Suprathreshold Stimuli Research Articles

A Randomized, Controlled Investigation of Motor Cortex Transcranial Magnetic Stimulation (TMS) Effects on Quantitative Sensory Measures in Healthy Adults

There is emerging evidence that transcranial magnetic stimulation (TMS) can produce analgesic effects in clinical samples and in healthy adults undergoing experimentally induced pain; and the field of minimally invasive brain stimulation for the management of pain is expanding rapidly. Although motor cortex is the most widely used cortical target for TMS in the management of neuropathic pain, few studies have systematically investigated the analgesic effects of a full range of device parameters to provide initial hints about what stimulation intensities and frequencies are most helpful (or even potentially harmful) to patients. Further, there is considerable inconsistency between studies with respect to laboratory pain measurement procedures, TMS treatment parameters, sophistication of the sham methods, and sample sizes. This study used a sham-controlled, within-subject, cross-over design to examine the effects of 5 different TMS treatment parameters across several quantitative sensory measures in a sample of healthy adult volunteers. Sixty-five participants underwent quantitative sensory testing procedures pre and post-40-minutes of real and sham motor cortex TMS. TMS was delivered at 1 Hz 80% resting motor threshold (rMT), 1 Hz 100% rMT, 10 Hz 80% rMT, 10 Hz 100% rMT, or 50 Hz triplets at 90% of active motor threshold (intermittent theta-burst). The mean painfulness rating of real TMS stimulation itself was 3.0 (SE=0.36) out of 10 and was significantly greater than zero [t(64)=8.17, P<0.0001]. The sham TMS methods used permitted matching between real and sham TMS-induced scalp sensations and participants were successfully blinded to condition (real versus sham). Findings suggest that the effects of motor cortex TMS on quantitative sensory tests in healthy adults vary across different treatment parameters with the smallest observed effect for intermittent theta-burst stimulation (Cohen's d=0.03) and the largest for 10 Hz 100% rMT (d=0.34). Overall, TMS was associated with statistically significant effects on warm and cool sensory thresholds, cold pain thresholds, suprathreshold stimulus unpleasantness ratings, and wind-up pain. With respect to device parameter effects, higher frequency stimulation seems to be associated with the most analgesic and antisensitivity effects with the exception of intermittent theta-burst stimulation. The present findings support several clinical research findings suggesting that higher TMS frequencies tend to be associated with the most clinical benefit in patients with chronic pain.

Blink Frequency and Duration during Perimetry and Their Relationship to Test–Retest Threshold Variability

To describe different patterns of blinking in patients undergoing a visual field test and to establish whether the blink parameters are related to threshold variability. Thirty-nine patients with diagnosed or suspected glaucoma were recruited to undertake a perimetric task twice. Blinks were detected with a video eye-tracker system that records at a sampling rate of 60 Hz. Blink frequency, duration, and episodes of microsleep (eye closures >500 ms) were analyzed, and correlated with test-retest threshold variability. The timing of blinks with respect to stimulus presentation was analyzed and the percentage of seen stimuli for all presentations (POS(overall)) and those overlapped with blinks (POS(overlapped)) were compared. Blink frequency ranged from 0 to 58 per minute. A significant increase in blink frequency was observed in the second test (P < 0.001), whereas blink duration and microsleep episodes were not significantly different between the two tests. The relationship between test-retest threshold variability and all blink parameters was not significant. For suprathreshold stimulus presentations, blinks often occurred after presentation, whereas for subthreshold presentations, their timing was independent of stimulus timing. The difference between POS(overall) and POS(overlapped) was significant (P < 0.001), and a slight decrease in POS(overlapped) was observed with the increase of overlap duration. A wide range of blink frequencies was observed during perimetric testing. Although no blink parameters showed significant influence on threshold variability, when the blinks overlapped with a stimulus presentation, the probability of seeing was reduced. For suprathreshold stimuli, blinks often occurred after the presentation, whereas for subthreshold presentations, there was no relationship to presentation time.

The influence of body-ownership cues on tactile sensitivity

To some extent the bodies of others and one's own body are represented differently in the human brain. This study investigates how these different body representations are used during tactile perception. Two types of cues––purely visual cues (pictures of hands) and multisensory cues (equivalent to the rubber hand illusion paradigm)––were used to control whether a seen hand was one's own hand or somebody else's hand. We found that viewing one's own hand improves nonspatial tactile discrimination of supra-threshold stimuli, but attenuates tactile detection performance. Furthermore, when multisensory information signals that the viewed hand is not one's own hand, tactile nonspatial performance seems to be generally sensitized as compared to not viewing a hand. Such body-ownership-specific modulations were present only when multisensory cues signaled body ownership.

Duration Discrimination by Musicians and Nonmusicians

This study investigated the effects of stimulus modality, standard duration, sex, and laterality in duration discrimination by musicians and nonmusicians. Seventeen musicians (M age = 24.1 yr.) and 22 nonmusicians (M age = 26.8 yr.) participated. Auditory (1,000 Hz) and tactile (250 Hz) sinusoidal suprathreshold stimuli with varying durations were used. The standard durations tested were 0.5 and 3.0 sec. Participants discriminated comparison stimuli which had durations slightly longer and shorter than the standard durations. Difference limens were found by the method of limits and converted to Weber fractions based on the standard durations. Musicians had lower, i.e., better, Weber fractions than nonmusicians in the auditory modality, but there was no significant difference between musicians and nonmusicians in the tactile modality. Auditory discrimination was better than tactile discrimination. Discrimination improved when the standard duration was increased both for musicians and nonmusicians. These results support previous findings of superior auditory processing by musicians. Significant differences between discrimination in the millisecond and second ranges may be due to a deviation from Weber's law and the discontinuity of timing in different duration ranges reported in the literature.

A Role of Corneal Mechanical Adaptation in Contact Lens–Related Dry Eye Symptoms

To compare corneal mechanical adaptation measured psychophysically in contact lens wearers with or without dry eye symptoms. Two groups of contact lens wearers were recruited. One group (symptomatic) consisted of subjects with dry eye symptoms (according to the subjective evaluation of symptom of dryness [SeSoD] questionnaire). The second control group (asymptomatic) consisted of subjects reporting no symptoms. There were 32 (aged 20 to 42 years, 6 males and 26 females) and 29 subjects (aged 21 to 36 years, 9 males and 20 females) in the symptomatic and asymptomatic groups, respectively. Mechanical stimulus thresholds of the cornea were determined using a Belmonte pneumatic esthesiometer and the ascending method of limits. Then three stimulus intensity groups (subthreshold, threshold, and suprathreshold) were applied to the eye in random order, each 20 times. Subjects rated the intensity of the stimuli using a scale of zero to four. The rating data from the two groups were compared by Friedman nonparametric ANOVA. Adaptation was defined as the reduction in subsequent ratings compared with earlier ones. No significant difference was seen in subjects' thresholds in both groups (P = 0.22). The symptomatic group rated their sensations to suprathreshold stimuli higher than the asymptomatic group. More importantly, there was significant adaptation with suprathreshold mechanical stimulation in the asymptomatic group (P = 0.006) but not in the symptomatic group (P = 0.08). There was no adaptation during threshold and subthreshold stimulus sessions in either group. Adaptation was found to suprathreshold mechanical stimuli in the asymptomatic group but not in the symptomatic group.

Limitations of Equivalent Circuit Models in Data-Driven Simulation of the Neuron-Electrode Interface

Noninvasive neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and biosensors. Traditionally, neuron-electrode interfaces have been modeled as linear point or area contact equivalent circuits but such models have not been able to explain the shapes and magnitudes of the experimentally recorded extracellular signals. Also, previous work with Volterra-Wiener characterization of the planar neuron-microelectrode junction using bandlimited Gaussian white noise had shown that the mechanism of signal transduction across the nanoscale neuron-microelectrode cleft region might be nonlinear. In this optimization based study we compared and contrasted experimental and simulation data for point contact models of the extracellular ‘on-cell’ neuron-patch electrode and the planar neuron-microelectrode interface. The nonlinear contributions of the neurons to the dynamics of the equivalent circuit representation of the interfacial medium were systematically isolated by an independent estimation of the ion-channel parameters through a fitting of the simulated intracellular signals to the experimentally recorded voltage and current clamp signals. These ion-channel parameters were then employed in the optimization of the cell-electrode interface parameters based on extracellular recordings obtained from a neuron simultaneously interfaced to the ‘on-cell’ patch-electrode and the planar microelectrode using sub- and supra-threshold stimuli. An examination of the optimized model parameters for the experimental extracellular recordings from sub- and supra-threshold stimulations of the neuron-electrode junctions allowed us to draw important distinctions between the ‘on-cell’ neuron-patch electrode and neuron-microelectrode interfaces that could be attributed to the presence of electric double layer (EDL) and ionic electrodiffusion effects. Based on these results, we then discuss and point out the limitations of the equivalent circuit models in their failure to take account of the nonlinear EDL and ionic electrodiffusion effects occurring during the process of signal transduction at the neuron-electrode interface.

Electrophysiological recordings from the giant fiber pathway of D. melanogaster.

When startled adult D. melanogaster react by jumping into the air and flying away. In many invertebrate species, including D. melanogaster, the "escape" (or "startle") response during the adult stage is mediated by the multi-component neuronal circuit called the Giant Fiber System (GFS). The comparative large size of the neurons, their distinctive morphology and simple connectivity make the GFS an attractive model system for studying neuronal circuitry. The GFS pathway is composed of two bilaterally symmetrical Giant Fiber (GF) interneurons whose axons descend from the brain along the midline into the thoracic ganglion via the cervical connective. In the mesothoracic neuromere (T2) of the ventral ganglia the GFs form electro-chemical synapses with 1) the large medial dendrite of the ipsilateral motorneuron (TTMn) which drives the tergotrochanteral muscle (TTM), the main extensor for the mesothoracic femur/leg, and 2) the contralateral peripherally synapsing interneuron (PSI) which in turn forms chemical (cholinergic) synapses with the motorneurons (DLMns) of the dorsal longitudinal muscles (DLMs), the wing depressors. The neuronal pathway(s) to the dorsovental muscles (DVMs), the wing elevators, has not yet been worked out (the DLMs and DVMs are known jointly as indirect flight muscles - they are not attached directly to the wings, but rather move the wings indirectly by distorting the nearby thoracic cuticle) (King and Wyman, 1980; Allen et al., 2006). The di-synaptic activation of the DLMs (via PSI) causes a small but important delay in the timing of the contraction of these muscles relative to the monosynaptic activation of TTM (~0.5 ms) allowing the TTMs to first extend the femur and propel the fly off the ground. The TTMs simultaneously stretch-activate the DLMs which in turn mutually stretch-activate the DVMs for the duration of the flight. The GF pathway can be activated either indirectly by applying a sensory (e.g."air-puff" or "lights-off") stimulus, or directly by a supra-threshold electrical stimulus to the brain (described here). In both cases, an action potential reaches the TTMs and DLMs solely via the GFs, PSIs, and TTM/DLM motoneurons, although the TTMns and DLMns do have other, as yet unidentified, sensory inputs. Measuring "latency response" (the time between the stimulation and muscle depolarization) and the "following to high frequency stimulation" (the number of successful responses to a certain number of high frequency stimuli) provides a way to reproducibly and quantitatively assess the functional status of the GFS components, including both central synapses (GF-TTMn, GF-PSI, PSI-DLMn) and the chemical (glutamatergic) neuromuscular junctions (TTMn-TTM and DLMn-DLM). It has been used to identify genes involved in central synapse formation and to assess CNS function.

Electrophysiological Recordings from the Giant Fiber Pathway of &lt;em&gt;D. melanogaster&lt;/em&gt;

When startled adult D. melanogaster react by jumping into the air and flying away. In many invertebrate species, including D. melanogaster, the "escape" (or "startle") response during the adult stage is mediated by the multi-component neuronal circuit called the Giant Fiber System (GFS). The comparative large size of the neurons, their distinctive morphology and simple connectivity make the GFS an attractive model system for studying neuronal circuitry. The GFS pathway is composed of two bilaterally symmetrical Giant Fiber (GF) interneurons whose axons descend from the brain along the midline into the thoracic ganglion via the cervical connective. In the mesothoracic neuromere (T2) of the ventral ganglia the GFs form electro-chemical synapses with 1) the large medial dendrite of the ipsilateral motorneuron (TTMn) which drives the tergotrochanteral muscle (TTM), the main extensor for the mesothoracic femur/leg, and 2) the contralateral peripherally synapsing interneuron (PSI) which in turn forms chemical (cholinergic) synapses with the motorneurons (DLMns) of the dorsal longitudinal muscles (DLMs), the wing depressors. The neuronal pathway(s) to the dorsovental muscles (DVMs), the wing elevators, has not yet been worked out (the DLMs and DVMs are known jointly as indirect flight muscles - they are not attached directly to the wings, but rather move the wings indirectly by distorting the nearby thoracic cuticle) (King and Wyman, 1980; Allen et al., 2006). The di-synaptic activation of the DLMs (via PSI) causes a small but important delay in the timing of the contraction of these muscles relative to the monosynaptic activation of TTM (~0.5 ms) allowing the TTMs to first extend the femur and propel the fly off the ground. The TTMs simultaneously stretch-activate the DLMs which in turn mutually stretch-activate the DVMs for the duration of the flight. The GF pathway can be activated either indirectly by applying a sensory (e.g."air-puff" or "lights-off") stimulus, or directly by a supra-threshold electrical stimulus to the brain (described here). In both cases, an action potential reaches the TTMs and DLMs solely via the GFs, PSIs, and TTM/DLM motoneurons, although the TTMns and DLMns do have other, as yet unidentified, sensory inputs. Measuring "latency response" (the time between the stimulation and muscle depolarization) and the "following to high frequency stimulation" (the number of successful responses to a certain number of high frequency stimuli) provides a way to reproducibly and quantitatively assess the functional status of the GFS components, including both central synapses (GF-TTMn, GF-PSI, PSI-DLMn) and the chemical (glutamatergic) neuromuscular junctions (TTMn-TTM and DLMn-DLM). It has been used to identify genes involved in central synapse formation and to assess CNS function.

Role of different brain areas in peripheral nerve injury-induced neuropathic pain

Neuropathic pain has been described as the “most terrible of all tortures which a nerve wound may inflict” and arises as a consequence of nerve injury either of the peripheral or central nervous system. Following peripheral nerve injury, a cascade of events in the primary afferents leads to peripheral sensitization resulting in spontaneous nociceptor activity, decreased threshold and increased response to supra-threshold stimuli. A series of molecular changes in spinal cord and brain centers are associated with central sensitization which is responsible for the pain to non-injured extra-territory regions (extraterritorial pain) and contralateral parts (mirror-image pain). The peripheral nerve injury has been reported to induce neuroplastic changes in different brain regions including the anterior cingulate cortex, insular cortex, ventrolateral orbitofrontal area, amygdala, striatum, thalamus, hypothalamus, rostral ventromedial medulla, periaqueductal gray, pons (locus coeruleus), red nucleus, and medulla oblongata. The present review article discusses the involvement of these different brain areas in the development of peripheral nerve injury-induced neuropathic pain.

Good vibrations, bad vibrations: Oscillatory brain activity in the attentional blink

The attentional blink (AB) is a deficit in reporting the second (T2) of two targets (T1, T2) when presented in close temporal succession and within a stream of distractor stimuli. The AB has received a great deal of attention in the past two decades because it allows to study the mechanisms that influence the rate and depth of information processing in various setups and therefore provides an elegant way to study correlates of conscious perception in supra-threshold stimuli. Recently evidence has accumulated suggesting that oscillatory signals play a significant role in temporally coordinating information between brain areas. This review focuses on studies looking into oscillatory brain activity in the AB. The results of these studies indicate that the AB is related to modulations in oscillatory brain activity in the theta, alpha, beta, and gamma frequency bands. These modulations are sometimes restricted to a circumscribed brain area but more frequently include several brain regions. They occur before targets are presented as well as after the presentation of the targets. We will argue that the complexity of the findings supports the idea that the AB is not the result of a processing impairment in one particular process or brain area, but the consequence of a dynamic interplay between several processes and/or parts of a neural network.

The perception threshold counterpart to dynamic and static mechanical allodynia assessed using von Frey filaments in peripheral neuropathic pain patients

Background and aim Pain due to a usually non-painful mechanical stimulus, mechanical allodynia, is an oppressive symptom in subgroups of patients with neuropathic pain. Dynamic mechanical allodynia (DMA) is evoked by a normally innocuous light moving mechanical stimulus on the skin and static mechanical allodynia (SMA) by a sustained, normally innocuous pressure against the skin. DMA is claimed to be mediated by myelinated fibres and SMA by C-fibres. Also A-delta fibres have been implicated in the static subtype. A low intensity vertically applied stimulus of 1 second (s) is expected to activate predominantly rapidly adapting A-beta mechanoreceptors thus recruiting the same peripheral substrate as a horizontally moving brush on top of the skin. In patients with SMA we assumed an activation of C- but also A-delta fibres from a static 10 s von Frey filament stimulus. The aim was to investigate if DMA and SMA could be assessed at perception threshold level using short or longer lasting usually non-painful von Frey filament prodding of the neuropathic skin. Patients and methods Eighteen patients with painful unilateral partial peripheral traumatic nerve injury suffering from SMA ( n = 9) and/or DMA ( n = 18) in a limb were studied. A compression/ischemia-induced (differential) nerve block in conjunction with repeated quantitative sensory testing of A-delta and C-fibre function using cold and warm stimuli was used to assess which nerve fibre population that contributes to pain at perception threshold level using 1 s (vF1) and 10 s (vF10) von Frey filament stimulation of the skin. Results The main outcome was the finding that elevation of vF1 and vF10 occurred simultaneously and significantly prior to an increase in the perception level to cold or warmth during the continuous nerve block. Single patients demonstrated a slight decrease in cold perception levels at the time of elevation of vF1 or vF10 and a possible contribution to mechanical allodynia from A-delta-fibres can therefore not completely be ruled out although the recorded alterations were minor. None of the patients reported an elevation of the perception level to warmth at the time of elevation of vF1 or vF10 excluding contribution from C-fibres. Further, only patients with clinically established SMA ( n = 9) reported continuous pain to a sustained 10 s von Frey filament stimulation (vF10). Patients with only DMA ( n = 9) reported pain merely for the initial 1–3 s of the total stimulus duration of 10 s and for a few seconds after the filament was lifted from the skin. Conclusions These findings support the role of A-beta fibres as peripheral mediators of both vF1 and vF10 although different receptor organs may be involved, i.e., rapidly (RA) and slowly (SA-I) adapting mechanoreceptors. Implications Techniques to quantify the different allodynias at perception threshold level deserve further attention as possible adjuncts to suprathreshold stimuli in intervention studies aimed at modifying these stimulus-evoked phenomena.

Mislocalization of near‐threshold tactile stimuli in humans: a central or peripheral phenomenon?

Principles of brain function can be disclosed by studying their limits during performance. Tactile stimuli with near-threshold intensities have been used to assess features of somatosensory processing. When stimulating fingers of one hand using near-threshold intensities, localization errors are observed that deviate significantly from responses obtained by guessing - incorrectly located stimuli are attributed more often to fingers neighbouring the stimulated one than to more distant fingers. Two hypotheses to explain the findings are proposed. The 'central hypothesis' posits that the degree of overlap of cortical tactile representations depends on stimulus intensity, with representations less separated for near-threshold stimuli than for suprathreshold stimuli. The 'peripheral hypothesis' assumes that systematic mislocalizations are due to activation of different sets of skin receptors with specific thresholds. The present experiments were designed to decide between the two hypotheses. Taking advantage of the frequency tuning of somatosensory receptors, their contribution to systematic misclocalizations was studied. In the first experiment, mislocalization profiles were investigated using vibratory stimuli with frequencies of 10, 20 and 100 Hz. Unambiguous mislocalization effects were only obtained for the 10-Hz stimulation, precluding the involvement of Pacinian corpuscles in systematic mislocalization. In the second experiment, Pacinian corpuscles were functionally eliminated by applying a constant 100-Hz vibratory masking stimulus together with near-threshold pulses. Despite masking, systematic mislocation patterns were observed rendering the involvement of Pacinian corpuscles unlikely. The results of both experiments are in favor of the 'central hypothesis' assuming that the extent of overlap in somatosensory representations is modulated by stimulus intensity.

Independence between implicit and explicit processing as revealed by the Simon effect

Studies showing human behavior influenced by subliminal stimuli mainly focus on implicit processing per se, and little is known about its interaction with explicit processing. We examined this by using the Simon effect, wherein a task-irrelevant spatial distracter interferes with lateralized response. Lo and Yeh (2008) found that the visual Simon effect, although it occurred when participants were aware of the visual distracters, did not occur with subliminal visual distracters. We used the same paradigm and examined whether subliminal and supra-threshold stimuli are processed independently by adding a supra-threshold auditory distracter to ascertain whether it would interact with the subliminal visual distracter. Results showed auditory Simon effect, but there was still no visual Simon effect, indicating that supra-threshold and subliminal stimuli are processed separately in independent streams. In contrast to the traditional view that implicit processing precedes explicit processing, our results suggest that they operate independently in a parallel fashion.

Perceptual learning, aging, and improved visual performance in early stages of visual processing

In the present study, we examined whether perceptual learning methods can be used to improve performance of older individuals. Subjects performed a texture discrimination task in the peripheral visual field and a letter discrimination task in central vision. The SOA threshold was derived by presenting a mask following the stimuli. Older subjects (age greater than 65 years) were either trained for 2 days using near threshold stimuli (experimental group) or were trained with the task with supra-threshold stimuli (older control group). The experimental group showed significant improvement in the task as a result of training whereas the older control group showed no significant improvement. The improved performance post-training equaled that of a younger control group and was maintained for at least 3 months. The results of two additional experiments indicate that the improved performance was not due to changes in divided attention, that the effect of perceptual learning was location specific, and that the pattern of learning was similar to that of younger subjects. These results indicate that perceptual learning with near threshold training can be used to improve visual performance among older individuals, that the improvements are not the result of practice with the visual task, and that the improvements do not transfer to non-trained locations.

An Increase in Persistent Sodium Current Contributes to Intrinsic Neuronal Bursting After Status Epilepticus

Brain damage causes multiple changes in synaptic function and intrinsic properties of surviving neurons, leading to the development of chronic epilepsy. In the widely used pilocarpine-status epilepticus (SE) rat model of temporal lobe epilepsy (TLE), a major alteration is the marked increase in the fraction of intrinsically bursting CA1 pyramidal cells. Here we have differentiated between two types of bursting phenotypes: 1) bursting in response to threshold-straddling excitatory current pulses (low-threshold bursting) and 2) bursting only in response to suprathreshold stimuli (high-threshold bursting). Low-threshold bursting prevailed in 46.5% of SE-experienced neurons sampled 1-4 wk after pilocarpine-SE, but was rarely seen in control neurons (1.9%). As previously shown, it appeared to be driven predominantly by a T-type Ca(2+) current (I(CaT)) in the apical dendrites. After blocking low-threshold bursting with Ni(2+), the same neurons still manifested a high-threshold bursting phenotype. Another 40.1% of SE-experienced neurons displayed only a high-threshold bursting phenotype and the remaining 13.4% of these neurons were nonbursters. Altogether, high-threshold bursting prevailed in 86.6% of SE-experienced neurons, but only in 33.0% of control neurons. Several lines of evidence indicated that high-threshold bursting is driven by persistent Na(+) current (I(NaP)) at or near the soma. Congruently, I(NaP) was 1.5-fold larger in SE-experienced versus control neurons. We conclude that an increase in I(NaP), conjointly with an increase in I(CaT), strongly contributes to the predominance of bursting phenotypes in CA1 pyramidal cells early after pilocarpine-SE and thus likely plays a role in the development of a chronic epileptic condition in this TLE model.

Response to Kellner et al. Letter

Back to table of contents Previous article Next article Communications and UpdatesFull AccessResponse to Kellner et al. LetterMarc Zisselman, M.D., and Richard Jaffe, M.D.Marc ZisselmanSearch for more papers by this author, M.D., and Richard JaffePhiladelphia, Pa.Search for more papers by this author, M.D.Published Online:1 Sep 2010https://doi.org/10.1176/appi.ajp.2010.10020261rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We appreciate the opportunity to respond to Kellner et al.'s comments underscoring the clinical urgency associated with the treatment of acute catatonia and important aspects of ECT stimulus dosing in this syndrome.Our stimulus setting for the initial treatment took into account the recommendations of the half-age formula but also accounted for other factors that may have affected seizure threshold. Our patient's age and gender may have reduced her seizure threshold, while recent benzodiazepine treatment, possible dehydration, and use of bilateral electrode placement may have raised it. These complexities preclude a precise dosage determination. Furthermore, Kellner et al.'s suggestion that a more aggressive (suprathreshold) stimulus would have produced a more therapeutic seizure reflects research relevant to unilateral ECT treatment (1). There is no evidence that suprathreshold bilateral ECT yields a more rapid or robust clinical response. The suggestion of en bloc ECT in this setting is interesting but not one we would currently endorse. The evidence base for this treatment approach is anecdotal and includes cases of neuroleptic malignant syndrome. The only prospective, randomized comparison of single- and double-ECT stimulations studied treatment-resistant depressed populations (2). Indeed, catatonic patients are often exquisitely responsive to ECT and may even show response after one treatment (3), making the initial administration of multiple seizures unnecessarily aggressive.A further variation in treatment not mentioned by Kellner et al., the application of daily rather than thrice weekly treatments for the acutely ill woman, could not be undertaken due to cardiac complications associated with the initial treatment. Interdisciplinary re-evaluation and further consent discussion were necessary before ECT treatment could recommence. The most important factor preventing a more rapid intervention was the legal hurdle of obtaining emergency guardianship. The process took 20 days and might have been further prolonged if an involved, reliable caregiver had not been available. Aggressive legal action and a responsive judicial system are often the most crucial aspects of urgent care.Philadelphia, Pa.accepted for publication in April 2010.The authors' disclosures accompany the original article.

Neuropathic pain-like alterations in muscle nociceptor function associated with vibration-induced muscle pain

We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ∼15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ∼44Hz during a 1min suprathreshold stimulus) much greater than that has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration-exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome.

S‐cone excitation ratios for reaction times to blue‐yellow suprathreshold changes at isoluminance

We examined different contrast metrics to scale visual latencies for suprathreshold stimuli modulated along tritan confusion lines. S-cone increments ('blue') and decrements ('yellow') were isolated along two different tritan confusion lines, each one having a different luminance value. Reaction times (RT) were evaluated as a function of the Weber contrast and the S-cone excitation ratio between the test stimulus and the background. RTs were described using a model that generalizes Piéron's law and incorporates the notion of threshold units and power law scaling. Our results show that RTs for S-cone increments and decrements equate better when using the S-cone excitation ratio. However, a single function did not describe all RT data. S-cone RTs are better described by separate functions. We conclude that S-cone increments and decrements do not scale in the same manner. Both Weber contrast and the S-cone excitation ratio are plausible metrics at isoluminance. The implications for the S-cone pathways are discussed.

Suprathreshold Heat Pain Response Is Associated With Clinical Pain Intensity for Patients With Shoulder Pain

Quantitative sensory testing (QST) has become commonly used for the assessment of pain in subjects with clinical conditions. However, there is no consensus about which type of QST is the best predictor of clinical pain responses. The purposes of this study were to determine: a) the QST measure with the strongest association with clinical pain intensity; and b) if the QST measure continued to predict clinical pain intensity in a model including relevant psychological factors. Fifty-nine patients seeking treatment for shoulder pain underwent experimental pain assessment involving heat and pressure stimuli. The patients also completed validated questionnaires for pain intensity, pain catastrophizing, anxiety, and depression. The 5th pain rating in a series of suprathreshold heat pain stimuli accounted for a significant amount of variance in clinical pain intensity, with no other QST measure contributing to the model. The 5th pain rating remained a significant contributor to clinical pain intensity when psychological factors were included in the model. Furthermore, subjects with elevated 5th pain rating, pain catastrophizing, and depression scores had higher clinical pain intensity ratings in pre- and postoperative assessments. These data suggest that assessment of pain should include suprathreshold heat stimuli and psychological factors separately, and a combination of these factors may be predictive of pain intensity outcomes. The current study provides evidence for a suprathreshold heat pain response as a clinically relevant QST measure for patients with shoulder pain, even after psychological factors were considered. The present findings suggest that the 5th pain rating from a series of suprathreshold stimuli, pain catastrophizing, and depression might play a role in predicting pain intensity outcomes.

Role of subthreshold stimuli in task-performance and its underlying mechanism

Considerable evidence exists indicating that a stimulus which is subthreshold and thus consciously invisible, influences brain activity and behavioral performance. However, it is not clear how subthreshold stimuli are processed in the brain. We found that a task-irrelevant subthreshold coherent motion leads to stronger disturbance in task performance than suprathreshold motion. With the subthreshold motion, fMRI activity in the visual cortex was higher, but activity in the dorsolateral prefrontal cortex (DLPFC) was lower, than with suprathreshold motion. The results of the present study demonstrate two important points. First, a weak task-irrelevant stimulus feature which is below but near the perceptual threshold more strongly activates visual area (MT+) which is highly related to the stimulus feature and more greatly disrupts task performance. This contradicts the general view that irrelevant signals that are stronger in stimulus properties more greatly influence the brain and performance and that the influence of a subthreshold stimulus is smaller than that of suprathreshold stimuli. Second, the results may reveal important bidirectional interactions between a cognitive controlling system and the visual system. LPFC, which has been suggested to provide inhibitory control on task-irrelevant signals, may have a higher detection threshold for incoming signals than the visual cortex. Task-irrelevant signals around the threshold level may be sufficiently strong to be processed in the visual system but not strong enough for LPFC to “notice” and, therefore, to provide effective inhibitory control on the signals. In this case, such signals may remain uninhibited, take more resources for a task-irrelevant distractor, and leave fewer resources for a given task, and disrupt task performance more than a suprathreshold signal. On the other hand, suprathreshold coherent motion may be “noticed”, given successful inhibitory control by LPFC, and leave more resources for a task. This mechanism may underlie the present paradoxical finding that subthreshold task-irrelevant stimuli activate the visual area strongly and disrupt task performance more and could also be one of the reasons why subthreshold stimuli tend to lead to relatively robust effects.