Cortical correlates of TMS-induced phantom hand movements revealed with concurrent TMS-fMRI

We studied an amputee patient who experiences a conscious sense of movement (SoM) in her phantom hand, without significant activity in remaining muscles, when transcranial magnetic stimulation (TMS) is applied at appropriate intensity over the corresponding sector of contralateral motor cortex. We used the novel methodological combination of TMS during fMRI to reveal the neural correlates of her phantom SoM. A critical contrast concerned trials at intermediate TMS intensities: low enough not to produce overt activity in remaining muscles; but high enough to produce a phantom SoM on approximately half such trials. Comparing trials with versus without a phantom SoM reported phenomenally, for the same intermediate TMS intensities, factored out any non-specific TMS effects on brain activity to reveal neural correlates of the phantom SoM itself. Areas activated included primary motor cortex, dorsal premotor cortex, anterior intraparietal sulcus, and caudal supplementary motor area, regions that are also involved in some hand movement illusions and motor imagery in normals. This adds support to proposals that a conscious sense of movement for the hand can be conveyed by activity within corresponding motor-related cortical structures.

[1]  L. Garcia-Larrea,et al.  Timing and characteristics of perceptual attenuation by transcranial stimulation: a study using magnetic cortical stimulation and somatosensory-evoked potentials. , 1999, Psychophysiology.

[2]  V S Ramachandran,et al.  Consciousness and body image: lessons from phantom limbs, Capgras syndrome and pain asymbolia. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[3]  Jens Frahm,et al.  Functional somatotopy of finger representations in human primary motor cortex , 2003, Human brain mapping.

[4]  J C Rothwell,et al.  Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation. , 1994, Journal of neurophysiology.

[5]  B U Meyer,et al.  Long-term reorganization of motor cortex outputs after arm amputation , 1999, Neurology.

[6]  N. Birbaumer,et al.  Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain? , 1999, Nature Neuroscience.

[7]  Jens Frahm,et al.  Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS , 2003, NeuroImage.

[8]  S. Bestmann,et al.  Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS) , 2001, Neuroreport.

[9]  D. Bohning,et al.  Performance of a system for interleaving transcranial magnetic stimulation with steady-state magnetic resonance imaging. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[10]  A. Woodhouse,et al.  Phantom limb sensation , 2005, Clinical and experimental pharmacology & physiology.

[11]  J Valls-Solé,et al.  Rapid modulation of human cortical motor outputs following ischaemic nerve block. , 1993, Brain : a journal of neurology.

[12]  H. Flor,et al.  Phantom movements and pain. An fMRI study in upper limb amputees. , 2001, Brain : a journal of neurology.

[13]  P. Roland,et al.  I Feel My Hand Moving A New Role of the Primary Motor Cortex in Somatic Perception of Limb Movement , 2002, Neuron.

[14]  M. Diamond,et al.  Primary Motor and Sensory Cortex Activation during Motor Performance and Motor Imagery: A Functional Magnetic Resonance Imaging Study , 1996, The Journal of Neuroscience.

[15]  Ziad Nahas,et al.  A combined TMS/fMRI study of intensity-dependent TMS over motor cortex , 1999, Biological Psychiatry.

[16]  D. Bohning,et al.  Cortical and subcortical brain effects of Transcranial Magnetic Stimulation (TMS)-induced movement: An interleaved TMS/functional magnetic resonance imaging study , 2005, Biological Psychiatry.

[17]  E M Wassermann,et al.  BOLD‐f MRI response to single‐pulse transcranial magnetic stimulation (TMS) , 2000, Journal of magnetic resonance imaging : JMRI.

[18]  W. Penfield,et al.  SOMATIC MOTOR AND SENSORY REPRESENTATION IN THE CEREBRAL CORTEX OF MAN AS STUDIED BY ELECTRICAL STIMULATION , 1937 .

[19]  J. Lorberbaum,et al.  Motor Cortex Brain Activity Induced by 1-Hz Transcranial Magnetic Stimulation Is Similar in Location and Level to That for Volitional Movement , 2000, Investigative radiology.

[20]  E Naito,et al.  Kinesthetic illusion of wrist movement activates motor-related areas , 2001, Neuroreport.

[21]  J. Decety Do imagined and executed actions share the same neural substrate? , 1996, Brain research. Cognitive brain research.

[22]  C. Frith,et al.  Whose arm is it anyway? An fMRI case study of supernumerary phantom limb. , 2002, Brain : a journal of neurology.

[23]  K. Zilles,et al.  Illusory Arm Movements Activate Cortical Motor Areas: A Positron Emission Tomography Study , 1999, The Journal of Neuroscience.

[24]  V. Amassian,et al.  A sense of movement elicited in paralyzed distal arm by focal magnetic coil stimulation of human motor cortex , 1989, Brain Research.

[25]  A. Prochazka,et al.  The sense of movement elicited by transcranial magnetic stimulation in humans is due to sensory feedback , 2004, The Journal of physiology.

[26]  M. Jeannerod,et al.  Mental imaging of motor activity in humans , 1999, Current Opinion in Neurobiology.

[27]  J. Roll,et al.  Motor and parietal cortical areas both underlie kinaesthesia. , 2003, Brain research. Cognitive brain research.

[28]  V. Ramachandran,et al.  The perception of phantom limbs. The D. O. Hebb lecture. , 1998, Brain : a journal of neurology.

[29]  M. Erb,et al.  Activation of Cortical and Cerebellar Motor Areas during Executed and Imagined Hand Movements: An fMRI Study , 1999, Journal of Cognitive Neuroscience.

[30]  M. Hallett,et al.  Leg paresthesias induced by magnetic brain stimulation in patients with thoracic spinal cord injury , 1991, Neurology.

[31]  N Birbaumer,et al.  Reorganization of Motor and Somatosensory Cortex in Upper Extremity Amputees with Phantom Limb Pain , 2001, The Journal of Neuroscience.

[32]  R M Müri,et al.  Beyond re-membering: phantom sensations of congenitally absent limbs. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  S. Bandinelli,et al.  Motor reorganization after upper limb amputation in man. A study with focal magnetic stimulation. , 1991, Brain : a journal of neurology.

[34]  Á. Pascual-Leone,et al.  Reorganization of human cortical motor output maps following traumatic forearm amputation , 1996, Neuroreport.

[35]  J. Rothwell,et al.  Intracortical inhibition and facilitation in different representations of the human motor cortex. , 1998, Journal of neurophysiology.

[36]  Karl J. Friston,et al.  Classical and Bayesian Inference in Neuroimaging: Theory , 2002, NeuroImage.

[37]  R. Passingham,et al.  That's My Hand! Activity in Premotor Cortex Reflects Feeling of Ownership of a Limb , 2004, Science.

[38]  Karl J. Friston,et al.  Modelling Geometric Deformations in Epi Time Series , 2022 .

[39]  A. Lundervold,et al.  Different Brain Areas Activated during Imagery of Painful and Non-painful ‘Finger Movements’ in a Subject with an Amputated Arm , 2001, Neurocase.

[40]  Stephan A Brandt,et al.  Spatial reorganization of cortical motor output maps of stump muscles in human upper-limb amputees , 2002, Neuroscience Letters.

[41]  P. Dechent,et al.  Is the human primary motor cortex involved in motor imagery? , 2004, Brain research. Cognitive brain research.

[42]  R. van Ee,et al.  Activation in Visual Cortex Correlates with the Awareness of Stereoscopic Depth , 2005 .

[43]  J. Baudewig,et al.  Artifacts caused by transcranial magnetic stimulation coils and EEG electrodes in T(2)*-weighted echo-planar imaging. , 2000, Magnetic resonance imaging.

[44]  Karl J. Friston,et al.  The Neural Structures Expressing Perceptual Hysteresis in Visual Letter Recognition , 2002, Neuron.

[45]  Isabelle Berry,et al.  Cortical Areas Involved in Virtual Movement of Phantom Limbs: Comparison with Normal Subjects , 2003, Neurosurgery.

[46]  J. Lorberbaum,et al.  Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial magnetic stimulation. , 1998, Investigative radiology.

[47]  M. Hallett,et al.  Repetitive transcranial magnetic stimulation. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[48]  Leslie G. Ungerleider,et al.  Dominance of the right hemisphere and role of area 2 in human kinesthesia. , 2005, Journal of neurophysiology.

[49]  Lars Ersland,et al.  Phantom limb imaginary fingertapping causes primary motor cortex activation: an fMRI study , 1996, Neuroreport.

[50]  H. Siebner,et al.  Effector‐independent representations of simple and complex imagined finger movements: a combined fMRI and TMS study , 2003, The European journal of neuroscience.

[51]  S. Bestmann,et al.  On the synchronization of transcranial magnetic stimulation and functional echo‐planar imaging , 2003, Journal of magnetic resonance imaging : JMRI.

[52]  M. Hallett,et al.  Noninvasive mapping of muscle representations in human motor cortex. , 1992, Electroencephalography and clinical neurophysiology.

[53]  M Schwaiger,et al.  Phantom limb pain in the human brain: Unraveling neural circuitries of phantom limb sensations using positron emission tomography , 2000, Annals of neurology.

[54]  J G Ojemann,et al.  Cortical stimulation mapping of phantom limb rolandic cortex. Case report. , 1995, Journal of neurosurgery.

[55]  J. Rothwell,et al.  Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits , 2004, The European journal of neuroscience.