Cross Modal Sensory Processing Assessments in Rodent Models of Early Brain Damage

1
Cross Modal Sensory Processing Assessments in
Rodent Models of Early Brain Damage Chen J.,
McClure, M., Fitch, R.H. Markus, E.J. Psych.
Dept., Behav. Neurosci. Div., Univ of Conn.,
Storrs, CT 06269
919.3
METHODS CONT.
PRELIMINARY RESULTS
INTRODUCTION
VISUAL
AUDITORY
Complex Processing In visual
frequency-grating detection, the SES was preceded
by presentation of a black/white checker-board of
variable frequency (conditions 1-7) prior to
presentation of the SES, while uncued trials were
again characterized by continued presentation of
grey screen prior to the SES. Luminance levels
were equivalent for the black-white gratings, and
gray background.
Accumulated evidence suggests that language
disabilities associated with perinatal brain
damage (e.g., injuries typically seen in
premature/very low birthweight (VLBW)
populations) may be related to fundamental
deficits in processing of rapid auditory
information. Accordingly, rapid auditory
processing deficits are seen in language
impaired, dyslexic, and premature/VLBW
populations (e.g., 1, 2). Moreover, these
effects are not limited to the auditory modality,
given that deficits in processing rapidly
changing visual cues have been reported for these
same populations as well. Overall evidence
suggests that disruptions of key
neurodevelopmental events may lead to pervasive
cross-modal alterations in basic sensory
processing, which may in turn underlie some
disruptions of language development. To further
characterize this neurobehavioral association, we
have studied rodent models of early brain damage
using an array of auditory processing measures.
Results consistently show that focal
developmental malformations of cortex, and
perinatal hypoxic-ischemic insults, are
associated with disruptions of rapid auditory
processing (e.g., 3, 4). More recently, we have
begun to examine the degree to which these
effects are also evident for assessments of
visual processing. In the current studies, adult
male Wistar rats with induced early brain
injuries, and their sham littermates, were
behaviorally evaluated on both auditory and
visual versions of a modified startle reduction
paradigm. Questions examined included 1) How do
basic optimal timing parameters compare across
simple visual and auditory startle reduction
tasks? 2) What aspects of auditory/visual
processing are affected by early brain injury?
3) Are cross-correlations in individual
performance seen across sensory modalities? and
if so 4) Can cross-modal indices provide a
reliable and robust assessment of processing
deficits in impaired subjects?
A.
B.
Single-Tone Auditory Startle Reduction N8 adult
male sham wistar rats
Black-White Visual Startle Reduction N12 adult
male wistar rats (6 sham, 6 HI, no group
differences)
Baseline Processing
Attenuated Startle ()
.
The above task used only sham subjects,
comparable simple acoustic startle tasks
performed on the subject group in D. (below)
failed to show any HI/sham differences.
B. Auditory Startle Reduction Task
No group (HI/sham) differences were seen on this
task.
Cross modal (visual-auditory) startle reduction
required longer processing time than unimodal
(auditory)
Test Apparatus Subjects were placed in a
transparent cylinder on a PHM-250 load cell
platform. A 50ms burst of white noise (105-123db)
again served as the startle eliciting stimulus
(SES), and was played through speakers placed
above the cylinder. Subject movement was
transformed into voltage by a load cell and
analyzed with AcqKnowledge (Biopac Inc.)
software. Procedure A varying number of trials
were presented per test session, depending on the
stimulus being used. For single-tone trials in
50 of trials (cued) the startle burst was
preceded by an auditory (single frequency tone)
cue, after which silence followed. Silence was
presented throughout uncued trials prior to the
SES. In oddball trials, two-tone sequences
(2300Hz and 1100 Hz, both presented at 75dB) of
varying inter-stimulus duration were presented
repeatedly in a background format. On cued
trials, the tone pair was reversed ("oddball")
immediately prior to the SES on uncued trial,
the standard background pair was presented before
the SES. In FM trials, a linear frequency sweep
(2300Hz to 1900Hz, 75 dB) of variable duration
was presented repeatedly as a background. On cued
trials, the direction of the sweep was reversed
on uncued trials, the standard background sweep
was presented before the SES.
D. Variable OddBall Two-Tone Sequence Startle
Reduction
C. Variable Checkerboard Grating Startle Reduction
Complex Processing
METHODS
A. Visual Startle Reduction Task
Visual Cue Level (grating frequency)
OddBall Two-Tone Pair Stimulus Duration (in ms)
Test Apparatus Subjects were placed in a
transparent cylinder on a PHM-250 load cell
platform. Three flat-screen monitors were placed
on the sides the platform a 50ms burst of white
noise (105-123db) served as the startle eliciting
stimulus (SES), and was played through speakers
placed above the cylinder. Movement was
transformed into voltage by a load cell and
analyzed with AcqKnowledge (Biopac Inc.)
software.
Tendency even in this small sample for shams to
perform better than HI rats (Plt.09). In the past
we have shown significant differences in short
delay but not on comparable long-duration
auditory stimulus tasks.
Tendency for sham rats to show a stronger
attenuation than HI (p.1)
Hypoxic-Ischemic animals tend to show an
impairment in processing more complex stimuli
Cross-modal correlations Significant performance
correlations were seen across individual
performance scores on the visual grating
detection and short-duration auditory tasks
(e.g., oddball 2-tone sequence duration 10 - 65
ms), but not simpler versions of the tasks
(e.g.,black-white detection (visual), single tone
detection (auditory), or long duration oddball
and/or FM sweep detection (auditory).

• SUMMARY AND CONCLUSIONS
• Optimal stimulus processing time differed for
  simple versions of visual and auditory startle
  reduction (250 - 350 ms total duration for
  optimal response to a black-white visual cue 57
  - 107 ms total duration for optimal response to
  an auditory cue), indicate that the visual
  version of this task is more difficult and
  requires more processing time as compared to an
  auditory version of the task.
• Despite the difference in processing time, both
  paradigms appear to reveal certain deficits (or a
  trend towards deficits) in processing for
  subjects with early hypoxic-ischemic brain
  damage.
• 2) Individual performance on the most difficult
  conditions shows cross-modal individual
  correlations, indicating that a composite
  cross-modal processing score may ultimately be
  the most useful index to identify impairments in
  populations with early forms of brain injury.

Uncued startle response
Cued startle response
Baseline Processing 50 trials were presented per
test session. For simple visual (black-white)
detection, in 50 of trials (cued), the SES was
preceded by a visual (black-white screen) cue,
after which screens returned to grey background.
Grey screens were presented throughout uncued
trials.
C. Experimental Design
All subjects were male Wistar rats born to dams
ordered from Charles River, and raised at
the University of Connecticut in accordance with
all IACUC regulations. Early hypoxic-ischemic
(HI) injuries were induced via a combination of
unilateral carotid ligation followed by exposure
to a hypoxic (8 O2) chamber (see McClure et al.,
919.1 for more details). Baseline auditory
processing data was obtained from intact adult
male Wistar rats (n8). Data for baseline visual
processing, and complex auditory and visual
processing, was obtained from 2 series of testing
on adult male wistar rats who received neonatal
hypoxic-ischemic (HI) injuries, and their sham
operated littermates (series 1, n2 sham, 4 HI
series 2, n 6 sham, 6 HI).
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Supported by UConn FRS444880 445142 NIH
R29-A613941-01A1