Biomedical Engineering Reference
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activity and predicted treatment response has been observed in all of these studies.
Data presented in these reports, however, generally does not permit evaluation on
an individual-case-prediction level that would facilitate evaluation of the LDAEP
approach for use in guiding clinical decisions. Furthermore, some other reports have
suggested that the interpretation of the LDAEP may be more complex than solely
indicating central serotonergic activity levels and that it may not be highly selective
for serotonergic versus noradrenergic medications [101, 102]. LDAEP values gener-
ally were calculated using dipole source analysis methods and data from full-head
EEG electrode arrays.
11.2.2.3 Anterior Cingulate Activity Prior to Treatment
The third approach links resting-state pretreatment measures of activity in the
rostral anterior cingulate cortex (rACC) to outcome with a variety of treatments,
including sleep deprivation [103, 104] or a number of different medications [105]
including the SRI paroxetine [106]. All of these investigations utilized PET methods
to study regional brain metabolism, and found that higher rACC activity was signifi-
cantly associated with good treatment response.
Additionally several studies have used the LORETA EEG method [107] to deter-
mine the level of electrical activity (current density) at current sources attributed to
rACC [100, 108]. LORETA uses surface EEGs to solve the “inverse problem,” and
in order to find a unique solution for the three-dimensional distribution among the
infinite set of different possible solutions, “this method assumes that neighboring
neurons are simultaneously and synchronously activated,” [107]; that is, the
smoothest distribution of current sources constrained to gray matter is most likely
correct.
Using a linear transformation matrix, LORETA yields current vectors at each of
2,394 voxels positioned stereotactically in cortical gray matter according to the
Montreal Neurological Institute's model [109]. It has been widely validated with
other functional neuroimaging methods, including MRI [110], fMRI [111], PET
[12, 112], and subdural electrocorticography [111]. The studies using LORETA in
MDD have shown that better response to treatment with nortriptyline [108] and
reboxetine or citalopram [100] was associated with higher pretreatment current
density in the ACC in the theta band (6.5 to 8 Hz). Furthermore, ACC theta current
density correlates positively with glucose metabolism [112].
An inexpensive, noninvasive measure of ACC activity, such as EEG, is an
intriguing approach to improving treatment of depression. However, more research
is needed with this methodology to evaluate clinical applicability.
11.2.2.4 Pretreatment Hemispheric Asymmetry Measures
The asymmetric nature of cerebral processing is widely recognized, and includes
such everyday experiences as preferred handedness for writing. Questions have been
raised about lateralization of function and physiological aspects of depression. A
large number of studies have given frontal EEG asymmetry a sizable degree of con-
struct validity as a measure of an underlying “approach-withdrawal” related moti-
vational style [113, 114], though, as Allen and Kline [115] observed “the evidence
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