Lecture 2 TMS & Lesions PoCN 2024 PDF

Dr Silke Göbel Methods: Lesions & TMS  Objectives Give an overview of the basic principles underlying lesion studies and brain stimulation Describe elements of good experimental design for TMS and lesion studies Discuss characteristic strengths and  Overview Lesi...

Dr Silke Göbel Methods: Lesions & TMS  Objectives Give an overview of the basic principles underlying lesion studies and brain stimulation Describe elements of good experimental design for TMS and lesion studies Discuss characteristic strengths and  Overview Lesion studies Basic idea Single dissociation Double dissociation Transcranial Magnetic Stimulation (TMS) History & Principles Designing TMS studies Lesion studies “If you don’t know what it does, destroy it and see what happens!” Lesion Studies: Basic Idea When a specific brain region is purposefully or incidentally damaged, and consequentially specific cognitive functions are affected, these functions are causally connected to processing in this region. Lesion Studies: Basic Idea When a specific brain region is purposefully or incidentally damaged, and consequentially specific cognitive functions are affected, these functions are causally connected to processing in this region. Lesion Studies: Methods Overview Invasive Methods Destroy processing Non-invasive Methods in brain region of Studying patients with interest incidental lesions in Can for instance be specific parts of their brains done by removing brain tissue or Using brain stimulation cooling the region to temporally impair neural processing (next Ethically very section!) problematic  Lesion Mapping in Patients Lesion mapping requires the use of structural imaging (e.g., magnetic resonance imaging) Carefully mapping the damaged cortical regions allows for establishing spatially specific and causal Goodale et al., 1991 relationships between brain activations and cognitive functions Single dissociations Single dissociation: A lesion to a specific region leads to an impairment in a specific task (but not in other tasks) Problem: Single dissociations my be found when the two tasks are differently sensitive (e.g., different task demands or difficulty) This problem of single dissociations is aggravated by the fact that participants may have unspecific impairments that impair their performance in various tasks with high sensitivity  Example of a single dissociation Example: Single dissociation between dorsal and ventral stream functions in the visual system Traumatic lesion in human ventral stream (patient D.F.) leads to impaired object Goodale et al., 1991 perception, but leaves object-guided action intact  Example of a single dissociation Example: Single dissociation between dorsal and ventral stream functions in the visual system Traumatic lesion in human ventral stream (patient D.F.) leads to impaired object Goodale et al., 1991 perception, but leaves object-guided action intact Another single dissociation: Acalculia Lee (2000): 56 year old woman, impaired in multiplication but not in subtraction and addition  Subtraction and multiplication Areas more active in subtraction (in red) and in multiplication (in green) This can explain the frequent dissociation of the two operations From Lee (2000) Double dissociation Double dissociation: A lesion to one region leads to an impairment in a specific task (but not the second task), and a lesion to another region leads to an impairment in another specific task (but not the first task) Reveals unequivocal links between lesion and putative brain function, that are not explicable by the tasks’ sensitivity Double dissociation Example: Double dissociation between dorsal and ventral stream functions in the primate visual system  eam str l sa or D Ventral stream Double dissociation Mishkin et al. (1983) Double dissociation Example: Double dissociation between dorsal and ventral stream functions in the primate visual system Artificial lesions in animals’ ventral stream leads to an impairment in discrimination Mishkin et al., 1983 Animals cannot perform a task where they need to match the shape of two targets to obtain a reward Double dissociation Example: Double dissociation between dorsal and ventral stream functions in the primate visual system Artificial lesions in animals’ dorsal stream leads to an impairment in localization Animals cannot perform a Mishkin et al., 1983 task where they need to discriminate the position of a probe relative to two targets to obtain a reward Single vs. double dissociation Vaidya et al., 2019  Subtraction and multiplication Areas more active in subtraction (in red) and in multiplication (in green) From Lee (2000) Calculation Impairments Cipolotti & van Harskamp, 2001 Dissociations and Modularity  Varietiesof system that can produce dissociations when damaged (theoretical) From Shallice, T. (1995). From Neuropsychology to Mental Structure. Lesions: problem space Lesions: problem space Lesion studies Weaknesses Strengths Low temporal precision Reveals causal Low spatial precision links between (when studying brain regions incidental lesions) and function Confounding High spatial impairments are not precision (when unlikely done invasively) Experimentation can be difficult, costly, and unethical Brain stimulation Driving neural activation to understand brain function Brain stimulation: basic idea When neurons communicate, they change their membrane potentials and eventually fire action potentials. By inducing electrical currents into neurons, we can either push neurons to fire more (or to be more excitable) or induce chaotic activations that prevent coordinated firing. Brain stimulation: Methods overview Invasive Methods Electric stimulation Non-invasive Methods of neurons in Using fast changing magnetic fields particular brain (Transcranial Magnetic regions Stimulations) to In humans: Rarely stimulate neurons possible for patients [Using transcranial direct with implanted (tDCS) or alternating (tACS) current electrodes (e.g., for stimulation across the informing epilepsy head to modulate treatment) activity] Introduction to TMS Click icon to add picture What is TMS? History Walsh & Cowey (2000 History of TMS 1896: d’Arsonval Painless stimulation of the nervous system by electromagneti c induction History History of TMS First successful Click icon to add picture generation of magnetically induced phosphenes: 1896: d’Arsonval 1902: Beer 1910: Thompson History of TMS Arrangement of Click icon to add picture coils to provide a magnetic field of sufficient strength to induce phosphenes: Magnussen & Stevenson History History of TMS Barker et al. Click icon to add picture (1985) Sheffield The current era of TMS machines begins TMS lab at YNIC Opened Click icon to add picture in November 2008 For more information see lab website: York NeuroImaging Centre Principles of TMS Hallett (2007) Principles of TMS Hallett (2007) Principles of TMS Cortical Effect of TMS Barker’s model Cortical Effect of TMS  Two modes: 1. Disruptive mode Induces neural noise Deactivation of selected brain areas using TMS 0 -> 2.40 Cortical Effect of TMS  Two modes: 1. Disruptive mode Induces neural noise 2. Productive mode produces phosphenes, hand movements  TMS is an interference technique  fMRI and MEG measure correlations Design of TMS studies TMS protocols:  Single pulse  Trains of pulses (repetitive TMS – rTMS) ▪ High frequency – typically online ▪ E.g. 5 pulses at 10 Hz ▪ Low frequency – typically offline ▪ E.g. 1 Hz rTMS for 10 minutes ▪ Theta burst (Huang et al., 2005) 50 Hz Physiological basis of TMS  Human primary motor cortex (M1):  TMS can depolarize corticospinal tract neurons  evokes contralateral hand muscle movements (measured in MEP)  Other brain regions:  TMS effect not constrained to stimulation site  propagates into connected and functionally coupled areas, including subcortical areas Physiological basis of TMS Allen et al. (2007):  short rTMS trains (1-4 s) at various frequencies (1-8 Hz) in cat visual cortex  Using measures of single unit activity, local field potential tissue oxygenation and haemodynamic recordings  Physiological basis of TMS Allen et al. (2007): Three key findings: 1. Effects more pronounced with longer trains and higher frequency 1. Enhancement of spontaneous activity of up to 200% lasting up to 1 min after TMS 2. Activity in the visual cortex evoked by sinusoidal gratings suppressed by up to 60% after TMS and gradually recovered after 10min or longer 3. Effects depend on stimulation frequency and duration  Physiological basis of TMS Allen et al. (2007): Three key findings: 2. TMS perturbs phase relationship among neural responses Neural spikes were decoupled from ongoing oscillations for ca. 30s across all frequency bands TMS: spatial resolution  Paus et al. (1997), TMS & PET  positive correlation between CBF and number of trains at the stimulation site  Changes in 1-2 cm in diameter  Observed also distal CBF changes  Ilmoniemi et al. (1997)  EEG responses spread to other hemisphere within 20-30ms  Difference between physiological TMS effect and functional TMS effect on behaviour TMS: temporal resolution  Critical time for TMS delivery coincides with time at which single unit responses can be recorded (earlier than ERPs)  Effects of a single TMS pulse may last up to 70ms (but not all physiologically active)  In behavioural studies: at least 10ms (Ashbridge et al. 1997) TMS problem space Design of TMS studies In order to show the specificity of a given TMS effect:  Control tasks  Control sites Number processing & TMS rTMS for 500 ms 1000 ms 64 on screen until response 1000 ms 31 on screen until response Göbel et al. (2001). NeuroImag Stimulation sites Superior parietal lobule (SPL) Intraparietal sulcus (IPS) Supramarginal gyrus anterior IPL Angular gyrus posterior IPL  horizontal sulcus Number processing & TMS angular gyrus Angular n=5 gyrus post-central sulcus supramarginal central sulcus gyrus Supra- margin al n=4 gyrus Göbel et al. (2001). NeuroImag  Number processing & TMS  Left ANG LEFT RIGHT 900 900 850 850 control control 800 800 rTMS rTMS 750 750 700 700 RT 650 RT 650 600 600 550 550 500 500 450 450 400 400 20 40 60 80 100 120 20 40 60 80 100 120 Number Number Göbel et al. (2001). NeuroImag  Number processing & TMS  Left SMG LEFT RIGHT 900 900 850 850 control control 800 800 rTMS rTMS 750 750 700 700 RT RT 650 650 600 600 550 550 500 500 450 450 400 400 20 40 60 80 100 120 20 40 60 80 100 120 Number Number Göbel et al. (2001). NeuroImag  Number processing & TMS  Control task, ANG LEFT RIGHT 600 600 580 580 560 560 540 540 520 520 500 500 480 480 460 460 RT RT 440 440 control 420 420 rTMS 400 400 380 380 360 360 340 340 320 320 300 300 0 2 4 6 8 10 0 2 4 6 8 10 Number Number  Number processing & TMS  Control task, SMG LEFT RIGHT 600 600 580 580 560 560 540 Col 4 vs rppc 540 520 520 Col 4 vs Col 6 500 500 480 480 460 RT 460 control RT 440 440 420 rTMS 420 400 400 380 380 360 360 340 340 320 320 300 300 0 2 4 6 8 10 0 2 4 6 8 10 Number Number Localisation of TMS sites  Different approaches 1. fMRI-guided TMS Neuronavigation 2. MRI-guided Neuronavigation 3. TMS Neuronavigation based on group coordinates 4. TMS based on the 10-20 EEG System (anatomical landmark approach) 5. functional TMS localiser Localisation of TMS sites  Brainsight 2 (used in our TMS lab)  Localisation of TMS sites 1. fMRI-guided TMS Neuronavigation: - TMS stimulation site is determined for each individual based on their personal activation peak for a specific fMRI contrast Localisation of TMS sites 2. MRI-guided Neuronavigation - TMS stimulation is based on individual MRI data (e.g. anterior IPS) Localisation of TMS sites 3. TMS Neuronavigation based on group coordinates Stimulation site is based on group peak activation of an fMRI experiment Localisation of TMS sites 4. TMS based on the 10-20 EEG System (anatomical landmark approach) - International 10-20 System for EEG placement is used (e.g. P4) Localisation of TMS sites 5. functional TMS localiser - For each participant the site at which TMS provides maximal disruption in a rTMS for 500 ms 4000 ms different task on screen until response, is determined (target absent trial) 4000 ms on screen until response, maximal for 750 ms (example for target present trial) Localisation of TMS sites  Sack et al. (2008) compared methods 1- 4  Number of required participants to reach significance: Group coordinates EEG Landmark (P4) Examples of TMS experiments  Makingthe blindsighted see  Combining TMS & fMRI  Making the blindsighted see  Silvanto et al. (2007)  Blindsight:  Destruction of the primary visual cortex (V1)  Above chance ability to detect and localize stimuli in the blind field  PatientGY (no left V1) Blindsight Making the blindsighted see  Uni/bilateral TMS stimulation:  Over V5/MT  As determined by individual MRI/fMRI for GY  Defined functionally for control participants Making the blindsighted see  Subjective report of control participant  (a) unilateral (B) bilateral TMS Making the blindsighted see  Subjective report of GY  (a) unilateral (B) bilateral TMS Making the blindsighted see  GY experiences TMS induced visual qualia in his blind field for bilateral TMS stimulation  V1 necessary for awareness Combining TMS & fMRI  Changes seen in brain activations after a stroke: 1. Is this due to altered brain structure? 2. Or related to reorganisation of brain function? Combining TMS & fMRI Combining TMS & fMRI Select > Execute R L Combining TMS & fMRI Select > Execute R L Combining TMS & fMRI Select > Execute R L Combining TMS & fMRI  Aftera unilateral stroke affecting the dorsal premotor cortex in one hemisphere the dorsal premotor cortex in the intact hemisphere is often more active 1. Is this due to altered brain structure/connectivity? 2. Or is it related to reorganisation of brain Combining TMS & fMRI Select > Execute TM S R L Combining TMS & fMRI Select > Execute TM S R L Combining TMS & fMRI O’Shea et al. (2007). Neuron. Combining TMS & fMRI Select > Execute TM S R L Combining TMS & fMRI Select > Execute TM S R L Combining TMS & fMRI After 1 Hz TMS over left PMd Increase in BOLD response in the right PMd R L Combining TMS & fMRI After 1 Hz TMS over left PMd R L Combining TMS & fMRI After 1 Hz TMS over left SM No increase in BOLD response in the right PMd O’Shea et al. (2007). Neuron. Combining TMS & fMRI After 1 Hz TMS over left SM O’Shea et al. (2007). Neuron. Conclusion  Changes in stroke patients in right dorsal premotor cortex are  due to reorganisation of function  and not only due to changes in brain structure TMS studies Weaknesses Strengths Reveals causal links Underlying neural between brain regions mechanisms not yet and function well understood High temporal Widespread, remote precision, reasonable effects possible spatial precision Cannot specifically Experimentation is target all part of the relatively easy and brain cheap Next week Methods: EEG/MEG MSc MEG Project  Supervised by Silke Goebel & Tabea-Maria Haase  Using our brand-new OPM system at YNIC  The Centre's £1 million MEG scanner, using optically-pumped magnetometer (OPM) sensor technology  Topic: Number processing in adults  Combines educationally relevant topic with using cutting-edge neuroimaging technology OPM – a quantum leap for brain imaging?