Research | Baycrest

Levine Lab

Levine Lab

Dr. Brian Levine is a neuropsychologist interested in the function and dysfunction of large-scale neural systems as expressed in complex human behaviors, including episodic and autobiographical memory, self-regulation, and goal management. Much of his research concerns syndromes seen in patients with focal brain lesions due to strokes and tumors, traumatic brain injury, dementia, and psychiatric disorders, although he also studies healthy young and older adults. Dr. Levine is particularly interested in the real-life deficits faced by patients with brain disease. As these deficits are often not readily apparent in standard neuropsychological or neurological examinations, Dr. Levine uses novel assessment techniques, coupled with multimodal neuroimaging (structural and functional MRI, EEG, and MEG) in his research.

Recent Publications

Raja Beharelle, A., Tisserand, D., McIntosh, A.R., Levine, B. (2011) Brain activity patterns uniquely supporting visual feature integration after traumatic brain injury. Frontiers in Neuroscience, 5, 164. DOI: 10.3389/fnhum.2011.00164.

Raja Beharelle, A., Kovacevic, N., McIntosh, A.R., Levine, B. (in press). Brain signal variability relates to stability of behavior after recovery from diffuse brain injury. Neuroimage.

Mind and the frontal lobes: cognition, behavior, and brain imaging. Levine, B. & Craik, F.I.M., New York: Oxford University Press (2012).

Levine, B., Schweizer, T. A., O’Connor, C., Turner, G. R., Gillingham, S., Stuss, D. T., Manly, T., & Robertson, I.H. (2011). Rehabilitation of executive functioning in patients with frontal lobe brain damage with Goal Management Training. Frontiers in Human Neuroscience, 5:9. doi: 10.3389/fnhum.2011.00009.

Turner, G.R., McIntosh, A.R., & Levine, B. (2011). Compensatory neural recruitment during verbal working memory performance after TBI: evidence for an altered functional engagement hypothesis. Frontiers in Systems Neuroscience, 5:9. doi: 10.3389/fnsys.2011.00009.

O’Connor, C., Robertson, I.H., & Levine, B. (2011). Neural correlates of endogenous vs. exogenous engagement during performance of a sustained attention task. Neuropsychology.

Söderlund, H., Moscovitch, M., Kumar, N., Mandic, M., & Levine, B. (2011). As time goes by: Hippocampal connectivity changes with remoteness of autobiographical memory retrieval. Hippocampus.

Spreng, R.N., Rosen, H.J., Black, S.E., Chow, T.W., Diehl-Schmid, J., Freedman, M., Graff-Radford, N.R., Hodges, J.R., Lipton, A.M., Mendez, M.F., Morelli, S.A., Miller, B.L., & Levine, B. (2010). Occupation attributes relate to laterality of atrophy in frontotemporal lobar degeneration. Neuropsychologia, 48, 3634-3641.

Autobiographical memory and amnesia

Autobiographical remembering comprises multiple interacting mental activities.  Much of our research emphasizes the distinction between two elements of autobiographical memory: semantic and episodic.  Semantic autobiographical memory concerns historical facts, traits, and knowledge states that are not linked to a specific time and place.  Episodic autobiographical memory concerns recollection of specific events, accompanied by a state of consciousness that marks the experience as part of one's own personal history.  Evidence suggests that these two forms of autobiographical memory may be processed by separate brain systems.  Our research has examined this dissociation in neuropsychological patients and in healthy adults using functional brain imaging (fMRI).

Neuropsychological patients

One line of evidence comes from patients with amnesia restricted to either episodic or semantic autobiographical memory. Patient M.L. has isolated retrograde amnesia, a rare syndrome in which memories prior to the brain injury are lost yet new learning and memory are preserved (Levine et al., 1998).  M.L. was able to relearn semantic autobiographical memory, although his experience of this knowledge was in the third-person.  He remained unable to access episodic autobiographical memory. Studies on patient M.L. have been important in understanding the neuroanatomical and psychological correlates of episodic autobiographical amnesia. For more on our investigations of patient M.L.

We have argued that impaired episodic autobiographical memory in patients with brain disease is more common than is currently recognized.  This problem is in part due to a lack of psychometric technology for assessing autobiographical memory.  In collaboration with Morris Moscovitch, we have developed the Autobiographical Interview, which provides separate indices of episodic and semantic memory from within a single autobiographical recollection using text-based analysis of the transcribed protocol.  Our initial study with this instrument (Levine, Svoboda et al., 2002) indicated distinct styles of autobiographical memory in younger and older adults (see also St-Jacques & Levine, 2007).  We have also used this instrument to explore temporal gradients of episodic and semantic autobiographical memory loss in patients with semantic dementia (McKinnon et al., 2006) and in amnesic patients, including patient H.M. (Steinvorth et al., 2005; Rosenbaum et al., 2004; Rosenbaum et al., 2008; see also Addis et al. 2007, Brain, 130, 2327-42 for epilepsy). In patients with frontotemporal lobar degeneration (also known as frontotemporal degeneration [FTD] of Pick's disease), a common form of pre-senile dementia, we demonstrated specific impairment in episodic, but not semantic autobiogrpahical memory both cross-sectionally and longitudinally (McKinnon et al., 2008). Using our structural neuroimage analysis protcols, we were able to localize this impairment to a left-lateralized network centered on the medial temporal lobe. Taken together, these studies have demonstrated specific impairment in lifespan episodic (but not semantic) autobiographical memory in association with medial temporal lobe damage.

Functional neuroimaging

Functional neuroimaging allows us to examine the neuroanatomical correlates of mental activity in healthy adults.  Since the early 1990's, memory researchers studied the functional neuroanatomy of various mnemonic processes using laboratory tasks.  Far fewer imaging studies have employed more naturalistic autobiographical memory tasks.  These tasks typically require use self-generated autobiographical memories harvested before the scanning session or during the scan itself. For a recent meta-analytic review of this literature, see Svoboda et al. (2006).

In order to avoid the confounds inherent to self-generated autobiographical material, we developed a prospective "diary" method in which participants document unique episodes from their daily life using an audio recorder (Levine et al, 2004).  Recordings are then selected from this pool for exposure during scanning, much the same way words might be drawn from a pool in a traditional laboratory memory study, providing a level of control over autobiographical stimuli unattainable with self-generated memories.  In our first study using this method, we found distinct patterns of brain activation associated with hearing recordings documenting a specific episode from one's personal past versus personal semantic information (i.e., repeated events or states of being). 

This method allowed us to investigate the effects of rehearsal on episodic and semantic autobiographical memory (Svoboda & Levine, 2009). Rehearsal effects are inherent to distinctions between memory conditions, such as that between old and new autobiographical memories. Yet it is impossible to disentangle rehearsal effects from factors such as age, vividness, and emotional significance using naturalistic autobiographical stimuli. We controlled for these factors by randomly assigning recorded episodic autobiographical and semantic stimuli to different rehearsal conditions. We found that even a single rehearsal exposure induced a dramatic repetition suppression effect in the autobiographical memory network. Nonetheless, there was a distinction in brain activation patterns between episodic and semantic stimuli even after eight repetitions. This effect included the hippocampus, which was specifically engaged by the episodic autobiographical stimuli over and above semantic stimuli. This finding was interpreted as supporting Multiple Trace Theory, which states that the hippocampus is engaged by episodically rich representations in spite of the passage of time or amount of reactivations.
 

Patient ML

Episodic autobiographical amnesia Using high resolution, three-dimensional structural MRI, we documented an area of focal brain damage in the frontal projections of the right uncinate fasciculus, a frontal-temporal band of fibers previously identified as important to the retrieval of personal past memories. We investigated the effects of this damage on brain function during memory performance in two functional neuroimaging studies. These studies provided evidence to link M.L.'s self-reported subjective disconnection from anterograde events to deficits in specific neurocognitive systems with established functional neuroanatomy in healthy adults. Although M.L.'s anterograde learning and memory performance were normal, we reasoned that the processes underlying this performance may have been affected by the right frontal lobe injury. Using positron emission tomography (PET), we documented reduced right frontal blood flow and increased left hippocampal blood flow (Image) relative to controls during performance of an episodic memory retrieval task. These findings suggested altered functional neuroanatomy of anterograde memory processes. Behavioral correlation with these neuroanatomical findings was sought using the remember/know technique, a self-report measure of re-experiencing past events. M.L. reported fewer "remember" responses, corresponding to reduced re-experiencing of previously studied material. His intact memory test performance was instead supported by preserved semantic processes ("know" responses). While this study illuminated M.L.'s brain function during laboratory memory tasks, it did not directly address his main presenting problem of episodic autobiographical amnesia. We formally studied this by combining our prospective audio diary method for collection of autobiographical stimuli with the Autobiographical Interview scoring technique (Levine et al, 2009). M.L. created recordings of significant personal events over a ten month period. As expected, when presented with these recordings about nine months later, he reported reduced re-experiencing of these events relative to comparison subjects. Interestingly, "internal" or episodic autobiographical details were only marginally significantly lower than comparison subjects, suggesting that M.L. can produce episodic-like details in the absence of re-experiencing. When presented with the recordings during scanning with fMRI, M.L. showed reduced activation of elements of the autobiographical memory network, especially the in left medial prefrontal region (strongly implicated in self-related processes) and the posterior cingulate gyrus (important to mnemonic retrieval operations). M.L. also showed evidence of impaired self-regulation in both real-life and laboratory tasks (Levine et al., 1999), suggesting that access to episodic autobiographical memory may be important for on-line behavioral regulation and decision making.

Self Regulation

Consider two types of situations, structured and unstructured. In structured situations, such as your morning routine or putting gas in the car, behavior is driven by clues in the environment and habits strengthened through countless repetitions. In unstructured situations, such as disciplining a child or planning and organizing a social affair, the environment or habit are less informative and may in fact lead you astray. In these situations, the response will depend upon awareness and implementation of your personal goals.

Many people who have sustained a brain injury have a syndrome of serious behavior problems in unstructured situations, while their behavior in structured situations is normal. This syndrome affects their social and occupational functioning and, in some cases, seriously compromises independent living. When their abilities are assessed by a health care professional, however, they do not appear to be impaired as the typical assessment is a highly structured affair that does not require self-aware decision-making (see Levine et al., 1998; Levine et al., 2000; Stuss & Levine, 2002).

We call this syndrome self-regulatory disorder (SRD). The purpose of our research is to improve the diagnosis and treatment of SRD and to better understand the mechanisms of self-regulation in humans. These mechanisms and their neural underpinnings are extraordinarily complex, involving multiple interacting neurocognitive systems. We are studying the relationship of relationship of self-regulation to self (autonoetic) awareness. This aspect of our research is influenced by Tulving’s notion of the autonoetic awareness and its role in re-experiencing the past (see Wheeler et al., 1995, Psychological Bulletin, 121, 331-354). We hypothesize that self-regulation depends upon a unified awareness of the self in the past and in the future.  Information derived from this form of awareness is held on line to govern behavior.  For evidence in support of the correspondence between past and future thought, see Levine et al., (1999); Spreng & Levine (2006).

Brain injury recovery and rehabilitation

Traumatic brain injury (TBI) involves a blow to the head followed by an alteration in consciousness. Depending on the severity of the injury, consciousness alteration can range from a few moments of confusion to coma lasting weeks or even months. The degree of handicap in terms of independent function is related to the severity of injury, but the nature of this relationship is unknown. Some patients with moderate to severe injuries make complete or nearly complete recoveries, while others are permanently disabled.

The answer to this puzzle may lie in improving the technologies for assessing both injury severity and behavior (Levine et al., 2006). Brain injury severity is usually assessed indirectly by measures of coma depth at the time of injury. While such indices are indispensible for acute neurotrauma management, their utility diminishes with time.

The Toronto TBI Study
In the Toronto TBI study, 70 patients spanning the full range of TBI severity were assessed at one year post-injury with extensive behavioral testing and concurrent high-resolution structural MRI. Structural MRI data were analyzed with our locally developed image analysis pipeline (Kovacevic et al., 2002; Dade et al., 2004). We demonstrated that quantified MRI is highly sensitive to TBI severity, with distributed volume loss even in patients without large focal lesions (Levine et al., 2008). We are now investigating the relationship of this volume loss to behavioral measures (e.g., Fujiwara et al., 2008).

Functional Neuroimaging of TBI
We are also conducting activation functional neuroimaging studies to examine changes in brain networks in response to tasks of memory and attention. For an early example using positron emission tomography (PET; Levine et al., 2002), click here. More recently, Gary Turner has examined the effects of significant head injury on brain networks supporting complex short-term (working) memory operations (Turner & Levine, 2008). In addition to better specifying brain impairments due to TBI, this research may illustrate processes of natural recovery, neural plasticity, and functional reorganization.

Rehabilitation
Much of our research pertains to rehabilitation through the application of metacognitive strategies to train people with disorganized behavior to compensate for their deficits. Results from a randomized-control trial of a brief version of our protocol and a longer case-study trial in a post-encephalitic patient, support the efficacy of this treatment protocol (Levine et al., 2000). We have also applied a version of this protocol in a healthy eldery sample (Levine et al., 2007) and in a case study of cerebellar damage (Schweizer et al., 2007). We are currently applying an expanded version of our program in a larger scale randomized-control rehabilitation program.

Scientist

Brian Levine, Ph.D.

Postdoctoral Fellows

Carrie Esopenko, Ph.D.

Carrie Esopenko

During my graduate studies I examined the neuroanatomical and behavioural underpinnings of embodied cognition. I used functional magnetic resonance imaging and behavioural measures to investigate how action-related stimuli are processed in healthy participants and in two individuals’ post-hemispherectomy. My current research focus is on the study of traumatic brain injury and brain health during aging. Specifically, I am looking at how repetitive brain injuries affect neurocognitive processing in athletes using high resolution functional and structural neuroimaging, as well as behavioural and neuropsychological measures. My other research interests include examining deficits in the processing embodied stimuli and the role of the human mirror neuron system, language deficits due to stroke and other acquired brain injuries, and how cognitive rehabilitation strategies can be used to decrease impairment due to traumatic and acquired brain injuries.

Louis Renoult, Ph.D.

Louis Renoult

My general interest is in the field of cognitive neuroscience of memory and more precisely in the characterization of the similarities, differences and interactions between the semantic and episodic systems. Recent interests include personal semantic memory and how this type of memory may be situated in relation to the two broad systems of declarative memory. This involves investigating the neural bases of personal semantic memory with event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) and comparing them with those of general semantic and episodic memory. Other interests include the nature of semantic representations in the brain, the neural correlates of consciousness, and the similarities between perception and imagination.

Signy Sheldon, Ph.D.

Signy Sheldon

My PhD thesis examined the role of recollection as it is supported by the hippocampus in non-mnemonic tasks, such as open-ended problem solving and semantic retrieval. I am interested in exploring this topic further by examining the contributions of recollection to tasks such as mentalizing and imagery and how this contribution is modulated by task features. Additionally, I am interested in how characteristics of an individual can affect the level of detail to which one can mentally travel through time.

Rebecca Todd, Ph.D.

Rebecca Todd

My doctoral research focused on mapping brain activation patterns underlying emotional processing in young children, as well as studying individual differences in temperament and the development of self-control in childhood. Current research interests include investigating the effects of emotional arousal on the subjective experience of perceptual vividness following traumatic experience, and links between perceptual vividness and emotional memory. I am also interested in the influence of positive emotional states on both perceptual and conceptual processing, and the neural mechanisms underlying such influences.

Graduate Students (Primary)

Charlene O'Connor

More to come...

Nadine Richard

Nadine Richard

I still pretty much look like this. But these days, in addition to my love of Lego and comfy sleepwear, I’m also into cognitive and clinical neuropsychology. I’m especially interested in the idea of adaptive neural networks, and the impact of white matter injury on networks involving the frontal lobes. To study brain changes associated with injury, recovery, and neuroplasticity, I work with people who have had a traumatic brain injury (TBI) or have multiple sclerosis (MS). I have used fMRI, and am now using EEG, to look at the brain bases of attention and executive abilities in these populations, particularly as these relate to self-regulation and goal-driven behaviour. As part of the Levine Lab Rehab Sub-Committee, I am also running a RCT comparing two programs we have designed for people with MS who have deficits in attention and executive abilities. All of which leaves me little time to play with my Lego, but I guess that's (part of) the price of a PhD...

Daniela Palombo

Daniela Palombo

I have been a part of Levinia for a few years, which have been lots of fun (and lots of work!). When I joined the lab, my experience had been in non-human research, but I became more interested in facets of memory that are difficult to study in rodents, so I switched to human research. I am primarily interested in episodic autobiographical memory (AM), which is a particular type of memory that allows individuals to subjectively “re-live” personal events. There is great deal of variability of this capacity among healthy people. While some individuals have superior episodic AM, others show great difficulty in remembering personal events. For my PhD research, I am exploring some of the factors that relate to these individual differences, using a combination of methods. The first part of this study investigates cognitive factors that relate to episodic AM, using an online questionnaire that we have recently developed. Click here if you want to learn a bit more about this study. In the second part of this study, I am using functional neuroimaging to exploring the neural correlates of these individual differences. The final part of this research program involves exploring genetic variants that influence episodic AM. Click here to learn more about the DNA Affect and Memory Project (D.A.M.P). Aside, from my PhD work, I am part of a research team that investigates the neural correlates of traumatic memory in near plane crash survivors. Click here for more information on this study. In my spare time, away from Levinia, I enjoy fine (student) dining, travelling, going to concerts, playing Nintendo, redecorating my office, and daydreaming!

Michael Armson

Michael Armson

I recently graduated from McGill University with a B.A. & Sc. in Psychology, Anthropology, and English. For my undergraduate thesis, I conducted research to find out if the beta-blocker propranolol could disrupt the reconsolidation of a morphine place preference in rats. In the Levine lab, I plan on continuing my study of memory, but in humans rather than animals. In particular, I will be using functional neuroimaging and behavioural methods to explore individual differences in autobiographical memory. Outside of the lab, I enjoy listening to all genres of music, jamming on my saxophone, playing soccer, hockey, basketball and tennis, going for runs, eating good food, and watching good movies.

Ayan Dey

A graduate of the Honours Psychology, Neuroscience and Behavioural Program at McMaster University, I am now enrolled in the combined MD.PhD Program with IMS as my graduate department. After completing my first year of medical school, I have now started working towards my PhD at the Rotman Research Institute at Baycrest Hospital under the supervision of Dr. Brian Levine in collaboration with the Centre for Stroke Recovery at Sunnybrook Hospital. My research at Baycrest focuses on investigating what neural processes, triggered by cognitive rehabilitation, support stroke recovery. Specifically my project entails the application and assessment of a novel intervention for executive dysfunction (goal management training) using multimodal brain imaging techniques. Outside of graduate school, one of my biggest passions and what originally convinced me to pursue a career as a clinician scientist is my passion for innovation and my desire to work in a way that is not only beneficial for my future patients but for the broader public as well. Ultimately I would like to strive towards finding new and innovative ways in which technology can be used to improve all aspects of patient care. On a personal level, photography is my hobby and I am currently working towards become a certified photographer in my spare time.

 

Graduate Students (Affiliated)

Anjali Raja

Anjali Raja

Anjali's research focuses on investigating neural networks underlying attention and language in healthy and brain-injured subjects (primarily TBI and stroke). More generally, she is interested in how measures of integration of neural processes (multiscale entropy, coherence) can be related to recovery from brain injury.

Research Assistants

Priya Kumar

Priya Kumar

I have recently graduated from the University of Toronto, with an Honours B.Sc. in Neuroscience and Psychology. For my honours thesis, I studied the conceptual representation of abstract concepts. In the future, I hope to pursue this line of research and be the first woman to go where no man has gone before...to form a complete, embodied and grounded theory of abstract concepts! In the Levine lab, my current responsibilities include assisting with the cognitive rehabilitation project for MS patients and scoring autobiographical memories. When I'm not in the lab, I'm either volunteering at CAMH, adding to my massive book collection, or watching reruns of Battlestar Galactica.

Wayne Khuu

Wayne Khuu

I've recently received my undergraduate degree from the University of Toronto in Human Behavioral Biology and Psychology. My undergraduate project in the Levine Lab focused on the electrophysiology of sustained attention in healthy individuals; this project was part of a larger on-going study that focuses on cognitive rehabilitation in MS and TBI patients. In addition to assisting with the MS and TBI cognitive rehabilitation projects, my work involves image processing for various other projects. In my spare time I try to take naps to consolidate the vast amount of information that is processed in a days work.

Alums (Grads/Postdocs)

Anjali Raja, M.A. (Rotman)

Gary Turner, Ph.D. (Berkeley/Sunnybrook)

Hedvig Söderlund, Ph.D. (Uppsala University)

Nathan Spreng, Ph.D. (Rotman/Harvard)

Eva Svoboda, Ph.D. (Baycrest)

Alexandra Percy, M.A. (UBC)

Esther Fujiwara, Ph.D. (U Alberta)

Danielle Tisserand, Ph.D. (Montreal)

Margaret McKinnon, Ph.D. (McMaster)

Lauren A. Dade, Ph.D. (Bloorview)

Janine F. Hay, Ph.D. (Bloorview)

General Inquiries

Phone: (416) 785-2500 ext. 3593
Fax: (416) 785-2862
 E-mail: blevine@rotman-baycrest.on.ca

Address

The Rotman Research Institute
3560 Bathurst Street, Room 938
Toronto, Ontario, M6A 2E1

Volunteering Opportunities

Phone: (416) 785-2500 ext. 2080
E-mail: volunteers@rotman-baycrest.on.ca