Locating primary somatosensory cortex in human brain stimulation studies: experimental evidence

Transcranial magnetic stimulation (TMS) over human primary somatosensory cortex (S1) does not produce immediate outputs. Researchers must therefore rely on indirect methods for TMS coil positioning. The “gold standard” is to use individual functional and structural magnetic resonance imaging (MRI) data, but the majority of studies don’t do this. The most common method to locate the hand area of S1 (S1-hand) is to move the coil posteriorly from the hand area of primary motor cortex (M1-hand). Yet, S1-hand is not directly posterior to M1-hand. We localized the index finger area of S1-hand (S1-index) experimentally in four ways. First, we reanalyzed functional MRI data from 20 participants who received vibrotactile stimulation to their 10 digits. Second, to assist the localization of S1-hand without MRI data, we constructed a probabilistic atlas of the central sulcus from 100 healthy adult MRIs and measured the likely scalp location of S1-index. Third, we conducted two experiments mapping the effects of TMS across the scalp on tactile discrimination performance. Fourth, we examined all available neuronavigation data from our laboratory on the scalp location of S1-index. Contrary to the prevailing method, and consistent with systematic review evidence, S1-index is close to the C3/C4 electroencephalography (EEG) electrode locations on the scalp, ~7–8 cm lateral to the vertex, and ~2 cm lateral and 0.5 cm posterior to the M1-hand scalp location. These results suggest that an immediate revision to the most commonly used heuristic to locate S1-hand is required. The results of many TMS studies of S1-hand need reassessment

Tactile localization biases are modulated by gaze direction

Identifying the spatial location of touch on the skin surface is a fundamental function of our somatosensory system. Despite the fact that stimulation of even single mechanoreceptive afferent fibres is sufficient to produce clearly localised percepts, tactile localisation can be modulated also by higher-level processes such as body posture. This suggests that tactile events are coded using multiple representations using different coordinate systems. Recent reports provide evidence for systematic biases on tactile localisation task, which are thought to result from a supramodal representation of the skin surface. While the influence of non-informative vision of the body and gaze direction on tactile discrimination tasks has been extensively studied, their effects on tactile localisation tasks remain largely unexplored. To address this question, participants performed a tactile localization task on their left hand under different visual conditions by means of a mirror box; in the mirror condition a single stimulus was delivered on participants’ hand while the reflexion of the right hand was seen through the mirror; in the object condition participants looked at a box through the mirror, and in the right hand condition participants looked directly at their right hand. Participants reported the location of the tactile stimuli using a silhouette of a hand. Results showed a shift in the localization of the touches towards the tip of the fingers (distal bias) and the thumb (radial biases) across conditions. Critically, distal biases were reduced when participants looked towards the mirror compared to when they looked at their right hand suggesting that gaze direction reduces the typical proximo-distal biases in tactile localization. Moreover, vision of the hand modulates the internal configuration of points’ locations, by elongating it, in the radio-ulnar axis

Finger posture modulates structural body representations

Patients with lesions of the left posterior parietal cortex commonly fail in identifying their fingers, a condition known as finger agnosia, yet are relatively unimpaired in sensation and skilled action. Such dissociations have traditionally been interpreted as evidence that structural body representations (BSR), such as the body structural description, are distinct from sensorimotor representations, such as the body schema. We investigated whether performance on tasks commonly used to assess finger agnosia is modulated by changes in hand posture. We used the ‘in between’ test in which participants estimate the number of unstimulated fingers between two touched fingers or a localization task in which participants judge which two fingers were stimulated. Across blocks, the fingers were placed in three levels of splay. Judged finger numerosity was analysed, in Exp. 1 by direct report and in Exp. 2 as the actual number of fingers between the fingers named. In both experiments, judgments were greater when non-adjacent stimulated fingers were positioned far apart compared to when they were close together or touching, whereas judgements were unaltered when adjacent fingers were stimulated. This demonstrates that BSRs are not fixed, but are modulated by the real-time physical distances between body parts

Distorted body representations are robust to differences in experimental instructions

Several recent reports have shown that even healthy adults maintain highly distorted representations of the size and shape of their body. These distortions have been shown to be highly consistent across different study designs and dependent measures. However, previous studies have found that visual judgments of size can be modulated by the experimental instructions used, for example, by asking for judgments of the participant’s subjective experience of stimulus size (i.e., apparent instructions) versus judgments of actual stimulus properties (i.e., objective instructions). Previous studies investigating internal body representations have relied exclusively on ‘apparent’ instructions. Here, we investigated whether apparent versus objective instructions modulate findings of distorted body representations underlying position sense (Exp. 1), tactile distance perception (Exp. 2), as well as the conscious body image (Exp. 3). Our results replicate the characteristic distortions previously reported for each of these tasks and further show that these distortions are not affected by instruction type (i.e., apparent vs. objective). These results show that the distortions measured with these paradigms are robust to differences in instructions and do not reflect a dissociation between perception and belief

Covid-19 in a young liver transplant recipient: Caution for drug-drug interactions

Immunosuppressed patients represent a vulnerable population, that may be at a higher risk for an atypical presentation and more severe courses of coronavirus disease (COVID-19). Here, we present the case of a 27-year old liver transplant recipient with a mild case of COVID-19, who was successfully treated with antivirals and hydroxychloroquine. However, the patient developed an important drug-drug interaction, with overexposure to tacrolimus and subsequent acute kidney injury, despite the discontinuation of the immunosuppressive therapy. This pragmatic case raises several concerns about the management of immunosuppression and the treatment of COVID-19 in solid organ transplant patients

The contribution of primary and secondary somatosensory cortices to the representation of body parts and body sides: an fMRI adaptation study

Although the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, whereas the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands)

High incidence of allograft dysfunction in liver transplanted patients treated with pegylated‐interferon alpha‐2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis?

BACKGROUND: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. METHODS: 9 of 44 liver transplanted patients who had been receiving pegylated‐interferon alpha‐2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on‐treatment HCV‐RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. RESULTS: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a “probable autoimmune hepatitis” (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti‐mitochondrial antibodies (AMA)‐positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre‐existing autoimmune hepatitis was excluded. Anti‐lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony‐stimulating factor to treat interferon‐induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). CONCLUSIONS: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon