Multiple Sclerosis And Stroke Findings In Rehabilitation Research

Kessler Foundation scientists and their colleagues will discuss their progress in rehabilitation research at the upcoming 65th Annual American Academy of Neurology Conference at the San Diego Convention Center in San Diego, CA, March 16 – 23.

A.M. Barrett, MD, director of Stroke Rehabilitation at Kessler Foundation will present on Pharmacologic Enhancement of Stroke Rehabilitation on Friday March 22, 2013 as part of a Specialty in Focus session on Neurorehabilitation Enhancement Techniques. This session addresses the contribution of brain stimulation, robotics, and circuitry-enhancing pharmacological agents to the understanding of basic brain mechanisms underlying motor recovery, language, attention, executive functioning, and social cognition. Dr. Barrett is chief of Neurorehabilitation Program Innovation at Kessler Institute for Rehabilitation and professor of physical medicine & rehabilitation at UMDNJNew Jersey Medical School.

The four abstracts being presented address cognitive complications of multiple sclerosis and stroke:

Wed. March 20, 2012 7:30 am PST

[P04.034] Aerobic exercise increases hippocampal volume and improves memory in persons with multiple sclerosis: pilot findings from a randomized controlled trial*

Victoria Leavitt 1,2, Amanda Cohen 1, Amanda Farag 2, Christopher Cirnigliaro 3 , Nancy Chiaravalloti 1,2, James F. Sumowski 1,2, John DeLuca 1,2

1 Kessler Foundation; 2 UMDNJ; 3 James Peters VA Medical Center
*Semi-finalist for presentation at ‘Neural Repair and Rehabilitation Highlights in the Field’ on Thursday, March 21st, 6:30-7:30 pm.

Wed. March 20, 2012 7:30 am PST

[P04.109] Evidence for brain reserve and cognitive reserve in multiple sclerosis: lifetime maximal brain growth and early life cognitive leisure independently but differentially protect against disease-related cognitive decline (NIH grant R00HD060765).

James Sumowski 1,2, Maria Rocca 3, Victoria Leavitt 1,2, Gianna Carla Riccitelli 3, Giancarlo Comi 3, John DeLuca 1,2, Massimo Filippi 3

1 Kessler Foundation, 2 UMDNJ, 3 Milan, Italy

Mon., March 18, 2013 2:00 pm PST
[P01.005] A game of networks: examining effective connectivity during task-switching National MS Society (# PP1364 to GW); NIDRR ARRT grant (H113P090009)

Abhijit Das, Glenn Wylie

Kessler Foundation, UMDNJ

Tues., March 19, 2013 2:00 pm PST
[P03.261] Classifying patients with spatial neglect by “aiming” versus “where” spatial bias may explain differential response to bromocriptine treatment
Amit Chaudhari 1, Priyanka Shah 2, Kelly Goedert 3, Uri Adler 1,4, A.M. Barrett 1,2,4 1 UMDNJ, 2 Kessler Foundation; 3 Seton Hall University, 4 Kessler Institute for Rehabilitation

Full Text of AAN Abstracts

[P04.109] Evidence for Brain Reserve and Cognitive Reserve in Multiple Sclerosis: Lifetime Maximal Brain Growth and Early Life Cognitive Leisure Independently but Differentially Protect Against Disease-Related Cognitive Decline

James Sumowski, West Orange, NJ, Maria Rocca, Milan, Italy, Victoria Leavitt, West Orange, NJ, Gianna Carla Riccitelli, Milano, Italy, Giancarlo Comi, Milan, Italy, John DeLuca, West Orange, NJ, Massimo Filippi, Milan, Italy

OBJECTIVE: This is the first study to investigate (a) the brain reserve (BR) hypothesis in MS, (b) whether cognitive reserve (CR) protects against disease-related cognitive impairment independently of BR in any population, and (c) whether BR and CR differentially protect against cognitive inefficiency and memory decline. BACKGROUND: The BR hypothesis states that larger lifetime brain growth/size (estimated with intracranial volume [ICV]) protects against disease-related cognitive impairment. BR is supported in aging/Alzheimer’s disease (AD), but is untested in multiple sclerosis (MS). The CR hypothesis states that greater lifetime enrichment (i.e., cognitive leisure) protects against disease-related cognitive impairment. Although supported in AD and MS, it is unknown whether CR (acquired through experience) protects against cognitive impairment independently of BR (determined by genetics). DESIGN/METHODS: Cognitive status was assessed in 62 MS patients (SDMT, PASAT, SRT, SPART). MRI was used to measure neuropathological burden (T2 lesion load [T2LL]) and BR (ICV). CR was estimated with survey of early life cognitive leisure (e.g., hobbies). BR hypothesis: hierarchical regression predicting cognitive status (step one: demographics; step two: T2LL; step three: ICV, step four: T2LLxICV). CR hypothesis: hierarchical regression predicting cognitive status (step one: all predictors in BR analysis; step two: education; step three: cognitive leisure; step four: T2LLxleisure interaction). Analyses repeated to predict cognitive efficiency (SDMT, PASAT) and memory (SRT, SPART) separately. RESULTS: T2LLxICV interaction (R²=.05, p=.030) showed that greater ICV reduced/moderated the negative impact of T2LL on cognitive status. BR protected against cognitive inefficiency, not memory decline. T2LLxleisure interaction (R²=.037, p=.037) revealed that higher leisure independently reduced/moderated the negative impact ofT2LL on cognitive status. CR was more protective against memory decline than cognitive inefficiency. CONCLUSIONS: BR was supported in MS, with larger lifetime brain growth/size protecting against cognitive decline. Cognitive leisure provided independent protection against cognitive impairment over-and-above BR. Voluntary lifestyle choices are protective over-and-above genetic sources of reserve.

Category – MS and Related Diseases: Clinical Science
Wednesday, March 20, 2013 7:30 AM
Session P04: Multiple Sclerosis: Cognition (7:30 AM-12:00 PM)

[P04.034] Aerobic Exercise Increases Hippocampal Volume and Improves Memory in Persons with Multiple Sclerosis: Pilot Findings from a Randomized Controlled Trial

Victoria Leavitt, West Orange, NJ, Amanda Cohen, West Orange, Amanda Farag, West Orange, Christopher Cirnigliaro, West Orange, NJ, Nancy Chiaravalloti, West Orange, NJ, James F. Sumowski, West Orange, John DeLuca, West Orange

OBJECTIVE: Aerobic exercise improves memory and promotes hippocampal neurogenesis in non-human animals. Its efficacy has not been verified in a memory-impaired neurologic sample. Here, a randomized controlled trial of aerobic versus non-aerobic exercise was piloted in multiple sclerosis (MS) patients with memory impairment. BACKGROUND: MS leads to prominent hippocampal atrophy: as much as 10% reduction of hippocampal volume is seen in persons with relapsing-remitting MS (RRMS), even after only five years. Hippocampal atrophy is linked to memory deficits; indeed, more than 50% of MS patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for MS, either pharmacological or behavioral. DESIGN/METHODS: Pilot data were collected from two ambulatory, memory-impaired MS participants randomized to non-aerobic (stretching) and aerobic (stationery cycling) conditions. Baseline and follow-up measurements: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30 minute sessions 3 times per week for 3 months. RESULTS: Aerobic exercise resulted in a 16.5% increase in hippocampal volume and a 53.7% increase in memory, as well as a large increase in hippocampal resting-state functional connectivity. In contrast, non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal resting-state functional connectivity. Effects of aerobic exercise were specific to the hippocampus and memory, as there were no comparable changes in overall cerebral gray matter (2.4%) or in non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), nor were there any changes in non-memory cognitive functioning (mean change: 0.0%). CONCLUSIONS: This is the first evidence for aerobic exercise to increase hippocampal volume, hippocampal connectivity, and improve memory in MS. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for MS patients.

Category – Neural Repair/Rehabilitation: Clinical: Multiple Sclerosis
Wednesday, March 20, 2013 7:30 AM
Session P04: Neural Repair: Neurorehabilitation: Treatments and Outcomes (7:30 AM-12:00 PM)

[P03.261] Classifying Patients with Spatial Neglect by “Aiming” Versus “Where” Spatial Bias May Explain Differential Response to Bromocriptine Treatment

Amit Chaudhari, Iselin, NJ, Priyanka Shah, West Orange, NJ, Kelly Goedert, South Orange, NJ, Uri Adler, West Orange, NJ, A. Barrett, West Orange, NJ

OBJECTIVE: To evaluate whether stroke survivors with “aiming” versus “where” spatial neglect demonstrate different bromocriptine treatment response. BACKGROUND: Based on animal studies (Marshall, 1979), Fleet et al. (1987) reported bromocriptine improved spatial neglect. However, in other studies (Grujic et al., 1998; Barrett et al., 1999) neglect symptoms worsened after treatment. We wished to learn whether “where” versus “aiming” spatial bias subgroups may predict bromocriptine treatment response, due to differences in brain network impairment (Adair and Barrett, 2008). DESIGN/METHODS: 10 spatial neglect patients (60.2 ± 11.06 years, range = 43-83) completed a computerized line bisection test, and were classified into three bias categories: “aiming”-only (n=4), “where”-only (n=3) and “aiming + where” (n=3). All patients were administered gradually increasing levels of bromocriptine, from 1.5mg to 15mg, over 8 sessions in a 7-week period during which functional improvement was assessed with the Catherine Bergego Scale (CBS). Controlling for baseline CBS, we used multilevel modeling (MLM) to assess patients’ CBS improvement trajectories in each of the three bias categories. RESULTS: MLM revealed that compared with “where”-only, “aiming”-only group demonstrated more improvement (b=-.21, p=0.008) and “aiming + where” group did not improve significantly (b=-0.001, p>0.05). Additionally, baseline functional status significantly predicted CBS improvement over sessions (b=0.73, p=0.001). CONCLUSIONS: Classifying spatial neglect may be vital to interpreting rehabilitation outcomes and treatment studies. In this group study, larger than those performed previously, patients with “aiming” bias appeared to respond favorably to bromocriptine. However, “aiming” neglect patients may also have had milder neglect than those with “where” bias. Therefore, identifying “aiming” bias may also identify milder forms of neglect likely to respond to bromocriptine. Future studies with more bias-characterized patients are indicated.

Category – Neural Repair/Rehabilitation: Clinical: Stroke
Tuesday, March 19, 2013 2:00 PM
Session P03: Neural Repair (2:00 PM-6:30 PM)

[P01.005] A Game of Networks: Examining Effective Connectivity during Task-Switching
Abhijit Das, West Orange, NJ, Glenn Wylie, West Orange, NJ

OBJECTIVE: To use extended-unified structural equation modeling (eu-SEM) to examine the effective connectivity in the brain during a cued task-switching paradigm in a group of healthy individuals. BACKGROUND: Task-switching studies using fMRI have shown specific areas of the dorso-lateral prefrontal cortex (DLPFC), supplementary motor cortex (SMA), inferior frontal cortex (IFC), anterior cingulate cortex (ACC), insula (IN) and inferior parietal lobe (IPL) show increased activity on switch trials relative to repeat trials. This study used eu-SEM to explore the interaction between these brain areas, as opposed to the magnitude of the response in these areas (as observed in traditional topographical activation studies). DESIGN/METHODS: 13 healthy, right-handed subjects (8 female; mean age 34.8 ± 12.4 yrs, mean education 16.3 ±1.1 yrs) were scanned in a 3T MRI while performing a cued task switching paradigm (subjects switched between two tasks: a color judgment task and a speed judgment task). Effective connectivity between twelve nodes of the brain network underlying task-switching [bilateral DLPFC, SMA, IFC, ACC, IN and IPL] was determined by using eu-SEM. RESULTS: During task-switches (from color to speed or vice-versa) subjects showed more effective connectivity compared to task-repeats (color to color or speed to speed). The connectivity between (L) IFC, (L) SMA and (L) IN was found to be common between the two trial types (switch vs repeat). There was more bilateral connectivity during switching (e.g., right to left DLPFC) and nodes in (R) DLPFC, (R) ACC and (R)IN showed effective connectivity only during switching. CONCLUSIONS: While the existing fMRI literature shows the brain areas that are more active on switch trials than repeat trials, this study shows how the information is transmitted between these areas. Switching appears to depend on increased involvement of the homologue of the left-sided areas that are used for repeating a given task (within the context of a task-switching experiment). Supported by: National Multiple Sclerosis Society funding (# PP1364 to GW).

Category – Behavioral Neurology: Frontal Lobes/Executive Functions
Monday, March 18, 2013 2:00 PM
Session P01: Behavioral Neurology: Attention and Executive Functions (2:00 PM-6:30 PM) 

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