Christian C. Ruff

Concurrent TMS-fMRI and Psychophysics Reveal Frontal Influences on Human Retinotopic Visual Cortex

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.

The neurobiology of rewards and values in social decision making.

How does our brain choose the best course of action? Choices between material goods are thought to be steered by neural value signals that encode the rewarding properties of the choice options. Social decisions, by contrast, are traditionally thought to rely on neural representations of the self and others. However, recent studies show that many types of social decisions may also involve neural value computations. This suggests a unified mechanism for motivational control of behaviour that may incorporate both social and non-social factors. In this Review, we outline a theoretical framework that may help to identify possible overlaps and differences between the neural processes that guide social and non-social decision making.

Reasoning, Models, and Images: Behavioral Measures and Cortical Activity

The goal of this study was to investigate the neurocognitive processes of mental imagery in deductive reasoning. Behavioral studies yielded four sorts of verbal relations: (1) visuospatial relations that are easy to envisage both visually and spatially; (2) visual relations that are easy to envisage visually but hard to envisage spatially; (3) spatial relations that are hard to envisage visually but easy to envisage spatially; and (4) control relations that are hard to envisage both visually and spatially. In three experiments, visual relations slowed the process of reasoning in comparison with control relations, whereas visuospatial and spatial relations yielded inferences comparable to those of control relations. An experiment using functional magnetic resonance imaging showed that in the absence of any correlated visual input (problems were presented acoustically via headphones), all types of reasoning problems evoked activity in the left middle temporal gyrus, in the right superior parietal cortex, and bilaterally in the precuneus. In the prefrontal cortex, increased activity was found in the middle and inferior frontal gyri. However, only the problems based on visual relations also activated areas of the visual association cortex corresponding to V2. The results indicate that cortical activity during reasoning depends on the nature of verbal relations. All relations elicit mental models that underlie reasoning, but visual relations in addition elicit visual images. This account resolves inconsistencies in the previous literature.

Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans

The aim of this study was to investigate the effect of laser acupuncture on cerebral activation. Using functional magnetic imaging (fMRI) cortical activations during laser acupuncture at the left foot (Bladder 67) and dummy acupuncture, were compared employing a block design in ten healthy male volunteers. All experiments were done on a 1.5 Tesla magnetic resonance scanner equipped with a circular polarized head coil. During laser acupuncture, we found activation in the cuneus corresponding to Brodmann Area (BA) 18 and the medial occipital gyrus (BA 19) of the ipsilateral visual cortex. Placebo stimulation did not show any activation. We could demonstrate that laser acupuncture of a specific acupoint, empirically related to ophthalmic disorders, leads to activation of visual brain areas, whereas placebo acupuncture does not. These results indicate that fMRI has the potential to elucidate effects of acupuncture on brain activity.

Right Supramarginal Gyrus Is Crucial to Overcome Emotional Egocentricity Bias in Social Judgments

Humans tend to use the self as a reference point to perceive the world and gain information about other peoples mental states. However, applying such a self-referential projection mechanism in situations where it is inappropriate can result in egocentrically biased judgments. To assess egocentricity bias in the emotional domain (EEB), we developed a novel visuo-tactile paradigm assessing the degree to which empathic judgments are biased by ones own emotions if they are incongruent to those of the person we empathize with. A first behavioral experiment confirmed the existence of such EEB, and two independent fMRI experiments revealed that overcoming biased empathic judgments is associated with increased activation in the right supramarginal gyrus (rSMG), in a location distinct from activations in right temporoparietal junction reported in previous social cognition studies. Using temporary disruption of rSMG with repetitive transcranial magnetic stimulation resulted in a substantial increase of EEB, and so did reducing visuo-tactile stimulation time as shown in an additional behavioral experiment. Our findings provide converging evidence from multiple methods and experiments that rSMG is crucial for overcoming emotional egocentricity. Effective connectivity analyses suggest that this may be achieved by early perceptual regulation processes disambiguating proprioceptive first-person information (touch) from exteroceptive third-person information (vision) during incongruency between self- and other-related affective states. Our study extends previous models of social cognition. It shows that although shared neural networks may underlie emotional understanding in some situations, an additional mechanism subserved by rSMG is needed to avoid biased social judgments in other situations.

Fmri evidence for a three-stage model of deductive reasoning

Deductive reasoning is fundamental to science, human culture, and the solution of problems in daily life. It starts with premises and yields a logically necessary conclusion that is not explicit in the premises. Here we investigated the neurocognitive processes underlying logical thinking with event-related functional magnetic resonance imaging. We specifically focused on three temporally separable phases: (1) the premise processing phase, (2) the premise integration phase, and (3) the validation phase in which reasoners decide whether a conclusion logically follows from the premises. We found distinct patterns of cortical activity during these phases, with initial temporo-occipital activation shifting to the prefrontal cortex and then to the parietal cortex during the reasoning process. Activity in these latter regions was specific to reasoning, as it was significantly decreased during matched working memory problems with identical premises and equal working memory load.

Mapping causal interregional influences with concurrent TMS-fMRI

Transcranial magnetic stimulation (TMS) produces a direct causal effect on brain activity that can now be studied by new approaches that simultaneously combine TMS with neuroimaging methods, such as functional magnetic resonance imaging (fMRI). In this review we highlight recent concurrent TMS–fMRI studies that illustrate how this novel combined technique may provide unique insights into causal interactions among brain regions in humans. We show how fMRI can detect the spatial topography of local and remote TMS effects and how these may vary with psychological factors such as task-state. Concurrent TMS–fMRI may furthermore reveal how the brain adapts to so-called virtual lesions induced by TMS, and the distributed activity changes that may underlie the behavioural consequences often observed during cortical stimulation with TMS. We argue that combining TMS with neuroimaging techniques allows a further step in understanding the physiological underpinnings of TMS, as well as the neural correlated of TMS-evoked consequences on perception and behaviour. This can provide powerful new insights about causal interactions among brain regions in both health and disease that may ultimately lead to developing more efficient protocols for basic research and therapeutic TMS applications.

Changing Social Norm Compliance with Noninvasive Brain Stimulation

Conform to the Norm Human societies have always enforced compliance with norms of acceptable behavior among their members by threatening punishment. It has been proposed that the human brain may have developed neural processes that support norm enforcement behavior and generate appropriate behavioral responses to social punishment threats. However, evidence for the neural circuitry underlying sanction-induced norm compliance in humans is limited. Using noninvasive brain stimulation, Ruff et al. (p. 482, published online 10 October) observed that alteration of the activity and excitability of the right lateral prefrontal cortex affected norm compliance, without affecting awareness of the content of the respective norms, or the expected sanctions. These alterations were much larger in a social, as compared to a nonsocial, context. Right lateral prefrontal cortex activity affects sanction-based compliance with behavioral norms in humans. All known human societies have maintained social order by enforcing compliance with social norms. The biological mechanisms underlying norm compliance are, however, hardly understood. We show that the right lateral prefrontal cortex (rLPFC) is involved in both voluntary and sanction-induced norm compliance. Both types of compliance could be changed by varying the neural excitability of this brain region with transcranial direct current stimulation, but they were affected in opposite ways, suggesting that the stimulated region plays a fundamentally different role in voluntary and sanction-based compliance. Brain stimulation had a particularly strong effect on compliance in the context of socially constituted sanctions, whereas it left beliefs about what the norm prescribes and about subjectively expected sanctions unaffected. Our findings suggest that rLPFC activity is a key biological prerequisite for an evolutionarily and socially important aspect of human behavior.

Source monitoring and memory confidence in schizophrenia

BACKGROUND The present study attempted to extend previous research on source monitoring deficits in schizophrenia. We hypothesized that patients would show a bias to attribute self-generated words to an external source. Furthermore, it was expected that schizophrenic patients would be overconfident regarding false memory attributions. METHOD Thirty schizophrenic and 21 healthy participants were instructed to provide a semantic association for 20 words. Subsequently, a list was read containing experimenter- and self-generated words as well as new words. The subject was required to identify each item as old/new, name the source. and state the degree of confidence for the source attribution. RESULTS Schizophrenic patients displayed a significantly increased number of source attribution errors and were significantly more confident than controls that a false source attribution response was true. The latter bias was ameliorated by higher doses of neuroleptics. CONCLUSIONS It is inferred that a core cognitive deficit underlying schizophrenia is a failure to distinguish false from true mnestic contents.

The Role of Contralesional Dorsal Premotor Cortex after Stroke as Studied with Concurrent TMS-fMRI

Contralesional dorsal premotor cortex (cPMd) may support residual motor function following stroke. We performed two complementary experiments to explore how cPMd might perform this role in a group of chronic human stroke patients. First, we used paired-coil transcranial magnetic stimulation (TMS) to establish the physiological influence of cPMd on ipsilesional primary motor cortex (iM1) at rest. We found that this influence became less inhibitory/more facilitatory in patients with greater clinical impairment. Second, we applied TMS over cPMd during functional magnetic resonance imaging (fMRI) in these patients to examine the causal influence of cPMd TMS on the whole network of surviving cortical motor areas in either hemisphere and whether these influences changed during affected hand movement. We confirmed that hand grip-related activation in cPMd was greater in more impaired patients. Furthermore, the peak ipsilesional sensorimotor cortex activity shifted posteriorly in more impaired patients. Critical new findings were that concurrent TMS-fMRI results correlated with the level of both clinical impairment and neurophysiological impairment (i.e., less inhibitory/more facilitatory cPMd-iM1 measure at rest as assessed with paired-coil TMS). Specifically, greater clinical and neurophysiological impairment was associated with a stronger facilitatory influence of cPMd TMS on blood oxygenation level-dependent signal in posterior parts of ipsilesional sensorimotor cortex during hand grip, corresponding to the posteriorly shifted sensorimotor activity seen in more impaired patients. cPMd TMS was not found to influence activity in other brain regions in either hemisphere. This state-dependent influence on ipsilesional sensorimotor regions may provide a mechanism by which cPMd supports recovered function after stroke.