Editing Vegetative state (section)

== Diagnosis ==
Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual [[cognitive]] functions may remain undetected and patients are diagnosed as being in a persistent vegetative state. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible.<ref>{{cite journal | vauthors = Owen AM, Coleman MR, Menon DK, Johnsrude IS, Rodd JM, Davis MH, Taylor K, Pickard JD | display-authors = 6 | title = Residual auditory function in persistent vegetative state: a combined PET and fMRI study | journal = Neuropsychological Rehabilitation | volume = 15 | issue = 3–4 | pages = 290–306 | date = 2005-07-01 | pmid = 16350973 | doi = 10.1080/09602010443000579 | s2cid = 7495756 }}</ref> In recent years, a number of studies have demonstrated an important role for [[functional neuroimaging]] in the identification of residual cognitive function in persistent vegetative state; this technology is providing new insights into [[Cerebrum|cerebral]] activity in patients with severe brain damage. Such studies, when successful, may be particularly useful where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected.

=== Diagnostic experiments ===
Researchers have begun to use functional neuroimaging studies to study implicit cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Activations in response to sensory stimuli with [[positron emission tomography]] (PET), [[functional magnetic resonance imaging]] (fMRI), and [[electrophysiological]] methods can provide information on the presence, degree, and location of any residual brain function. However, use of these techniques in people with severe brain damage is methodologically, clinically, and theoretically complex and needs careful quantitative analysis and interpretation.

For example, PET studies have shown the identification of residual cognitive function in persistent vegetative state. That is, an external stimulation, such as a painful stimulus, still activates "primary" sensory cortices in these patients but these areas are functionally disconnected from "higher order" associative areas needed for awareness. These results show that parts of the [[Cerebral cortex|cortex]] are indeed still functioning in "vegetative" patients.<ref>{{cite journal | vauthors = Matsuda W, Matsumura A, Komatsu Y, Yanaka K, Nose T | title = Awakenings from persistent vegetative state: report of three cases with parkinsonism and brain stem lesions on MRI | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 74 | issue = 11 | pages = 1571–73 | date = November 2003 | pmid = 14617720 | pmc = 1738238 | doi = 10.1136/jnnp.74.11.1571 }}</ref>

In addition, other PET studies have revealed preserved and consistent responses in predicted regions of [[auditory cortex]] in response to intelligible speech stimuli. Moreover, a preliminary [[fMRI]] examination revealed partially intact responses to semantically ambiguous stimuli, which are known to tap higher aspects of speech comprehension.<ref>{{cite journal | vauthors = Boly M, Faymonville ME, Peigneux P, Lambermont B, Damas P, Del Fiore G, Degueldre C, Franck G, Luxen A, Lamy M, Moonen G, Maquet P, Laureys S | display-authors = 6 | title = Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state | journal = Archives of Neurology | volume = 61 | issue = 2 | pages = 233–38 | date = February 2004 | pmid = 14967772 | doi = 10.1001/archneur.61.2.233 | doi-access = free }}</ref>

Furthermore, several studies have used PET to assess the central processing of [[Poison|noxious]] [[somatosensory]] stimuli in patients in PVS. Noxious somatosensory stimulation activated [[midbrain]], contralateral [[thalamus]], and [[primary somatosensory cortex]] in each and every PVS patient, even in the absence of detectable cortical [[evoked potential]]s. Somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices.<ref name="pmid12377148">{{cite journal | vauthors = Laureys S, Faymonville ME, Peigneux P, Damas P, Lambermont B, Del Fiore G, Degueldre C, Aerts J, Luxen A, Franck G, Lamy M, Moonen G, Maquet P | title = Cortical processing of noxious somatosensory stimuli in the persistent vegetative state | journal = NeuroImage | volume = 17 | issue = 2 | pages = 732–41 | date = October 2002 | pmid = 12377148 | doi = 10.1006/nimg.2002.1236 | s2cid = 16891079 }}</ref>

Also, there is evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in PVS with different behavioral features, researchers employed PET, MRI and [[magnetoencephalographic]] (MEG) responses to sensory stimulation. In three of the five patients, co-registered [[PET/MRI]] correlate areas of relatively preserved brain metabolism with isolated fragments of behavior. Two patients had had [[Hypoxia (medical)|anoxic]] injuries and demonstrated marked decreases in overall cerebral metabolism to 30–40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with higher [[metabolic]] rates, that ranged up to 50–80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the [[Cerebral cortex|cortical]] level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioral patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioral fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who sustained severe injury to the tegmental [[mesencephalon]] and paramedian [[thalamus]] showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical–pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains.<ref>{{cite journal | vauthors = Schiff ND, Ribary U, Moreno DR, Beattie B, Kronberg E, Blasberg R, Giacino J, McCagg C, Fins JJ, Llinás R, Plum F | display-authors = 6 | title = Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain | journal = Brain | volume = 125 | issue = Pt 6 | pages = 1210–34 | date = June 2002 | pmid = 12023311 | doi = 10.1093/brain/awf131 | doi-access = free }}</ref>

=== Misdiagnoses ===
Statistical PVS misdiagnosis is common. An example study with 40 patients in the [[United Kingdom]] diagnosed with PVS reported 43% of the patients were considered to have been misdiagnosed, and another 33% had recovered whilst the study was underway.<ref>{{cite journal | vauthors = Andrews K, Murphy L, Munday R, Littlewood C | title = Misdiagnosis of the vegetative state: retrospective study in a rehabilitation unit | journal = BMJ | volume = 313 | issue = 7048 | pages = 13–16 | date = July 1996 | pmid = 8664760 | pmc = 2351462 | doi = 10.1136/bmj.313.7048.13 }}</ref> Some PVS cases may actually be a misdiagnosis of patients being in an undiagnosed [[minimally conscious state]].<ref>{{cite journal | vauthors = Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND | display-authors = 6 | title = The minimally conscious state: definition and diagnostic criteria | journal = Neurology | volume = 58 | issue = 3 | pages = 349–53 | date = February 2002 | pmid = 11839831 | doi = 10.1212/wnl.58.3.349 | name-list-style = vanc | doi-access = free }}</ref> Since the exact diagnostic criteria of the minimally conscious state were only formulated in 2002, there may be chronic patients diagnosed as PVS before the secondary notion of the minimally conscious state became known.

Whether or not there is any conscious awareness with a patient's vegetative state is a prominent issue.  Three completely different aspects of this should be distinguished. First, some patients can be conscious simply because they are misdiagnosed (see above). In fact, they are not in vegetative states. Second, sometimes a patient was correctly diagnosed but is then examined during the early stages of recovery. Third, perhaps some day the notion itself of vegetative states will change so to include elements of conscious awareness. Inability to disentangle these three example cases causes confusion. An example of such confusion is the response to an experiment using [[functional magnetic resonance imaging]] which revealed that a woman diagnosed with PVS was able to activate predictable portions of her brain in response to the tester's requests that she imagine herself playing tennis or moving from room to room in her house. The brain activity in response to these instructions was indistinguishable from those of healthy patients.<ref>{{cite journal | vauthors = Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD | title = Detecting awareness in the vegetative state | journal = Science | volume = 313 | issue = 5792 | pages = 1402 | date = September 2006 | pmid = 16959998 | doi = 10.1126/science.1130197 | s2cid = 54524352 | citeseerx = 10.1.1.1022.2193 }}</ref><ref name="BBC news ">{{cite news | url=http://news.bbc.co.uk/2/hi/health/5320234.stm | title= Vegetative patient 'communicates': A patient in a vegetative state can communicate just through using her thoughts, according to research | date= September 7, 2006| work=BBC News | access-date=2008-08-14 }}</ref><ref name="Stein ">{{cite news | url=http://sfgate.com/cgi-bin/article.cgi?file=/c/a/2006/09/08/MNGI9L1IM81.DTL | title=Vegetative patient's brain active in test: Unprecedented experiment shows response to instructions to imagine playing tennis | vauthors = Stein R | date=September 8, 2006 | newspaper= San Francisco Chronicle| access-date=2007-09-26 }}</ref>

In 2010, Martin Monti and fellow researchers, working at the MRC Cognition and Brain Sciences Unit at the [[University of Cambridge]], reported in an article in the ''[[New England Journal of Medicine]]''<ref>{{cite journal | vauthors = Monti MM, Vanhaudenhuyse A, Coleman MR, Boly M, Pickard JD, Tshibanda L, Owen AM, Laureys S |title=Willful Modulation of Brain Activity in Disorders of Consciousness |journal=New England Journal of Medicine |date=18 February 2010 |volume=362 |issue=7 |pages=579–89 |doi=10.1056/NEJMoa0905370 |pmid=20130250 |s2cid=13358991 |doi-access=free }}</ref> that some patients in persistent vegetative states responded to verbal instructions by displaying different patterns of brain activity on [[fMRI]] scans. Five out of a total of 54 diagnosed patients were apparently able to respond when instructed to think about one of two different physical activities. One of these five was also able to "answer" yes or no questions, again by imagining one of these two activities.<ref name="alleynebeckford">{{cite web | vauthors = Alleyne R, Beckford M | url = https://www.telegraph.co.uk/health/healthnews/7150119/Patients-in-vegetative-state-can-think-and-communicate.html | archive-url = https://web.archive.org/web/20100206034817/http://www.telegraph.co.uk/health/healthnews/7150119/Patients-in-vegetative-state-can-think-and-communicate.html | url-status = dead | archive-date = 6 February 2010 | title = Patients in 'vegetative' state can think and communicate | work = Telegraph | location = United Kingdom | date = 4 February 2010 }}</ref> It is unclear, however, whether the fact that portions of the patients' brains light up on [[fMRI]] could help these patients assume their own medical decision making.<ref name="alleynebeckford"/>

In November 2011, a publication in ''The Lancet'' presented bedside EEG apparatus and indicated that its signal could be used to detect awareness in three of 16 patients diagnosed in the vegetative state.<ref>{{cite journal | vauthors = Cruse D, Chennu S, Chatelle C, Bekinschtein TA, Fernández-Espejo D, Pickard JD, Laureys S, Owen AM | display-authors = 6 | title = Bedside detection of awareness in the vegetative state: a cohort study | journal = Lancet | volume = 378 | issue = 9809 | pages = 2088–94 | date = December 2011 | pmid = 22078855 | doi = 10.1016/S0140-6736(11)61224-5 | s2cid = 1926221 | citeseerx = 10.1.1.368.3928 }}</ref>