The characteristic temporal relationship between actions and their sensory outcomes allows us to distinguish self- from externally generated sensory events. However, the complex sensory environment can cause transient delays between action and outcome calling for flexible recalibration of predicted sensorimotor timing. Since the neural underpinnings of this process are largely unknown this study investigated the involvement of the cerebellum by means of cerebellar transcranial direct current stimulation. While receiving anodal, cathodal, dual-hemisphere or sham ctDCS, in an (...) adaptation phase, participants were exposed to constant delays of 150 ms between actively or passively generated button presses and visual sensory outcomes. Recalibration in the same and in another sensory modality was assessed in a subsequent test phase during which variable delays between button press and visual or auditory outcome had to be detected. Results indicated that temporal recalibration occurred in audition after anodal ctDCS while it was absent in vision. As the adaptation modality was visual, effects in audition suggest that recalibration occurred on a supra-modal level. In active conditions, anodal ctDCS improved sensorimotor recalibration at the delay level closest to the adaptation delay, suggesting a precise cerebellar-dependent temporal recalibration mechanism. In passive conditions, the facilitation of inter-sensory recalibration by anodal ctDCS was overall stronger and tuned to larger delays. These findings point to a role of the cerebellum in supra-modal temporal recalibration across sensorimotor and perceptual domains, but the differential manifestation of the effect across delay levels in active and passive conditions points to differences in the underlying mechanisms depending on the availability of action-based predictions. Furthermore, these results suggest that anodal ctDCS can be a promising tool for facilitating effects of temporal recalibration in sensorimotor and inter-sensory contexts. (shrink)

It has been shown that various types of stress initiate different physiological and neuroendocrine disorders. Oxytocin is mainly produced in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. Hypothalamic OT has antistress effects and attenuates the hypothalamic–pituitary–adrenal axis. One mechanism behind the antistress effects of OT is mediated through the inhibition from GABAA receptors on corticotropin-releasing factor expression at the PVN. Various manual therapies such as acupuncture, transcutaneous electrical nerve stimulation, and massage initiate the stimulation (...) of somatosensory neurons of the body. It is well-known that TENS simulates OT expression, while it inhibits CRF expression at the PVN following chronic stress loading in rodents. Upregulation of OT expression at the hypothalamus is activated by the somatosensory stimulation, which is mediated via the spinothalamic pathway. Thus, somatosensory stimulation is beneficial in treating stress-associated symptoms. Hypothalamic OT is associated with the social behaviors, including maternal care and affiliation. Childhood neglect and/or child abuse are severely responsible for deleterious long-term effects on the cognitive/social activity and behavioral development. At parturition, a profound amount of OT is released into the systemic circulation in response to vaginal and cervical stimulation caused by the body of fetus, which induces the onset of maternal behavior. Peridural anesthesia effectively impairs the sensitivity to vaginal and cervical stimulation at parturition. OT levels in cerebrospinal fluid is significantly reduced following peridural anesthesia. The vaginal delivery mothers had significantly more OT pulses than the caesarian section mothers. Due to low levels of endogenous OT, maternal behavior could be interrupted by epidural anesthesia and CS at parturition because of the reduction of the usual sensory input from the genitalia. (shrink)

The processing of time intervals in the sub- to supra-second range by the brain is critical for the interaction of primates with their surroundings in activities, such as foraging and hunting. For an accurate processing of time intervals by the brain, representation of physical time within neuronal circuits is necessary. I propose that time dimension of the physical surrounding is represented in the brain by different types of neuronal oscillators, generating spikes or spike bursts at regular intervals. The proposed oscillators (...) include the pacemaker neurons, tonic inputs, and synchronized excitation and inhibition of inter-connected neurons. Oscillators, which are built inside various circuits of brain, help to form modular clocks, processing time intervals or other temporal characteristics specific to functions of a circuit. Relative or absolute duration is represented within neuronal oscillators by “neural temporal unit,” defined as the interval between regularly occurring spikes or spike bursts. Oscillator output is processed to produce changes in activities of neurons, named frequency modulator neuron, wired within a separate module, represented by the rate of change in frequency, and frequency of activities, proposed to encode time intervals. Inbuilt oscillators are calibrated by (a) feedback processes, (b) input of time intervals resulting from rhythmic external sensory stimulation, and (c) synchronous effects of feedback processes and evoked sensory activity. A single active clock is proposed per circuit, which is calibrated by one or more mechanisms. Multiple calibration mechanisms, inbuilt oscillators, and the presence of modular connections prevent a complete loss of interval timing functions of the brain. (shrink)

Oxytocin (OT) is one of the most intensively researched neuropeptides during the three past decades. In benign social contexts, OT exerts a range of desirable socioemotional, stress-reducing, and immunoregulatory effects in mammals and humans and influences mammalian parenting. Consequentially, research in potential pharmacological applications of OT toward human social deficits/disorders and physical illness has increased substantially. Regrettably, the results from the administration of exogenous OT are still relatively inconclusive. Research in rodent maternal developmental programming has demonstrated the susceptibility of (...) offspring endogenous OT systems to maternal somatosensory stimulation, with consequences for behavioral, epigenetic, cognitive, and neurological outcomes. A translation of this animal research into practically feasible human parenting recommendations has yet to happen, despite the significant prevention potential implied by the maternal developmental programming research. Extended physical contact with full-term healthy infants in the months following birth (infant carrying) might constitute the human equivalent of those specific rodent maternal behaviors, found to positively influence emerging OT systems. Findings from both OT and maternal programming research parallel those found for infants exposed to such extended parental physical contact, whether through skin-to-skin contact or infant carrying. Clinical support of parents to engage in extended physical contact represents a feasible intervention to create optimum conditions for the development of infant OT systems, with potential beneficial long-term health effects. (shrink)

Transcranial magnetic stimulation can cause measurable effects on neural activity and behavioral performance in healthy volunteers. In addition, TMS is increasingly used in clinical practice for treating various neuropsychiatric disorders. Unfortunately, TMS-induced effects show large intra- and inter-subject variability, hindering its reliability, and efficacy. One possible source of this variability may be the spontaneous fluctuations of neuronal oscillations. We present recent studies using multimodal TMS including TMS-EMG, TMS-tACS, and concurrent TMS-EEG-fMRI, to evaluate how individual oscillatory brain (...) state affects TMS signal propagation within targeted networks. We demonstrate how the spontaneous oscillatory state at the time of TMS influences both immediate and longer-lasting TMS effects. These findings indicate that at least part of the variability in TMS efficacy may be attributable to the current practice of ignoring oscillatory fluctuations during TMS. Ignoring this state-dependent spread of activity may cause great individual variability which so far is poorly understood and has proven impossible to control. We therefore also compare two technical solutions to directly account for oscillatory state during TMS, namely, to use tACS to externally control these oscillatory states and then apply TMS at the optimal brain state, or oscillatory state-triggered TMS. The described multimodal TMS approaches are paramount for establishing more robust TMS effects, and to allow enhanced control over the individual outcome of TMS interventions aimed at modulating information flow in the brain to achieve desirable changes in cognition, mood, and behavior. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Finding My Compass*Laura Inter+I was born in the 1980s, and much to my parents surprise, the doctors could not say whether I was a boy or a girl because my body had ambiguous genitalia. They then conducted a chromosome test and the result was XX chromosomes. I was assigned female and only later was diagnosed with congenital adrenal hyperplasia (CAH). Fortunately for me the endocrinologist who treated me (...) did not mention the option of surgery, so my medical treatment consisted only of taking cortisol. Apart from this, from the time I turned one, I was subjected to genital examinations twice a year, during which the endocrinologist would touch my genitals and look to see how they were developing.These unnecessary and intrusive examinations had a profound effect on me. As a young child, I did not understand why I had to lower my pants in front of a stranger—the endocrinologist—and let him touch me. The fact that my mother was present, and approved of this was something that made me feel completely helpless. All this seemed very strange to me; I found it confusing, and terribly uncomfortable, and I just felt it wasn’t right.I remember the doctor always spoke as if I wasn’t right there, and I did not always understand everything the doctor said when I was young, because of all the medical terms he used. I grew up with a feeling of being “inadequate,” of having a sense that something was wrong with me, though I didn’t know exactly what. These exams lasted until I was about 12 years old. Years later, as I began my adult, sexual life, I realized how much those displays had affected me emotionally.I discovered what was “wrong” with me during sex education classes in the first year of high school. There was a class session in which two images were shown: one displaying the external female sex organs, and the other the male sex organs. I noticed that my body was not like either of them. I was very distressed, thinking “I have deformed genitals!” I feared I could not perform sexually as either a man or a woman. I became very depressed. I was sure nobody would want me, that I would never have a relationship. I was unacceptable, “abnormal,” or at least that is what the doctors had said. And in any case my parents never spoke of it, and I didn’t know that I had CAH.Skip forward a few years: I was still looking for answers, I found my medical file and read in the documents “pseudo–hermaphrodite,” and [End Page 95] “congenital adrenal hyperplasia.” I searched the internet, but only found medical opinions that said that in the case of genital ambiguity, the best option was surgery. I wondered to myself: “Why didn’t they operate on me?”I put the question to my parents, and, at fifteen, I found myself being examined once more in the doctor’s office, this time to consider the possibility of a genital surgery which might once and for all, I believed, make me a “normal” person.I have never told anyone outside my family before, but one of those exams was the most humiliating experiences of my life. One doctor wanted to speak with me alone, so she made my mother wait outside the exam room. My mother agreed, thinking that after the doctor talked with me, my mother would be able to be present during the rest of the exam. The doctor asked me questions, some of which made me very uncomfortable: “Do you feel good about being a woman”? Did you ever feel like a man? Why don’t you dress up more, use more makeup? Are you a lesbian? Have you ever had sex? She then said she wanted to see my genitals. I felt awful and wanted my mother present, but I also wanted it to be over quickly, and said nothing. Examining my genitals, the doctor told me they “would not be adequate for sex,” and that she needed to “perform surgery.” Something else that made me uncomfortable was the presence of another doctor in... (shrink)

The effects of handling on the exploratory activity of rats in settings varying in level of sensory stimulation1 This study tests the assumptions of need for stimulation theory. According the main hypothesis of this theory, the stimulus seeking activity of an organism in an unfamiliar environment is affected by two main temperamental traits: emotional reactivity and need for stimulation. In a familiar setting, the influence of emotional reactivity disappears, while the need for stimulation persists. Two (...) experiments were run in which animals' emotionality was manipulated by means of presence or absence of handling and the level of environmental stimulation was manipulated by varying the intensity of light to which the animals were exposed. Sixty male Wistar rats were tested in the first experiment. Stimulus seeking activity was registered in the Skinner-type chambers where animals could switch the light on by every head dip into one of two holes, the so-called experimental hole. Animals were tested in five 30-minute sessions repeated every 48 hours. As predicted, the effect of emotionality on exploration emerged at the beginning of the experiment, whereas the effect of the level of environmental stimulation on the total number of head-dips emerged in all the experimental sessions. The second experiment involved 40 rats and followed a similar design, but the stimulus seeking activity was measured in the situation where the animals could switch the light off by dipping their heads into the experimental hole. Contrary to predictions, the experimental factors had no significant effect on the animals' stimulus seeking activity. Only the results of the first experiment confirm the assumptions of need for stimulation theory. (shrink)

Pain has not only sensory, but also emotional and cognitive, components. Some studies have explored the effect of pain on time perception, but the results remain controversial. Whether individual pain-related emotional and cognitive factors play roles in this process should also be explored. In this study, we investigated the effect of electrical stimulation–induced pain on interval timing using a temporal bisection task. During each task session, subjects received one of five types of stimulation randomly: no stimulus and (...) 100 and 300 ms of non-painful and painful stimulation. Pain-related emotional and cognitive factors were measured using a series of questionnaires. The proportion of “long” judgments of a 1,200-ms visual stimulus duration was significantly smaller with 300 ms painful stimulation than with no stimulus and 100 ms and 300 ms non-painful stimulation. The point of subjective equality did not differ among sessions, but the average Weber fraction was higher for painful sessions than for no-stimulus session. The pain fear score correlated positively with the PSE under 100 ms non-painful and painful and 300 ms painful stimulation. Pain catastrophizing and pain anxiety scores correlated significantly with the WF under no stimulus and 100 ms non-painful stimulation, respectively. These results suggest that electrical stimulation–induced pain affects temporal sensitivity, and that pain-related emotional and cognitive factors are associated with the processing of time perception. (shrink)

ObjectiveThe time interval between transcranial magnetic stimulation pulses affects evoked muscle responses when the targeted muscle is resting. This necessitates using sufficiently long inter-pulse intervals. However, there is some evidence that the IPI has no effect on the responses evoked in active muscles. Thus, we tested whether voluntary contraction could remove the effect of the IPI on TMS motor evoked potentials.MethodsIn our study, we delivered sets of 30 TMS pulses with three different IPIs to the left primary motor (...) cortex. These measurements were performed with the resting and active right hand first dorsal interosseous muscle in healthy participants. MEP amplitudes were recorded through electromyography.ResultsWe found that the IPI had no significant effect on the MEP amplitudes in the active muscle, whereas in the resting muscle, the IPI significantly affected the MEP amplitudes, decreasing the MEP amplitude of the 2 s IPI.ConclusionsThese results show that active muscle contraction removes the effect of the IPI on the MEP amplitude. Therefore, using active muscles in TMS motor mapping enables faster delivery of TMS pulses, reducing measurement time in novel TMS motor mapping studies. (shrink)

BackgroundDuring the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation.ObjectiveThis study extends our previous findings by further characterizing how the brain differentially processes physical ‘touch’ stimulation and ‘imagined’ stimulation.DesignEleven healthy women participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. (...) Two additional conditions – imagined dildo self-stimulation and imagined speculum stimulation – were included to characterize the effects of erotic versus non-erotic imagery.ResultsImagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipp... (shrink)

Consciousness alterations can be experienced during unstructured, monotonous stimuli. These effects have not been linked to particular cognitive operations; individual differences in response to such stimulation remain poorly understood. We examined the role of hypnotizability and dissociative tendencies in mind-wandering during a sensory homogenization procedure . We expected that the influence of ganzfeld on MW would be more pronounced among highly hypnotizable individuals , particularly those high in dissociative tendencies. High and low hypnotizables, also stratified by dissociation, (...) completed the sustained attention to response task during ganzfeld and control conditions. High dissociative highs made more commission errors during ganzfeld, suggesting increased MW, whereas the other groups displayed the opposite pattern. Increases in commission errors from the control condition to ganzfeld were associated with more alterations in consciousness and negative affect, but only among highs. Sensory homogenization had opposite effects on MW depending on the interaction of hypnotizability and dissociation. (shrink)

The measurement of sensory intensity has had a long history, attracting the attention of investigators from many disciplines including physiology, psychology, physics, mathematics, philosophy, and even chemistry. While there has been a continuing doubt by some that sensation has the properties necessary for measurement, experiments designed to obtain estimates of sensory intensity have found that a general rule applies: Equal stimulus ratios produce equal sensory ratios. Theories concerning the basis for this simple psychophysical rule are discussed, with (...) emphasis given to the physical correlate theory, which considers judgments of subjective magnitudes to be based upon estimates of physical dimensions that vary regularly with changes in degree of stimulation. For the most thoroughly investigated sensory scales, brightness and loudness, the physical correlate is considered to be distance. Our “tacit knowledge” of the sensory effects of changing distance plays an essential role in matching motor activities to environmental conditions and in ensuring accurate perceptual evaluations through brightness and loudness constancies. In psychophysical experiments, subjects apparently use this same tacit knowledge when required to estimate relative subjective magnitudes. The evidence related to the physical correlate theory is summarized, and it is concluded that, while under appropriate conditions we demonstrate considerable skill in evaluating environmental relationships, we are quite unable to estimate the neurophysiological nature or quantity of sensory response. A psychophysics devoted to studying conditions required for accuracy and conditions producing errors in the perception of environmental relationships would seem to be more valuable than one devoted to subjective magnitudes. (shrink)

Human behavior depends on the ability to effectively introspect about our performance. For simple perceptual decisions, this introspective or metacognitive ability varies substantially across individuals and is correlated with the structure of focal areas in prefrontal cortex. This raises the possibility that the ability to introspect about different perceptual decisions might be mediated by a common cognitive process. To test this hypothesis, we examined whether inter-individual differences in metacognitive ability were correlated across two different perceptual tasks where individuals made (...) judgments about different and unrelated visual stimulus properties. We found that inter-individual differences were strongly correlated between the two tasks for metacognitive ability but not objective performance. Such stability of an individual’s metacognitive ability across different perceptual tasks indicates a general mechanism supporting metacognition independent of the specific task. (shrink)

What makes some firms more innovative than others and what determines the source of these innovations are questions that are still not adequately answered due to the complex, often esoteric, nature of the innovation process. This paper considers the effect of one externally oriented strategy (extent of formal inter-organizational linkages) and one internally oriented strategy (degree of knowledge intensity) on overall levels of innovativeness and the source of these innovations. Using data collected from firms operating in the bioscience-technology industries (...) in both New York and Utah, our results suggest that both of these strategies have a significant effect upon innovation levels and the source of innovation (internally versus externally stimulated). Interestingly, there were few firms that undertook both of these strategies simultaneously and thus the proposed interaction effect where increased absorptive capacity (on the basis of knowledge intensity) would make external linkages even more valuable could not be discerned. (shrink)

Sensory cues provided by compression garments can improve movement accuracy and potentially reduce inter-limb balance asymmetries and the associated risk of injury. The aim of this study was to analyze the effects of CG wearing on inter-limb balance asymmetries. The hypothesis was that CG would reduce inter-limb balance asymmetries, especially in subjects with high level of asymmetries. Twenty-five sportsmen were recruited. They had to stand as motionless as possible in a one-leg stance in two postural (...) tasks, while wearing CG or not. Asymmetry indexes were calculated from center of foot pressure parameters. The effects of CG wearing were analyzed according to participants’ baseline level of asymmetry with correlation analyses. A qualitative analysis was also performed after a dichotomization procedure to check for a specific influence of CG on the dominant and non-dominant leg. Inter-limb balance asymmetries were reduced with CG in participants with high levels of asymmetries at baseline. However, asymmetries were increased with CG in participants with low levels of asymmetries at baseline. The dominant leg was more affected by this negative effect. CG wearing could reduce inter-limb balance asymmetries and the related injury risk in subjects with high levels of inter-limb balance asymmetries at baseline. Nevertheless, CG should not be used in individuals with low baseline balance asymmetries since it can increase asymmetries in these subjects, likely by confusing and overloading the sensorimotor processing on the dominant leg. (shrink)

Reduced Environmental Stimulation Therapy (REST) alters the balance of sensory input to the nervous system by systematically attenuating sensory signals from visual, auditory, thermal, tactile, vestibular, and proprioceptive channels. Previous research from our group has shown that REST via floatation acutely reduces anxiety and blood pressure while simultaneously heightening interoceptive awareness in clinically anxious populations. Anorexia nervosa (AN) is an eating disorder characterized by elevated anxiety, distorted body representation, and abnormal interoception, raising the question of whether REST (...) might positively impact these symptoms. However, this approach has never been studied in eating disorders and it is unknown whether exposure to REST might worsen AN symptoms. To examine these possibilities we conducted an open-label study to investigate the safety and tolerability of REST in AN. We also explored the impact of REST on affective symptoms, body image disturbance, and interoception. Twenty-one partially weight-restored AN outpatients completed a protocol involving four sequential sessions of REST: reclining in a zero-gravity chair, floating in an open pool, and two sessions of floating in an enclosed pool. All sessions were 90 minutes, approximately one week apart. We measured orthostatic blood pressure before and immediately after each session (primary outcome), in addition to collecting blood pressure readings every 10 minutes during the session using a wireless waterproof system as a secondary outcome measure. Each participant's affective state, awareness of interoceptive sensations, and body image was assessed before and after every session (exploratory outcomes). There was no evidence of orthostatic hypotension following floating, and no adverse events (primary outcome). Secondary analyses revealed that REST induced statistically significant reductions in blood pressure, anxiety and negative affect, heightened awareness of cardiorespiratory but not gastrointestinal sensations, and reduced body image dissatisfaction. The findings from this initial trial suggest that individuals with AN can safely tolerate the physical effects of REST via floatation. Future randomized controlled trials will need to investigate whether these initial observations of improved anxiety, interoception, and body image disturbance can be effectively extended to acutely ill AN populations. (shrink)

After spinal cord injury (SCI), motoneuron death occurs at and around the level of injury which induces changes in function and organization throughout the nervous system, including cortical changes. Muscle affected by SCI may consist of both innervated (accessible to voluntary drive) and denervated (inaccessible to voluntary drive) muscle fibers. Voluntary activation measured with transcranial magnetic stimulation (VATMS) can quantify voluntary cortical/subcortical drive to muscle but is limited by technical challenges including suboptimal stimulation of target muscle relative to (...) its antagonist. The motor evoked potential (MEP) in the biceps compared to the triceps (i.e., MEP ratio) may be a key parameter in the measurement of biceps VATMS after SCI. We used paired pulse TMS, which can inhibit or facilitate MEPs, to determine whether the MEP ratio affects VATMS in individuals with tetraplegia. Ten individuals with tetraplegia following cervical SCI and ten non-impaired individuals completed single pulse and paired pulse VATMS protocols. Paired pulse stimulation was delivered at 1.5, 10, and 30 ms inter-stimulus intervals (ISI). In both the SCI and non-impaired groups, the main effect of the stimulation pulse (paired pulse compared to single pulse) on VATMS was not significant in the linear mixed-effects models. In both groups for the stimulation parameters we tested, the MEP ratio was not modulated across all effort levels and did not affect VATMS. Linearity of the voluntary moment and superimposed twitch moment relation was lower in SCI participants compared to non-impaired. Poor linearity in the SCI group limits interpretation of VATMS. Future work is needed to address methodological issues that limit clinical application of VATMS. (shrink)

In 1943, a distinguished child psychiatrist at Johns Hopkins University, Leo Kanner, published what would become a landmark article: a description of 11 children who suffered from a distinct disorder he called ‘infantile autism’. While initially quite obscure, in the early 1950s Kanner’s report garnered much attention, as clinicians and researchers interpreted these case studies as exemplifying the ill-effects of maternal deprivation, a new theory that rapidly gained currency in the United States. Sensory deprivation experiments, performed in the (...) mid-1950s, further complicated the picture, as experts debated whether maternal deprivation was unique or simply a form of environmental stimulation. As experts strove to make sense of this new disorder, they relied on concepts of maternal and sensory deprivation, both to promote their own theories and to critique or refute those of their colleagues. This interplay between the two theories also informed new forms of intervention, including ‘rage reduction therapy’, which served as a precursor for controversial forms of therapy today termed as the ‘attachment therapies’. This article sheds light on a little-known aspect of the history of autism, and examines the far-reaching effect popular etiological theories have in shaping debates over emerging medical concerns. (shrink)

Functional electrical stimulation (FES), a method for inducing muscle contraction, has been successfully used in gait rehabilitation for patients with deficits after neurological disorders and several clinical studies have found that it can improve gait function after stroke and spinal cord injury. However, FES gait training is not suitable for patients with walking difficulty, such as those with severe motor paralysis of the lower limbs. We have previously shown that action observation combined with motor imagery (AO + MI) of (...) walking induces walking-related cortical activity. Therefore, we combined FES, which alternately generates dorsiflexion and plantar flexion, with AO + MI as an alternative to gait training. The present study investigates the transient effects of 20-min of FES simultaneously with and without AO + MI of walking on corticospinal and spinal reflex excitability in able-bodied participants. We measured motor evoked potentials and Hoffmann-reflexes to assess corticospinal and spinal reflex excitability at rest before and after the 20-min FES with and without the AO + MI. Our results show that FES without AO + MI did not change excitability (p > 0.05), while FES with AO + MI facilitated corticospinal excitability (p < 0.05). This facilitation likely occurred due to the synchronization of sensory inputs from FES and cortical activity during AO + MI. Facilitation was observed only in the dorsiflexor but not the plantar flexor muscle (p < 0.05), suggesting muscle specificity of the facilitation. These results demonstrate the effectiveness of combining FES with AO + MI and pave the way for novel neurorehabilitation strategies for patients with neurological gait deficits. (shrink)

BackgroundConventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality (“non-focal”). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality.AimTo determine the regional volume parameters that differentiate the (...) focal and non-focal groups.MethodsT1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV’s showed a significant main effect or interaction involving the focality group, then that ROI was classified as a “focal ROI.”ResultsRegional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ –0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses.ConclusionThe CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL). (shrink)

Working memory is a cognitive process that involves maintaining and manipulating information for a short period of time. WM is central to many cognitive processes and declines rapidly with age. Deficits in WM are seen in older adults and in patients with dementia, schizophrenia, major depression, mild cognitive impairment, Alzheimer’s disease, etc. The frontal, parietal, and occipital cortices are significantly involved in WM processing and all brain oscillations are implicated in tackling WM tasks, particularly theta and gamma bands. The theta/gamma (...) neural code hypothesis assumes that retained memory items are recorded via theta-nested gamma cycles. Neuronal oscillations can be manipulated by sensory, invasive- and non-invasive brain stimulations. Transcranial alternating-current stimulation and repetitive transcranial magnetic stimulation are frequency-tuned non-invasive brain stimulation techniques that have been used to entrain endogenous oscillations in a frequency-specific manner. Compared to rTMS, tACS demonstrates superior cost, tolerability, portability, and safety profile, making it an attractive potential tool for improving cognitive performance. Although cognitive research with tACS is still in its infancy compared to rTMS, a number of studies have shown a promising WM enhancement effect, especially in the elderly and patients with cognitive deficits. This review focuses on the various methods and outcomes of tACS on WM in healthy and unhealthy human adults and highlights the established findings, unknowns, challenges, and perspectives important for translating laboratory tACS into realistic clinical settings. This will allow researchers to identify gaps in the literature and develop frequency-tuned tACS protocols with promising safety and efficacy outcomes. Therefore, research efforts in this direction should help to consider frequency-tuned tACS as a non-pharmacological tool of cognitive rehabilitation in physiological aging and patients with cognitive deficits. (shrink)

In the inter-war period physicians elaborated numerous ‘biotherapies’ grounded in the complex interactions between physiology, bacteriology and immunology. The elaboration of these non-specific biological treatments was stimulated by the theory of generalized anaphylaxis that linked the violent reaction to a foreign protein to a broad array of chronic diseases, from asthma and urticaria to rheumatism or chronic colitis. Such diseases were perceived as the result of an ‘abnormal reactivity’ to a sensitisation of tissues and organs by bacteria and by (...) foreign proteins, a view that provided an effective bridge between new concepts derived from bacteriology and immunology and the long-standing pathological tradition. Accordingly, physicians attempted to treat these conditions through specific desensitisation and non-specific biological therapies: peptone treatment, protein therapy, haemotherapy, ‘antivirus’ or ‘opotherapy’. Therapies that attempted to neutralise the harmful effects of chronic infections through ‘desensitisation’ were not seen as marginal medical practices, but were promoted by leading advocates of the ‘Pasteurian sciences’, such as Richet, Widal, Vallery-Radot, Wright and Fleming. They also led to development of new products by the pharmaceutical industry. (shrink)

In people with chronic low back pain, maladaptive structural and functional changes on a cortical level have been identified. On a functional level, somatosensory cortical excitability has been shown to be reduced in chronic pain conditions, resulting in cortical disinhibition. The occurrence of structural and/or functional maladaptive cortical changes in people with CLBP could play a role in maintaining the pain. There is currently no measurement protocol for cortical excitability that employs stimulation directly to the lower back. We developed (...) a protocol for the measurement of single pulse somatosensory evoked potential waveforms and paired-pulse behavior generated from sensory nerves of the lower back and quantified its test–retest reliability in a sample of 30 healthy individuals to gain insights into the normal variability of cortical responses, which could then be compared to results from people with CLBP. We investigated cortical excitability by measuring SEPs and PPB. PPB was defined as the ratio of the amplitude of the second cortical response divided by the first cortical response. A2s was determined by subtracting the response to single-pulse stimuli from the paired pulse stimuli response to account for linear superposition effects. The test–retest reliability of the protocol was very poor with no evidence of systematic bias but a high amount of random variability between sessions. There was no significant difference in the right side PPB for session 1 and session 2 ; mean session difference [ = −0.44 ; t = −1.17, p = 0.26]. The ICC3.1 for the outlier-removed right side PPB were 0.19 and 0.43 for left side PPB. This finding potentially has wider implications for PPB protocols. If these findings were replicated in other groups and other nerves, it would question the validity of this measure more generally. However, these findings are restricted to healthy people and sensory nerves of the lower back and may not be generalizable. (shrink)

ObjectiveTwo subregions of the dorsolateral prefrontal cortex have been identified as effective repetitive transcranial magnetic stimulation targets for the “anxiosomatic” and “dysphoric” symptoms, respectively. We aimed to develop a convenient approach to locate these targets on the scalp.Materials and methodsIn a discovery experiment, the two personalized targets were precisely identified on 24 subjects using a neuronavigation system. Then, a localized approach was developed based on individual scalp landmarks. This “landmark-based approach” was replicated and validated in an independent cohort. Reliability (...) of the approach was tested by calculating the correlation of both the inter-rater and intra-rater results. Validity was tested by comparing the mean distance between the personalized and landmark-based targets to the TMS spatial resolution. We further conducted a total of 24 sham rTMS sessions to estimate the misplacement between the coil center and target during a 10-min stimulation without neuronavigation.ResultsThe parameters of the “landmark-based approach” in the discovery experiment were replicated well in an independent cohort. Using discovery parameters, we successfully identified the symptom-specific targets in the independent cohort. Specifically, the mean distance between the personalized and landmark-based targets on the cortex was not significantly larger than 5 mm. However, the personalized and landmark-based targets distance exceeded 5 mm in more than 50% of subjects. During the 10-min sham rTMS session, the average coil misplacement was significantly larger than 5 mm.ConclusionThe “landmark-based approach” can conveniently and reliably locate the two symptom-specific targets at group level. However, the accuracy was highly varied at individual level and further improvement is needed. (shrink)

Infants’ ability to monitor “sensorimotor contingencies,” i.e., the sensory effects of their own actions, is an important mechanism underlying learning. One method that has been used to investigate this is the “mobile paradigm,” in which a mobile above an infant’s crib is activated by motion of one of the infant’s limbs. Although successfully used in numerous experiments performed in infants’ homes to investigate memory and other types of learning, the paradigm seems less robust for demonstrating sensitivity to sensorimotor (...) contingencies when used in the laboratory. One purpose of the present work was to show that certain changes to the mobile paradigm would make it easier for infants to show their sensitivity to the contingency in the lab. In particular, we used proximal stimulation on infants’ wrists instead of the usual mobile, and our stimulation was coincident with the limbs that caused it. Our stimulation was either on or off, i.e., not modulated by the amount the infant moved. Finally, we used a “shaping” procedure to help the infant discover the contingency. In addition to these changes in the paradigm, by analyzing infants’ limb activity at 10-s resolution instead of the usual 1-min resolution, we were able to show that infants’ sensitivity to the contingency became apparent already within the first minute of establishment of the contingency. Finally, we showed how two alternate measures of sensitivity to contingency based on probability of repeated movements and on “stop and go” motion strategies may be of interest for future work. (shrink)

While cochlear implantation has benefitted many patients with single-sided deafness (SSD), there is great variability in cochlear implant (CI) outcomes and binaural performance remains poorer than that of normal-hearing (NH) listeners. Differences in sound quality across ears – temporal fine structure (TFS) information with acoustic hearing versus coarse spectro-temporal envelope information with electric hearing – may limit integration of acoustic and electric patterns. Binaural performance may also be limited by inter-aural mismatch between the acoustic input frequency and the place (...) of stimulation in the cochlea. SSD CI patients must learn to accommodate these differences between acoustic and electric stimulation to maximize binaural performance. It is possible that training may increase and/or accelerate accommodation and further improve binaural performance. In this study, we evaluated lateralization training in NH subjects listening to broad simulations of SSD CI signal processing. A 16-channel vocoder was used to simulate the coarse spectro-temporal cues available with electric hearing; the degree of inter-aural mismatch was varied by adjusting the simulated insertion depth (SID) to be 25 mm (SID25), 22 mm (SID22), and 19 mm (SID19) from the base of the cochlea. Lateralization was measured using headphones and head-related transfer functions (HRTFs). Baseline lateralization was measured for unprocessed speech (UN) delivered to the left ear to simulate SSD and for binaural performance with the acoustic ear combined with the 16-channel vocoders (UN+SID25, UN+SID22, and UN+SID19). After completing baseline measurements, subjects completed 6 lateralization training exercises with the UN+SID22 condition, after which performance was re-measured for all baseline conditions. Post-training performance was significantly better than baseline for all conditions (p<0.05 in all cases), with no significant difference in training benefits among conditions. Given that there was no significant difference between the SSD and the SSD CI conditions before or after training, the results suggest that NH listeners were unable to integrate TFS and coarse spectro-temporal cues across ears for lateralization, and that inter-aural mismatch played a secondary role at best. While lateralization training may benefit SSD CI patients, the training may largely improve spectral analysis with the acoustic ear alone, rather than improve integration of acoustic and electric hearing. (shrink)

Starting from the early 2000s, paired associative stimulation protocols have been used in humans to study brain connectivity in motor and sensory networks by exploiting the intrinsic properties of timing-dependent cortical plasticity. In the last 10 years, PAS have also been developed to investigate the plastic properties of complex cerebral systems, such as the frontal ones, with promising results. In the present work, we review the most recent advances of this technique, focusing on protocols targeting frontal cortices to (...) investigate connectivity and its plastic properties, subtending high-order cognitive functions like memory, decision-making, attentional, or emotional processing. Overall, current evidence reveals that PAS can be effectively used to assess, enhance or depress physiological connectivity within frontal networks in a timing-dependent way, in turn modulating cognitive processing in healthy and pathological conditions. (shrink)

Recent advances in second-person neuroscience have allowed the underlying neural mechanisms involved in teaching-learning interactions to be better understood. Teaching is not merely a one-way transfer of information from teacher to student; it is a complex interaction that requires metacognitive and mentalizing skills to understand others’ intentions and integrate information regarding oneself and others. Physiotherapy involving therapists instructing patients on how to improve their motor skills is a clinical field in which teaching-learning interactions play a central role. Accumulating evidence suggests (...) that non-invasive brain stimulation modulates cognitive functions; however, NIBS approaches to teaching-learning interactions are yet to be utilized in rehabilitation. In this review, I evaluate the present research into NIBS and its role in enhancing metacognitive and mentalizing abilities; I then review hyperscanning studies of teaching-learning interactions and explore the potential clinical applications of NIBS in rehabilitation. Dual-brain stimulation using NIBS has been developed based on findings of brain-to-brain synchrony in hyperscanning studies, and it is delivered simultaneously to two individuals to increase inter-brain synchronized oscillations at the stimulated frequency. Artificial induction of brain-to-brain synchrony has the potential to promote instruction-based learning. The brain-to-brain interface, which induces inter-brain synchronization by adjusting the patient’s brain activity, using NIBS, to the therapist’s brain activity, could have a positive effect on both therapist-patient interactions and rehabilitation outcomes. NIBS based on second-person neuroscience has the potential to serve as a useful addition to the current neuroscientific methods used in complementary interventions for rehabilitation. (shrink)

During sensory stimulation, visual cortical neurons undergo massive synaptic bombardment. This increases their input conductance, and action potentials mainly result from membrane potential fluctuations. To understand the response properties of neurons operating in this regime, we studied a model neuron with synaptic inputs represented by transient membrane conductance changes. We show that with a simultaneous increase of excitation and inhibition, the firing rate first increases, reaches a maximum, and then decreases at higher input rates. Comodulation of excitation and (...) inhibition, therefore, does not provide a straightforward way of controlling the neuronal firing rate, in contrast to coding mechanisms postulated previously. The synaptically induced conductance increase plays a key role in this effect: it decreases firing rate by shunting membrane potential fluctuations, and increases it by reducing the membrane time constant, allowing for faster membrane potential transients. These findings do not depend on details of the model and, hence, are relevant to cells of other cortical areas as well. (shrink)

Deep Brain Stimulation (DBS) is a relatively new, experimental treatment for patients suffering from treatment-refractory Obsessive Compulsive Disorder (OCD). The effects of treatment are typically assessed with psychopathological scales that measure the amount of symptoms. However, clinical experience indicates that the effects of DBS are not limited to symptoms only: patients for instance report changes in perception, feeling stronger and more confident, and doing things unreflectively. Our aim is to get a better overview of the whole variety (...) of changes that OCD patients experience during DBS treatment. For that purpose we conducted in-depth, semi-structured interviews with 18 OCD patients. In this paper, we present the results from this qualitative study.We list the changes grouped in four domains: with regard to (a) person, (b) (social) world, (c)characteristics of person-world interactions, and (d) existential stance. We subsequently provide an interpretation of these results. In particular, we suggest that many of these changes can be seen as different expressions of the same process; namely that the experience of anxiety and tension gives way to an increased basic trust and increased reliance on one’s abilities. We then discuss the clinical implications of our findings, especially with regard to properly informing patients of what they can expect from treatment, the usefulness of including CBT in treatment, and the limitations of current measures of treatment success. We end by making several concrete suggestions for further research. (shrink)