gyri, primary and secondary visual areas includ-
ing the calcarine sulcus, and precuneus. The
pattern of brain activations for normal speech
in this patient overlapped with that in the
normal controls. However, different from the
normals, neither patient activated in response to
reversed speech. The findings also indicate
that the functional MRI technique alone is in-
sufficient to characterize the presumably wide
differences in brain function that separate the
patients and the control subjects. In addition,
unlike PVS patients who fail to produce acti-
vation of polymodal association cortices in re-
sponse to natural stimuli, the two MCS pa-
tients retain potentially recruitable cerebral
networks that underlie language comprehen-
sion and expression despite their inability to
execute motor commands or communicate re-
liably. The preservation of large-scale fore-
brain networks associated with higher cogni-
tive functions such as language provides a
clinical foundation for wide fluctuations some-
times observed in MCS patients. Other inves-
tigators have obtained similar neuroimaging
findings from single MCS patients.
99,125
The same limitations of imaging techniques
for determining awareness in VS/PVS patients
also limit assessment in MCS patients. One can-
not determine whether or not the functional
MRI activations indicate awareness without
communication, and by definition these patients
cannot communicate. In addition, when they
do awaken, they typically are amnestic for this
period of time. Neuroimaging studies of visual
Figure 9–11. Diffusion tensor imaging studies of a patient with late recovery (19 years) from the minimally conscious
state. (A) Magnetic resonance imaging demonstrating diffuse atrophy. (B) Fractional anisotropy maps showing fiber tracks:
red, fibers with left-right directionality; blue, fibers with up-down directionality; green, fibers with anterior-posterior
directionality. Images show volume loss of the corpus callosum throughout the medial component and regions in parieto-
occipital white matter with prominent left-right directionality. (C) Fractional anisotropy maps obtained 18 months after
studies shown in (B) demonstrate reduction of left-right direction in parieto-occipital regions with increased anisotropy
noted in the midline cerebellum (see text). (D) Quantitative comparison of midline cerebellum fractional anisotropy versus
left-right directionality. Open circle, values obtained from patient’s first scan; open square, values obtained from second
scan; filled circles, values from 20 normal subjects. (From Voss et al.,
132
with permission.)
Consciousness, Mechanisms Underlying Outcomes, and Ethical Considerations
371
awareness in patients and normal subjects im-
plicate certain patterns of coactivation across
cortical networks as the principal correlates of
awareness, including coactivation of prefrontal
and parietal cortices along with the occipital-
temporal cortex.
126
Although the activation
patterns identified in the MCS patient shown
in Figure 9–10 include several of these specific
regions, the patient is unable to communi-
cate reliably to indicate whether visual or self-
reflective awareness is present. The coactiva-
tion of prefrontal, parietal, and occipital regions
suggests awareness but is potentially consis-
tentwithotherinterpretations.Similarconcerns
arise in the interpretation of the Owen
120
find-
ings shown in Figure 9–9.
In the future, functional brain imaging tech-
niques in combination with electrodiagnostics
may identify patients with rehabilitative po-
tential, and conversely, those in whom further
recovery is not expected. The introduction of
the MCS nosologic category is aimed at direct-
ing efforts to identify patients who may have
some substrate for further recovery despite
very limited behavioral evidence of awareness.
On the other hand, fragmentary cortical net-
works may remain in VS patients without her-
alding further recovery or signifying aware-
ness. The ‘‘gray zone’’ between VS and the
lower functional boundary of MCS in Figure
9–1 reflects a probable overlap region where
patients may acquire a reliable sensory-motor
loop response of very limited cerebral systems
that, despite contingency with environmental
stimuli, may not reflect awareness or poten-
tial for further recovery. It is critical, then, to
identify residual capacity as opposed to isolated
functional activity in the cortex. This will re-
quire prospective studies of large numbers of
patients with early VS, to determine if there are
indices on functional imaging that can predict
eventual improvement.
POTENTIAL MECHANISMS
UNDERLYING RESIDUAL
FUNCTIONAL CAPACITY IN
SEVERELY DISABLED PATIENTS
The neuroimaging studies reviewed above
raise the question of what mechanisms might
limit further recovery in MCS patients who
harbor widely connected and responsive cere-
bral networks. Fluctuations of cognitive func-
tion in MCS patients
91,127
(and occasional late
spontaneous emergence from MCS [see be-
low]) demonstrate an underlying residual cog-
nitive capacity in some severely injured brains.
At present, no studies have addressed this
question by systematically correlating brain
structural integrity, cerebral metabolism, and
electrophysiology across a large sample of pa-
tients with severe disability. Nonetheless, sev-
eral careful observations of variations in struc-
tural injury patterns, patterns of normal resting
metabolic activity, and abnormal brain dynam-
ics provide potentially important clues and di-
rections for future research.
Variations of Structural Substrates
Underlying Severe Disability
Clinical observations and quantitative mea-
surements of neuronal loss following complex
brain injuries do not support an invariably
straightforward relationship of recovery of cog-
nitive function that is simply graded by the
degree of vascular, diffuse axonal, and direct
ischemic brain damage. Although indirectly
measured volumetric indices do offer some
prediction of long-term outcome in PVS fol-
lowing overwhelming traumatic
71
or anoxic
brain injury,
38
pathologic studies comparing
patients remaining severely disabled following
brain injuries to those remaining in VS dem-
onstrate that severely disabled and some MCS
patients may have only focal brain damage,
whereas PVS patients suffer diffuse axonal in-
jury.
128
Severely disabled patients with diffuse
axonal injury appeared to have lesser quanti-
tative damage than PVS patients. These find-
ings suggest that significant variations in un-
derlying mechanisms of cognitive disabilities
and residual brain function accompany MCS
and other severe but less disabling brain
injuries.
It is also well known that enduring global
disorders of consciousness can arise in the
setting of only focal injuries.
129
These injuries
are typically concentrated in the rostral teg-
mental mesencephalon and paramedian thal-
amus.
112,130
Patients with moderate, diffuse
axonal injury combined with limited focal dam-
age to these paramedian structures have not
been systematically studied, but this pathology
372
Plum and Posner’s Diagnosis of Stupor and Coma