Pharmaceutical Effects on Brain Function  

College student with narcolepsy on modafinil (Provigil®) drug treatment.
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Age: 19

Female

This case study is a great example of possibilities that exist in which patients show activation in the “wrong” areas of the brain while performing a task. Often this can be readily interpreted as a compensatory action following brain injury.

This patient is a 19 year old female college student with severe narcolepsy treated with modafinil. Among a full battery of fMRI and neuropsychological assessments, the patient was administered the f-FMT™. The patient was tested both off and on medication. A comparison of these conditions showed dramatically different activation outcomes. However, the magnitude of these differences was only apparent when using normative data from an unimpaired comparison group to evaluate her activation patterns.

As the f-FMT™ is a face memory encoding test, two major brain areas that are expected to be active during this task are the frontal lobe (left side of the figures below with yellow arrows pointing to it) and the hippocampus (right side of the figures below noted with blue crosshairs). The upper row of the figure shows activation off medication, and the lower row shows activation on medication. Even to the untrained eye, it is obvious that there is more activation in the frontal lobe (yellow arrows) on medication, and there is more activation in the hippocampus (blue crosshairs) off medication. But even for a seasoned fMRI expert, it would be hard to determine with certainty whether there is too little activation, too much activation, or just the right amount in either brain region in either condition—this is particularly true for the activation seen in the hippocampus in the off-medication condition.

Off Modafinil (32 hours since Modafinil dose)


 

On Modafinil (within 4 hours of Modafinil dose)


 
An evaluation based on normative data, however, (see below) allows one to determine that off medication, there too much activation in the hippocampus (almost 3 standard deviations above the mean) and too little activation in the frontal lobe (more than 2 standard deviations below the mean). However, on medication, activation is brought down to normal levels in the hippocampus (to about 0 SD), and increased significantly in frontal lobes (to about +1 SD). Thus, treatment with modafinil for this patient appears to have a “normalizing” effect on brain functioning.

Note also that off medication the patient’s task performance, which was a measure of how well she actually performed in the memory test, was about -3 SD below normal, and on medication it was +1.3 SD above normal. So her overall performance in the memory task greatly improved on modafinil.

Off Modafinil (32 hours since Modafinil dose)


 

On Modafinil (within 4 hours of Modafinil dose)

 

Conclusion
• Modafinil was prescribed to address sleepiness symptoms in this narcolepsy patient
• When untreated for Narcolepsy, the patient’s brain appears to be depending too heavily on one brain area (hippocampus) and not enough on another brain area (frontal lobe), where both are important to proper functioning
• Cognitive impairment, especially on memory performance, is an overlooked symptom of narcolepsy
• However, modafinil had obvious benefits for cognitive functioning for this patient as well
• This has potential implications for changing allowable indicated uses of modafinil for narcolepsy and other patients with cognitive impairment, as physicians may currently only prescribe modafinil for wakefulness promoting use (e.g., shift workers and narcolepsy patients) but not for cognitive enhancement


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