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Introduction Changing drug dosage is common in clinical practice. Recent evidence showed that psychological factors may affect the therapeutic outcome. The aim of this study is to test whether verbal communication about drug dosage changes motor performance and fatigue in Parkinson's Disease (PD) patients. Methods We performed clinical (Unified PD Rating Scale), motor (number of finger flexions and perceived fatigue), and electrophysiological measurements (readiness potential, RP) in PD patients during medication-off and medication-on conditions in three groups. The first group got a full dose of l -dopa and was told it was a full dose. The second group got half dose and was told it was half dose. The third group got half dose, but it was told it was a full standard dose. Results We found that overt half dose was less effective than the full dose for clinical improvement, motor performance, and readiness potential. However, if half dose was given along with verbal instructions that it was a full dose, clinical improvement, motor performance and readiness potential were not significantly different from the full dose. Conclusions Our findings indicate that verbal communication about dose reduction is as effective as the 50% dose reduction itself, demonstrating that deceptive information about the dose may have an important impact on the therapeutic outcome. Moreover, the supplementary motor area, source of the RP, seems to be involved in this psychological effect.

Background High frequency (130 Hz) subthalamic Deep-Brain-Stimulation (STN-DBS) optimally improves cardinal motor symptoms in Parkinson disease (PD). Low stimulation frequencies (60–80 Hz) improve axial symptoms in some patients and, according to preliminary evidences, may also have a beneficial effect on the cognitive component of motor planning. Objective To analyze the configuration of the P300 component of cortical event-related auditory potentials (ERPs), a reliable index of attentive cognitive functions, at different stimulation frequencies in STN-DBS in PD patients. Methods 12 PD patients underwent ERPs recordings using a standard oddball auditory paradigm with STN-DBS at 60 Hz, 80 Hz, 130 Hz, and OFF-stimulation, applied in a randomized double-blind sequence. ERPs analysis considered the peak amplitude and latency of the P300 components at midline electrode positions (Fz, Cz, Pz). Results P300 latency over Cz and Pz electrodes significantly increased with STN-DBS at 130 Hz compared to OFF-stimulation. P300 latency was also significantly increased, though to a lesser degree, over Pz electrode with stimulation at 80 Hz. No significant P300 latency modifications were detected at 60 Hz stimulation compared to OFF-stimulation condition. P300 amplitude did not change significantly for any of the stimulation conditions tested. Conclusions Low frequency STN-DBS is associated with minor modifications of P300 latency compared to conventional stimulation at 130 Hz, possibly suggesting that 60 and 80 Hz may have less interference with attentive and cognitive processes in PD patients.

In this paper we report the effect of a combined transcranial direct current stimulation (tDCS) and speech language therapy on linguistic deficits following left brain damage in a stroke case. We show that simultaneous electrical excitatory stimulation to the left and inhibitory stimulation to the right parietal regions (dual-tDCS) affected writing and reading rehabilitation, enhancing speech therapy outcomes. The results of a comparison with healthy controls showed that application of dual-tDCS could improve, in particular, sub-lexical transcoding and, specifically, the reading of non-words with increasing length and complexity. Positive repercussions on patient's quality of functional communication were also ascertained. Significant changes were also found in other language and cognitive tasks not directly treated (comprehension and constructive apraxia).

The spontaneous tendency to synchronize our facial expressions with those of others is often termed emotional contagion. It is unclear, however, whether emotional contagion depends on visual awareness of the eliciting stimulus and which processes underlie the unfolding of expressive reactions in the observer. It has been suggested either that emotional contagion is driven by motor imitation (i.e., mimicry), or that it is one observable aspect of the emotional state arising when we see the corresponding emotion in others. Emotional contagion reactions to different classes of consciously seen and “unseen” stimuli were compared by presenting pictures of facial or bodily expressions either to the intact or blind visual field of two patients with unilateral destruction of the visual cortex and ensuing phenomenal blindness. Facial reactions were recorded using electromyography, and arousal responses were measured with pupil dilatation. Passive exposure to unseen expressions evoked faster facial reactions and higher arousal compared with seen stimuli, therefore indicating that emotional contagion occurs also when the triggering stimulus cannot be consciously perceived because of cortical blindness. Furthermore, stimuli that are very different in their visual characteristics, such as facial and bodily gestures, induced highly similar expressive responses. This shows that the patients did not simply imitate the motor pattern observed in the stimuli, but resonated to their affective meaning. Emotional contagion thus represents an instance of truly affective reactions that may be mediated by visual pathways of old evolutionary origin bypassing cortical vision while still providing a cornerstone for emotion communication and affect sharing.

Pain management in elderly people with cognitive impairment poses special challenges, due to difficulties in pain assessment and specific neurodegenerative changes along pain pathways. Most studies have concentrated on Alzheimer's disease (AD) patients, in whom some contrasting findings have been found. For example, while psychophysical data suggest a selective blunting of the affective dimension of pain, pain-related fMRI signal increases have also been described. Few data have been reported in patients with frontotemporal dementia (FTD). By electrical stimulation, we have measured pain threshold and pain tolerance in clinically diagnosed FTD patients with SPECT cerebral hypoperfusion. We performed our analysis on two separate and overlapping subgroups selected on the basis of (1) neuropsychological scores below cut-off values (2) a strictly localized frontal and/or temporal hypoperfusion. We observed increased pain threshold in the first group and increased pain threshold and pain tolerance in the second group. Our results suggest differences in pain processing changes in distinct types of dementia, while at the same time caution that pain perception assessment may depend on the criteria adopted for diagnosis.

The aim of the present study was to further investigate the electroencephalogram (EEG) connectivity in schizophrenic patients by means of mutual information (MI), an analysis capable of detecting both the linear and nonlinear components of EEG. 19-lead EEGs were recorded in stable schizophrenic patients ( N = 17) and healthy controls ( N = 17) in two different conditions: closed eyes (CE) and open eyes (OE). In patients, higher MI values were observed in temporal-parietal-occipital regions compared with controls. In controls, an increase in brain connectivity in frontal regions was observed in the CE condition. This increase was not present in patients. Our results suggest that patients with schizophrenia present changes of brain connectivity that can be detected through MI analysis.

Despite the increasing research on placebos in recent times, little is known about the nocebo effect, a phenomenon that is opposite to the placebo effect and whereby expectations of symptom worsening play a crucial role. By studying experimental ischemic arm pain in healthy volunteers and by using a neuropharmacological approach, we found that verbally induced nocebo hyperalgesia was associated to hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, as assessed by means of adrenocorticotropic hormone and cortisol plasma concentrations. Both nocebo hyperalgesia and HPA hyperactivity were antagonized by the benzodiazepine diazepam, suggesting that anxiety played a major role in these effects. The administration of the mixed cholecystokinin (CCK) type-A/B receptor antagonist proglumide blocked nocebo hyperalgesia completely but had no effect on HPA hyperactivity, which suggests a specific involvement of CCK in the hyperalgesic but not in the anxiety component of the nocebo effect. Importantly, both diazepam and proglumide did not show analgesic properties on basal pain, because they acted only on the nocebo-induced pain increase. These data indicate a close relationship between anxiety and nocebo hyperalgesia, in which the CCKergic systems play a key role in anxiety-induced hyperalgesia. These results, together with previous findings showing that placebo analgesia is mediated by endogenous opioids, suggest that the analgesic placebo/hyperalgesic nocebo phenomenon may involve the opposite activation of endogenous opioidergic and CCKergic systems.

Placebo-activated endogenous opioids act on pain mechanisms inducing analgesia, as well as on the respiratory centers inducing respiratory depression. Here, we show that placebo analgesia is accompanied by a reduced beta-adrenergic activity of the heart. We measured heart rate during placebo-induced expectation of analgesia, both in the clinical and the laboratory setting. In the clinical setting, we found that the placebo analgesic response to an electrical noxious stimulus was accompanied by a reduced heart rate response. In order to investigate this effect from a pharmacological viewpoint, we reproduced the same effect in the laboratory setting by using experimental ischemic arm pain. We found that the opioid antagonist naloxone completely antagonized both placebo analgesia and the concomitant reduced heart rate response, whereas the beta-blocker propranolol antagonized the placebo heart rate reduction, but not placebo analgesia. By contrast, both placebo responses were present during muscarinic blockade with atropine, indicating no involvement of the parasympathetic system. In order to better understand the effects of naloxone and propranolol, we performed a spectral analysis of the heart rate variability for the identification of the sympathetic and parasympathetic components, and found that the beta-adrenergic low frequency (0.15 Hz) spectral component was reduced during placebo analgesia, an effect that was reversed by naloxone. These findings indicate that placebo analgesia is accompanied by a complex cascade of events which affect the cardiovascular system.

Frontotemporal lobar degeneration (FTLD) is a form of dementia characterized by a profound alteration in personality and social behavior and is associated with atrophy in the frontal and temporal brain regions. Despite recent advances, diagnosis of FTLD remains challenging. In the last decade, different studies have combined EEG analysis with mathematical models and theories that consider EEG signals as the result of nonlinear chaotic activity. The aim of the present study was to determine whether new nonlinear dynamic analysis can provide useful information on brain activity in FTLD patients. 19-lead EEG was recorded in patients with clinical diagnosis of FTLD and in healthy controls under two different conditions: closed eyes and open eyes. A nonlinear measure of complexity, correlation dimension (D2), was calculated. Our results show an increase in D2 in healthy individuals when the eyes are open, in keeping with an increase in information processing. Conversely, in FTLD patients, no increase in D2 occurred in the open eyes condition, and D2 was significantly lower than that observed in controls. Our results suggest that the dynamic processes underlying the EEG are less chaotic and complex in FTLD patients compared with normal individuals, thus providing important information on both brain functioning and possible clinical diagnostic applications.

Objective: This study was aimed at analyzing the degree of intercostal nerve impairment in posterolateral and muscle-sparing thoracotomy and at correlating the nerve damage to the severity of long-lasting postthoracotomy pain. Methods: Neurophysiologic recordings were performed 1 month after either posterolateral or muscle-sparing thoracotomy to assess the presence of the superficial abdominal reflexes (mediated in part by the intercostal nerves), the somatosensory-evoked responses after electrical stimulation of the surgical scar, and the electrical thresholds for tactile and pain sensations of the surgical incision. Results: The patients who underwent a posterolateral thoracotomy showed a higher degree of intercostal nerve impairment than the muscle-sparing thoracotomy patients as revealed by the disappearance of the abdominal reflexes, a larger reduction in amplitude of the somatosensory-evoked potentials, and a larger increase of the sensory thresholds to electrical stimulation for both tactile perception and pain. In addition, these neurophysiologic parameters were highly correlated to the postthoracotomy pain experienced by the patients 1 month after surgery, indicating a causal role for nerve impairment in the long-lasting postoperative pain. Conclusions: This study shows for the first time the pathophysiologic differences between posterolateral and muscle-sparing thoracotomy and suggests that the minor long-lasting postthoracotomy pain in muscle-sparing thoracotomy patients is partly due to a minor nerve damage. In addition, because nerve impairment is responsible for the long-lasting neuropathic component of postoperative pain, it is necessary to match specific treatments to the neuropathic pain-generating mechanisms. (J Thorac Cardiovasc Surg 1998;115:841-7)

The treatment of neuropathic pain with opioid analgesics is a matter of controversy among clinicians and clinician scientists. Although neuropathic pain is usually believed to be only slightly responsive to opioids, several studies show that satisfactory analgesia can be obtained if adequate doses are administered. In the present study, we tested the effectiveness of buprenorphine in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1 month after surgery in the same 21 patients who developed postthoracotomy neuropathic pain with a burning, electrical and shooting quality. According to a double-blind randomized study, the analgesic dose (AD) of buprenorphine needed to reduce the long-term neuropathic pain by 50% (AD50) was calculated and compared to the AD50 in the immediate postoperative period. We found that long-term neuropathic pain could be adequately reduced by buprenorphine. However, the AD50 in neuropathic pain was significantly higher relative to the AD50 in the short-term postoperative pain, indicating a lower responsiveness of neuropathic pain to opioids. We also found a strict relationship between the short-term and long-term AD50, characterized by a saturating effect. In fact, if the AD50 soon after surgery was low, the AD50 increase in the long-term neuropathic pain was threefold. By contrast, if the AD50 soon after surgery was high, the AD50 in neuropathic pain was only slightly increased. This suggests that, though neuropathic pain is indeed less sensitive to opioids, in some neuropathic patients a large amount of opioid resistance is already present in other painful conditions.

Propofol, an intravenous general anaesthetic, has been reported to relieve some forms of pruritus at subhypnotic doses. We assessed its effectiveness in 32 patients with several kinds of non-malignant chronic pain, in a placebo-controlled, double-blind study. We found that central pain, but not neuropathic pain, is at least partially controlled by propofol at subhypnotic doses, without major side-effects. In particular, allodynia associated with central, but no neuropathic, pain has been completely controlled. Propofol analgesia leads to renormalization of brain metabolism as seen on single photon emission computed tomography. We conclude that propofol may help in the diagnosis of central pain, particularly in unclear cases, and also in treatment. Possible mechanisms of action are discussed.

Background: In spite of the large number of studies on schizophrenia, a full understanding of its core pathology still eludes us. The application of the nonlinear theory of electroencephalography (EEG) analysis provides an interesting tool to differentiate between physiologic conditions (e.g., resting state and mathematical task) and normal and pathologic brain activities. The aim of the present study was to investigate nonlinear EEG activity in patients with schizophrenia. Methods: We recorded 19-lead EEGs in patients with stable schizophrenia and healthy controls under 4 different conditions: eyes closed, eyes open, forward counting and backward counting. A nonlinear measure of complexity was calculated by means of correlation dimension (D2). Results: We included 17 patients and 17 controls in our analysis. Comparing the 2 populations, we observed greater D2 values in the patient group. In controls, increased D2 values were observed during active states (eyes open and the 2 cognitive tasks) compared with baseline conditions. This increase of brain complexity, which can be interpreted as an increase of information processing and integration, was not preserved in the patient population. Limitations: Patients with schizophrenia were taking antipsychotic medications, so the presence of medication effects cannot be excluded. Conclusion: Our results suggest that patients with schizophrenia present changes in brain activity compared with healthy controls, and this pathologic alteration can be successfully studied with nonlinear EEG analysis.

This study reports the effects of intraoperative stimulation of the subthalamic nucleus on brain electrical activity in advanced Parkinson's patients. To our knowledge, this is the first study about electroencephalographic responses in the very early phase of deep brain stimulation, during the implantation of the electrodes. We found an increase of gamma band bilaterally over the sensorimotor cortex in the range 45-55 Hz, which was associated with clinical improvement as assessed by means of muscle rigidity decrease. These results indicate that the electroencephalographic gamma responses to deep brain stimulation are present at the very beginning of the treatment process, and may help better understand the short and long-tem effects of deep brain stimulation.

Pain perception and autonomic responses to pain are known to be altered in dementia, although the mechanisms are poorly understood. We studied patients with Alzheimer's disease (AD) whose cognitive status was assessed through the Mini Mental State Examination test and whose brain electrical activity was measured by means of quantitative electroencephalography. After assessment of both cognitive impairment and brain electrical activity deterioration, these patients underwent sensory measurements in which the minimum stimulus intensity for both stimulus detection and pain sensation was determined. In addition, heart rate responses to pain threshold×1.5 were recorded. We found that neither stimulus detection nor pain threshold was correlated to cognitive status and brain electrical activity decline. By contrast, we found a correlation between heart rate responses and deterioration of both cognitive functions and brain electrical activity. In particular, the heart rate increase after pain stimulation was correlated to the presence of slow brain electrical activity (delta and theta frequencies). This correlation was also found for the anticipatory heart rate increase just before pain stimulation. These results indicate that pain anticipation and reactivity depend on both the cognitive status and the frequency bands of the electroencephalogram, whereas both stimulus detection and pain threshold are not affected by the progression of AD. These findings indicate that, whereas the sensory-discriminative components of pain are preserved even in advanced stages of AD, the cognitive and affective functions, which are related to both anticipation and autonomic reactivity, are severely affected. This sensory-affective dissociation is well correlated with the neuropathological findings in AD.

We analysed the effects of electrical noxious stimulation on the autonomic nervous system of Alzheimer’s disease (AD) patients who were assessed by means of the Mini Mental State Examination test (MMSE). To do this, we used electrical stimuli at two different intensities: just above pain threshold and twice pain threshold. We recorded heart rate and systolic blood pressure by using conventional electrocardiography and finger photo-plethysmography. When a pain stimulus just above threshold was delivered, AD patients were found to have blunted autonomic responses compared to controls of the same age. Similarly, prestimulus expectation produced a less pronounced increase of the responses in AD patients compared to the controls. However, when the painful stimulus was increased to twice the pain threshold, the systolic blood pressure increase of AD patients did not differ from the controls, whereas heart rate increase was still slightly diminished. By contrast, pain perception was similar in the two groups when the stimulus was at pain threshold, whereas it was blunted in AD patients when the stimulus was twice the pain threshold. These findings show that in AD mild noxious stimulation produces blunted autonomic responses and normal pain perception, whereas strong noxious stimulation produces quasi-normal autonomic responses and blunted pain perception. These results indicate that AD patients have an increased threshold for both autonomic activation and pain tolerance.

We tested both pain thresholds and pain tolerance in patients with Alzheimer's disease (AD) by means of phasic and tonic noxious stimuli. In the first case, electrical stimulation was used, whereas in the second case arm ischemia was studied. By comparing AD patients with normal subjects of the same age, we found no differences in stimulus detection and pain thresholds, whereas a clearcut increase in pain tolerance was present in AD patients. The severity of AD was assessed by means of the Mini Mental State Examination test (MMSE) and the spectral analysis of the electroencephalogram (EEG). There was a straightforward correlation between MMSE scores and pain tolerance such that the more severe the cognitive impairment the higher the tolerance to pain. In addition, analysis of the EEG power spectra indicated that patients with low alpha and high delta peaks showed an increase in pain tolerance to both electrical stimulation and ischemia. These findings show that, whereas the sensory-discriminative component of pain is maintained in AD patients, pain tolerance is altered and depends on cognitive and affective factors. Thus, pain tolerance is tightly related to the severity of the disease according to the rule, 'the more severe the MMSE and EEG changes, the higher the tolerance to pain'.