reviewed in 1). Since its initial introduction 6, this design has proven particularly versatile and influential in the elucidation of various aspects concerning the neural correlates of the detrimental impact of emotional distraction on cognition, with a focus on working memory (WM), and of coping with such distraction 7,11, in both healthy 8-11 and clinical participants 12-14.

We present a protocol that allows investigation of the neural mechanisms mediating the detrimental impact of emotion on cognition, using functional magnetic resonance imaging. This protocol can be used with both healthy and clinical participants.

Emotions can impact cognition by exerting both enhancing (e.g., better memory for emotional events) and impairing (e.g., increased emotional ...

Enabling High Grayscale Resolution Displays and Accurate Response Time Measurements on Conventional Computers

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments in vision research require displays with more than 12 bits of luminance resolution. Several solutions are available. Bit++ 1 and DataPixx 2 use the Digital Visual Interface (DVI) output from graphics cards and high resolution (14 or 16-bit) digital-to-analog converters to drive analog display devices. The VideoSwitcher 3 described here combines analog video signals from the red and blue channels of graphics cards with different weights using a passive resister network 4 and an active circuit to deliver identical video signals to the three channels of color monitors. The method provides an inexpensive way to enable high-resolution monochromatic displays using conventional graphics cards and analog monitors. It can also provide trigger signals that can be used to mark stimulus onsets, making it easy to synchronize visual displays with physiological recordings or response time measurements.
Although computer keyboards and mice are frequently used in measuring response times (RT), the accuracy of these measurements is quite low. The RTbox is a specialized hardware and software solution for accurate RT measurements. Connected to the host computer through a USB connection, the driver of the RTbox is compatible with all conventional operating systems. It uses a microprocessor and high-resolution clock to record the identities and timing of button events, which are buffered until the host computer retrieves them. The recorded button events are not affected by potential timing uncertainties or biases associated with data transmission and processing in the host computer. The asynchronous storage greatly simplifies the design of user programs. Several methods are available to synchronize the clocks of the RTbox and the host computer. The RTbox can also receive external triggers and be used to measure RT with respect to external events. 
Both VideoSwitcher and RTbox are available for users to purchase. The relevant information and many demonstration programs can be found at <a href="http://lobes.usc.edu/">http://lobes.usc.edu/</a>.

Conventional computer hardware can not generate visual stimuli with sufficiently high grayscale resolution and measure response times with sufficient accuracy. We describe how to use the VideoSwitcher to produce high-resolution monochromatic displays, and the RTbox to measure response times with high accuracy on conventional computer hardware.

Display systems based on conventional computer graphics cards are capable of generating images with 8-bit gray level resolution. However, most experiments ...

Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixed brain sections. This protocol will describe in detail an approach for live imaging of mitosis in ex vivo embryonic brain slices. We will describe the critical steps for this procedure, which include: brain extraction, brain embedding, vibratome sectioning of brain slices, staining and culturing of slices, and time-lapse imaging. We will then demonstrate and describe in detail how to perform post-acquisition analysis of mitosis. We include representative results from this assay using the vital dye Syto11, transgenic mice (histone H2B-EGFP and centrin-EGFP), and in utero electroporation (mCherry-&#945;-tubulin). We will discuss how this procedure can be best optimized and how it can be modified for study of genetic regulation of mitosis. Live imaging of mitosis in brain slices is a flexible approach to assess the impact of age, anatomy, and genetic perturbation in a controlled environment, and to generate a large amount of data with high temporal and spatial resolution. Hence this protocol will complement existing tools for analysis of neural progenitor mitosis.

Neural progenitor mitosis is a critical parameter of neurogenesis. Much of our understanding of neural progenitor mitosis is based on analysis of fixed tissue. Live imaging in embryonic brain slices is a versatile technique to assess mitosis with high temporal and spatial resolution in a controlled environment.

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the ...

Live Imaging of the Ependymal Cilia in the Lateral Ventricles of the Mouse Brain

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo&#8217;s Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. Incubation of the brain&#8217;s slices in a customized glass-bottom plate containing Dulbecco&#8217;s Modified Eagle&#8217;s Medium (DMEM)/High-Glucose at 37 &#176;C in the presence of 95%/5% O2/CO2 mixture is essential to keep the tissue alive during the experiment. A video of the cilia beating is then recorded using a high-resolution differential interference contrast microscope. The video is then analyzed frame by frame to calculate the ciliary beating frequency. This allows distinct classification of the ependymal cells into three categories or types based on their ciliary beating frequency and angle. Furthermore, this technique allows the use of high-speed fluorescence imaging analysis to characterize the unique intracellular calcium oscillation properties of ependymal cells as well as the effect of pharmacological agents on the calcium oscillations and the ciliary beating frequency. In addition, this technique is suitable for immunofluorescence imaging for ciliary structure and ciliary protein localization studies. This is particularly important in disease diagnosis and phenotype studies. The main limitation of the technique is attributed to the decrease in live motile cilia movement as the brain tissue starts to die.

Using high-resolution differential interference contrast (DIC) microscopy, an ex vivo observation of the beating of motile ependymal cilia located within the mouse brain ventricles is demonstrated by live-imaging. The technique allows a recording of the unique ciliary beating frequency and beating angle as well as their intracellular calcium oscillation pacing properties.

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Large-scale Three-dimensional Imaging of Cellular Organization in the Mouse Neocortex

The mammalian neocortex is composed of many types of excitatory and inhibitory neurons, each with specific electrophysiological and biochemical properties, synaptic connections, and in vivo functions, but their basic functional and anatomical organization from cellular to network scale is poorly understood. Here we describe a method for the three-dimensional imaging of fluorescently-labeled neurons across large areas of the brain for the investigation of the cortical cellular organization. Specific types of neurons are labeled by the injection of fluorescent retrograde neuronal tracers or expression of fluorescent proteins in transgenic mice. Block brain samples, e.g., a hemisphere, are prepared after fixation, made transparent with tissue clearing methods, and subjected to fluorescent immunolabeling of the specific cell types. Large areas are scanned using confocal or two-photon microscopes equipped with large working distance objectives and motorized stages. This method can resolve the periodic organization of the cell type-specific microcolumn functional modules in the mouse neocortex. The procedure can be useful for the study of three-dimensional cellular architecture in the diverse brain areas and other complex tissues.

Here we describe a procedure for tissue clearing, fluorescent labeling, and large-scale imaging of mouse brain tissue which, thereby, enables visualization of the three-dimensional organization of cell types in the neocortex.

The mammalian neocortex is composed of many types of excitatory and inhibitory neurons, each with specific electrophysiological and biochemical ...

Advanced Diffusion Imaging in The Hippocampus of Rats with Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common type of acquired brain injury. Since patients with traumatic brain injury show a tremendous variability and heterogeneity (age, gender, type of trauma, other possible pathologies, etc.), animal models play a key role in unraveling factors that are limitations in clinical research. They provide a standardized and controlled setting to investigate the biological mechanisms of injury and repair following TBI. However, not all animal models mimic the diffuse and subtle nature of mTBI effectively. For example, the commonly used controlled cortical impact (CCI) and lateral fluid percussion injury (LFPI) models make use of a craniotomy to expose the brain and induce widespread focal trauma, which are not commonly seen in mTBI. Therefore, these experimental models are not valid to mimic mTBI. Thus, an appropriate model should be used to investigate mTBI. The Marmarou weight drop model for rats induces similar microstructural alterations and cognitive impairments as seen in patients who sustain mild trauma; therefore, this model was selected for this protocol. Conventional computed tomography and magnetic resonance imaging (MRI) scans commonly show no damage following a mild injury, because mTBI induces often only subtle and diffuse injuries. With diffusion weighted MRI, it is possible to investigate microstructural properties of brain tissue, which can provide more insight into the microscopic alterations following mild trauma. Therefore, the goal of this study is to obtain quantitative information of a selected region-of-interest (i.e., hippocampus) to follow up disease progression after obtaining a mild and diffuse brain injury.

The overall goal of this procedure is to obtain quantitative microstructural information of the hippocampus in a rat with mild traumatic brain injury. This is done using an advanced diffusion-weighted magnetic resonance imaging protocol and region-of-interest based analysis of parametric diffusion maps.