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. Author manuscript; available in PMC: 2015 Mar 1.
Published in final edited form as: J ECT. 2014 Mar;30(1):47–61. doi: 10.1097/YCT.0b013e31828b34d8

Table 2.

Advantages and Disadvantages

Biomarker Type Biomarker Advantages Disadvantages


Neuroimaging 		fMRI
  • -

    Detects regional blood flow in cerebral areas

  • -

    Analyzes variations in signal intensity from hemoglobin according to blood oxygen level dependence (BOLD effect)

  • -

    Signal intensity can be used as indirect measure of excitatory input to neurons

  • -

    Total scan time can be very short as opposed to PET

  • -

    No additional scans for neuroanatomical correlative information as in PET

  • -

    TMS-fMRI has better time and spatial resolution than PET

  • -

    TMS-fMRI does not expose participants to radioactive tracers

  • -

    Can be repeated without limitation

  • -

    TMS-fMRI can map corticocortical and corticosubcortical connectivity in brain
  • -

    BOLD responses can only measure hemodynamic changes in blood flow, blood volume etc., but does not provide complete answers to the relationship between cerebral hemodynamic changes and neural activation.

  • -

    Technically challenging, difficult handling, and imaging artifacts due to interference of magnetic fields of TMS and MR scanner
PET
  • -

    Allows real-time view of brain functioning

  • -

    Ability to reconstruct 3-D image of active brain areas

  • -

    Higher image quality due to higher image resolution and sensitivity than SPECT

  • -

    Usually uses chemical elements that are naturally present in the human body for labeling

  • -

    PET isotopes can be labeled to almost every organic molecule

  • -

    PET measurements can be quantified absolutely

  • -

    TMS-PET allows for the ability to examine and visualize corticocortical and corticosubcortical connectivity in the brain

  • -

    TMS-PET seems to be a valid tool to examine the connectivity in the brain, based on tracer studies done in monkeys

  • -

    TMS-PET can be used to compare voluntary and external activation of networks in the brain.

  • -

    TMS-PET has the capability to assess specific neurotransmitter system activity
  • -

    Requires cyclotron for image generation

  • -

    More expensive than SPECT

  • -

    Shorter half-life of gamma rays does not allow for observation in vivo.

  • -

    Requires more intensive staff training

  • -

    Limited repetition due to radioactive tracers
SPECT
  • -

    Allows real-time view of brain functioning

  • -

    Does not require a cyclotron for image generation

  • -

    Ability to reconstruct 3-D image of active brain areas

  • -

    Less expensive than PET

  • -

    Longer half-lives of gamma rays allow for observation of biological processes in vivo.

  • -

    Training of staff is less intensive than PET
  • -

    Maps limited brain areas

  • -

    Lower image quality than PET

  • -

    Uses tracers that often behave differently and that are designed with certain compromises

  • -

    Variety of radiopharmaceuticals is limited

  • -

    Measurements can not be quantified absolutely
MRS
  • -

    Allows thorough view of brain chemical activity

  • -

    TMS-MRS can be used to examine the underlying mechanisms of long-term changes in brain excitability

  • -

    Measures the levels of most important inhibitory (GABA) and excitatory neurotransmitter (glutamate)

  • -

    Direct and non-invasive

  • -

    May be used to investigate the metabolic and neurotransmitter effects of rTMS and tDCS
  • -

    Low sensitivity

  • -

    Lower spatial and temporal resolution

  • -

    Offers fewer metabolic BM that can be followed in vivo.


Electrophysiological 		EEG
  • -

    Allows for measurement of TMS effects within the brain with high temporal and spatial resolution regardless of the location of stimulation

  • -

    EEG electrodes can immediately record the TMS evoked potential (TEP) after TMS pulse, which very likely results from the activation of the stimulated brain area

  • -

    Can be used to assess effective connectivity of remote, but anatomically connected areas of the brain

  • -

    In TMS-EEG, the TEP can be considered an evoked brain oscillation

  • -

    TMS-EEG is able to gather information on cortical excitability at the time of the applied TMS pulse

  • -

    Advance analysis using quantitative assessment and mathematical modeling
  • -

    TMS-EEG is technically challenging

  • -

    TMS-EEG requires TMS-compatible EEG amplifiers

  • -

    TMS-EEG highly state dependent, so results may not be generalizable
Cortical Excitability
  • -

    Excitability can be related to concentration of neurotransmitters

  • -

    Assesses integrity of motor pathways

  • -

    Provides physiological information regarding inhibitory vs. excitatory modulation in brain activity

  • -

    Can target different circuits depending on intensity of stimulation
  • -

    There is a possibility that rTMS may not produce changes in brain activity that are local to the area of stimulation
Saccadic Eye Movements
  • -

    Effect of single pulse TMS is specific to area of brain stimulated and timing of stimulation

  • -

    rTMS can influence specific eye-movement control

  • -

    Small intrapersonal variability so results pre and post-TMS are comparable and subjects can act as their own controls

  • -

    May be used to examine the lateralization of ocular motor control
  • -

    Effects of rTMS are not always inhibitory or excitatory and are highly parameter dependent

  • -

    Mechanism of rTMS effects in saccadic activity are not yet fully understood

Neuroimmunoendocrine 		BDNF
  • -

    Provides an objective measure of BDNF levels

  • -

    BDNF is known to play a large role in the hippocampus which is responsible for memory, learning and emotions, which may effect depression

  • -

    Relatively inexpensive to obtain
  • -

    Requires blood draw

  • -

    Requires time intensive processing to calculate BDNF serum levels
Serum Cortisol
  • -

    Hypothalamic-pituitary-adrenocortical system has been identified in the pathogenesis of depression, making it a good target

  • -

    Dexamethasone and the DEX/CRH suppression test has reasonable sensitivity and specificity for depression

  • -

    Provides an objective measure of cortisol levels
  • -

    Requires blood draw

  • -

    Medications can easily influence results, so subjects must be medication free prior to the study

  • -

    Dexamethasone and DEX/CRH tests require subjects to ingest an oral dose of each during the trial
Serum thyroid hormones
  • -

    TSH follows a natural circadian pattern, making it easier to see if rTMS can actually counter TSH decline

  • -

    Provides an objective measure of thyroid hormone levels
  • -

    Requires blood draw

  • -

    Underlying thyroid disease may be a confounding illness
Dopamine and Serotonin
  • -

    Dopamine and serotonin are highly involved with pleasurable feelings and mood

  • -

    Since these are the two main targets of antidepressant medications, it is a good point of comparison to determine the effects of TMS
  • -

    Neuroendocrine measures can be complex and may be influenced by a number of other physiological processes