A new unified framework for making and implementing decisions.
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Biomedical subjects
Publications and source records attributed to Sven Bestmann.
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The neural processes underlying tactile decisions in the human brain remain elusive. We addressed this question in a functional magnetic resonance imaging study using a somatosensory discrimination task, requiring participants to compare the frequency of two successive tactile stimuli. Tactile stimuli per se engaged somatosensory, parietal, and frontal cortical regions. Using a statistical model that accounted for the relative difference in frequencies (i.e., Weber fraction) and discrimination accuracy (i.e., correct or incorrect), we show that trial-by-trial relative frequency difference is represented linearly by activity changes in the left dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex, and bilateral anterior insular cortices. However, a circumscribed region within the left DLPFC showed a different response pattern expressed as activity changes that were monotonically related to relative stimulation difference only for correct but not for incorrect trials. Our findings suggest that activity in the left DLPFC encodes stimulus representations that underlie veridical tactile decisions in humans.
BACKGROUND: Regions in human frontal cortex may have modulatory top-down influences on retinotopic visual cortex, but to date neuroimaging methods have only been able to provide indirect evidence for such functional interactions between remote but interconnected brain regions. Here we combined transcranial magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging (fMRI), plus psychophysics, to show that stimulation of the right human frontal eye-field (FEF) produced a characteristic topographic pattern of activity changes in retinotopic visual areas V1-V4, with functional consequences for visual perception. RESULTS: FEF TMS led to activity increases for retinotopic representations of the peripheral visual field, but to activity decreases for the central field, in areas V1-V4. These frontal influences on visual cortex occurred in a top-down manner, independently of visual input. TMS of a control site (vertex) did not elicit such visual modulations, and saccades, blinks, or pupil dilation could not account for our results. Finally, the effects of FEF TMS on activity in retinotopic visual cortex led to a behavioral prediction that we confirmed psychophysically by showing that TMS of the frontal site (again compared with vertex) enhanced perceived contrast for peripheral relative to central visual stimuli. CONCLUSIONS: Our results provide causal evidence that circuits originating in the human FEF can modulate activity in retinotopic visual cortex, in a manner that differentiates the central and peripheral visual field, with functional consequences for perception. More generally, our study illustrates how the new approach of concurrent TMS-fMRI can now reveal causal interactions between remote but interconnected areas of the human brain.
Repetitive transcranial magnetic stimulation (rTMS) is an established technique for non-invasive stimulation of human cortex. Although studies have shown an influence of rTMS on single cortical regions and on simple behavioral response patterns, its influences on the dynamics of task-related activity in cortical networks have not been characterized. We provide such a characterization by showing that 5 Hz rTMS over primary somatosensory cortex (SI) induces a reconfiguration of activity patterns in a sensorimotor network, comprising the stimulated region and ipsilateral primary motor cortex (MI). These plastic changes endure for up to 120 min and are correlated with behavioral improvement in discrimination. Dynamic causal modeling showed that this reconfiguration could be explained by an rTMS-induced increase in SI excitability (self-connection) and an increase in the effective connectivity from SI to MI. Thus, our data demonstrate that rTMS can temporarily induce behaviorally relevant reorganization within a complex cortical network underlying human somatosensory experience.
Twelve right-handed volunteers were asked to judge the laterality of a hand stimulus by pressing a button with one of their toes. Judgements were based on two-dimensional drawings of the back or palm of a right or left hand at various orientations. Suprathreshold single-pulse transcranial magnetic stimulation (TMS) was given to the left primary motor hand area (M1-HAND) at 0, 200, 400, 600, 800 or 1000 ms after stimulus onset to probe the functional involvement of the dominant left M1 at various stages of handedness recognition. We found that mean reaction times and error rates increased with angle of rotation depending on the actual biomechanical constraints of the hand but suprathreshold TMS had no influence on task performance regardless of the timing of TMS. However, the excitability of the corticomotor output from the left M1-HAND was modulated during the reaction. Judging left hand drawings was associated with an attenuation of motor-evoked potentials 300-100 ms before the response, whereas judging right hand drawings facilitated the motor-evoked potentials only immediately before the response. These effects were the same for pictures of backs and palms and were independent of the angle of rotation. The failure of TMS to affect task performance suggests that there is no time window during which the M1-HAND makes a critical contribution to mental rotation of the hand. The modulation of motor-evoked potentials according to the laterality of the stimulus indicates a secondary effect of the task on corticomotor excitability that is not directly related to mental rotation itself.
This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial magnetic stimulation delivered to primary motor and premotor areas. Trains of rTMS have lasting effects on the excitability of intrinsic and corticofugal neurones, altering the responsiveness of local and remote sites. These effects lead to distributed changes in synaptic activity at rest, and during a range of motor tasks. It is possible to impair or improve performance following rTMS, but for most simple motor tasks performance is unaltered. Changes in distributed activity observed with functional imaging during motor behaviour may represent compensatory activity, enabling maintenance of performance; stimulation of additional cortical areas appears to impair performance. A detailed understanding of the distributed changes in excitability following rTMS may facilitate future attempts to modulate motor behaviour in the healthy brain and for therapeutic purposes.
Functional magnetic resonance imaging (fMRI) studies in humans have hitherto failed to demonstrate activity changes in the direct vicinity of transcranial magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory feedback or a spread of excitation. In order to investigate the underlying activity changes at the site of stimulation as well as in remote connected regions, we applied short trains of high-intensity (110% of resting motor threshold) and low-intensity (90% of active motor threshold) repetitive TMS (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI responses were observed with rTMS at both 90% and 110% RMT in connected brain regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and caudate nucleus. Responses were generally smaller during low-intensity rTMS. The results indicate that short trains of TMS can modify local hemodynamics in the absence of overt motor responses. In addition, premotor rTMS cannot only effectively stimulate cortico-cortical but also cortico-subcortical connections even at low stimulation intensities.
Transcranial magnetic stimulation (TMS) of the occipital lobe is frequently used to induce visual percepts by direct stimulation of visual cortex. The threshold magnetic field strength necessary to elicit a visual percept is often regarded as a measure of electrical excitability of visual cortex. Using single-pulse TMS during visual motion stimulus presentation, we investigated the relationship between different degrees of visual cortical preactivation and cortical phosphene threshold (PT). The two possible, mutually exclusive, predictions on the outcome of this experiment were that a) PT increases with stronger preactivation because of a decrease in the signal-to-noise ratio, or b) that PT decreases with increased preactivation because of the increase in neuronal response towards some threshold. PTs for single-pulse stimulation of the occipital lobe were determined for eight subjects while they passively viewed a horizontally drifting luminance-modulated sinewave grating. Gratings used were of four different luminance contrasts while the spatial and temporal frequencies remained constant. PTs were shown to increase significantly as the background grating increased in contrast. These results suggest that the neural activity underlying the perception of a phosphene can be considered a type of signal that can be partially masked by another signal, in this case the visual cortical activation produced by passive viewing of drifting gratings.
Recent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo-planar imaging with blood-oxygenation-level-dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high-frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra- and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI-detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re-afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.
PURPOSE: To minimize artifacts in echo-planar imaging (EPI) of human brain function introduced by simultaneous transcranial magnetic stimulation (TMS). MATERIALS AND METHODS: Distortions due to TMS pulses (0.25 msec, 2.0 T) were studied at 2.0 T before and during EPI. RESULTS: Best results were obtained if both the EPI section orientation and the frequency-encoding gradient were parallel to the plane of the TMS coil. Under these conditions, a TMS pulse caused image distortions when preceding the EPI sequence by less than 100 msec. Recordings with a magnetic field gradient pick-up coil revealed transient magnetic fields after TMS, which are generated by eddy currents in the TMS coil. TMS during image acquisition completely spoiled all transverse magnetizations and induced disturbances ranging from image corruption to mild image blurring, depending on the affected low and high spatial frequencies. Simultaneous TMS and radio-frequency (RF) excitation gave rise to T1-dependent signal changes that lasted for several seconds and yielded pronounced false-positive activations during functional brain mapping. CONCLUSION: To ensure reliable and robust combinations, TMS should be applied at least 100 msec before EPI while completely avoiding any pulses during imaging.
To elucidate changes in human brain activity evoked by repetitive transcranial magnetic stimulation (rTMS), sub- and suprathreshold rTMS (4 Hz, 10 s) over the left primary sensorimotor cortex (M1/S1) was interleaved with blood-oxygenation-level-dependent (BOLD) echo-planar imaging of primary and secondary motor areas. Suprathreshold rTMS over left M1/S1 caused marked increases in BOLD signal in the stimulated area and SMA-proper in seven of eight subjects. By contrast, we found no change in BOLD signal in the stimulated M1/S1, when rTMS was given at intensities that were subthreshold for inducing motor responses in the contralateral hand. However, five of eight subjects showed consistent increases in BOLD MRI signal in the SMA-proper and, to a lesser extent, in bilateral lateral premotor cortex (LPMC) during subthreshold rTMS. A decrease in BOLD MRI signal was found in contralateral (right) M1/S1 in 6/8 subjects across all conditions. No significant changes were observed in the pre-SMA. The results support the notion that BOLD MRI responses to suprathreshold rTMS over M1/S1 are dominated by neuronal activity related to reafferent processing of TMS-induced hand movements. At subthreshold intensity, a short train of high-frequency rTMS seems to predominantly modulate activity of corticocortical connections which link the stimulated area with remote frontal premotor areas.
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The pathophysiology of primary writing tremor (PWT) is still unknown: it has been classified as a focal form of essential tremor and as a tremulous form of writer's cramp. We studied cortical and spinal excitability in patients with PWT and compared the results with published data of patients with essential tremor, and writer's cramp. We used electrical stimulation of median and radial nerve to study reciprocal inhibition of forearm antagonist muscles and paired transcranial magnetic stimulation at short and long interstimulus intervals (ISIs) to assess intracortical excitability. Both studies were conducted on patients with PWT and on control subjects. The early (presynaptic) and late (disynaptic) phases of reciprocal inhibition were normal as was intracortical excitability at short and long ISIs. Our study suggests that the pathophysiology of PWT is different from that of writer's cramp and partially also from that of essential tremor.