Kenneth Yuen

Neural Mechanisms of Placebo Anxiolysis

The beneficial effects of placebo treatments on fear and anxiety (placebo anxiolysis) are well known from clinical practice, and there is strong evidence indicating a contribution of treatment expectations to the efficacy of anxiolytic drugs. Although clinically highly relevant, the neural mechanisms underlying placebo anxiolysis are poorly understood. In two studies in humans, we tested whether the administration of an inactive treatment along with verbal suggestions of anxiolysis can attenuate experimentally induced states of phasic fear and/or sustained anxiety. Phasic fear is the response to a well defined threat and includes attentional focusing on the source of threat and concomitant phasic increases of autonomic arousal, whereas in sustained states of anxiety potential and unclear danger requires vigilant scanning of the environment and elevated tonic arousal levels. Our placebo manipulation consistently reduced vigilance measured in terms of undifferentiated reactivity to salient cues (indexed by subjective ratings, skin conductance responses and EEG event-related potentials) and tonic arousal [indexed by cue-unrelated skin conductance levels and enhanced EEG alpha (8–12 Hz) activity], indicating a downregulation of sustained anxiety rather than phasic fear. We also observed a placebo-dependent sustained increase of frontal midline EEG theta (4–7 Hz) power and frontoposterior theta coupling, suggesting the recruitment of frontally based cognitive control functions. Our results thus support the crucial role of treatment expectations in placebo anxiolysis and provide insight into the underlying neural mechanisms.

Opening an emotional dimension in me: Changes in emotional reactivity and emotion regulation in a case of executive impairment after left fronto-parietal damage

Dysexecutive impairment is a common problem after brain injury, particularly after damage to the lateral surface of the frontal lobes. There is a large literature describing the cognitive deficits associated with executive impairment after dorsolateral damage; however, little is known about its impact on emotional functioning. This case study describes changes in a 72-year-old man (Professor F) who became markedly dysexecutive after a left fron-to-parietal stroke. Professor Fs case is remarkable in that, despite exhibiting typical executive impairments, abstraction and working memory capacities were spared. Such preservation of insight-related capacities allowed him to offer a detailed account of his emotional changes. Quantitative and qualitative tools were used to explore changes in several well-known emotional processes. The results suggest that Professor Fs two main emotional changes were in the domain of emotional reactivity (increased experience of both positive and negative emotions) and emotion regulation (down-regulation of sadness). Professor F related both changes to difficulties in his thinking process, especially a difficulty generating and manipulating thoughts during moments of negative arousal. These results are discussed in relation to the literature on executive function and emotion regulation. The relevance of these findings for neuropsychological rehabilitation and for the debate on the neural basis of emotional processes is addressed.

Revisiting the left convexity hypothesis: changes in the mental apparatus after left dorso-medial prefrontal damage

It has been 15 years since Kaplan-Solms and Solms published their Clinical Studies in Neuropsychoanalysis, where they proposed a neuroanatomy of the mental apparatus. One of their main observations was that damage to certain areas of the left prefrontal cortex (PFC), particularly those related to expressive language (Broca’s area), did not generate changes in the mental apparatus. However, a limitation of their model was that it did not include patients with damage to other areas of the left PFC. The main goal of this paper is to update Kaplan-Solms and Solms’ model through the description of id, ego and superego changes in a case of left dorso-medial prefrontal damage (Professor F). Data from a 7-year psychoanalytic psychotherapy with Professor F were collected through the review of clinical notes and session voice recordings. This material was analyzed under the light of existing evidence on the neuropsychological functions supported by the left dorso-medial PFC. Results from this analysis support the hypothesis that damage to other areas of the left PFC, beyond Broca’s area, can in fact generate deep changes in the mental apparatus. The most remarkable change observed here was a modification of the dynamic functions of the ego, as an inability to regulate affect via preconscious verbal thinking. This transformation impacted the baseline arrangement between ego and id, with somatic states becoming more salient. Finally, changes in the superego were also observed, particularly in relation to its flexibility during moments of conflict, or the silencing of superego voices outside moments of negative arousal.

A basic need theory approach to problematic Internet use and the mediating effect of psychological distress

The Internet provides an easily accessible way to meet certain needs. Over-reliance on it leads to problematic use, which studies show can be predicted by psychological distress. Self-determination theory proposes that we all have the basic need for autonomy, competency, and relatedness. This has been shown to explain the motivations behind problematic Internet use. This study hypothesizes that individuals who are psychologically disturbed because their basic needs are not being met are more vulnerable to becoming reliant on the Internet when they seek such needs satisfaction from online activities, and tests a model in which basic needs predict problematic Internet use, fully mediated by psychological distress. Problematic Internet use, psychological distress, and basic needs satisfaction were psychometrically measured in a sample of 229 Hong Kong University students and structural equation modeling was used to test the hypothesized model. All indices showed the model has a good fit. Further, statistical testing supported a mediation effect for psychological distress between needs satisfaction and problematic Internet use. The results extend our understanding of the development and prevention of problematic Internet use based on the framework of self-determination theory. Psychological distress could be used as an early predictor, while preventing and treating problematic Internet use should emphasize the fulfillment of unmet needs.

‘Just can’t hide it’: a behavioral and lesion study on emotional response modulation after right prefrontal damage

INTRODUCTION Historically, emotion regulation problems have been reported as a common consequence of right prefrontal cortex (rPFC) damage. It has been proposed that the rPFC, particularly the rIFG, has a key role inhibiting prepotent reflexive actions, thus contributing to emotion regulation and self-regulation. This study is the first to directly explore this hypothesis, by testing whether damage to the rIFG compromises the voluntary modulation of emotional responses, and whether performance on inhibition tasks is associated with emotion regulation. METHOD 10 individuals with unilateral right prefrontal damage and 15 matched healthy controls were compared on a well-known response modulation task. During the task participants had to amplify and suppress their facial emotional expressions, while watching film clips eliciting amusement. Measures of executive control, emotion regulation strategies usage and symptomatology were also collected. RESULTS As a group, individuals with rPFC damage presented a significantly reduced range of response modulation compared with controls. In addition, performance in the suppression task was associated with measures of cognitive inhibition and suppression usage. Interestingly, these effects were driven primarily by a subgroup of individuals with rPFC damage, all of whom also had damage to the right posterior insula, and who presented a marked impairment in suppressing facial emotional expressions.

Automatic numerical-spatial association in synaesthesia: An fMRI investigation

ABSTRACT A horizontal mental number line (MNL) is used to describe how quantities are represented across space. In humans, the neural correlates associated with such a representation are found in different areas of the posterior parietal cortex, especially, the intraparietal sulcus (IPS). In a phenomenon known as number‐space synaesthesia, individuals visualise numbers in specific spatial locations. The experience of a MNL for number‐space synaesthetes is explicit, idiosyncratic, and highly stable over time. It remains an open question whether the mechanisms underlying numerical‐spatial association are shared by synaesthetes and nonsynaesthetes. We address the neural correlates of number‐space association by examining the brain response in a number‐space synaestheste (MkM) whose MNL differs dramatically in its ordinality and direction from that of a control group. MkM and 15 nonsynaesthetes compared the physical size of two numbers, while ignoring their numerical value, during an event‐related functional magnetic resonance imaging session (fMRI). Two factors were analysed: the numerical distance effect (NDE; e.g., 2−4 small distance vs. 1−6 large distance), and the size congruity effect (e.g., 2−8 congruent vs. 2−8 incongruent). Only for MkM, the NDE elicited significant activity in the left and right IPS, supramarginal gyrus (bilateral), and in the left angular gyrus. These results strongly support the role of the parietal cortex in the automatic coding of space and quantity in number‐space synaesthesia, even when numerical values are task‐irrelevant. HIGHLIGHTSNumber‐space synaesthetes visualise number in specific spatial locations.We addressed the neural correlates of such representation using fMRI.A synaesthete (MkM) and controls reported the physical size of numbers.Only for the synaesthete task‐irrelevant numbers elicited parietal activity.Results implicate the parietal cortex in the automatic coding of space and numbers.

Neuroanatomical basis of number synaesthesias: A voxel-based morphometry study

In synaesthesia, a specific sensory dimension leads to an involuntary sensation in another sensory dimension not commonly associated with it; for example, synaesthetes may experience a specific colour when listening or thinking of numbers or letters. Large-scale behavioural studies provide a rich description of different synaesthesia phenotypes, and a great amount of research has been oriented to uncovering whether a single or multiple brain mechanisms underlie these various synaesthesia phenotypes. Interestingly, most of the synaesthetic inducers are conceptual stimuli such as numbers, letters, and months. However, the impact of these concepts on the synaesthetic brain remains largely unexplored. Numbers appear as the most typical inducer in two common types of synaesthesia: grapheme-colour and sequence-space. Numbers are symbols that denote quantity information and their processing recruits a specific neural network. Therefore, numbers may play an important role in the brain mechanisms underlying some types of synaesthesia. We used voxel-based morphometry (VBM) to compare grey matter (GM) volume in synaesthetes and controls. Relative to controls, synaesthetes showed increase in GM in the right amygdala and in the left cerebellum. Within the synaestheste group, comparing synaesthetes who reported numbers as the inducer with synaesthetes who reported other stimuli as the inducer revealed increase in GM in the left angular gyrus, which is associated with the verbal aspect of number processing. These results reveal neuroanatomical differences between synaesthetes and controls, and show the impact of the type of inducer in the synaesthetic brain. We discuss these findings in line with current neurobiological models of synaesthesia.

The Functional Role of Large-scale Brain Network Coordination in Placebo-induced Anxiolysis

Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.

Tactile enumeration: A case study of acalculia

HighlightsTactile enumeration and brain plasticity in acalculia following left IPS infarct.Steep RT slope in acute phase and gradual decrease in slope over time.VBM analysis shows increase in gray matter (GM) in right middle occipital cortex.Results support tactile subitizing based on embodied pattern recognition.Improved enumeration coincides with GM change supports “sense of magnitude” theory. ABSTRACT Enumeration is one of the building blocks of arithmetic and fingers are used as a counting tool in early steps. Subitizing—fast and accurate enumeration of small quantities—has been vastly studied in the visual modality, but less in the tactile modality. We explored tactile enumeration using fingers, and gray matter (GM) changes using voxel‐based morphometry (VBM), in acalculia. We examined JD, a 22‐year‐old female with acalculia following a stroke to the left inferior parietal cortex. JD and a neurologically healthy normal comparison (NC) group reported how many fingers were stimulated. JD was tested at several time points, including at acute and chronic phases. Using the sensory intact hand for tactile enumeration, JD showed deficit in the acute phase, compared to the NC group, and improvement in the chronic phase of (1) the RT slope of enumerating up to four stimuli, (2) enumerating neighboring fingers, and (3) arithmetic fluency performance. Moreover, VBM analysis showed a larger GM volume for JD relative to the NC group in the right middle occipital cortex, most profoundly in the chronic phase. JDs performance serves as a first glance of tactile enumeration in acalculia. Pattern‐recognition‐based results support the suggestion of subitizing being the enumeration process when using one hand. Moreover, the increase in GM in the occipital cortex lays the groundwork for studying the innate and primitive ability to perceive and evaluate sizes or amounts—“sense of magnitude”— as a multisensory magnitude area and as part of a recovery path for deficits in basic numerical abilities.