Up and down-regulation of visual cortex by posterior parietal cortex modulates selection-by-saliency: evidence from combined TMS-fMRI

Up and down-regulation of visual cortex by posterior parietal cortex modulates selection-by-saliency: evidence from combined TMS-fMRI

Abstracts TMS Poster Only 32 Effects of LTP-like versus LTD-like plasticity on subsequent motor learning in healthy subjects Jung P1, Ziemann U2, 1J...

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Abstracts TMS Poster Only 32

Effects of LTP-like versus LTD-like plasticity on subsequent motor learning in healthy subjects

Jung P1, Ziemann U2, 1J.W. Goethe-University (Frankfurt am Main, DE); 2 J.W. Goethe-University (Frankfurt am Main, DE) Objective: In accordance with the Bienenstock-Cooper-Munro (BCM) theory of bidirectional synaptic metaplasticity, previous experiments on animals and humans have demonstrated that motor learning suppresses subsequent processes dependent on long-term potentiation (LTP) and enhances subsequent processes dependent on long-term depression (LTD). In the present study we investigated the effects of LTP- and LTD-like plasticity on immediate and delayed subsequent motor learning. Methods: In 9 healthy subjects, LTP-like (PASN20 1 2) and LTD-like (PASN20-5) plasticity in primary motor cortex (M1) was induced by an established paired associative TMS protocol (PAS) [Ziemann et al. 2004, J Neurosci 24: 1666]. As control condition, an interstimulus interval of 100 ms was used (PAS100). Motor practice (MP) was performed with fastest possible thumb flexion movements at a rate of 0.25 Hz over 2 3 15 minutes. Motor learning was quantified by the increase in peak acceleration of the practiced thumb movement. In experiment 1, MP started immediately after PAS intervention; in experiment 2, MP began with a delay of 90 minutes after PAS. This delay was chosen because PAS induced changes in motor cortical excitability typically have worn off at this time while interactions with subsequent learning according to the BCM theory may still persist. Results: Experiment 1: LTD-like plasticity (PASN20-5) resulted in better motor learning (stronger increase in peak acceleration) than LTP-like plasticity (PASN20 1 2) or the control condition (PAS100). Moreover, PASN20 1 2 led to slightly enhanced motor learning compared PAS100. Experiment 2: Results were similar to those of experiment 1 with the important difference that, in comparison to PAS100, motor learning after PASN20 1 2 was now significantly depressed. Conclusion: Results of experiments 2 (delayed MP) support the BCM theory whereas interactions between PAS induced plasticity and immediately subsequent motor learning (experiment 1) are not sufficiently explained by the BCM theory. Superimposed gating effects with shorter duration than PAS effects might account for the different interactions between PAS and immediate vs. delayed motor learning. Findings are important for therapeutic strategies that aim to enhance learning by conditioning cortical stimulation.

Clinical Studies Poster Only 34

Cortical responsivity in traumatic brain injury patients with chronic symptoms

Tallus J1, Mattila J1, Lioumis P2, Ha¨ma¨la¨inen H1, Ka¨hko¨nen S2, Tenovuo O1, 1University of Turku (Turku, FI); 2Helsinki University Central Hospital (Helsinki, FI) Objective: Persistent cognitive and emotional symptoms are often seen after traumatic brain injury (TBI), even when the primary injury is classified as mild. The neural basis of these symptoms is not well known and presents a challenge for the present imaging methods. We examine the hypothesis that abnormal cortical responsivity may underlie these symptoms. Method: Eight patients with chronic TBI symptoms but with normal MRIs have been studied. The patients had no other neurological or psychiatric illnesses and did not use medication affecting the central nervous system. The results are compared to eight healthy controls. Navigated TMS (nTMS) was applied over the left dorsolateral prefrontal cortex (DLPFC) and the left primary motor cortex (MI) with intensities of 90%, 100% and 110% of the motor threshold (MT). A hundred pulses were applied with each intensity at each site of stimulation. The interstimulus interval was 3.3 s. The responses were recorded with a 60-channel whole head TMS-compatible EEG amplifier.

249 Results: The N100 response, which may represent cortical inhibition, is abnormal during the DLPFC stimulation in the TBI patients. In healthy controls, the amplitude of the N100 increases with increasing TMS intensity, but on visual inspection this increase is lacking in the TBI patients. Moreover, a number of patients display a pattern where a 100% stimulation increases certain early negativities compared to 90% stimulation, but a 110% stimulation decreases them. In MI stimulation, all peak responses increase with intensity in contrast to DLPFC TMS. Exception is P180, which shows some deviancy within the patient group. Conclusion: DLPFC TMS–evoked EEG responses of TBI patients differ from healthy volunteers responses. The prefrontal cortex is associated with cognitive control and executive functions, which are typically impaired in persisting symptoms after TBI. MRIs of this patient group did not show any traumatic lesions; thus, TMS combined with EEG may be a valuable tool for quantifying brain abnormalities not detected with standard imaging methods.

rTMS Poster Only 35

Immediate effects of repetitive transcranial magnetic stimulation on attentional processes are associated with antidepressant treatment outcome

Vanderhasselt M1, De Raedt R1, Leyman L1, Baeken C2, 1Ghent University (Ghent, BE); 2university Hospital Brussels (Brussels, BE) Objective: Repetitive Transcranial Magnetic Stimulation (rTMS), applied on the dorsolateral prefrontal cortex (DLPFC), is a new treatment procedure that holds promise of more insight into the pathophysiology of depression. The DLPFC may play an important role in the interplay between emotional and attentional information processing. This research will investigate whether acute neurocognitive effects of repetitive Transcranial Magnetic Stimulation are associated with antidepressant treatment outcome. Methods: We examined the effects of a single session and two weeks of rTMS treatment over the left DLPFC on cognition and mood in therapy-resistant depressed patients. We used a crossover placebo-controlled double-blind design for a single session of rTMS. After two weeks of real stimulation, we differentiated rTMS treatment responders and non-responders. A task switching paradigm with two different modalities, was used to measure cognitive functioning. Results: After two weeks of High Frequency (HF) rTMS over the left DLPFC, depressive symptoms improved in more than half (53%) of our therapy-resistant population (cfr. treatment responders). After a single HFrTMS session, mood did not improve but attentional control was increased solely within our group of treatment responders. Conclusion: Cognitive reactivity after a single rTMS session over the left DLPFC may hold promise as a predictor for positive treatment outcome. Moreover, within the group of rTMS responders, attentional control appears to play an important role in the development of mood disorders.

rTMS Poster Only 36

Up and down-regulation of visual cortex by posterior parietal cortex modulates selection-by-saliency: evidence from combined TMS-fMRI

Mevorach C1, Allen H1, Hodsoll J1, Humphreys G1, Shalev L2, 1The University of Birmingham (Birmingham, UK); 2The Hebrew University (Jerusalem, IL) Objective: Using TMS over the parietal cortex, we have recently shown (Mevorach et al., 2006) that selection and suppression of saliency are lateralised in the brain with the right pIPS critical for the selection of salient targets and left pIPS critical for the suppression of salient but

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Abstracts

irrelevant information. Whereas the effects of TMS on behaviour were clearly observed the neural correlates of those effects is unknown. For instance, it is not known whether TMS applied over the parietal cortex also results in changes of brain activity in other functionally related areas. In the present study we combined offline TMS with functional brain imaging to assess the differences in brain activity induced by TMS that underlie the changes in behaviour. Method: In two sessions 13 participants performed a Global/Local task where the relative saliency of target and distractor levels was manipulated. In each session participants performed the task twice while functional brain imaging data (as well as behavioural data) were collected. In between those scans 20 minutes of offline TMS (at 90% of individual motor threshold) was applied over either the left or right pIPS. Result: The behavioural data indicated dissociable effects for left and right IPS stimulation in accordance with the left pIPS being critical for the suppression of saliency and the right pIPS for selecting salient targets. A whole brain analysis revealed differential effects of left and right pIPS stimulation on the visual cortex, with increased activity following TMS over the left pIPS compared with TMS over right pIPS. Conclusion: The data support the notion that TMS over a particular site can lead to activation change in other remote (but potentially functionally related) brain regions. In particular it suggests that selection of salient information benefits from an increase in brain activity in visual cortex (which is modulated by the right pIPS), whereas suppression of saliency benefits from a reduction in brain activity in visual cortex (which is modulated by the left pIPS).

Clinical Studies Poster Only 37

TMS-associated neurobehavioral gains during coma recovery

Pape T1, Rosenow J2, Lewis G3, Ahmed G2, Walker M2, Guernon A4, Roth H5, 1United States Department of Veteran Affa (Hines, IL, US); 2 Northwestern University (Chicago, IL, US); 3AUT University (Auckland, NZ); 4Marianjoy Rehabilitation Hospital (Wheaton, IL, US); 5 The Rehabilitation Institute of Chicago (Chicago, IL, US) Objective: This report presents findings from the first participant of a safety and efficacy study examining a therapeutic repetitive TMS (rTMS) protocol for persons with severe traumatic brain injury (TBI). The primary hypothesis was that there will be no adverse events related to the provision of a 6-week repetitive TMS protocol for persons with severe TBI who remain, at best, in a minimally conscious state for longer than three months. The secondary hypothesis was that the TMS protocol would induce significant neurobehavioral gains during treatment and that these would persist at six-week follow-up. Methods: A 6-week repetitive paired-pulse TMS protocol (30 sessions total) was delivered to a 26-year old male who remained in a vegetative state 287 days after severe TBI. Stimulation was directed over the right dorsolateral prefrontal cortex. Repeated safety measures, neurobehavioral assessments, clinical exams, evoked potentials and functional magnetic resonance imaging scans were obtained at baseline, every 5th TMS session (weekly) and at a 6-week follow-up. Results: There were no adverse events related to the provision of rTMS treatment. A trend toward significant (p 5 .066) neurobehavioral gains was temporally related to provision of rTMS. Left sided brain stem auditory evoked potential Waves I -V peak latencies and Wave V latencies improved along with the patient’s neurobehavioral functioning during provision of rTMS. Spatial Expansion and reduction in the number of activated voxels in a given brain region occurred after 15th (p 5 .033) and 30th (p 5 .004) TMS sessions. The majority (66%) of changes in activation are attributed to increases (311 positive ranks/472 directional changes) whereas 34% are attributed to reductions in neural activation Number of brain regions activated over time range from 1 to 7 for non-familiar voice contrasts, from 2 to 3 for familiar voice contrasts and 2 to 5 for non-vocal sounds.

Conclusions: Repetitive TMS merits further investigation as a safe, therapeutic intervention to alter and modulate neural activity during coma recovery to facilitate recovery. A pattern of increases and decreases in activation co-occurring with neurobehavioral gains and declines and provision and withdraw of TMS suggests that recruitment of additional neural circuitry is one mechanism supporting neurobehavioral gains.

Movement Disorders Poster Only 38

Multimodal approach for mapping effects of subthreshold motor cortex rTMS in parkinsonian patients

Kicic D1, Bikmullina R2, Lioumis P2, Nurminen J2, Ma¨kela¨ JP2, Kaakkola S2, Pekkonen E2, 1Helsinki University of Technology (Espoo, FI); 2Helsinki University Central Hospital (Helsinki, FI) Objective: Repetitive transcranial magnetic stimulation (rTMS) to primary motor cortex (M1) modulates dopaminergic activity in the basal ganglia in Parkinson’s disease (PD). We characterized the short-term effects of rTMS in PD patients by recording spontaneous (SP) magnetoencephalogram (MEG, 306-channel Elekta NeuromagÒ) to see whether subthreshold rTMS to M1 affects the 10–20 Hz cortical oscillations (mu rhythm). TMSevoked electroencephalographic (TMS-EEG) potentials were also analyzed to see whether rTMS to M1 induces long-term potentiation (LTP). The recorded signals were correlated with clinical motor scores. Methods: In 9 non-demented PD patients, the hemisphere contralateral to the most affected limb was stimulated (Magstim Rapid) in two consecutive days. Twenty trains of 100 pulses at 10 Hz with intensity of 80% of patient’s motor threshold (MT) were delivered with 1-min inter-train interval, separately for MEG and TMS-EEG (Magstim 200 and 60-channel whole-head system eXimia EEG) measurements. We analyzed spectral power in alpha and beta bands before and after the rTMS with emphasis on 10-Hz activity and its 20-Hz harmonics. Single TMS pulses (105 to each hemisphere, intensity 80% MT) were targeted using eXimia-NBS system; TMS-evoked EEG responses were collected before and after rTMS. Global mean field amplitude was calculated as an index of total TMS-evoked EEG activity. UPDRS scores were measured before and after rTMS. Results: UPDRS scores improved significantly only on the first day after the rTMS. In 6 out of 9 patients the rTMS significantly facilitated mu rhythm. The first treatment modulated mu rhythm more than the second one. Patients had significantly decreased rigidity and hypokinesia, but not tremor. rTMS to M1 did not induce LTP of TMS-EEG responses. MTs were not changed. Conclusion: Mu rhythm may reflect the akinetic features of PD. Pathophysiological mechanisms related to PD may inhibit the spreading of TMS-induced long-range excitatory activity, required for LTP to induce larger EEG responses. Contrary to healthy subjects, rTMS did not induce LTP in EEG.

rTMS Poster Only 39

20Hz offline rTMS of human posterior parietal cortex perturbs visuospatial attention

Jin Y, Hilgetag CC, Jacobs University Bremen (Bremen, DE) Objective: The contribution of different cortical regions to visuospatial attention can be probed with the help of transcranial magnetic stimulation (TMS). Repetitive TMS has also been suggested as a tool for the therapy of brain injuries, by altering neural excitability of injured or intact brain regions. Low- and high-frequency rTMS were shown to result in subsequent (offline TMS) reductions or increases of local cortical excitability, respectively. Previous studies demonstrated that low-frequency (1Hz) rTMS of posterior parietal cortex (PPC) produced significantly reduced detection of stimuli in the visual hemifield contralateral to the stimulation site, as well as increased ipsilateral detection. We here explored the functional impact of high-frequency (20 Hz) rTMS in a comparable attentional paradigm.