Assessments of Cognitive Function Following Traumatic Brain Injury - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 215

the cortex that are involved in working memory and attention ( 5 ).
Likewise, strategic encoding and retrieval processes, thought to be
centered in temporal lobe structures and the hippocampus, also
engage areas of the frontal cortex ( 6, 7 ). Therefore, it must be
remembered that these cognitive processes are served by a distributed
network of interacting brain regions, rather than being localized
to a single region. Keeping this in mind, cognitive impairments
following TBI likely involve many brain regions and dysfunction in
a number of circuits. Although, cell death is common following
TBI, evidence suggests cognitive dysfunction exists even in the
absence of overt cell death ( 8 ). Therefore, cognitive impairments
should not be attributed to any one brain region.

2. Cognitive
Assessments
Following
Traumatic Brain
Injury

The Morris water maze has been the most standard outcome measure
for assessing cognitive defi cits associated with TBI in preclinical
animal models ( 9, 10 ). In the spatial reference memory task
(described below), animals learn to fi nd a submerged escape plat-
form occupying a fi xed location in a large pool of water based on
its location relative to extra-maze cues located in the testing room.
There are several advantages for using the MWM. The maze is a
relatively simple procedure to administer, and sham-injured rats
learn the task rapidly. The defi cits observed on this task are not
confounded by visual, motor, or other noncognitive factors following
injury ( 11 ). Moreover, the maze does not require food depriva-
tion, which may confound results following injury. The MWM is a
hippocampal-dependant task and has been shown to be a sensitive
test for injury-induced cognitive dysfunction for up to 1 year post-
injury ( 8, 12, 13 ). The maze has also been shown to be sensitive
for detecting memory defi cits following the most common experi-
mental TBI paradigms (e.g., Fluid Percussion, Controlled Cortical
Impact, and Weight Drop-impact-acceleration models). Although
the MWM can be used to evaluate cognitive defi cits at varying time
points post-injury, the most standard time point used for assessment
has been post-injury days (PID) 11-15. This standard time point
allows for comparisons of therapeutic interventions across different
studies. A probe trial (described below) can be used to evaluate
spatial memory retention following standard MWM training.
A modifi ed version of the MWM task (described below) has
also been used to investigate working memory (WM) defi cits
following experimental brain injury ( 14, 15 ). WM is another
domain of memory that is selectively disrupted following injury in
both humans and rats ( 1, 14, 16 ). WM is complex but is defi ned
as the ability to hold information for short periods of time in order
to guide goal-directed behavior. WM defi cits in patients may lead

2.1. The Morris Water
Maze