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Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms

  • J. Ferri (a1) (a2), J. M. Ford (a1) (a2), B. J. Roach (a2), J. A. Turner (a3), T. G. van Erp (a4), J. Voyvodic (a5), A. Preda (a4), A. Belger (a6), J. Bustillo (a7), D. O'Leary (a8), B. A. Mueller (a9), K. O. Lim (a9), S. C. McEwen (a10), V. D. Calhoun (a3) (a7) (a11), M. Diaz (a5), G. Glover (a12), D. Greve (a13), C. G. Wible (a14) (a15), J. G. Vaidya (a8), S. G. Potkin (a4) and D. H. Mathalon (a1) (a2)...



Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.


Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.


HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.


Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.


Corresponding author

Author for correspondence: D. H. Mathalon, E-mail:


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Allen, P, Larøi, F, McGuire, PK and Aleman, A (2008) The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neuroscience & Biobehavioral Reviews 32, 175191.
Andreasen, NC (1983) Scale for the Assessment of Negative Symptoms (SANS). Iowa City: University of Iowa.
Andreasen, NC (1984) Scale for the Assessment of Positive Symptoms: (SAPS). Iowa City: University of Iowa.
Andreasen, NC, Paradiso, S and O'leary, DS (1998) “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophrenia Bulletin 24, 203218.
Andreasen, NC and Pierson, R (2008) The role of the cerebellum in schizophrenia. Biological Psychiatry 64, 8188.
Anticevic, A, Cole, MW, Repovs, G, Murray, JD, Brumbaugh, MS, Winkler, AM et al. (2014 a) Characterizing thalamo-cortical disturbances in schizophrenia and bipolar illness. Cerebral Cortex 24, 31163130.
Anticevic, A, Haut, K, Murray, JD, Yang, GJ, Diehl, C, McEwen, SC et al. (2015) Association of thalamic dysconnectivity and conversion to psychosis in youth and young adults at elevated clinical risk. JAMA Psychiatry 72, 882891.
Anticevic, A, Yang, G, Savic, A, Murray, JD, Cole, MW, Repovs, G et al. (2014 b) Mediodorsal and visual thalamic connectivity differ in schizophrenia and bipolar disorder with and without psychosis history. Schizophrenia Bulletin 6, 12271243.
Behzadi, Y, Restom, K, Liau, J and Liu, TT (2007) A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. NeuroImage 37, 90101.
Brandt, MJ, Ijzerman, H, Dijksterhuis, A, Farach, FJ, Geller, J, Giner-Sorolla, R et al. (2014) The replication recipe: what makes for a convincing replication? Journal of Experimental Social Psychology 50, 217224.
Brent, BK, Thermenos, HW, Keshavan, MS and Seidman, LJ (2013) Gray matter alterations in schizophrenia high-risk youth and early-onset schizophrenia: a review of structural MRI findings. Child and Adolescent Psychiatric Clinics of North America 22, 689714.
Button, KS, Ioannidis, JP, Mokrysz, C, Nosek, BA, Flint, J, Robinson, ES et al. (2013) Power failure: why small sample size undermines the reliability of neuroscience. Nature Reviews Neuroscience 14, 365376.
Çetin, MS, Christensen, F, Abbott, CC, Stephen, JM, Mayer, AR, Cañive, JM et al. (2014) Thalamus and posterior temporal lobe show greater inter-network connectivity at rest and across sensory paradigms in schizophrenia. NeuroImage 97, 117126.
Cheng, W, Palaniyappan, L, Li, M, Kendrick, KM, Zhang, J, Luo, Q et al. (2015) Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry. npj Schizophrenia 1, 15016.
Cobia, DJ, Smith, MJ, Wang, L and Csernansky, JG (2012) Longitudinal progression of frontal and temporal lobe changes in schizophrenia. Schizophrenia Research 139, 16.
Collin, G, Pol, HEH, Haijma, SV, Cahn, W, Kahn, RS and van den Heuvel, MP (2011) Impaired cerebellar functional connectivity in schizophrenia patients and their healthy siblings. Frontiers Psychiatry 2, 73.
Damaraju, E, Allen, E, Belger, A, Ford, J, McEwen, S, Mathalon, D et al. (2014) Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia. NeuroImage: Clinical 5, 298308.
Fagerstrom, KO (1978) Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addictive Behaviors 3, 235241.
Feinberg, I (1978) Efference copy and corollary discharge: implications for thinking and its disorders. Schizophrenia Bulletin 4, 636.
Feinberg, I and Guazzelli, M (1999) Schizophrenia – a disorder of the corollary discharge systems that integrate the motor systems of thought with the sensory systems of consciousness. British Journal of Psychiatry 174, 196204.
First, MB, Spitzer, RL, Gibbon, MG and Williams, JBW (2002 a) Structured Clinical Interview for DSM-IV-TR Axis I Disorders – Non-Patient Edition (SCID-I/NP). New York: Biometrics Research, New York State Psychiatric Institute.
First, MB, Spitzer, RL, Gibbon, MG and Williams, JBW (2002 b) Structured Clinical Interview for DSM-IV-TR Axis I Disorders – Patient Edition (SCID-I/P, 11/2002 revision). New York: Biometrics Research, New York State Psychiatric Institute.
Frith, CD, Blakemore, S-J and Wolpert, DM (2000) Explaining the symptoms of schizophrenia: abnormalities in the awareness of action. Brain Research Reviews 31, 357363.
Giraldo-Chica, M and Woodward, ND (2016) Review of thalamocortical resting-state fMRI studies in schizophrenia. Schizophrenia Research 180, 5863.
Hollingstead, AB (1975) Four Factor Index of Social Status. New Haven, CT: Yale University.
Huang, X, Nichols, TE, Kim, B and Foster, N (2007) Accounting for missing data in neuroimaging analyses. In 3th Annual Meeting of the Organization for Human Brain Mapping. Chicago, Illinois: NeuroImage, p. #341.
Jardri, R, Pouchet, A, Pins, D and Thomas, P (2011) Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. American Journal of Psychiatry 168, 7381.
Kastner, S, Schneider, KA and Wunderlich, K (2006) Beyond a relay nucleus: neuroimaging views on the human LGN. Progress in Brain Research 155, 125143.
Klingner, CM, Langbein, K, Dietzek, M, Smesny, S, Witte, OW, Sauer, H et al. (2014) Thalamocortical connectivity during resting state in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 264, 111119.
Lancaster, JL, Woldorff, MG, Parsons, LM, Liotti, M, Freitas, CS, Rainey, L et al. (2000) Automated Talairach atlas labels for functional brain mapping. Human Brain Mapping 10, 120131.
Li, T, Wang, Q, Zhang, J, Rolls, ET, Yang, W, Palaniyappan, L et al. (2016) Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia. Schizophrenia Bulletin 43, 436448.
Mathalon, DH and Ford, JM (2008) Corollary discharge dysfunction in schizophrenia: evidence for an elemental deficit. Clinical EEG and Neuroscience 39, 8286.
Mathalon, DH and Ford, JM (2012) Neurobiology of schizophrenia: search for the elusive correlation with symptoms. Frontiers in Human Neuroscience 6, 136.
Niendam, TA, Laird, AR, Ray, KL, Dean, YM, Glahn, DC and Carter, CS (2012) Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cognitive, Affective, & Behavioral Neuroscience 12, 241268.
Nishio, Y, Hashimoto, M, Ishii, K and Mori, E (2011) Neuroanatomy of a neurobehavioral disturbance in the left anterior thalamic infarction. Journal of Neurology, Neurosurgery & Psychiatry 82, 11951200.
Oldfield, RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97113.
Ramnani, N (2006) The primate cortico-cerebellar system: anatomy and function. Nature Reviews Neuroscience 7, 511522.
Schmid, MC, Singer, W and Fries, P (2012) Thalamic coordination of cortical communication. Neuron 75, 551552.
Sherman, SM (2007) The thalamus is more than just a relay. Current Opinion in Neurobiology 17, 417422.
Sherman, SM (2016) Thalamus plays a central role in ongoing cortical functioning. Nature Neuroscience 16, 533541.
Stephan, KE, Baldeweg, T and Friston, KJ (2006) Synaptic plasticity and dysconnection in schizophrenia. Biological Psychiatry 59, 929939.
Stephan, KE, Friston, KJ and Frith, CD (2009) Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophrenia Bulletin 35, 509527.
Tang, J, Liao, Y, Zhou, B, Tan, C, Liu, W, Wang, D et al. (2012) Decrease in temporal gyrus gray matter volume in first-episode, early onset schizophrenia: an MRI study. PloS ONE 7, e40247.
Uttl, B (2002) North American adult reading test: age norms, reliability, and validity. Journal of Clinical and Experimental Neuropsychology 24, 11231137.
Wang, H-LS, Rau, C-L, Li, Y-M, Chen, Y-P and Yu, R (2015) Disrupted thalamic resting-state functional networks in schizophrenia. Frontiers in Behavioral Neuroscience 9, 45.
Watanabe, Y and Funahashi, S (2012) Thalamic mediodorsal nucleus and working memory. Neuroscience & Biobehavioral Reviews 36, 134142.
Whitfield-Gabrieli, S and Nieto-Castanon, A (2012) Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity 2, 125141.
Woodward, ND and Heckers, S (2015) Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders. Biological Psychiatry 79, 10161025.
Woodward, ND, Karbasforoushan, H and Heckers, S (2012) Thalamocortical dysconnectivity in schizophrenia. American Journal of Psychiatry 10, 10921099.


Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms

  • J. Ferri (a1) (a2), J. M. Ford (a1) (a2), B. J. Roach (a2), J. A. Turner (a3), T. G. van Erp (a4), J. Voyvodic (a5), A. Preda (a4), A. Belger (a6), J. Bustillo (a7), D. O'Leary (a8), B. A. Mueller (a9), K. O. Lim (a9), S. C. McEwen (a10), V. D. Calhoun (a3) (a7) (a11), M. Diaz (a5), G. Glover (a12), D. Greve (a13), C. G. Wible (a14) (a15), J. G. Vaidya (a8), S. G. Potkin (a4) and D. H. Mathalon (a1) (a2)...


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