Joan A. Camprodon

Disruption of the right temporoparietal junction with transcranial magnetic stimulation reduces the role of beliefs in moral judgments

When we judge an action as morally right or wrong, we rely on our capacity to infer the actors mental states (e.g., beliefs, intentions). Here, we test the hypothesis that the right temporoparietal junction (RTPJ), an area involved in mental state reasoning, is necessary for making moral judgments. In two experiments, we used transcranial magnetic stimulation (TMS) to disrupt neural activity in the RTPJ transiently before moral judgment (experiment 1, offline stimulation) and during moral judgment (experiment 2, online stimulation). In both experiments, TMS to the RTPJ led participants to rely less on the actors mental states. A particularly striking effect occurred for attempted harms (e.g., actors who intended but failed to do harm): Relative to TMS to a control site, TMS to the RTPJ caused participants to judge attempted harms as less morally forbidden and more morally permissible. Thus, interfering with activity in the RTPJ disrupts the capacity to use mental states in moral judgment, especially in the case of attempted harms.

Shape conveyed by visual-to-auditory sensory substitution activates the lateral occipital complex.

The lateral-occipital tactile-visual area (LOtv) is activated when objects are recognized by vision or touch. We report here that the LOtv is also activated in sighted and blind humans who recognize objects by extracting shape information from visual-to-auditory sensory substitution soundscapes. Recognizing objects by their typical sounds or learning to associate specific soundscapes with specific objects do not activate this region. This suggests that LOtv is driven by the presence of shape information.

Neuromodulation of decision-making in the addictive brain.

Noninvasive brain stimulation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation and transcranial direct current stimulation can modify decision-making behaviors in healthy subjects. The same type of noninvasive brain stimulation can suppress drug craving in substance user patients, who often display impaired decision-making behaviors. We discuss the implications of these studies for the cognitive neurosciences and their translational applications to the treatment of addictions. We propose a neurocognitive model that can account for our findings and suggests a promising therapeutic role of brain stimulation in the treatment of substance abuse and addictive behavior disorders.

Two phases of v1 activity for visual recognition of natural images

Present theories of visual recognition emphasize the role of interactive processing across populations of neurons within a given network, but the nature of these interactions remains unresolved. In particular, data describing the sufficiency of feedforward algorithms for conscious vision and studies revealing the functional relevance of feedback connections to the striate cortex seem to offer contradictory accounts of visual information processing. TMS is a good method to experimentally address this issue, given its excellent temporal resolution and its capacity to establish causal relations between brain function and behavior. We studied 20 healthy volunteers in a visual recognition task. Subjects were briefly presented with images of animals (birds or mammals) in natural scenes and were asked to indicate the animal category. MRI-guided stereotaxic single TMS pulses were used to transiently disrupt striate cortex function at different times after image onset (SOA). Visual recognition was significantly impaired when TMS was applied over the occipital pole at SOAs of 100 and 220 msec. The first interval has consistently been described in previous TMS studies and is explained as the interruption of the feedforward volley of activity. Given the late latency and discrete nature of the second peak, we hypothesize that it represents the disruption of a feedback projection to V1, probably from other areas in the visual network. These results provide causal evidence for the necessity of recurrent interactive processing, through feedforward and feedback connections, in visual recognition of natural complex images.

Neural and behavioral correlates of drawing in an early blind painter: A case study

Humans rely heavily on vision to identify objects in the world and can create mental representations of the objects they encounter. Objects can also be identified and mentally represented through haptic exploration. However, it is unclear whether prior visual experience is necessary to generate these internal representations. Subject EA, an early blind artist, provides insight into this question. Like other blind individuals, EA captures the external world by touch. However, he is also able to reveal his internal representations through highly detailed drawings that are unequivocally understandable by a sighted person. We employed fMRI to investigate the neural correlates associated with EAs ability to transform tactilely explored three-dimensional objects into drawings and contrasted these findings with a series of control conditions (e.g. nonsensical scribbling as a sensory-motor control). Activation during drawing (compared to scribbling) occurred in brain areas normally associated with vision, including the striate cortex along with frontal and parietal cortical regions. Some of these areas showed overlap when EA was asked to mentally imagine the pictures he had to draw (albeit to a lesser anatomical extent and signal magnitude). These results have important implications as regards our understanding of the ways in which tactile information can generate mental representations of shapes and scenes in the absence of normal visual development. Furthermore, these findings suggest the occipital cortex plays a key role in supporting mental representations even without prior visual experience.

Predictors of Hypomania During Ventral Capsule/Ventral Striatum Deep Brain Stimulation

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a novel therapy for neuropsychiatric disorders. Hypomania is a known complication of VC/VS DBS, but who is at risk is less understood. Factors such as family history, combined with details of DBS programming, might quantify that risk. The authors performed an iterative modeling procedure on a VC/VS DBS patient registry to identify key predictors. Hypomania was less common for men and for patients stimulated on the ventral right contact. It was more common with right monopolar stimulation. These findings may help to establish decision rules to reduce complications of VC/VS DBS.

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study

BACKGROUND Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. OBJECTIVE To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. METHODS Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. RESULTS An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. CONCLUSIONS Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response.

The neuropsychiatry of tinnitus: a circuit-based approach to the causes and treatments available

Patients presenting with tinnitus commonly have neuropsychiatric symptoms with which physicians need to be familiar. We provide an overview of tinnitus, including its types and pathophysiology. We discuss how recent methods such as transcranial magnetic stimulation, positron emission tomography, MRI, magnetoencephalography and quantitative EEG improve our understanding of the pathophysiology of tinnitus and connect tinnitus to the neuropsychiatric symptoms. We then explain why treatment of the tinnitus patient falls within the purview of neuropsychiatry. Psychiatric problems such as depression, anxiety and personality disorders are discussed. We also discuss how stress, headache, cognitive processing speed and sleep disturbance are associated with tinnitus. Finally, we provide a brief overview of treatment options and discuss the efficacy of various medications, including benzodiazepines, antidepressants, antipsychotics and mood-stabilising agents, and various non-pharmacological treatment options, such as cognitive behavioural therapy, habituation therapy and acupuncture. We also discuss how brain stimulation therapies are being developed for the treatment of tinnitus. In conclusion, a review of the literature demonstrates the varied neuropsychiatric manifestations of tinnitus. Imaging studies help to explain the mechanism of the association. However, more research is needed to elucidate the neurocircuitry underlying the association.

Multimodal Applications of Transcranial Magnetic Stimulation for Circuit-Based Psychiatry.

A growing body of research is advancing our understanding of the anatomy and physiology of brain networks and the mechanisms by which they process cognition, behavior, and emotion.1 This “circuit revolution” is changing our conceptualization of psychiatric pathophysiology and calls for technologies to reliably and safely assess the structure and function of brain circuits in humans. Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation technique that applies powerful and rapidly changing magneticfieldsoverthesurfaceoftheskullandgeneratestargetedelectrical currents in the brain, leading to neuronal action potentials. Transcranial magnetic stimulation has a well-established safety profile and is able to modulate brain activitywithoutsurgery,anesthesia, or the induction of seizures.2 Transcranial magnetic stimulation is a widely used technique in cognitive and systems neuroscience, and a number of clinical applications, both diagnostic and therapeutic, exist. Diagnostically, it is used by clinical neurophysiologists in conjunction with electromyography to assess pathologies that compromise the motor system.3,4 In addition, the use of neuronavigated TMS for presurgical cortical mapping was recently cleared by the US Food and Drug Administration. Therapeutically, high-frequency TMS to the left dorsolateral prefrontal cortex was cleared by the US Food and Drug Administration in 2008 for the treatment of major depressive disorder, and a total of 4 different TMS systems have been cleared since. After 1985, protocols were quickly developed to assess the physiology of the human motor system, including cortical excitability, inhibitory and excitatory mechanisms, conduction time, connectivity, and plasticity. These are the exact same properties that we now need to understand across affective, behavioral, and cognitive circuits, to establish solid circuit-based models of neuropsychiatric disease with the potential to affect clinical practice. Therefore, TMS can be a critical tool in psychiatry, with scientific and clinical relevance beyond its current therapeutic applications. To achieve its full potential, though, multimodal combined technologies are needed to measure the neurobiological effects of TMS beyond the motor cortex.Solutionsforthereliablereal-timeintegrationofTMSwithelectroencephalography (EEG), positron emission tomography, magnetic resonance imaging, and other neuroimaging methods have been developed and are increasingly available.5 Transcranial magnetic stimulation protocols, while diverse, fall under 3 main categories: singlepulse, paired-pulse, and repetitive TMS. Single-pulse TMS is used in motor conduction studies to assess the integrity of the corticospinal motor pathway, a measure of connectivity.3,4 One pulse of appropriate intensity is applied over the motor cortex, and the response in the muscle (ie, the motor-evoked potential [MEP]) is measured by use of electromyography. By assessing the time between the TMS pulse and the beginning of the MEP, one can identify pathological changes in neurons and synapses. Single pulses are also used for motor threshold (MT) determination, a measure of cortical excitability that reflects the state of neuronal membranes, synapses, and their glutamate receptors.6 The MT is defined as the minimum TMS intensity needed to induce a muscle contraction or MEP larger than 50 μV in at least 50% of the trials.3,4 The resting MT is measured with the muscle at rest, and the active MT is measured during isometric contraction (the active MT is typically lower). These measures are stable and reproducible, but can change with factors that modulate cortical excitability, including medications or pathological states. A related protocol is the cortical silent period, a period of electromyographic suppression following a TMS pulse to the motor cortex during active isometric contraction of the contralateral muscle (not during rest). The cortical silent period measures cortical inhibition mediated by γ-aminobutyric acid receptor class B (GABAB). 6 Thesesimpleprotocols illustrate2fundamentalpropertiesofTMS. First, the physiological effects are circuit-wide and not limited to the target brain region; if a single TMS pulse over the motor cortex induces a contralateral muscle contraction, it must change the properties of the primary and secondary motor neurons all the way to the motor unit. The cortical target therefore provides access to an entire functional circuit. Second, the effects of stimulation are state-dependent; the fact that the active MT is lower than the resting MT and the fact that the silent period is only observed when the targeted muscle is active demonstratethattheeffectsofTMSdependonthephysiologicalstateofthe brain regions and networks that it is trying to change. These 2 principles applytomotorandnonmotorneurostimulation;complexnetworksthat support affect, behavior, and cognition dynamically fluctuate across different states (in health and in disease), and these physiological oscillations condition the biological and clinical effects of TMS. Paired-pulse protocols have been established to study intracortical inhibition and facilitation. They require the application of 2 TMS pulses of different intensities (typically between 80% and 120% of the MT) and interstimulus intervals (usually in the order of a few milliseconds). Combined studies using TMS and pharmacology have identified the neurotransmitters involved in these physiological dynamics.6 The 2 most studied protocols are short-interval cortical inhibition and intracortical facilitation.3,4 Short-interval cortical inhibition consists in the application of a first (conditioning) subthreshold stimulus (eg, 80% of the MT, but unable to elicit MEPs) followed by a second (test) suprathreshold stimulus (eg, 120%),withashortinterstimulusintervalof1to5milliseconds.TheMEP from the test stimulus is compared with an identical TMS test stimulus that was not preceded by a conditioning pulse. This intervention results in an inhibitory response, characterized by a reduction of the MEP amplitude thought to be mediated by GABAA receptors. 6 Related article page 337 Clinical Review & Education

Transcranial Direct Current Stimulation (tDCS): Modulation of Executive Function in Health and Disease

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation used in human basic and clinical neuroscience. In this article we review its use in the cognitive neurosciences to study executive function, and current preliminary explorations of its therapeutic value as a cognitive enhancer for patients with compromised dysexecutive symptoms. We discuss published studies analyzing their methodology and results. A number of experiments describe improvement in experimental measures of inhibitory control, working memory, and verbal fluency with anodal stimulation over the dorsolateral prefrontal cortex. Positive findings are also described in different clinical populations. Despite the growing promise and interest in tDCS given its safety, simplicity, and low cost, findings are not always consistent across studies due to a host of variables we discuss (study design, stimulation parameters, neuroanatomy, genetics, etc.), highlighting the need for a better mechanistic understanding of the effects of tDCS.