The cortical representation of pain

Anatomical and physiological studies in animals, as well as functional imaging studies in humans have shown that multiple cortical areas are activated by painful stimuli. The view that pain is perceived only as a result of thalamic processing has, therefore, been abandoned, and has been replaced by the question of what functions can be assigned to individual cortical areas. The following cortical areas have been shown to be involved in the processing of painful stimuli: primary somatosensory cortex, secondary somatosensory cortex and its vicinity in the parietal operculum, insula, anterior cingulate cortex and prefrontal cortex. These areas probably process different aspects of pain in parallel. Previous psychophysical research has emphasized the importance of separating pain experience into sensory-discriminative and affective-motivational components. The sensory-discriminative component of pain can be considered a sensory modality similar to vision or olfaction; it becomes more and more evident that it is subserved by its own apparatus up to the cortical level. The affective-motivational component is close to what may be considered 'suffering from pain'; it is clearly related to aspects of emotion, arousal and the programming of behaviour. This dichotomy, however, has turned out to be too simple to explain the functional significance of nociceptive cortical networks. Recent progress in imaging technology has, therefore, provided a new impetus to study the multiple dimensions of pain.     

Design considerations for a wearable monitor to measure finger posture

BACKGROUND: Objective measures of hand function as individuals participate in home and community activities are needed in order to better plan and evaluate rehabilitation treatments. Traditional measures collected in the clinical setting are often not reflective of actual functional performance. Recent advances in technology, however, enable the development of a lightweight, comfortable data collection monitor to measure hand kinematics. METHODS: This paper presents the design analysis of a wearable sensor glove with a specific focus on the sensors selected to measure bend. The most important requirement for the glove is easy donning and removal for individuals with significantly reduced range of motion in the hands and fingers. Additional requirements include comfort and durability, cost effectiveness, and measurement repeatability. These requirements eliminate existing measurement gloves from consideration. Glove construction is introduced, and the sensor selection and glove evaluation process are presented. RESULTS: Evaluation of commercial bend sensors shows that although most are not appropriate for repeatable measurements of finger flexion, one has been successfully identified. A case study for sensor glove repeatability using the final glove configuration and sensors does show a high degree of repeatability in both the gripped and flat hand positions (average coefficient of variability = 2.96% and 0.10%, respectively). CONCLUSION: Measuring functional outcomes in a portable manner can provide a wealth of information important to clinicians for the evaluation and treatment of movement disorders in the hand and fingers. This device is an important step in that direction as both a research and an evaluation method.     

The cortical representation of simple mathematical expressions

Written mathematical notation conveys, in a compact visual form, the nested functional relations among abstract concepts such as operators, numbers or sets. Is the comprehension of mathematical expressions derived from the human capacity for processing the recursive structure of language? Or does algebraic processing rely only on a language-independent network, jointly involving the visual system for parsing the string of mathematical symbols and the intraparietal system for representing numbers and operators? We tested these competing hypotheses by scanning mathematically trained adults while they viewed simple strings ranging from randomly arranged characters to mathematical expressions with up to three levels of nested parentheses. Syntactic effects were observed in behavior and in brain activation measured with functional magnetic resonance imaging (fMRI) and magneto-encephalography (MEG). Bilateral occipito-temporal cortices and right parietal and precentral cortices appeared as the primary nodes for mathematical syntax. MEG estimated that a mathematical expression could be parsed by posterior visual regions in less than 180 ms. Nevertheless, a small increase in activation with increasing expression complexity was observed in linguistic regions of interest, including the left inferior frontal gyrus and the posterior superior temporal sulcus. We suggest that mathematical syntax, although arising historically from language competence, becomes "compiled" into visuo-spatial areas in well-trained mathematics students.     

Distal-to-proximal representation of volar index finger in human area 3b

In area 3b of the monkey primary somatosensory cortex SI, the proximal phalanges of the fingers are represented close to the surface and the fingertips in the depth of the central sulcus. To study whether a similar arrangement might exist in humans, we applied tactile stimuli to the distal and proximal phalanges of the index finger in 11 healthy adults. Cortical somatosensory evoked fields were recorded with a whole-scalp neuromagnetometer. The sources of the responses were situated in the posterior wall of the central sulcus, statistically significantly more superior to proximal than distal stimuli, with a mean difference of 3.1 mm. Thus the distal-to-proximal representation of the index finger shows a similar order in human and monkey SI cortex.     

Effects of keyswitch design and finger posture on finger joint kinematics and dynamics during tapping on computer keyswitches

OBJECTIVE: To examine the effects of postural and keyswitch characteristics on musculoskeletal tissue loading during tapping on computer keyswitches. DESIGN: We hypothesized that joint torques, stiffness and work parameters differ across keyswitch designs and finger postures typical of those observed during computer keyboard typing. We experimentally measured joint kinematics and calculated joint torques while tapping on different keyswitches in different postures, and analyzed the data using mechanical impedance models. METHODS: Sixteen human subjects tapped with the index finger on computer keyswitches mounted on a sensor which measured vertical and horizontal forces. Miniature electro-optical goniometers mounted dorsally across each finger joint measured joint kinematics. Joint torques were calculated from endpoint forces and joint kinematics using an inverse dynamics algorithm. A linear spring-damper impedance model was fitted to joint torque, position, and velocity during the contact period of each tap. Subjects tapped in three postures approximating those employed during tapping on three rows of a computer keyboard, on four different keyswitches, resulting in 12 conditions. RESULTS: More extended finger posture was associated with greater joint torques, energies, and stiffnesses, despite minimal differences in endpoint forces across posture. Greater keyswitch make forces were associated with increased forces, joint torques and joint stiffnesses, however this relationship was not monotonic. CONCLUSIONS: Joint torques and stiffness parameters differed across keyswitch designs and finger postures. Estimates of joint impedance and work provided a unique perspective into finger dynamics. RELEVANCE: Determining the causes of work-related musculoskeletal disorders is facilitated by characterizing workplace task biomechanics, which can be linked to specific injury mechanisms.     

Motor speech perception modulates the cortical language areas

Traditionally, the left frontal and parietal lobes have been associated with language production while regions in the temporal lobe are seen as crucial for language comprehension. However, recent evidence suggests that the classical language areas constitute an integrated network where each area plays a crucial role both in speech production and perception. We used functional MRI to examine whether observing speech motor movements (without auditory speech) relative to non-speech motor movements preferentially activates the cortical speech areas. Furthermore, we tested whether the activation in these regions was modulated by task difficulty. This dissociates between areas that are actively involved with speech perception from regions that show an obligatory activation in response to speech movements (e.g. areas that automatically activate in preparation for a motoric response). Specifically, we hypothesized that regions involved with decoding oral speech would show increasing activation with increasing difficulty. We found that speech movements preferentially activate the frontal and temporal language areas. In contrast, non-speech movements preferentially activate the parietal region. Degraded speech stimuli increased both frontal and parietal lobe activity but did not differentially excite the temporal region. These findings suggest that the frontal language area plays a role in visual speech perception and highlight the differential roles of the classical speech and language areas in processing others' motor speech movements.     

Impact of finger posture on mapping from muscle activation to joint torque

BACKGROUND: The mapping from muscle activation to joint torque production can be difficult to determine for the multi-articular muscles of the fingers. This relationship was examined in vivo as a function of posture in the index finger. METHODS: Five healthy adults participated in an experiment in which the seven muscles of the index finger were sequentially electrically stimulated using intramuscular electrodes. Each muscle was stimulated at 12 different finger postures consisting of specified flexion of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, while fingertip forces and moments were recorded. FINDINGS: Repeated measures analysis of variance revealed that joint torques resulting from the stimulation were significantly dependent upon finger posture (p < 0.05). The magnitude of the change in joint torque across postures was generally greater than 60%. This value is much larger than the difference attributable to the increase in active muscle force that occurs at longer muscle length, in accordance with the force-length curve (10-20% for the estimated length changes). In addition, the relative distribution of the joint torques generated by a given muscle activation was dependent upon finger posture for the intrinsic muscles and the long finger flexors (p < 0.05); the ratio of one joint torque to another varied with posture for these muscles, in some cases by more than 50%. INTERPRETATION: Joint torque is a product of both muscle force and the corresponding moment arm. As the change in active muscle force was limited, these data suggest that substantial changes in muscle moment arms occur with posture. Therefore, this postural dependence should be considered when constructing biomechanical models of the hand or planning tendon transfers for the fingers.     

Common substrate for mental arithmetic and finger representation in the parietal cortex

The history of mathematics provides several examples of the use of fingers to count or calculate. These observations converge with developmental data showing that fingers play a critical role in the acquisition of arithmetic knowledge. Further studies evidenced specific interference of finger movements with arithmetic problem solving in adults, raising the question of whether or not finger and number manipulations rely on common brain areas. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the possible overlap between the brain areas involved in mental arithmetic and those involved in finger discrimination. Solving subtraction and multiplication problems was found to increase cerebral activation bilaterally in the horizontal part of the intraparietal sulcus (hIPS) and in the posterior part of the superior parietal lobule (PSPL). Finger discrimination was associated with increased activity in a bilateral occipito-parieto-precentral network extending from the extrastriate body area to the primary somatosensory and motor cortices. A conjunction analysis showed common areas for mental arithmetic and finger representation in the hIPS and PSPL bilaterally. Voxelwise correlations further showed that finger discrimination and mental arithmetic induced a similar pattern of activity within the parietal areas only. Pattern similarity was more important for the left than for the right hIPS and for subtraction than for multiplication. These findings provide the first evidence that the brain circuits involved in finger representation also underlie arithmetic operations in adults.     

Inhibitory impact of subliminal electrical finger stimulation on SI representation and perceptual sensitivity of an adjacent finger

Simultaneous stimulation of two adjacent fingers above sensory perception threshold (supraliminal stimulation) leads to an inhibitory interaction effect on responses in primary somatosensory cortex (SI). Moreover, during electrical finger stimulation closely below threshold for conscious perception (subliminal stimulation) inhibitory interneurons in cortical layer 4 are assumed to be activated preferentially as compared to excitatory interneurons. Using fMRI in humans, here we show that interspersed subliminal electrical stimulation of an adjacent finger reduces the response to target finger stimulation in contralateral SI. This effect was shown in a complementary study to be associated behaviorally with a diminished detectability of test pulses on the target finger. We propose the mechanism underlying this lateral inhibitory effect to be related to a representational overlap of inhibitory interneurons in SI based on the divergence of thalamocortical feedforward projections, or to intracortical lateral inhibitory projections targeting juxtaposed receptive fields, or both.     

Luminal vasopressin modulates transport in the rabbit cortical collecting duct.

We explored the action of luminal AVP in rabbit CCD perfused in vitro at 37 degrees C. Nanomolar concentrations of luminal AVP induced a sustained hyperpolarization of transepithelial voltage (Vt) in contrast to a transient hyperpolarization caused by basolateral AVP. 10 microM basolateral ouabain abolished the latter but not the former change in Vt. Despite a sustained hyperpolarization (from -20.7 +/- 2.9 to -34.1 +/- 4.7 mV; P less than 0.01), 10 nM luminal AVP only slightly altered net Na+ and K+ fluxes (7.6% stimulation and no significant change, respectively). Instead, luminal AVP appeared to modulate an acetazolamide-sensitive electrogenic ion transport because 200 microM basolateral acetazolamide suppressed the luminal AVP-induced hyperpolarization (percentage of Vt from -50.4 +/- 10.8 to -5.1 +/- 1.4; P less than 0.005). In terms of water transport, 10 nM luminal AVP did not change hydraulic conductivity (Lp, x 10(-7) cm/atm per s) (from 3.9 +/- 0.8 to 5.0 +/- 1.2), but suppressed the increase in Lp induced by 20 pM basolateral AVP (134.9 +/- 19.2 vs. 204.3 +/- 21.1 in control; P less than 0.05). These findings demonstrate distinct luminal action of AVP, suggesting amphilateral regulation of epithelial transport by AVP in the CCD.     

Nociceptin/orphanin FQ modulates cortical activity and trigeminal nociception

(Headache 2011;51:1245‐1253) Background.— Alterations in the levels of nociceptin/orphanin FQ (N/OFQ) have been reported in patients with primary headaches, including migraines and cluster headaches. These clinical observations suggest that N/OFQ is involved in the pathogenesis of primary headaches. Objectives.— The present study was conducted to determine the role of N/OFQ in the control of trigeminal nociception and cortical excitation. Methods.— Cortical spreading depression (CSD) was elicited in Wistar rats by cortical application of potassium chloride, and electrocorticograms were recorded. N/OFQ was administered via an intracisternal injection. The presence of CSD‐evoked trigeminal nociception was determined with Fos and transient receptor potential vanilloid 1 (TRPV1) immunoreactivity. Results.— Nociceptin/orphanin FQ produced a biphasic effect on CSD generation, characterized by an initial attenuation followed by delayed potentiation. The amplitude of CSD waves were lower in the initial period but increased in the later period. The total number of CSD waves recorded in 1 hour was greater in the N/OFQ‐treated group. Exposure to N/OFQ significantly increased the number of Fos‐immunoreactive cells in the trigeminal nucleus caudalis and the number of TRPV1‐immunoreactive cells in the trigeminal ganglia, indicating the enhancement of trigeminal nociception. Conclusion.— These results indicate that N/OFQ can lead to biphasic effect characterized by an initial inhibition, and delay potentiation that eventually intensify CSD‐evoked trigeminal nociception.     

Smoking experience modulates the cortical integration of vision and haptics

Human neuroplasticity of multisensory integration has been studied mainly in the context of natural or artificial training situations in healthy subjects. However, regular smokers also offer the opportunity to assess the impact of intensive daily multisensory interactions with smoking-related objects on the neural correlates of crossmodal object processing. The present functional magnetic resonance imaging study revealed that smokers show a comparable visuo-haptic integration pattern for both smoking paraphernalia and control objects in the left lateral occipital complex, a region playing a crucial role in crossmodal object recognition. Moreover, the degree of nicotine dependence correlated positively with the magnitude of visuo-haptic integration in the left lateral occipital complex (LOC) for smoking-associated but not for control objects. In contrast, in the left LOC non-smokers displayed a visuo-haptic integration pattern for control objects, but not for smoking paraphernalia. This suggests that prolonged smoking-related multisensory experiences in smokers facilitate the merging of visual and haptic inputs in the lateral occipital complex for the respective stimuli. Studying clinical populations who engage in compulsive activities may represent an ecologically valid approach to investigating the neuroplasticity of multisensory integration.     

Reduced cortical activity during maximal bilateral contractions of the index finger

The bilateral deficit refers to the phenomenon in which homologous muscles produce per muscle less force when contracting simultaneously than when contracting individually. The mechanism underlying the bilateral deficit is still unknown, but the most likely cause is a decline in the activation of motor units during bilateral contractions. In the present study, we used functional magnetic resonance imaging (fMRI) to measure the degree of brain activity during unilateral and bilateral maximal contractions in combination with force and EMG measurements. Subjects performed, in a semi-randomized order, maximal isometric contractions (MVC) with the right index finger, the left index finger and with both fingers simultaneously. During the task, brain activation was measured with a 3 T MR scanner, in combination with force and EMG recordings. The most important activated areas in the brain during the contractions were the sensorimotor cortex (precentral and postcentral gyrus), cerebellum, premotor cortex and supplementary motor area. During bilateral contractions, a significant decline in force and EMG values was found and detailed analysis of the brain activation data showed that this decline was accompanied with a significant decline in the activation of the precentral gyrus. This result suggests that the bilateral decline is the resultant of a decline in input to the primary motor area and shows that the main source of the bilateral deficit lies upstream of the primary motor cortex.     

Dual representation of the hand in the cerebellum: activation with voluntary and passive finger movement

Early electrophysiological studies during sensory stimulation in the anesthetized cat and more recent functional imaging studies during voluntary movement in humans have provided evidence for two separate representations of the body in the anterior and posterior lobes of the cerebellum; however, the functional role of these body maps in motor and sensory processing is not known. The aims of the present study were to determine whether this dual representation is also present during passive movement, and to compare the pattern of activation with that obtained during voluntary movement. Functional MRI measurements were undertaken in 14 subjects who performed right index finger flexion and extension movements at approximately 1 Hz, or had their finger moved passively at the same rate and through the same angle using a pneumatic device. During passive movement, dual activation was detected in the ipsilateral cerebellum, in the anterior lobe, and in the posterior lobe. A similar pattern of activation was observed during voluntary movement; however, the overall magnitude was about doubled. These data provide evidence for a dual ipsilateral representation of the hand in the rostral and caudal cerebellar cortex during passive as well as voluntary movements, with the rostral representation being the dominant one, and indicate that both of these areas are involved in kinesthetic sensory and motor processing.     

Ethanol modulates cortical activity: direct evidence with combined TMS and EEG

The motor cortex of 10 healthy subjects was stimulated by transcranial magnetic stimulation (TMS) before and after ethanol challenge (0.8 g/kg resulting in blood concentration of 0.77 +/- 0.14 ml/liter). The electrical brain activity resulting from the brief electromagnetic pulse was recorded with high-resolution electroencephalography (EEG) and located using inversion algorithms. Focal magnetic pulses to the left motor cortex were delivered with a figure-of-eight coil at the random interstimulus interval of 1.5-2.5 s. The stimulation intensity was adjusted to the motor threshold of abductor digiti minimi. Two conditions before and after ethanol ingestion (30 min) were applied: (1) real TMS, with the coil pressed against the scalp; and (2) control condition, with the coil separated from the scalp by a 2-cm-thick piece of plastic. A separate EMG control recording of one subject during TMS was made with two bipolar platinum needle electrodes inserted to the left temporal muscle. In each condition, 120 pulses were delivered. The EEG was recorded from 60 scalp electrodes. A peak in the EEG signals was observed at 43 ms after the TMS pulse in the real-TMS condition but not in the control condition or in the control scalp EMG. Potential maps before and after ethanol ingestion were significantly different from each other (P = 0.01), but no differences were found in the control condition. Ethanol changed the TMS-evoked potentials over right frontal and left parietal areas, the underlying effect appearing to be largest in the right prefrontal area. Our findings suggest that ethanol may have changed the functional connectivity between prefrontal and motor cortices. This new noninvasive method provides direct evidence about the modulation of cortical connectivity after ethanol challenge.     

全身免疫炎症指数在消化系统疾病中的研究进展

全身免疫炎症指数（SII）是由Hu等于2014年首次在炎症和免疫的预后评分的基础上提出,它的计算公式为血小板计数×中性粒细胞计数/淋巴细胞计数,且因其为非侵入性、易于计算、成本低等被广泛应用于临床。已有研究表明SII反映了宿主免疫和炎症状态两者间的平衡,SII高水平通常可以预测恶性肿瘤的不良结局,此外其还与某些疾病的严...     

Circular representation of human cortical networks for subject and population-level connectomic visualization

Cortical network architecture has predominantly been investigated visually using graph theory representations. In the context of human connectomics, such representations are not however always satisfactory because canonical methods for vertex-edge relationship representation do not always offer optimal insight regarding functional and structural neural connectivity. This article introduces an innovative framework for the depiction of human connectomics by employing a circular visualization method which is highly suitable to the exploration of central nervous system architecture. This type of representation, which we name a 'connectogram', has the capability of classifying neuroconnectivity relationships intuitively and elegantly. A multimodal protocol for MRI/DTI neuroimaging data acquisition is here combined with automatic image segmentation to (1) extract cortical and non-cortical anatomical structures, (2) calculate associated volumetrics and morphometrics, and (3) determine patient-specific connectivity profiles to generate subject-level and population-level connectograms. The scalability of our approach is demonstrated for a population of 50 adults. Two essential advantages of the connectogram are (1) the enormous potential for mapping and analyzing the human connectome, and (2) the unconstrained ability to expand and extend this analysis framework to the investigation of clinical populations and animal models.     

Motor cortical representation in patients with complex regional pain syndrome: a TMS study

In a group of patients with short- and long-term (chronic) duration of complex regional pain syndrome type I (CRPS I) motor cortical representation was determined, using a transcranial magnetic stimulation (TMS) mapping method. This was done, starting with suprathreshold intensities at the location of the largest MEP amplitude, mapping systematically in all directions. Patients were compared to a group of healthy subjects. In both patient groups we found significantly larger motor cortical representation for the unaffected hand muscles compared to the affected side. This asymmetry was absent in healthy subjects. Such motor cortical representation asymmetry can be considered an effect of altered sensomotor cortical representation. On the other hand, one must also consider the increased use of the unaffected hand and the presence of pain as cortical influencing variables. The real cause must remain speculative at this time.