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  • Grey Matter Abnormalities--Boys--Tourette--Study

    Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry

    ANDREA G. LUDOLPH, MD
    Department of Child and Adolescent Psychiatry, University of Ulm, Germany

    FREIMUT D. JUENGLING, MD
    Department of Nuclear Medicine, University of Bern, Switzerland

    GERHARD LIBAL, MD
    Department of Child and Adolescent Psychiatry, University of Ulm

    ALBERT C. LUDOLPH, MD
    Department of Neurology, University of Ulm

    J?RG M. FEGERT, MD
    Department of Child and Adolescent Psychiatry, University of Ulm

    JAN KASSUBEK, MD
    Department of Neurology, University of Ulm, Germany

    Correspondence: Jan Kassubek, MD, Department of Neurology, University of Ulm, Oberer Eselsberg 45, 889081 Ulm, Germany. Tel: + 49 731 1771206; Fax: + 49 731 1771202; e-mail: jan.kassubek@uni-ulm.de

    Abstract:

    The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed. Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys with Tourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P<0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus. This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.

    British Journal of Psyciatry (2006) 188: 484-485. doi: 10.1192/bjp.bp.105.008813
    Steve
    TouretteLinks Forum

  • #2
    Grey Matter Abnormalities--Boys--Tourette--Study

    Since the hippocampus is responsible for memory, learning, and emotion, does the regional decreases in grey matter in this area play a role in rage associated with TS?

    Another common symptom to consider is a higher baseline of anxiety or the decreased ability to understand social cues.

    Would more of a decrease in grey matter play a role in the severity of TS?

    I wish I could read the entire article, it sounds very interesting. Steph

    Comment


    • #3
      Say What???

      Hi Steve,

      That all sounds very technical and like they found something! Could you explain what this means to us regular folks? Thanks.

      Grammy

      Comment


      • #4
        Grey Matter Abnormalities--Boys--Tourette--Study

        I am doing some research and trying to contact some of my resources for an interpretation of the significance of the article.

        Unfortunaley the full article is available only to people who subscribe to the British Journal of Psychiatry.

        Perhaps one of our Forum members has access to a resource person who can help interpret the article.
        Steve
        TouretteLinks Forum

        Comment


        • #5
          Grey Matter Abnormalities--Boys--Tourette--Study

          does the regional decreases in grey matter in this area play a role in rage associated with TS?
          But 'rage' isn't associated with Tourette's...


          Leslie Packer's THE MYTH OF "RAGE ATTACKS" BEING PART OF TOURETTE'S SYNDROMEhttp://www.tourettesyndrome.net/rage_overview.htm

          Comment


          • #6
            Grey Matter Abnormalities--Boys--Tourette--Study

            Haejinn,

            This is what the website you provided states.

            there is no evidence (and never has been) that people who have Tourette's Syndrome without any other conditions are more likely to have "rage attacks."
            If there is no evidence to say that rage attacks are not associated, then you cannot state that rage attacks is or is not associated!

            At the bottom of that page on the website you provided, it states in the footnote that the source is only one (when 5 is the least amount that I was taught before any practice is changed).

            We have had this converstation before! Come over to my house and see my husband rage! When I point out to him that you are having a rage attack, then he can switch it off like a button. This is not how people with anger react, they cannot turn it off like that. Steph

            Comment


            • #7
              Grey Matter Abnormalities--Boys--Tourette--Study

              We're gonna have to agree to disagree.. :D

              Comment


              • #8
                Grey Matter Abnormalities--Boys--Tourette--Study

                there is no evidence (and never has been) that people who have Tourette's Syndrome without any other conditions are more likely to have "rage attacks."
                Here is my 2-cents. Most of us living with TS or living with someone who has TS would probably agree that the rage is due to the fact that there are associated behaviors involved. I would interpret this statement to be that there is no evidence that people with just TS are more likely to have rage... reality is that the people we live with typically have TSplus... it's the plus factors that are often the root of the rage attacks. I don't know anyone with just TS everyone I know has TSplus and I, like Steph's husband can pull in my emotions once I am made aware I am raging.... but I can honestly say it is my low tolerance (from my ADHD) that triggers my rage episodes. With such a better understanding of rage and my increased self-awareness... I rarely rage now and if I feel that I am becoming frustrated I can self manage (sometimes that may be just timing myself out in my room)
                Janet

                TSFC Homepage

                Comment


                • #9
                  Grey Matter Abnormalities--Boys--Tourette--Study

                  yeah, that's what the studies seem to indicate, so that's what I'm going with for now. :D

                  I know quite a few people with only TS, myself. They usually are diagnosed only after their children are cuz since they only ticced, they never sought professional help.. they're in the online TS community due to their children, rather than themselves. I consider myself to only have Tourette's, and not TS+ in the way that TS+ has come to mean.

                  I like your expression "time myself out". :D

                  Comment


                  • #10
                    Grey Matter Abnormalities--Boys--Tourette--Study

                    Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry

                    ANDREA G. LUDOLPH, FREIMUT D. JUENGLING, GERHARD LIBAL, ALBERT C. LUDOLPH, JORG M. FEGERTand JAN KASSUBEK

                    Summary The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed.Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys withTourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus.This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.

                    Declaration of interest None.

                    There is mounting evidence that Tourette syndrome is an inherited developmental alteration of synaptic neurotransmission within the cortico-striatal-thalamic-cortical circuitry (CSTC). Abnormalities in the striatum and in medial temporal structures have repeatedly been found in imaging studies using nuclear medicine techniques. To investigate morphological alterations in vivo, a number of region-based volu-metric analyses of structural magnetic reso-nance imaging (MR1) data in patients of various ages with Tourette syndrome have been performed, but these differ considerably in their core findings with respect to basal ganglia volumes (Gerard &C Peterson, 2003). In our study the whole-brain three-dimen-sional MRI analysis technique of voxel-based morphometry, which avoids the biases inher-ent in operator-dependent techniques, was applied in boys with Tourette syndrome to test the specific hypothesis that differences exist between patients with this disorder and healthy controls in the striatum and medial temporal areas.

                    METHOD
                    The protocol was approved by the ethics committee of the University of Ulm, and written informed consent was obtained from the parents of all participants. Four-teen patients (mean age 12.5 years) were investigated; only boys were included to control for possible gender effects. The criteria for a definite diagnosis of Tourette syndrome according to the Tourette Syndome Classification Study Group (1993) were applied to all patients. Stimulants were the only medication used by the patients (?=4). For clinical characterisation, the German version of the Yale Global Tic Severity Scale (YGTSS; Steinhausen, 2002) was applied. Attention-deficit hyperactivity disorder (ADHD) comorbidity was assessed using the DSM-IV criteria checklist (American Psychiatric Association, 1994); the mean value was 6.6 (s.d.=5.6). To provide an age-matched MRI control database, MRI scans of 15 healthy boys (mean age 13.4 years) without any neurological or psy-chiatric diagnosis were acquired. Patients and controls were well matched for age, handedness and IQ.

                    High-resolution, whole-head three-dimensional MRI data for all patients and controls were collected on the same 1.5T clinical scanner (Siemens, Erlangen, Germany) and processed in the same way using methods implemented in Statistical Parametric Mapping software (SPM2; http://www.fil.ion.ucl.ac.uk/spm). Voxel-based morphometry was performed accord-ing to the principles described by Good et al (2001) as the 'optimised' protocol. First, all images were normalised by use of an affine-only procedure and a template built from children aged 5?18 years by researchers from the Imaging Research Center at Cincinnati Children's Hospital Medical Center; see http://www.irc.chmcc.org). After creation of customised tissue prob-ability maps, the MRI data were segmen-ted, cleaned, normalised to the study-specific template, segmented and cleaned a second time, then modulated by the Jaco-bian determinants and finally smoothed (6 mm isotropic Gaussian kernel) (Good et al, 2001).
                    Within the framework of the general linear model, the grey-matter images of the Tourette syndrome group were statisti-cally compared with the normal database in a parametric group analysis. Data were analysed in SPM for effects of diagnosis, including individual total grey-matter volume, age and individual scores on the DSM-FV criteria checklist for ADHD as covariates of no interest and individual YGTSS values as the covariate of interest. To detect whether each voxel in the patient data had a greater or lesser grey-matter volume than in controls, the appropriate two contrasts were calculated. For general analysis of effects in areas with an a priori hypothesis - the basal ganglia (striaturn) and mesiotemporal regions - significance was set at P< 0.001, uncorrected for multi-ple comparisons, and then a small-volume correction was made using a 10mm radius volume of interest (Wilke et al, 2004).

                    RESULTS_______________
                    In the optimised voxel-based morphometry analysis, both contrasts 'patients > controls' and 'controls > patients' yielded significant results at a threshold of small-volume corrected P< 0.001. Patients were found to have regional increases in grey-matter volumes in the area of the ventral putamen bilaterally (*, y, z=25, 13, (-5) and (-20), 17, (-6) respectively) (Fig. 1(A)). In the search for syndrome-associated regions of decreased grey-matter volumes, significant mediotemporal voxel clusters were localised in the bilateral hippocampal area (x, y, z=27, ( ? 19), (-17) and (-20), (-19), (-21) respec-tively (Fig. 1(B)). In the covariance analysis including disease severity, these two areas of increased and of decreased grey-matter density were both found to covary significantly with YGTSS at P< 0.001.

                    DISCUSSION____________
                    The morphological changes in striatal and left mediotemporal (hippocampal) areas detected correspond to integral components of the CSTC involving its temporolimbic associations. These results are consistent with functional neuroimaging data, since early functional imaging studies identified different parts of CSTC (including temporo-limbic, sensorimotor, orbitofrontal and asso-ciation pathways) to be altered with respect to metabolism and blood flow (Peterson, 2001). Later radioligand studies of presynaptic/synaptic function and the post-synaptic dopaminergic system achieved in-consistent findings, with partly decreased, partly increased and partly normal striatal bindings (cf. Gerard 8c Peterson, 2003). Our data do not provide evidence that the frequent comorbidity of Tourette syndrome and ADHD, which was present but mild in our patients according to DSM-IV checklist criteria, was relevant for the involvement of limbic pathways, since the individual ADHD values were covaried out.

                    The change in putamen volume is in general agreement with previous investi-gations; note that the putaminal volume changes in our study were local increases in grey matter. Previous investigations of functional networks in Tourette syndrome using [15H2O]-positron emission tomo-graphy (PET) or functional MRI (Peterson et al, 1998; Stern et al, 2000) suggested that basal ganglia seem to be overactive (disin-hibited), in accordance with a more recent study using ["CJdihydrotetrabenazine-PET to quantify striatal monoaminergic in-nervation in this syndrome which showed increased binding in the ventral striatum (Albin et al, 2003). Thus, it seems plausible that in the course of the disorder the in-creased activity might be mirrored by in-creased signal properties due to neuronal volume changes, at least in a subset of patients. It has to be kept in mind that children and not adults were investigated in our study and that previous volumetric studies in affected children mostly found no reduction of basal ganglia volumes, although a large-scale volumetric study reported reduced volumes of the caudate nuclei, but not of lenticular nuclei (Peterson et al, 2003).

                    The ventral striatum which we found to be altered in our patient cohort is thought of as the part of the basal ganglia partici-pating in temporolimbic pathways of the CSTC. We found the left hippocampal gyrus to be a part of the limbic system significantly decreased in volume, a finding not described previously in Tourette syn-drome or in ADHD to our knowledge. The hippocampal cortex is a polymodal convergence area and a core component of the limbic system loops of the CSTC (Peterson, 2001). This constellation implies that two elements of this pathway were found to be altered in volume in our study and that the temporolimbic CSTC pathway seems to be important for Tourette-related symptoms. This finding is strongly supported by the significant covariance of tic severity and the striatal and hippocampal volume changes.

                    Using voxel-based morphometric analysis as a sensitive and unbiased com-parison of regional brain morphology, we found evidence for grey-matter changes in temporolimbic CSTC pathways which
                    might be the morphological correlate of a dopaminergic hyperfunction. Our rinding of decreased hippocampal grey-matter volumes needs to be correlated with neuropsychologi-cal deficits in patients with Tourette syn-drome in future studies. The results of this type of analysis may be useful in recognising regions that are of particular relevance to a specific disorder, even when the neuro-morphometric abnormalities are subtle.

                    ACKNOWLEDGEMENT_____
                    We thank Mrs Sonja Fuchs for help with acquisition of the MRI data.

                    REFERENCES___________
                    American Piychiatrk Allocation (1*94) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV).Washington. DC: APA.
                    Albin, R. L., Koeppe, R. A., Bohnen, N. I., *t al (2003)
                    Increased ventral striatal monoaminergk innervation in Tourette syndrome. Neurology. 41, 310-315.
                    Gerard, E. * Petenon, B. S. (1003) Developmental processes and brain imaging studies inTourette syndrome. Journal of Psychosomatic Research. 55,13-22.
                    Good, C. D.. Johnirude, I. S., Alhbumer, )., ft al (2001) A voxel-based morphometric study of ageing in 465 normal adult human brains. Neurolmoge. M. 21-36.
                    Petenon, B. S. (2001) Neuroimaging studies of Tourette syndrome: a decade of progress. Advonces in Neurology. ?5,179-196.
                    Petenon, B. S., Skudlarfki, P., Andenon, A.W., ? al (I99i) A functional magnetic resonance imaging study of tic suppression inTourette syndrome. Archives of Generaf Psychiatry: 55. 326-333.
                    Petenon, B. S.,Thomai, P., Kane M.J., et al (2003)
                    Basal ganglia volumes in patients with Gilles de la Tourette syndrome. Archives of Genera/ Psychiatry, 60, 415-424.
                    Steinhauien, H.-C. (2002) Psychiatric Disorders in Children and Adolescents (in German). Munich: Urban & Fischer.
                    Stern, E., Silbenweii, D. A., Chee, K. V., tt al (2000)
                    A functional neuroanatomy of tics inTourette syndrome. Archives of General Psychiatry, 57,741-748.
                    Iburette Syndrome Classification Study Group (1993) Definitions and classification of tic disorders. Archives of Neurology. 50.1013-1016.
                    Wilke. M., Kowatch, R. A., DelBello, M. P., et al (2004) Voxel-based morphometry in adolescents with bipolar disorder: first results. Psychiatry Reseorch, 131. 57-69.
                    ANDREA G. UJDOLPH, MD, Department of Child and Adolescent Psychiatry, University of Ulm, Germany; FREIMUT D. JUENGLING, MD. Department of Nuclear Medicine. University of Bern. Switzerland; GERHARD LIBAL, MD, Department of Child and Adolescent Psychiatry, University of Ulm; ALBERTC. LUDOLPH, MD. Department of Neurology, University of Ulm; JORG M. FEGERT, MD, Department of Child and Adolescent Psychiatry, University of Ulm; JAN KASSUBEK, MD, Department of Neurology, University of Ulm, Germany
                    Correspondence:Jan Kassubek, MD, Department of Neurology. University of Ulm.Oberer Eselsberg 45. 89081 Ulm,Germany.Tel: + 49731 1771206; Fax: +49731 1771202; e-mail: jan.kassubek@uni-ulm.de
                    (First received 13 January 2005, final revision 5 June 2005, accepted I September 2005)
                    Steve
                    TouretteLinks Forum

                    Comment


                    • #11
                      Grey Matter Abnormalities--Boys--Tourette--Study

                      I found this really interesting:

                      Patients were found to have regional increases in grey-matter volumes.
                      I always knew my boy was smarter than the average bear.

                      Stephanie

                      Comment


                      • #12
                        Grey Matter Abnormalities--Boys--Tourette--Study

                        Ok, I myself (like haejinn) only have TS. I think the argument is actually something totally different. We argue if people with TS have "rage" but the word "rage", what is it? Seriously, if everyone sent me a pm (not to see anyone elses answers) I would probably get a few different answers. The fact is the "rage" in this use has no exact definaition so it cant really be used as an accurate label.

                        Also, we have had this discussion before and I stated this before. Now I cant speak for everyone obviously, but people say to me that I have a "temper" or "rage" attacks, but I have thought about this alot because every attempt to "remedy" this from the standpoint that it is inheirent(spelling?) that I will have rage, nothing works.

                        When I have a "fit" or "rage" attack, its not merely "my fuse is lit and ready to blow up at any second". Like anyone in an argument (the definition of an argument here is a disagreement that is being debated. It DOES NOT have to invole bad emotion. If steve says he like baseball and I say I like football and thats all thats said and we are in a good mood, we technically just had an argument, the slang styreotype of the word is wrong), but back to my point. Like anyone in an argument, I want to either "win" or at least have my side heard and interprited correct. (please exscuse my horrible spelling). This is common between most everyone. Now, when a "normal" (in this case, anyone normal is a non-TS sufferer, but in reality we are all normal or maybe no one is normal! lol) person has an argument with another normal person, the proper thing is to have each side state their case/point and if further support or discussion is needed than the two parties do so.

                        In the case of a TS sufferer and a normal person (again, Im not speaking for 100% of case, but most should apply) there are problems that arise. The first and foremost problem is that TS isnt a common knowledge disorder, even sometimes to people WITH TS! So now when these problems occur, the parties dont have a permanent support of fact or proper structure to follow.

                        If I was in an argument with "BOB" (made up person) about why I think football is the best sport. (again, this doesnt have to be a heated argument, although it could be) Now BOB, like any argument goes, states his view. He says, "football is boring. It always takes breaks between plays and there are only 16 games in a season." And now like any other argument goes, I state my view, but there will be a slight difference. See if you can notice the difference. (any time you see a * it represents an action) "Bob, your wrong. Football *twitch* is better than *finger clench* other sports *twitch twitch*. Football has better *vocal grunt* hits *twitch* than hockey or bas*sniffletwitch*, baseball and you enjoy each game *vocal grunt* mor *vocal grunt vocal grunt* more than you do *finger clench twitch* other sports. *Finger clench finger clench fingerclenchtwitchvocalgrunttwitch* Now, hopefully that was understandable to read.

                        Now as in any argument, your emotions rise, even the one with myself and steve over the "better" sport. (this also is a made up argument from above) Even though we both made it short and were still in a good mood, you dont have to "alter" your mood to have an emotional surge.

                        Now I hope anyone with TS can agree with me and support me, when you tic, it can sometimes be "annoying" and maybe stressful. We should also agree that an increase in ANY emotion can set off tics. Anger, sadness, happiness, exercise, depression, etc. Well, when myself and BOB are having a disagreement, my emotions are rising, although I may not seem angrier or happier or whatever emotion is rising. Now, if you add the two things togather, you are adding two emotional "risers". With that, an increase of tics will occur. Well, at some point, it becomes "noticable" to the TS person and they will develope an increase of a specific emotion. It usually is anger or "rage", but if you disagree, please say so. So now, the TS person is becoming more upset, but not with the other person or even the argument itself, it more becomes a deep rooted thought process of the TS person not able to "function" in this situation like everyone else and this increase of tics is making it harder to preform that task. (which also can cause more tics).

                        If someone were going to school full time and working full time but still barely living "money wise" and very stressed and angry all the time, this person would not have "rage", they would have an exscuse to be upset cause its outside factors causing it. Well, the same here. Although it looks like its the TS persons "problem" for his tics, its the "outside" world and the common thought of a certain situation and how the TS sufferer has issues with preforming this task. Some people never have money problems, some do. Some people never have TS, some do. Same thing.

                        Back to me and BOB! So now Bob and I are discussing this topic further and like before, my tics are increasing. Now, not only physically is tourettes affecting me, but mentally too. I cant stop thinking about the tics. I personally sometimes feel paranoid like everyone can see me twitch and is laugh, although they are not. Well, that paranoid feeling doesnt go away when Bob and I are arguing. So you add that to me being stressed about always ticing and the increase of tics and the argument itself, I still want to win the argument ot have my view understood. You can also add other common stressful things in life, everyone has them. Now, my tics are soo bad, I can barely speak. "No bob, I *twitch grunt twitch finger clench* I don*faceclench twitch head jerk finger clench* I dont agree with you on *grunt, louder grunt twitch*......" And bob, who does not have TS cant relate to me. And if Bob has not been around tourettes before, he may not even understand what Im doing. So bob gets confused and may cut me off. Maybe he is scared and doesnt wanna even finish the argument. Maybe he is confused and resorts to making a joke about my TS. Maybe he uses my in-ablility to talk fully and talks louder and faster.

                        Now, my last resort is to SCREAM AND YELL AND THROW THINGS!!!! Why? not because Im just an atomic bomb waiting to explode, but because with all the normal "stresses" in life that everyone has, in this situation I have another major stress that hampers on my ablilty to preform this task or function. The reason I scream and yell, is that Im sooo upset with everything really. Why did I have to have TS, why doesnt anyone else understand, why doesnt bob agree with me on football, why do my tics increase with anger, why cant I stop, why do most motor tics physically hurt, why do I think everyone is starring at me and laughing, why doesnt anyone understand me, and every other "common" thing you worry about. Some of these sound selfish and immature but I dont know one human being who doesnt have immature or selfish tendencies. Some people say when your angry, take your anger out on a pillow. Well, there isnt always a pillow available and TS is ALWAYS happening! It doesnt happen once every couple of days like how a normal person might argue or get upset. And TS and the common world right now, just arnt on the same page and so the stress of it is taken out on the people with AND without TS!

                        So, by now no one is still probably reading this but me, lol, but my point is, people with TS dont have "rage" cause rage is not a commonly known "idea". People with TS do get angery quicker, but again, the common idea through the public for why we do, is NOT correct. Unfrotunately, if you never have TS, you will never know. Im male, I will never know what childbirth is like, so when a woman says its very painful, I can only agree caue I THINK it is or diagree cause I THINK it is. (I definately DO AGREE with the idea women have more of a pain threshold than men, if I stub my toe its bad! lol) Anyways, thats my take, maybe no one agrees but I just dont want people styreotyping people with TS on something when I really dont think it is accurate.

                        -adam
                        The other day at a local grocery store, I saw a rack with books on it and one of them said, "pregancy for dummies"............

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