Home About Login Current Archives Announcements Editorial Board
Submit Now For Authors Call for Submissions Statistics Contact
Home > Archives > Volume 12, No 2 (2014) > Article

DOI: 10.14704/nq.2014.12.2.758

Co-Variations Among Cognition, Cerebellar Disorders and Cortical Areas With Regional Glucose-Metabolic Activities in a Homogeneous Sample with Uner Tan Syndrome: Holistic Functioning of the Human Brain

Uner Tan


Background: Patients with Uner Tan syndrome (UTS) exhibit habitual quadrupedal locomotion (QL), intellectual disability, dysarthric speech and truncal ataxia. Examination of cognitive ability in this syndrome has not yet been demonstrated in the scientific literature. Aims: (i) To analyze the cognitive abilities of the siblings with UTS; (ii) to assess the grade of their ataxia in relation to cerebellar disorders; (iii) to measure the metabolic activities of various cerebral regions in comparison with healthy individuals; (iv) to detect the interrelationships among all of the measured variables (IQ test scores, ataxia scores, cerebro-cerebellar areas and their metabolic activity levels) to reveal the holistic activity of the brain. Methods: The Minimental State Examination (MMSE) and Wechsler Adult Intelligence Scale (WAIS-R) were applied to the affected cases and healthy subjects. Cerebellar disorders were assessed by the International Cooperative Ataxia Rating Scale (ICARS). Brain MRI scans were performed and cerebro-cerebellar areas were measured on MRI scans, including their metabolic activities (SUV), measured by positron emission tomography (PET) scanning. Results: MMSE and WAIS-R scores both correlated with cerebro-cerebellar areas. Cerebello-vermial areas and their metabolic activities were significantly smaller in patients than in normal controls; areas of the remaining structures were not significantly different between patients and healthy subjects. Brain areas significantly inter-correlated: ICARS negatively correlated with WAIS-R, MMSE scores, SUV, and cerebro-cerebellar areas, which significantly correlated with each other. Conclusions: The results suggested (i) ICARS may not only be a test for cerebellar disorders, but also may be related to global functioning of all of the cerebro-cerebellar regions; (ii) ICARS, WAIS-R and MMSE may be measures of emergent properties of the holistic activity of the brain; (iii) the psychomotor disorders in UTS may be related to decreased brain metabolism.


Uner Tan syndrome; ataxia; intelligence; neural network; holistic brain

Full Text



Boccaletti S, Latora V, Moreno Y, Chavez M, Hwang D-U. Complex networks: structure and dynamics. Physics Reports 2006; 424:175-308.

Childs WJ. Across Asia Minor on Foot: Edinburgh and London: William Blackwood and Sons, 1917.

Deacon TW. Holism and associationism in neuropsychology: In: Integrating theory and practice in clinical neuropsychology, E. Perecman (ed.), Erlbaum. Hilsdale, NJ; 1989.

Epir S, Iskir U. Wechsler yetişkinler zeka olcegi türkce cevirisinin ön analizi ve üniversite danismanlik merkezlerindeki uygulama potansiyeli. Hacettepe Sosyal ve Beseri Bilimler Dergisi 1972;4:198-205.

Faustman JA, Moses Jr JG, Csernansky JH. Limitations of the Mini-Mental State Examination in predicting neuropsychological functioning in a psychiatric sample. Acta Psychiatr Scand 1990; 81:126-131.

Feczko E, Augustinack JC, Fischi B, Bradford C, Dickerson C. An MRI-based method for measuring volume, thickness and surface area of entorhinal, perirhinal, and posterior parahippocampal cortex. Neurobiol Aging 2009; 30:420-431.

Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading cognitive state of patients fort the clinician. J Psychatr Res1975; 12:189-198.

Fox MD, Snyder AZ, Zacks JM, Raichle ME. Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses. Nat Neurosci.2006; 9:23-25.

Guertin PA. Central pattern generator for locomotion: anatomical, physiological, and pathophysiological considerations. Front Neurol 2013; 3, article 183, doi: 10.3389/fneur.2012.00183.

Gulsuner S. Quadrupedal gait in humans: identification and partial characterization of a novel gene WD repeat domain 81 /WDR81). Thesis, Bilkent University, Ankara, 2011.

Güngen C, Ertan T, Eker E, et al. Standardized Mini Mental Test’in Türk toplumunda hafif dementia tanısında geçerlik ve güvenilirliği. Türk Psikiyatri Dergisi 2002; 13:273-281.

Ivanenko YP, Wright WG, St George RJ, Gurfinkel VS. Trunk orientation, stability, and quadrupedalism. Frontiers in Neurology 2013; 4, article 20, doi: 10.3389/fneur.2013.00020.

Mungas D. In-office mental status testing: a practical guide. Geriatrics 1991; 46:54-58.

Onat OE, Gulsuner S, Bilguvar K, Basak AN, et al. Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion. Eur J Hum Genet 2012; 21:281-285.

Ozcelik T, Akarsu N, Uz B, Caglayan S, Gulsuner S, Onat OE, et al. Mutations in the very low density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans. Proc Natl Acad Sci USA 2008; 105:4232-4236.

Rakic P. Defects of neuronal migration and the pathogenesis of cortical malformations. Prog Brain Res 1988; 73:15-37.

Schmahmann JD. The cerebellar contribution to higher function. Arch Neurol 1991;48:1178-1187.

Schoch B, Regel JP, Frings M et al. Reliability and validity of ICARS in focal cerebellar lesions. Mov Dis 2007; 22:2162-2169.

Sporns O. Brain network disease. In Networks of the brain, O. Sporns (Ed.), The MIT Press: Cambridge, Massachusetts, London, England; 2011.

Storey E, Tuck K, Hughes A, Churchyard A. Inter-rater reliability of the international Cooperative Ataxia Rating Scale (ICARS). Mov Dis 2004; 19:190-212.

Stuart DG. Integration of posture and movement: contributions of Sherrington, Hess, and Bernstein. Hum Mov Sci 2005; 24:621-643.

Tan U. Unertan syndrome; quadrupedality, primitive language, and severe mental retardation; a new theory on the evolution of human mind. NeuroQuantology 2005; 4:250-255.

Tan U. Uner Tan syndrome: history, clinical evaluations, genetics, and the dynamics of human quadrupedalism. The Open Neurol J 2010; 4:78-89.

Tan U, Karaca S, Tan M, Yilmaz B, Bagci NK, et al. Unertan syndrome: a case series demonstrating human devolution. Int J Neurosci 2008;118:1-25.

Tan U, Tamam Y, Karaca S, Tan M, Tan U. Uner Tan syndrome: review and emergence of human quadrupedalism in self-organization, attractors and evolutionary perspectives. In:Tan U (Ed.), Latest Findings in Intellectual and Developmental Disabilities Research. Croatia, InTech Publications; 2012.

Tarlaci S. A historical view of the relation between quantum mechanics and the brain: a neuroquantologic perspective. NeuroQuantology 2010; 8:120-136.

Thelen E, Smith LB. A dynamic systems approach to the development of cognition and action. The MIT Press: Cambridge, Massachussetts, London, England; 1994.

Tobias PV. The upright head in hominid evolutionâ€, in The head-neck sensory motor system. A Berthoz, W Graf, PP Vidal (eds.), New York: Oxford University Press; 1992.

Wechsler D. WAIS-R manual: Wechsler Adult Intelligence Scale-Revised. New York: The Psychological Corporation; 1981.

Woolsey TA, Rovainen CM, Cox SB, Hnegar MH, Liang GE, Liu D, Moskalenko YE, Sui J, Wei L. Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain. Cereb Cortex 1996; 6:647-660.

Zemanova L, Zhou C, Kurths J.Structural and functional clusters of complex brain networks. Physica D 2006; 224:202-212.