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Title: The effects of caloric vestibular stimulation on denial of illness and psychopathology


1
The effects of caloric vestibular stimulation on
denial of illness and psychopathology
2
History
3
  • In the last decade, the pendulum between
    pharmacological and non-pharmacological
    biological therapeutic interventions in severe
    mental disorders seems to move slowly in the
    direction of the latter interventions.
  • A variety of non-pharmacological neurostimulatory
    techniques are being investigated with regard to
    their potential diagnostic and therapeutic
    effects in mental disorders.

4
  • These techniques included
  • Transcranial magnetic stimulation
  • Deep brain stimulation
  • Vagal nerve stimulation and
  • A current study explores the therapeutic effects
    of trigeminal nerve stimulation (DeGiorgio et al,
    2006).

5
Are the relatively non localized brain
stimulation techniques OUT ? and the more
localized brain stimulation techniques IN ?

6
Cerlleti
out
Munitz
7
  • The availability and spread of Neuroimaging
    data is enabling the development of specific
    stimulatory interventions in the fields of
    psychiatry
  • in the same magnitude as
  • the availability and spread of economical data
    via internet trafficking enables the development
    of novel interventions in economical systems

8
  • Caloric vestibular stimulation CVS is one of a
    number of related techniques that have been shown
    to induce brain activation of a multimodal
    network.
  • Others include galvanic and rotational vestibular
    stimulation (GVS and RVS, respectively), neck
    muscle vibration (NMV via proprioceptors) and
    optokinetic stimulation (OKS via visual
    stimulation).

9
  • The use of tDCS and CVS as methods of
    non-invasive brain stimulation
  • Gregory Been, Trung T. Ngo, Steven M. Miller and
    Paul B. Fitzgerald
  • Caloric vestibular stimulation (CVS) is a
    safe methods for selectively modulating cortical
    excitability and activation, respectively, which
    have recently received increased interest
    regarding possible clinical applications.
  • CVS involves irrigating the auditory canal
    with cold water which induces a temperature
    gradient across the semicircular canals of the
    vestibular apparatus. This has been shown in
    functional brain-imaging studies to result in
    activation in several contralateral cortical and
    subcortical brain regions.
  • Brain Research Reviews Volume 56, Issue 2,
    December 2007, Pages 346-361

10
  • The use of tDCS and CVS as methods of
    non-invasive brain stimulation
  • Gregory Been, Trung T. Ngo, Steven M. Miller and
    Paul B. Fitzgerald
  • CVS has also been shown to have effects on a
    wide range of visual and cognitive phenomena, as
    well as on post-stroke conditions, mania and
    chronic pain states.
  • CVS has been shown to modulate a range of
    brain functions, and display potential as
    clinical treatment. Importantly, the procedure is
    inexpensive relative to other brain stimulation
    techniques such as electroconvulsive therapy
    (ECT) and transcranial magnetic stimulation
    (TMS).
  • Brain Research Reviews Volume 56, Issue 2,
    December 2007, Pages 346-361

11
  • Caloric vestibular nerve stimulation (CVS)
    usually with cold (30ºC) or warm (44ºC) water is
    a common clinical procedure routinely employed
    during testing of vestibulocochlear nerve
    function.
  • A stronger stimulation may be obtained by the use
    of ice water (4ºC).

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16
  • System of balance
  • Membranous and bony labyrinth embedded in petrous
    bone
  • 5 distinct end organs
  • 3 semicircular canals superior, lateral,
    posterior
  • 2 otolith organs utricle and saccule

17
  • Semicircular canals sense angular acceleration
  • Otolithic organs (utricle and saccule) sense
    linear acceleration

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19
The use CVS as methods of non-invasive brain
stimulation - MECHANISM
  • The caloric stimulation procedure involves
    irrigation of the external auditory canal with
    cold or warm water (or air). It has traditionally
    been believed to achieve its effects by inducing
    a temperature change across the semicircular
    canals, thus altering the density of the
    endolymphatic fluid ( Bárány, 1906). This creates
    convection currents that cause cupular
    deflection, leading to stimulation of the
    vestibular nerve and vestibular nuclei with
    elicitation of the vestibulo-ocular reflex and
    resultant nystagmus.
  • Regardless of its peripheral mechanism of action,
    CVS results in a brisk phase of nystagmus with
    the direction contralateral to the ear irrigated
    following cold-water irrigation.

20
  • This CVS neurostimulatory technique if
    proved to carry therapeutic effects in major
    mental disorders may have several advantages
    including
  • a it is a non-invasive procedure compared with
    VNS or DBS
  • b this simple procedure is easy to perform
    without the use of sophisticated devices and thus
    may be applied in a variety of settings
  • c it reliably affects the same brain structures
    repeatedly without the need for navigators and/or
    stereotactic procedures applied in TMS and DBS
  • d it is an inexpensive procedure that can be
    used in developing countries and lower
    socioieconomic status populations.
  • Unfortunately, for this very reason, the
    private sector will probably refrain from
    financing studies designed to examine the
    efficacy of this "orphan" procedure.

21
Brain imaging studies
  • Earlier studies measuring EEG patterns during
    CVS (herewith 'CVS' indicates cold-water
    stimulation, unless otherwise specified) have
    suggested greater hemispheric activation
    contralateral to the side of irrigation (e.g .,
    Barac, 1967).
  • More recently, PET and functional MRI (fMRI)
    studies have been more informative in identifying
    the neural structures activated following CVS.
    These areas include temporalparietal cortex
    (superior temporal gyrus, inferior parietal lobe,
    and temporalparietal junction), anterior
    cingulate cortex (ACC), insular cortex, and
    putamen in the basal ganglia ( Bottini et al.,
    1994, Bottini et al., 1995, Bottini et al.,
    2001, Emri et al., 2003, Kisely et al.,
    2002, Tuohimaa et al., 1983, Vitte et al.,
    1996 and Wenzel et al., 1996 Fig. 1A).

22
Brain imaging studies
  • Along with temporoparietal and insular
    cortical areas, other CVS-activated regions such
    as somatosensory area SII and the parietal
    operculum have also been regarded as representing
    the human homologue of monkey parietoinsular
    vestibular cortex, the core region of the
    multimodal network (as mentioned above Bottini
    et al., 1995, Bottini et al., 2001, Blanke et
    al., 2000, Duque-Parra, 2004, Eickhoff et
    al., 2006, Kahane et al., 2003 and Petit and
    Beauchamp, 2003).

23
  • Imaging studies have shown widespread though
    largely contralateral hemispheric activation
    following cold water CVS. PET and functional MRI
    studies have identified the neural structures
    activated following CVS.
  • These areas include among others
  • a the temporalparietal cortex
  • b the anterior cingulate cortex (ACC) and
  • c the insular cortex
  • (Been et al, 2007 Miller Ngo, 2007 Suzuki M
    et al, 2001).
  • Ice water (4C) vestibular caloric
    irrigation of the left ear may thus lead to
    activation of these key areas in the
    contralateral right hemisphere.
  • The ACC and the insula were repeatedly
    suggested to be involved in major mental
    disorders characterized by delusional thoughts
    and lack of insight-judgment
  • (see Fornito et al, 2008 Nagai et al, 2007).

24
INSULA A circumscribed body or patch on the skin
25
Insula
26
Insula
27
  • Eur Psychiatry. 2007 Sep22(6)387-94.
    Epub 2007 Apr 9.
  • Insular cortex and neuropsychiatric
    disorders a review of recent literature.Nagai
    M, Kishi K, Kato S.Department of Internal
    Medicine, Shobara Red Cross Hospital, Hiroshima,
    Japan. nagai10m_at_r6.dion.ne.jp
  • In this article, the literature on the
    relationship between the insular cortex and
    neuropsychiatric disorders was summarized
    following a computer search.
  • Recent neuroimaging data, including voxel
    based morphometry, PET and fMRI, revealed that
    the insular cortex was involved in various
    neuropsychiatric diseases such as mood
    disorders.. and schizophrenia.

28
CINGULATE Having a girdle of bands or markings
29
Schizophr Bull. 2008 Apr 23. Epub ahead of
print Anatomical Abnormalities of the Anterior
Cingulate Cortex in Schizophrenia Bridging the
Gap Between Neuroimaging and Neuropathology.Forni
to A, Yücel M, Dean B, Wood SJ, Pantelis C.
  • The anterior cingulate cortex (ACC) is a
    functionally heterogeneous region involved in
    diverse cognitive and emotional processes that
    support goal-directed behaviour.
  • Structural magnetic resonance imaging (MRI) and
    neuropathological findings over the past two
    decades have converged to suggest abnormalities
    in the region may represent a neurobiological
    basis for many of the clinical manifestations of
    schizophrenia.
  • In this article, we review structural
    neuroimaging and neuropathological studies of the
    ACC, focusing on the unique information they
    provide. The available imaging data suggest grey
    matter reductions in the ACC precede psychosis
    onset in some categories of high-risk
    individuals, show sub-regional specificity, and
    may progress with illness duration.

30
Psychiatry Res. 2009 Feb 22. Epub ahead of
print Creatine abnormalities in schizophrenia
and bipolar disorder.Ongür D, Prescot AP, Jensen
JE, Cohen BM, Renshaw PF.
  • We quantified Cr levels in 22 healthy controls,
    15 acutely manic patients with bipolar disorder
    and 15 acutely ill patients with schizophrenia
    using (1)H MRS in the anterior cingulate cortex,
    and the parieto-occipital cortex at 4 Tesla.
  • Patients with schizophrenia had a statistically
    significant reduction in Cr levels as compared
    with controls bipolar disorder patients showed
    no difference in Cr as compared with controls.

31
  • Ice water (4C) vestibular caloric irrigation of
    the left ear may lead to activation of key areas
    in the contralateral right hemisphere - including
    the ACC and the insular cortex.

32
Vilayanur S. Ramachandran a
neurologist best known for his work in the fields
of behavioral neurology and psychophysics. He is
currently the Director of the , Professor in the
Psychology Department and Neurosciences Program
at the University of California, San Diego, and
Adjunct Professor of Biology at the Salk
Institute for Biological Studies.
  • Interestingly, Ramachandran stated recently that
    "evidence from neurological diseases suggests
    that the right hemisphere may act on discrepant
    sensory input to cause a re-evaluation of one's
    world view" and this re-evaluation of one's
    delusions and views about illness seems to be a
    necessary step towards a more realistic
    acceptance of the external world.

33
  • Several case reports and small studies suggest
    short term and transient improvement of personal
    and/or extrapersonal neglect and anosognosia
    (denial of illness) following ice water
    vestibular caloric irrigation of the left ear in
    patients with right parieto/temporo hemispheric
    infarct (Rode et al, 1992 Vallar et al, 1990
    Rode et al, 1998 Schiff Pulver, 1999).
  • Bächtold et al (2001) suggested that unilateral
    caloric stimulation leads to a selective
    activation of contralateral cerebral structures
    and speeds up cognitive processes mediated by
    these structures.

34
  • Improvement of a face perception deficit via
    subsensory galvanic vestibular stimulation
  • DAVID  WILKINSON, PHILIP  KO, PATRICK  KILDUFF,
    REGINA  McGLINCHEY and WILLIAM  MILBERG 
  • Abstract
  • The remediative effect of galvanic vestibular
    stimulation (GVS) was investigated in a patient
    who, following right hemisphere damage, is
    profoundly unable to recognize faces.
  • Although our study involved only a single
    case, the data provide preliminary evidence that
    a deficit in perceptual face matching can be
    reduced by GVS. This raises the intriguing
    possibility that other unilateral visual
    disorders may also respond in such a manner.
    (JINS, 2005, 11, 925929.)

Geriatric Neuropsychology Laboratory, New England
Geriatric Research, Education Clinical Center,
Veterans Affairs, Boston Medical Center and
Department of Psychiatry, Harvard Medical School,
Boston, Massachusetts
35
Vilayanur S. Ramachandran a
neurologist best known for his work in the fields
of behavioral neurology and psychophysics. He is
currently the Director of the , Professor in the
Psychology Department and Neurosciences Program
at the University of California, San Diego, and
Adjunct Professor of Biology at the Salk
Institute for Biological Studies.
  • Ramachandran et al (2007a, 2007b) suggested that
    the same procedure with ice water applied to the
    left ear may alleviate thalamic pain syndrome
    proposing that vestibular stimulation may
    activates the posterior insula, which in turn may
    inhibits the generation of pain in the anterior
    cingulate.

36
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37
Edoardo Bisiach
  • ........??? ???? ???, ?????? ?? ?????? ??????
    ???? ???? 1987 ????????? ??????? ??????? ??????,
    ????? ????? ?????? ?? ????? ???????.
  • ?????? ???? ???? ??? ??? ???? ?? ???? ?????
    ??????? ?? ?????......???? ????? ???? ???? ?????
    ???? ?????? ?????? ????? ????? ??????, ???? ?????
    ?????? ??? ????? ?????? ?????, ??? ??????? ????
    ??????? ?? ????? ????? ?? ?????? ?????? ??????
    ?????? ???? ??????? ???? ????? ?????? ??????.
  • ???????? ??? ?? ???? ?????? ??? ??? ????? ??????
    ????????? ??? ???? ?????? ????? ????? ??????
    ?????? ???????! ????? ?????? ?????? ???? ????? ??
    ????? ??????? ???? ?????? ?????? (?? ?? ?????)
    ???????? ???..........

38
  • Proc Biol Sci. 1999 Feb 22266(1417)421-3.

    Does vestibular stimulation
    activate thalamocortical mechanisms that
    reintegrate impaired cortical regions?
  • Schiff ND, Pulver M.
  •  
  •  
  • Neurocase. 2007 Jun13(3)185-8.

    Rapid relief of thalamic
    pain syndrome induced by vestibular caloric
    stimulation. Ramachandran VS, McGeoch PD,
    Williams L, Arcilla G.Med Hypotheses.
    200769(3)486-8. Epub 2007 Feb 23.
  • Can vestibular caloric stimulation be used
    to treat Dejerine-Roussy Syndrome? Ramachandran
    VS, McGeoch PD, Williams L.Med Hypotheses.
    200769(2)250-2. Epub 2007 Feb 9.
    Can
    vestibular caloric stimulation be used to treat
    apotemnophilia? Ramachandran VS, McGeoch
    P.         Conscious Cogn. 1995
    Mar4(1)22-51

    Anosognosia in parietal lobe
    syndrome.Ramachandran VS.
  • Center for Research on Brain and Cognition,
    University of California, San Diego, La Jolla
    92093-0109, USA.

39
Vestibular function IN schizophrenia
40
  • Extensive research was done in the 1960's up
    to the 1980's to study possible vestibular
    response abnormalities in schizophrenia.
  • These studies were reviewed by Levy et al
    (1983) who stated that the empirical findings
    linking vestibular response abnormalities to
    schizophrenia indicate that these data do not
    unequivocally document the presence of peripheral
    or central disease of the vestibular system in
    any patient group.

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  • The reasons for this ambiguity include
  • 1 the use of imprecise stimulation
    techniques
  • 2 inaccurate measures of responsiveness
  • 3 unreliable measures of quantification and
  • 4 the absence of experimental control over
    extravestibular variables.

43
  • Surprisingly, none of these studies explored the
    short term therapeutic effect of caloric
    vestibular stimulation.
  • Possibly those authors did not expect any
    therapeutic effect of such procedure/
  • Louis Pasteur in this regard stated that. In
    the field of observation, chance favors only the
    prepared mind...

44
Vestibular function IN depresssssion
45
  • Asymmetries of vestibular dysfunction in major
    depression. Soza Ried AM, Aviles M.
    Neuroscience. 2007 Jan 5144(1)128-34. Epub 2006
    Oct 30
  • we studied the vestibulo-ocular reflex (VOR) in
    depressive patients who were not taking
    medication and healthy control subjects,
  • Ocular reflex movement depends on vestibular
    nuclei activity, and compared with controls we
    found that at 30 degrees C stimulation the right
    vestibular system in depressive patients has
    approximately half the activity of the left side.

46
  • Asymmetries of vestibular dysfunction in major
    depression. Soza Ried AM, Aviles M.
    Neuroscience. 2007 Jan 5144(1)128-34. Epub 2006
    Oct 30
  • We also found a significant decrease in the slow
    phase (16.92/-9.13 degrees/s) of the reflex in
    the depressed group as compared with the control
    group (43.77/-16.04 degrees/s).
  • The vestibular nuclei of the right and left sides
    are hypoactive. Specifically, the right
    vestibular nucleus is hypoactive in depressed
    people and can easily be measured using VOR.
  • These results support the abnormal asymmetries
    hypothesis of depression and suggest that these
    asymmetries also exist at the level of the brain
    stem or neuronal centers that are afferents to
    right vestibular nuclei, like SCN or raphe
    nuclei.

47
There is still a lot we can find about
the effects of biological neurostimulatory
techniques on psychopathology
48
  • There is however preliminary data showing
    immediate positive effects of left ear CVS with
    ice water irrigation upon
  • illness denial
  • cognitive processes and
  • delusions.

49
  • In the early 1990s Bisiach et al (1991) explored
    the effects of ice water vestibular stimulation
    on somatoparaphrenic delusion in a patient
    suffering from a fronto-temporo-parietal
    infarction located in the right hemisphere.
  • Transitory remission of the patient's delusional
    belief was consistently observed during
    unilateral vestibular activation obtained by
    means of cold-water irrigation of the left
    (contralesional) ear.
  • Recently Dodson (2004) reported an improvement in
    manic symptoms after ice water caloric vestibular
    stimulation to the left ear in a 29 year old
    woman with a 10 year history of bipolar affective
    disorder.

50
  • Thus although implausible at first sight, it is
    intriguing to explore whether ice water
    vestibular stimulation may treat
  • denial of illness and alleviate delusional
    thoughts in patients suffering from
  • schizophrenia and manic bipolar and
    schizoaffective disorders.

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  • Recently, we studied 3 patients with left versus
    right ear ice water (4C) CVS.
  • One patient, an adult male, had a chronic history
    of schizoaffective disorder and recent mild left
    extremity weakness following suspected right
    hemispheric CVA.
  • The other two patients, an otherwise healthy
    adult male and female, had chronic schizophrenia
    with prominent delusions.
  • All subjects demonstrated a clinically
    significant short-term transient improvement in
    delusional thoughts and insight of illness with
    left versus right ice water CVS. This improvement
    was maintained for at least 20 minutes and then
    diminished over 60 minutes.

53
  • All patients were evaluated with the Delusions
    item of the PANSS (Item P1), the total PANSS
    positive symptoms subscale score (t-P-PANSS) and
    the lack of insight-judgment item of the PANSS
    (Item G12) to assess their clinical status at
    baseline prior to the CVS stimulation of one ear,
    immediately after and at 20, 60 minutes and 24
    hours later.
  • The same procedure was repeated on the other ear
    several days later.

54
  • In one patient the stimulation of both right
    and left vestibular nerves were also validated by
    videonystagmography, and a more robust effect on
    the brain was reflected by quantitative
    electroencephalography (QEEG) with left versus
    right CVS.

55
  • The following is a case report where ice
    water (4C) were administered to left ear and the
    patient was followed immediately after, 20
    minutes, 60 minutes and 24 hours later.
  • The same procedure was repeated to the right ear
    4 days later.
  • This whole procedure to both ears will be called
    a trial.
  • And such 3 trial were done with this patient.

56
  • The first one had a qualitative nature and meant
    to examine whether such procedure may at all
    influence the patient symptomatology and denial
    of illness.
  • in the second trial the function of the
    vestibular system was first thoroughly studied by
    the use of videonystagmography then a trail with
    ice water vestibular stimulation was done to both
    left and right ears as described above in trial
    one. Videonestgmograpy recording of the
    vestibular stimulation showed a clear stimulation
    of the Rt and Lt vestibular nerves by the
    procedure.
  • In the third trial the whole procedure as
    detailed in trial one was done while QEEG
    recording describing the effects of such
    procedure on the brainwere done.

57
Videonistagmography
Videonystagmography (VNG) technologies are used
for testing inner ear and central motor
functions. VNG testing is considered the new
standard for testing inner ear functions over
Electronystagmography (ENG), because VNG measures
the movements of the eyes directly through
infrared cameras, instead of measuring the
muscles around the eyes with electrodes like the
previous ENG version.
58
Videonystagmography (VNG)        
  • VNG testing is more accurate, more consistent,
    and more comfortable for the patient.
  • By having the patient more comfortable and
    relaxed, consistent and accurate test results are
    more easily achieved.

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  • Recording of the EEG was done with Deymed
    Truescan 32 system.
  • During measurement the impedance of all the
    electrode were kept below 5K.

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Each point in each topographical "head" reflects
one electrode according to the international
10-20 system.
64
  • Each topographical "head" is drawn from above
    with the left ear on the left, right ear on the
    right. The nose on the top represents the frontal
    area.
  • The raw EEG was visually scanned and artifacts
    were omitted and then it was subjected to Fast
    Fourier transformation (FFT).
  • The topographical heads show the relative power
    of the FFT. The values can be calculated
    according to the scale below each "head". It is
    in squared micro-volt units.

65
LORETA
                                                
              We deal here with the
66
  • LORETA- low resolution brain
    electromagnetic tomography
  • Scalp electric potentials (EEG) arise from
    neuronal post-synaptic processes.
  • what is the exact contributions of the
    different brain parts to a given EEG signal ?
  • One of the solutions to this problem is the
    LORETA. The LORETA could, in theory, assign a
    brain location to a specific EEG pattern that is
    measured over the scalp. The technical and
    mathematical considerations for this algorithm is
    beyond the scope of this lecture and could be
    found in previous publications.
  • 1. Pascual-Marqui RD. Review of methods for
    solving the EEG inverse problem.
  • International Journal of Bioelectromagnetism
    1999, 1 75-86.
  • 2. Pascual-Marqui RD, Esslen M, Kochi K, Lehmann
    D. Functional imaging with
  • low resolution brain electromagnetic tomography
    (LORETA) review, new
  • comparisons, and new validation. Japanese Journal
    of Clinical Neurophysiology
  • 2002, 3081-94.
  • 3. Pascual-Marqui RD, Michel CM, Lehmann D. Low
    resolution electromagnetic
  • tomography a new method for localizing
    electrical activity in the brain.
  • International Journal of Psychophysiology. 1994,
    1849-65.

67
Formally, LORETA is a particular 3D, discrete,
distributed, linear solution to the inverse
EEG/MEG problem. Informally, LORETA is
described in the first published abstrac
68
  • SEE THE POSTER FOR THE CLINICAL RESULTS AS WELL
    AS FOR THE QEEG AND LORETA RESUTLTS

69
MECHANISM ?
70
  • Mast FW, Merfeld DM, Kosslyn SM. Visual mental
    imagery during caloric vestibular stimulation.
    Neuropsychologia. 200644(1)101-9
  • We investigated high-resolution mental imagery
    and mental rotation, while the participants
    received caloric vestibular stimulation.
  • we predicted that vestibular stimulation would
    disrupt high-resolution mental imagery
  • this prediction was confirmed. In contrast,
    such stimulation did not affect performance of a
    low-imagery control task.
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