Application of CMINDS® at UCI

 

Overview of Design

In a five year long National Institute of Child Health and Development (NICHD) funded study, brain structure and developmental abnormalities including measures of the HPA axis, behavior, and cognition were evaluated in children. Six hundred children between the ages of 6-11 participated in the study. For each child an extensive pre- and peri- natal history was collected, including measures of maternal psychosocial stress, endocrine markers of stress and medical history collected serially during pregnancy from as early as week 12 of gestation through 6-8 weeks postpartum. In this application, endocrine and behavioral responses to stress were assessed in children from the prenatal cohort using salivary cortisol assessments and standardized questionnaires. Cognitive function and development was assessed with two different batteries: 1) a computerized neuropsychological assessment system (CMINDS®, NeuroComp Systems Inc., Irvine, CA) and 2) a set of standardized measures of intelligence.

 

Prenatal Protocol

Prenatal assessments of biological and psychosocial measures of stress were collected serially from approximately week 14 through week 36 week of gestation. Biophysical measures of fetal development were collected with ultrasound at 14, 20 and 26 weeks gestation. Assessment of fetal behavior was made at gestational weeks 26 and 32. In addition, an extensive medical history interview was conducted at the initial visit with follow-up medical interviews at each subsequent visit to document changes in medical conditions. Subjects were followed to term and birth outcome was recorded. At six to eight weeks postpartum, assessments of the mother and infant were conducted (stress, medical history, infant health and well-being, infant temperament).

 

CMINDS® Computerized Neuropsychological Evaluations

CMINDS has been applied in this long term study aimed at examining the effects of prenatal stress on brain structure and developmental abnormalities including measures of the HPA axis, behavior, and cognition. The CMINDS® Sequential Memory Test, Set Shifting Test, Go/No-Go Test, Continuous Recognition Memory Test, Finger Tapping Test, and Flanker Test were selected for their sensitivity to memory and executive functioning.
 
In the CMINDS® Sequential Memory Test (Figure 1), the child receives digitized aural instructions to use the pen to tap a sequence of boxes on the screen in the same order in which they are observed to light up on the screen. This task is used to assess a child’s capacity for holding a visual-spatial sequence in working memory.

Figure 1
Figure 1


The CMINDS® Set Shifting Test (Figure 2) is designed to evaluate executive functions such as cognitive flexibility and capacity to learn from experience. In the CMINDS Set Shifting Test, the child has five seconds to use the pen to select the doghouse that “Skippy” the dog should go to. The child begins with the single alternation shift (a move back and forth between houses) and is not informed of the specific rule needed to perform this task successfully. After each decision, the child is informed whether his or her response was either correct or incorrect. Depending on the feedback from the computer, the child tries to determine the correct strategy and maintain it over time, or develop a new strategy that elicits success. The correct strategy is deduced from the corrective feedback provided after each decision is made. After the child makes 10 consecutive correct responses, the rule shift occurs. The double alternation shift consists of Skippy moving to the same house twice, then to the other house twice, repeating the pattern. The rule changes one time during the test and the child is not informed of this rule change. When the rule shift occurs, the child must shift his or her attention from the previous rule to the new rule.


Figure 2


In the CMINDS® Go/No-Go test the child must press the reaction button in response to “Go” stimuli, letters of the alphabet (Figure 3), and inhibit themselves from pressing the button in response to the “No Go” Stimulus, letter ‘X’ (Figure 4). This task is used to assess inhibitory control and may also be useful for assessing attention and concentration.

Figure 3 Figure 4


In the CMINDS® Continuous Recognition Memory test the child is presented with pictures and is asked to identify if the picture is “new” (one they have not seen before in the testing session) or “old” (one they have seen in the testing session). Half the pictures presented are concrete familiar objects that can be verbally labeled (Figure 5) and the half the pictures presented are abstract shapes that are not easily verbally labeled (Figure 6). The CMINDS® Continuous Recognition Memory test employs nonverbal, visual stimuli (both concrete and abstract) to assess the ability to discriminate between previously presented and “new” stimuli.

Figure 5 Figure 6
  The CMINDS® Finger Tapping Test requires the child to tap a button with their index finger as fast as they can, switching hands after each trial. This task is used to evaluate motor function in the upper extremities and also the ability to sustain motor functioning over a short time. Tests of fine motor functioning are included in most neuropsychological examinations to assess subtle motor and other cognitive impairments. The Finger Tapping Test has been shown to be sensitive to subtle motor deficits as well as cognitive impairments.

In the CMINDS® Flanker Test the child is given reaction buttons, one for each hand, and is instructed to follow the middle arrow. The middle arrow points left or right, and the child responds by pressing the reaction button either in their right hand or left hand, respectively. Additionally, there are the distracter arrows, flakers, on either side of the target stimulus. The flanker arrows are either congruent (pointing in the same direction) or incongruent (pointing in the opposite direction) to the target stimulus. Original data suggests that subjects had a faster reaction time (RT) when presented with congruent conditions compared to incongruent conditions; this is known as the flanker effect. There is a yellow hand pointing down at this arrow indicating that this is the target stimulus (Figure 7). The child is instructed to only follow this arrow. The example continues by presenting distracter arrows held by cartoon aliens on either side of the target stimulus (Figure 8) and the child is instructed that aliens would try to distract them. After the 4th example trial the aliens disappear and the pointing hand is removed after the 8th trial (Figure 9). The child is allotted five seconds to respond to each trial. This task is used as a measure of interference control in which the child is instructed to refrain from making an incorrect response brought forth by the presence of irrelevant information, distracter arrows. Interference control resides within the domain of selective or focused attention.


Figure 7



Figure 8



Figure 9


These computerized tests were administered on CMINDS® unique dual monitor computer system (Figure 10). This system allowed for an investigator to be seated next to the child with a separate monitor so that performance could be continuously observed. All task instructions were prerecorded for standardized presentation to participants and CMINDS automatically calculated and stored data in the database to ensured scoring was standardized.


Figure 10