The effects of caloric vestibular stimulation on

denial of illness and psychopathology

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.

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).

Are the relatively non localized brain stimulation techniques

OUT ?

and the more localized brain stimulation techniques

IN?

Cerlleti

Munitz

out

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

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).

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

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

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).

System of balance

Membranous and bony labyrinth embedded in petrous bone

5 distinct end organs3 semicircular canals: superior, lateral, posterior2 otolith organs: utricle and saccule

Semicircular canals sense angular acceleration

Otolithic organs (utricle and saccule) sense linear acceleration

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.

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.

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 temporal–parietal cortex (superior temporal gyrus, inferior parietal lobe, and temporal–parietal 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).

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]).

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 temporal–parietal 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 (4°C) 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).

INSULA

A circumscribed body or patch on the skin

Insula

Insula

Eur Psychiatry. 2007 Sep;22(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@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.

CINGULATE: Having a girdle of bands or markings

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.

Fornito 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.

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.

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.

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.

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.

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.

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, 925–929.)

Geriatric Neuropsychology Laboratory, New England Geriatric Research, Geriatric Neuropsychology Laboratory, New England Geriatric Research, Education & Clinical Center, Veterans Affairs, Boston Medical Center and Education & Clinical Center, Veterans Affairs, Boston Medical Center and Department of Psychiatry, Harvard Medical School, Boston, MassachusettsDepartment of Psychiatry, Harvard Medical School, Boston, Massachusetts

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.

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.

כדי לברר זאת, ניצלנו את הניסוי הגאוני שערך בשנת........ הנוירולוג האיטלקי אדוארדו ביסיאץ, בחולה שסבלה 1987

מהזנחה חד צדדית ומהכחשה. ביסיאץ מילא מזרק במי קרח ןשטף את תעלת האוזן

השמאלית של החולה......בתוך שניות החלו עיני החולה לנוע בחוזקה בתהליך הנקרא ריצוד עיניים, המים הקרים

יוצרים זרם הולכה בתעלות האוזן, וכך מתעתעים במוח וגורמים לו לחשוב שהראש זז ולעשות תנועות עיניים

מתקנות בלתי רצוניות שאנו מכנים ריצודי עיניים. שאל את חולת ההכחשה האם היא יכולה כשביסיאץ

להשתמש בזרועותיה היא ענתה בשלווה שאינה יכולה להשתמש בזרועה השמאלית! למרבה ההפתעה השטיפה

במים הקרים של אוזנה השמאלית גרמה להפוגה מוחלטת .......... (גם אם זמנית) באגנוזיה שלה

Edoardo Bisiach

Proc Biol Sci. 1999 Feb 22;266(1417):421-3.

Does vestibular stimulation activate thalamocortical mechanisms that reintegrate impaired cortical regions?

Schiff ND, Pulver M.  

Neurocase. 2007 Jun;13(3):185-8. Rapid relief of thalamic pain syndrome induced by vestibular caloric stimulation. Ramachandran VS, McGeoch PD, Williams L, Arcilla G.

Med Hypotheses. 2007;69(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. 2007;69(2):250-2. Epub 2007 Feb 9. Can vestibular caloric stimulation be used to treat apotemnophilia? Ramachandran VS, McGeoch P.

·         Conscious Cogn. 1995 Mar;4(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.

Vestibular function IN schizophrenia

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.

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.

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...”

Vestibular function IN depresssssion

Asymmetries of vestibular dysfunction in major depression. Soza Ried AM, Aviles M. Neuroscience. 2007 Jan 5;144(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.

Asymmetries of vestibular dysfunction in major depression. Soza Ried AM, Aviles M. Neuroscience. 2007 Jan 5;144(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.

There is still a lot we can find about the effects of biological neurostimulatory techniques

on psychopathology

There is however preliminary data showing immediate positive effects of left ear CVS with ice water irrigation upon:

illness denial;

cognitive processes; and

delusions.

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.

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.

Recently, we studied 3 patients with left versus right ear ice water (4°C) 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.

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.

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.

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.

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 brain—were done.

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.

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.

Recording of the EEG was done with Deymed Truescan 32 system.

During measurement the impedance of all the electrode were kept below 5K.

Each point in each topographical "head" reflects one electrode according to the

international 10-20 system .

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.

LORETA

                                                              We deal here with the

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 withlow resolution brain electromagnetic tomography (LORETA): review, newcomparisons, and new validation. Japanese Journal of Clinical Neurophysiology2002, 30:81-94.3. Pascual-Marqui RD, Michel CM, Lehmann D. Low resolution electromagnetictomography: a new method for localizing electrical activity in the brain.International Journal of Psychophysiology. 1994, 18:49-65.

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:

SEE THE POSTER FOR THE CLINICAL RESULTS AS WELL AS FOR THE QEEG AND LORETA RESUTLTS

MECHANISM?

Mast FW, Merfeld DM, Kosslyn SM. Visual mental imagery during caloric vestibular stimulation. Neuropsychologia. 2006;44(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.