Disconnected and Hyperactive: A Replication of Sensorimotor Cortex Abnormalities in Patients With Schizophrenia During Proactive Response Inhibition

Inhibitory failure represents a core dysfunction in patients with schizophrenia (SP), which has predominantly been tested in the literature using reactive (ie, altering behavior after a stimulus) rather than proactive (ie, purposefully changing behavior before a stimulus) response inhibition tasks. The current study replicates/extends our previous findings of SP exhibiting sensorimotor cortex (SMC) hyperactivity and connectivity abnormalities in independent samples of patients and controls. Specifically, 49 clinically well-characterized SP and 54 matched healthy controls (HC) performed a proactive response inhibition task while undergoing functional magnetic resonance imaging and resting-state data collection. Results indicated that the majority of SP (84%) and HC (88%) successfully inhibited all overt motor responses following a cue, eliminating behavioral confounds frequently present in this population. Observations of left SMC hyperactivity during proactive response inhibition, reduced cortical connectivity with left SMC, and increased connectivity between left SMC and ventrolateral thalamus were replicated for SP relative to HC in the current study. Similarly, negative symptoms (eg, motor retardation) were again associated with SMC functional and connectivity abnormalities. In contrast, findings of a negative blood oxygenation level-dependent response in the SMC of HC did not replicate. Collectively, current and previous findings suggest that SMC connectivity abnormalities may be more robust relative to evoked hemodynamic signals during proactive response inhibition. In addition, there is strong support that these SMC abnormalities are a key component of SP pathology, along with dysfunction within other sensory cortices, and may be associated with certain clinical deficits such as negative symptoms.

[1]  Niall W. Duncan,et al.  Abnormal Resting-State Connectivity in a Substantia Nigra-Related Striato-Thalamo-Cortical Network in a Large Sample of First-Episode Drug-Naïve Patients With Schizophrenia , 2018, Schizophrenia bulletin.

[2]  A. Federspiel,et al.  Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders , 2017, Schizophrenia bulletin.

[3]  J. Bernard,et al.  A case for motor network contributions to schizophrenia symptoms: Evidence from resting‐state connectivity , 2017, Human brain mapping.

[4]  Dov B. Lerman-Sinkoff,et al.  Transdiagnostic Associations Between Functional Brain Network Integrity and Cognition , 2017, JAMA psychiatry.

[5]  I. Melle,et al.  Thalamo-cortical functional connectivity in schizophrenia and bipolar disorder , 2017, Brain Imaging and Behavior.

[6]  Lars T. Westlye,et al.  Task modulations and clinical manifestations in the brain functional connectome in 1615 fMRI datasets , 2017, NeuroImage.

[7]  Heidi C Meyer,et al.  Neural and behavioral mechanisms of proactive and reactive inhibition , 2016, Learning & memory.

[8]  Andrew R Mayer,et al.  Proactive response inhibition abnormalities in the sensorimotor cortex of patients with schizophrenia. , 2016, Journal of psychiatry & neuroscience : JPN.

[9]  F. Hanlon,et al.  Hemodynamic response function abnormalities in schizophrenia during a multisensory detection task , 2016, Human brain mapping.

[10]  Tyrone D. Cannon,et al.  Association of Thalamic Dysconnectivity and Conversion to Psychosis in Youth and Young Adults at Elevated Clinical Risk. , 2015, JAMA psychiatry.

[11]  Michael C. Frank,et al.  Estimating the reproducibility of psychological science , 2015, Science.

[12]  Wei Cheng,et al.  Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry , 2015, npj Schizophrenia.

[13]  I. Melle,et al.  Disintegration of Sensorimotor Brain Networks in Schizophrenia. , 2015, Schizophrenia bulletin.

[14]  Jeffrey D. Schall,et al.  Response inhibition and response monitoring in a saccadic double-step task in schizophrenia , 2015, Brain and Cognition.

[15]  Michael W. Cole,et al.  Characterizing thalamo-cortical disturbances in schizophrenia and bipolar illness. , 2014, Cerebral cortex.

[16]  Vince D. Calhoun,et al.  Thalamus and posterior temporal lobe show greater inter-network connectivity at rest and across sensory paradigms in schizophrenia , 2014, NeuroImage.

[17]  A. Belger,et al.  Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia , 2014, NeuroImage: Clinical.

[18]  Juan Bustillo,et al.  Functional imaging of the hemodynamic sensory gating response in schizophrenia , 2013, Human brain mapping.

[19]  Stephen D. Mayhew,et al.  Poststimulus undershoots in cerebral blood flow and BOLD fMRI responses are modulated by poststimulus neuronal activity , 2013, Proceedings of the National Academy of Sciences.

[20]  Yue-Cune Chang,et al.  Clinical symptoms, mainly negative symptoms, mediate the influence of neurocognition and social cognition on functional outcome of schizophrenia , 2013, Schizophrenia Research.

[21]  Jong H. Yoon,et al.  Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia☆ , 2013, NeuroImage: Clinical.

[22]  Robert Chen,et al.  Transcallosal inhibition in patients with callosal infarction. , 2013, Journal of neurophysiology.

[23]  M. Criaud,et al.  Have we been asking the right questions when assessing response inhibition in go/no-go tasks with fMRI? A meta-analysis and critical review , 2013, Neuroscience & Biobehavioral Reviews.

[24]  Julia M Stephen,et al.  Modeling conflict and error in the medial frontal cortex , 2012, Human brain mapping.

[25]  Pratik K. Mutha,et al.  The Effects of Brain Lateralization on Motor Control and Adaptation , 2012, Journal of motor behavior.

[26]  Stephan Heckers,et al.  Thalamocortical dysconnectivity in schizophrenia. , 2012, The American journal of psychiatry.

[27]  P. Michie,et al.  Stop-signal response inhibition in schizophrenia: Behavioural, event-related potential and functional neuroimaging data , 2012, Biological Psychology.

[28]  R. Kahn,et al.  Reduced Proactive Inhibition in Schizophrenia Is Related to Corticostriatal Dysfunction and Poor Working Memory , 2011, Biological Psychiatry.

[29]  J. Barton,et al.  Abnormally persistent fMRI activation during antisaccades in schizophrenia: A neural correlate of perseveration? , 2011, Schizophrenia Research.

[30]  Alexander Kraskov,et al.  Ventral Premotor–Motor Cortex Interactions in the Macaque Monkey during Grasp: Response of Single Neurons to Intracortical Microstimulation , 2011, The Journal of Neuroscience.

[31]  Diane Swick,et al.  Are the neural correlates of stopping and not going identical? Quantitative meta-analysis of two response inhibition tasks , 2011, NeuroImage.

[32]  Kiyoto Kasai,et al.  Prefrontal cortex activity during response inhibition associated with excitement symptoms in schizophrenia , 2011, Brain Research.

[33]  R. Baldessarini,et al.  International consensus study of antipsychotic dosing. , 2010, The American journal of psychiatry.

[34]  D. Johnston,et al.  Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling , 2010, The Journal of Neuroscience.

[35]  Deanna M. Barch,et al.  Improving Prefrontal Cortex Function in Schizophrenia Through Focused Training of Cognitive Control , 2009, Front. Hum. Neurosci..

[36]  K. Nuechterlein,et al.  Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: A meta-analysis , 2009, Schizophrenia Research.

[37]  J. Pekar,et al.  Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent , 2008, Neuropsychologia.

[38]  J. Anton,et al.  Blunted activation in right ventrolateral prefrontal cortex during motor response inhibition in schizophrenia , 2007, Schizophrenia Research.

[39]  D. Kleinfeld,et al.  Is there a common origin to surround-inhibition as seen through electrical activity versus hemodynamic changes? Focus on "Duration-dependent response in SI to vibrotactile stimulation in squirrel monkey". , 2007, Journal of neurophysiology.

[40]  H. Meltzer Illuminating the molecular basis for some antipsychotic drug-induced metabolic burden , 2007, Proceedings of the National Academy of Sciences.

[41]  Jared X. Van Snellenberg,et al.  Functional neuroimaging of working memory in schizophrenia: task performance as a moderating variable. , 2006, Neuropsychology.

[42]  N. Logothetis,et al.  Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1 , 2006, Nature Neuroscience.

[43]  S. Swinnen,et al.  Dynamics of hemispheric specialization and integration in the context of motor control , 2006, Nature Reviews Neuroscience.

[44]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[45]  P. Fitzgerald,et al.  Reduced plastic brain responses in schizophrenia: a transcranial magnetic stimulation study , 2004, Schizophrenia Research.

[46]  Paul B. Fitzgerald,et al.  Repetitive transcranial magnetic stimulation reveals abnormal plastic response to premotor cortex stimulation in schizophrenia , 2004, Biological Psychiatry.

[47]  U. Ziemann,et al.  Hemispheric asymmetry of transcallosalinhibition in man , 2004, Experimental Brain Research.

[48]  Stefan Skare,et al.  How to correct susceptibility distortions in spin-echo echo-planar images: application to diffusion tensor imaging , 2003, NeuroImage.

[49]  J. Pekar,et al.  fMRI evidence that the neural basis of response inhibition is task-dependent. , 2003, Brain research. Cognitive brain research.

[50]  P. Fitzgerald,et al.  A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia , 2002, Psychiatry Research: Neuroimaging.

[51]  Marcel Brass,et al.  The Inhibition of Imitative Response Tendencies , 2001, NeuroImage.

[52]  Katya Rubia,et al.  An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function , 2001, Schizophrenia Research.

[53]  J. Pierri,et al.  Altered GABA neurotransmission and prefrontal cortical dysfunction in schizophrenia , 1999, Biological Psychiatry.

[54]  P. Goldman-Rakic,et al.  The reduced neuropil hypothesis: a circuit based model of schizophrenia , 1999, Biological Psychiatry.

[55]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[56]  M. First,et al.  Structured clinical interview for DSM-IV axis I disorders : SCID-I: clinical version : administration booklet , 1996 .

[57]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .