Interaction between local blood flow and tolerance to prolonged pain in the elderly.

PURPOSE: We aimed to explore the link between local vasodilation and pain perception in elderly subjects, testing the hypothesis that altered local cutaneous blood flow participates in the decrease in pain tolerance with age. METHOD: Sixty-eight young and 83 older participants performed a pain tolerance test in which they hold their hand in an airtight box in which air temperature was regulated at 65 °C until the pain became unbearable. Participants continuously estimated pain intensity. Skin temperature and local blood flow in the box-exposed hand were continuously monitored. RESULTS: In the young group, 97% of subjects resisted pain until the end of the test, whereas only 53% in the elderly group managed to do so, indicating that pain tolerance is impaired in the elderly. Among all participants, the skin temperature associated with the first pain sensation was below the threshold for nociceptor activation (43 °C). Interestingly, blood flow in the elderly group was correlated with pain judgment, whereas no such correlation was observed in the young. CONCLUSION: Our results suggest that the local vasodilator response induced by local heating may be involved in pain perception and may influence thermal pain tolerance with aging. These results could contribute to a better understanding of vascular deficits and the development of chronic pain in vascular pathologies.

An electronical stimulator for quantitative sensory testing and evoked potential analysis of tactile Aß nerve fibers.

OBJECTIVE: We aimed to determine the ability of an innovative device, the Cutaneous Mechanical Stimulator (CMS), to evaluate touch sensory pathways in Human. METHODS: Two experiments were conducted in 23 healthy volunteers aged 20-30 years. In the first, mechanical detection thresholds (MDTs) were assessed using Semmes-Weinstein monofilaments and the CMS. In the second experiment, touch-evoked potentials (TEPs) elicited by tactile stimulation of the CMS on the left hand dorsum and left foot dorsum were recorded. Electroencephalographic (EEG) data were recorded at each cutaneous stimulation site in blocks of 20 tactile stimulations delivered by the CMS. The data were segmented into 1000-ms epochs. RESULTS: MDTs measured by monofilaments and by the CMS were equivalent. Analyses of TEPs showed N2 and P2 components. The latencies of the N2 components on the hand dorsum and foot dorsum resulted in an estimated average conduction velocity of about 40 m.s-1, within the range of Aß fibers. CONCLUSIONS: These findings showed that the CMS could assess touch sensory pathways in young adults. SIGNIFICANCE: The CMS can offer new research perspectives, as this device allows easy assessment of the MDT and enables estimation of fiber conduction velocities after tactile stimulation by the device synchronized with EEG recordings.

Preserved distraction analgesia but greater impact of pain on task performance in older adults compared with younger subjects.

OBJECTIVE: In this study, we compared two working memory conditions to study the analgesic effect of a distraction in elderly vs young people and the effect of pain on performance on the distracting task. METHODS: Younger (n=27) and older (n= 34) subjects performed 1- and 2-Back working memory tasks, representing low and high cognitive loads, respectively. Infrequent, brief hot nociceptive and cold non-nociceptive stimulations were delivered 100 ms before visual N-Back stimuli. Contact heat-evoked and cold-evoked potentials (N2P2 component) were analyzed in the absence of cognitive tasks and during the N-Back tasks. We compared the pain and cold intensity ratings and reaction times in trials preceded by nociceptive and cold stimulations and in trials not preceded by thermal stimulations between groups and between N-Back conditions. RESULTS: In both groups, performing the 1- and 2-Back working memory tasks reduced the perceived intensity of nociceptive and cold stimuli. In elderly subjects performing 2-Back memory tasks, response times to trials after nociceptive stimulation were longer than those to trials after cold or non-stimulation. By contrast, thermal stimulations had no effect on reaction times in young subjects. The amplitude of the N2P2 component was lower in the older than in the younger group in the absence of a cognitive task. In the older group, N-Back tasks had no effect on the N2P2 amplitude, whereas they reduced N2P2 amplitude in the young. CONCLUSION: Distraction analgesia is preserved in elderly subjects. However, this successful pain modulation seems to be accompanied by performance costs in the distracting tasks.

Investigating cold Aδ fibers in the 0-40 °C temperature range: A quantitative sensory testing and evoked potentials study.

OBJECTIVE: To evaluate the activity of cold Aδ-type fibers to thermal stimuli above human skin temperature (i.e., >32 °C). METHODS: Twenty young adults aged 20-24 years participated in this study. The cold-detection threshold was measured from a basal temperature of 40 °C using an adaptive staircase method with high-speed cooling ramps (170 °C/s). A total of 150 stimulations at 36 °C, 32 °C, 28 °C, 24 °C, 20 °C, 16 °C, 12 °C, 8 °C, 4 °C and 0 °C (15 each) were performed. After each stimulation, subjects estimated the intensity of cold sensation using a visual analog scale, and evoked potentials were recorded. RESULTS: The average cold-detection threshold was 35 °C (SD = 1.8). Regardless of the stimulation temperature, subjects reported a cooling sensation. Interestingly, reported increments in sensation were prominent for stimulation temperatures between 32 °C and 20 °C, but below this latter temperature sensations varied only very slightly. Evoked potential recordings revealed that decreasing temperature stimuli from a baseline of 40 °C induced a previously unreported N2P2 component with a mean N2 peak latency of 275 ms (SD = 13.1). The peak-to-peak amplitude of the N2P2 complex increased as the intensity of the cooling stimulation increased, exhibiting a profile comparable to subject-perceived intensity, namely, a major increase up to 20 °C, followed by a plateau to 0 °C. CONCLUSIONS: The cool sensations reported by subjects were likely conveyed by Aδ fibers rather than by slow-conducting C fibers. Moreover, our rapid stimulation technique starting from a high temperature (40 °C) was capable of a) generating cold sensations at stimulation temperatures between 36 °C and 32 °C, and b) revealing the optimal activation range of Aδ fibers (20 °C-28 °C). Any decrease in temperature below this range did not result in a significant increase in sensation and thus probably did not evoke a significant increase in Aδ fiber activity. SIGNIFICANCE: The regular assessment of cold sensation in peripheral neuropathies (i.e., with temperatures below 32 °C), could be completed by investigating cold-detection thresholds at temperatures ranging from 40 °C to 32 °C. Indeed, the absolute threshold of cold perception appears to start at 35 °C. Changes in the activation threshold of cold fibers were more easily detectable at this level.

Accurate Determination of the Cold Detection Threshold with High-Speed Cooling of the Skin.

OBJECTIVE: This study used high-speed cooling of the skin and exact control of stimulus duration to measure the cold detection threshold in healthy participants. The objective was to compare the method of limits, in which the temperature is slowly and gradually increased/decreased until the subject perceives the stimulation, and the method of levels, in which the subject must detect brief thermal stimulations close to the threshold of perception. METHODS: Twenty healthy volunteers (nine women, 11 men) aged 20-30 years participated in the study. The method of limits and method of levels were performed in all subjects in a counterbalanced order. Four cold detection thresholds were measured with the method of levels, with a temperature ramp of 300°C/sec and stimulus durations of 50 ms, 100 ms, 300 ms, and 500 ms. Three thresholds were measured with the method of limits, with temperature ramps of 1°C/sec, 2°C/sec, and 4°C/sec. RESULTS: On average, the cold detection thresholds were -0.47°C below skin temperature with the method of levels and -1.67°C the method of limits. Interindividual variability was significantly lower with the method of levels than with the method of limits. CONCLUSIONS: These results suggest that the method of levels is more accurate than the method of limits for measuring cold detection threshold. The improvement of cold detection threshold measurement may provide new perspectives to more precisely assess the function of A-delta fibers and the spino-thalamic pathway.

Driving Skills Tested on Simulator After Strabismus Surgery: A Prospective Study.

Purpose: The sense of vision is responsible for 90% of the information obtained by the motorist. Improvement in binocular visual acuity (VA) and visual field (VF) achieved after strabismus surgery could have beneficial effects on driving. Our study sought to identify functional improvements (VA and VF) and improvements in driving ability following strabismus surgery. Methods: In a prospective cohort study, the following parameters are analyzed before and 3 months after strabismus surgery: simulated driving performance (including eye movements and actions on vehicle control), binocular VA, binocular VF, and self-confidence during driving. Results: Twenty patients participated in the study. The mean preoperative logMAR binocular VA and stereopsis do not significantly differ from the postoperative. The mean Esterman VF score increases from 91.3 (±17.2) preoperatively to 96.9 (±13.9) postoperatively (P = 0.045). The mean self-confidence directed at driving scores decreases from 20.5 (±10.3) points before surgery to 11.0 (±6.0) points after surgery (P < 0.001). The distance at which the road signs are identified is significantly higher after surgery. The average speed of the vehicle and the speed near the targets (30 m) increase significantly after strabismus surgery. A significant decrease in ocular movements near targets is also observed. The number of brake pedal depressions and the rate of brake pedal depressions slightly decrease after surgery. Conclusions: This study demonstrates the potential beneficial effects of strabismus surgery on driving ability, with significant improvements in self-confidence during driving, VF, and driving on a simulator. Translational Relevance: This was the first study to use a driving simulator in strabismus.

Involvement of Frontal Functions in Pain Tolerance in Aging: Evidence From Neuropsychological Assessments and Gamma-Band Oscillations.

Reduced pain tolerance may be one of the possible explanations for high prevalence of chronic pain among older people. We hypothesized that age-related alterations in pain tolerance are associated with functioning deterioration of the frontal cortex during normal aging. Twenty-one young and 41 elderly healthy participants underwent a tonic heat pain test, during which cerebral activity was recorded using electroencephalography (EEG). Elderly participants were divided into two subgroups according to their scores on executive tests, high performers (HPs; n = 21) and low performers (LPs; n = 20). Pain measures [exposure times (ETs) and perceived pain ratings] and cerebral activity were compared among the three groups. ETs were significantly lower in elderly LPs than in young participants and elderly HPs. Electroencephalographic analyses showed that gamma-band oscillations (GBOs) were significantly increased in pain state for all subjects, especially in the frontal sites. Source analysis showed that GBO increase in elderly LPs was contributed not only by frontal but also by central, parietal, and occipital regions. These findings suggest that better preservation of frontal functions may result in better pain tolerance by elderly subjects.

Thermal sensitivity in humans at the depth of thermal receptor endings beneath the skin: validation of a heat transfer model of the skin using high-temporal resolution stimuli.

PURPOSE: The bioheat transfer equation predicts temperature distribution in living tissues such as the skin. This study aimed at psychophysically validating this model in humans. METHODS: Three experiments were performed. In the first, participants were asked to judge the thermal intensity of stimuli with combinations of intensity and duration that yielded, according to the model, identical temperatures at the thermoreceptor's depth. In experiment 2, participants' thermal detection thresholds for stimuli of different durations were measured to verify whether these thresholds correspond, according to the model, to equivalent temperatures at the thermoreceptor's location. In experiment 3, an alternative forced choice method was used, in which subjects indicated which of the two consecutive thermal stimulations was more intense. RESULTS: The model predicted results that agreed with subjects' perceptions. Participants judged stimuli of different combinations of intensities and durations yielding identical temperature at the receptor level as having equivalent intensity. Moreover, although cold detection thresholds for stimuli of different durations differed for temperatures of the stimulating probe, stimulations using the model's parameters showed equivalence at the depth of the thermal receptors. Furthermore, stimuli with temperature/duration combinations for which the model predicts temperature equivalence at the depth of the receptors corresponded to subjective equalization. CONCLUSION: These findings indicate that heat transfer models provide good estimates of temperatures at the thermal receptors. Use of these models may facilitate comparisons among studies using different stimulation devices and may facilitate the establishment of standards involving all stimulation parameters.

Effects of thermosensory aging well demonstrated by cold stimulations with high temporal resolution.

INTRODUCTION: The method of limits (MLi) is the most commonly used paradigm to measure the threshold of thermal stimuli. However, the threshold measured by MLi is dependent on reaction time (RT). Because RT in adults increases with age, the inclusion of RT in the MLi paradigm may result in an overestimation of thermal threshold in the older individuals. METHODS: A device with a very rapid cooling rate (300°C/s) was employed to measure cool thresholds by using the method of levels (MLe), a method independent of RT, in 11 older patients and 14 younger adults. RESULTS: Compared with the MLi, the MLe resulted in a greater than 2°C gain in threshold measurement accuracy in older patients. DISCUSSION: The MLe confirmed that cool perception threshold is dependent on age. The use of MLe provides new opportunities for the study of mechanisms underlying age-associated alterations in thermal perception. Muscle Nerve 60: 141-146, 2019.

Modification of Descending Analgesia in Aging: Critical Role of the Prefrontal Cortex.

OBJECTIVE: Aging has been associated with increases in pain threshold and reductions in tolerance threshold, as well as a deficiency in endogenous pain inhibition. Top-down pain modulation mainly involves the frontal cortex network, which is also one of the most vulnerable brain regions in aging. As the frontal cortex also sustains executive functions, we aimed to determine whether reductions in executive functions subtended by the frontal network are associated with the lack of descending inhibitor control in pain-free elderly participants. METHODS: Executive functions were assessed in pain-free elderly participants using neuropsychological tests. Endogenous inhibition of pain was investigated using the paradigm of conditioned pain modulation. We compared pain thresholds before and after the conditioned pain modulation procedure in older and younger participants and in seniors with poor and good performances on executive tests. RESULTS: Younger participants showed a significant inhibitory effect of phasic pain during prolonged pain stimulation. Older participants with good performance on executive tests showed an absence of inhibiting effect, whereas older participants with poor performance showed a facilitating effect, indicating a significant link between cognitive functions and mechanisms of endogenous inhibition of pain. DISCUSSION: These results highlight a significant link between cognitive functions and mechanisms of endogenous inhibition of pain and open new perspectives in investigations of chronic pain in aging.

Electrophysiological individual face adaptation effects with fast periodic visual stimulation resist long interruptions in adaptation.

This study used fast periodic visual stimulation (FPVS) and electroencephalography (EEG) to investigate whether the reduction of face adaptation effects over time is due to the introduction of a novel stimulus. In adapting sequences, one individual face was presented at a rate of 6 Hz over 60 s. In testing sequences this adapted face was alternated with a novel individual face at the same rate for 20 s, so that face identity was repeated at a frequency of 3 Hz (i.e. 6 Hz/2). Testing sequences started immediately or 9-15 s after adapting sequences. Identity adaptation produced a selective response at 3 Hz over the right occipito-temporal cortex both with and without delay after adapting sequences. These results suggest that the adaptation effect persists for several seconds, and that the decay of the adaptation effect is due to the introduction of a novel face stimulus.

Reduced parahippocampal theta activity during spatial navigation in low, but not in high elderly performers.

OBJECTIVE: Cognitive aging varies widely among individuals. Whereas optimal cognitive agers show highly preserved cognitive functions throughout life, other subjects experience cognitive deficits in various cognitive domains. Among them, elderly individuals frequently report difficulties in spatial navigation. In this study, we aimed to determine whether elderly participants with different cognitive profiles would perform differently at a navigation task, and explore underlying medial hippocampal activity. METHOD: Two groups of elderly subjects were selected, high- and low-performing (HP and LP, respectively), based on their performance on a detailed neuropsychological examination. A group of young adults was recruited as controls. Cerebral activity was recorded by electroencephalography (EEG) during a virtual navigation task in which participants had 3 trials to find their way in mazes. We analyzed theta activity during navigation in the mazes and performed source reconstruction analyses. RESULTS: The LP group was less accurate than the HP group during the navigation task. Theta activity during navigation was greater in HP subjects compared with controls, whereas that theta activity was reduced in LP subjects. Moreover, theta activity in the left parahippocampal gyrus increased across trials in HP, but not in LP, subjects. CONCLUSION: Elderly participants performed differently at a navigation task according to their cognitive profile: elderly with cognitive deficits seem to have greater difficulties in spatial navigation than HP elderly. Navigational difficulties in elderly with cognitive deficits might be related to functional alteration of the parahippocampal gyrus. (PsycINFO Database Record

Gamma oscillatory activity is impaired in episodic memory encoding with age.

The present study proposes to investigate age-related episodic memory impairment in encoding. We collected ERPs in young and old participants performing a word-encoding task. For subsequently remembered words, young adults had greater activity at the left and anterior electrode sites, whereas old adults had greater posterior activity. Performance correlated positively with central sites in young adults but with left parietal hemisphere activity in old adults. Plus, a large left frontoparietal network increased its activity during the successful encoding for the Beta (13-30 Hz) and Gamma (30-100 Hz) bands in young adults. Old adults had increased activity in the right posterior parietal region for forgotten words in the Gamma band. Using a source localization analysis, we found that age leads to a decrease in Gamma band cerebral activity during encoding of words in the left hemisphere and the bilateral parahippocampal regions. These findings indicate that encoding impairment with age may be associated with dysfunctional Gamma oscillatory activity across a widespread network of left cortical regions.

Differential processing of hierarchical visual stimuli in young and older healthy adults: An event-related potentials (ERP) study.

OBJECTIVE: In tasks involving hierarchical stimuli, young subjects typically show faster RTs and higher accuracy rates in discriminating target stimuli at the global level than at the local level. This pattern of performance is called the global precedence effect (GPE). As individuals age, this patterns shifts to a local precedence effect (LPE). The purpose of this study was to determine whether the decline in GPE in older adults may be due to impairment of grouping processes. METHOD: The authors recorded event-related potentials (ERP) while young and elderly subjects performed a global/local task in response to hierarchical stimuli, and they focused on the P300 component as an index of grouping processes. RESULTS: Compared to young subjects, elderly individuals showed a lower rate of correct discrimination in global processing conditions, but a higher rate of correct responses in local processing conditions, confirming a shift from a GPE to a LPE during aging. Interestingly, the P300 amplitude increased selectively during global processing in young adults but was not modulated by processing level in older participants. By contrast, the modulation of the early component N2 as a function of precedence level remained preserved in older subjects. CONCLUSION: The results suggest that the precedence level may depend on early processes that are unaffected during aging. This may explain the preservation of local precedence effect in elderly individuals. However, global processing may depend on extra attentional processing occurring at later stages. The alteration of later processing may explain the decline in global precedence during aging. (PsycINFO Database Record

Decreased theta power at encoding and cognitive mapping deficits in elderly individuals during a spatial memory task.

The purpose of this study was to investigate the role of theta activity in cognitive mapping, and to determine whether age-associated decreased theta power may account for navigational difficulties in elderly individuals. Cerebral activity was recorded using electroencephalograph in young and older individuals performing a spatial memory task that required the creation of cognitive maps. Power spectra were computed in the frontal and parietal regions and correlated with recognition performance. We found that accuracy of cognitive mapping was positively correlated with left frontal theta activity during encoding in young adults but not in older individuals. Compared with young adults, older participants were impaired in the creation of cognitive maps and showed reduced theta and alpha activity at encoding. These results suggest that encoding processes are impaired in older individual, which may explain age-related cognitive mapping deficits.

Allocentric but not egocentric orientation is impaired during normal aging: an ERP study.

OBJECTIVE: Behavioral studies of spatial navigation in aging indicate that orientation using an allocentric reference frame (object-centered orientation) is impaired, whereas orientation using egocentric processes (self-centered orientation) is not. It has been proposed that navigational deficits may result from more general alterations of perception and attention or executive functions. The purpose of this study is to assess allocentric and egocentric representation in elderly individuals, and to determine if age-related deficits in spatial navigation are related to an attentional decline. METHOD: We assessed encoding of the position of geometrical shapes, depending specifically on an allocentric or egocentric reference frame, during ERP recording in young and old subjects. RESULTS: Aging was associated with a performance decline in allocentric, but not egocentric, encoding. Both allocentric and egocentric conditions elicited parietal early components P1 and N1, reflecting top-down modulation, and components P2 and N2, reflecting selective attention and stimulus categorization. We observed age-associated effects on N1 and N2 amplitudes and on N2 latency in both spatial conditions. Moreover, impaired allocentric performance in older subjects was associated with a greater P2 amplitude and delayed P2 latency compared with younger subjects. CONCLUSION: These results suggest that elderly individuals present with deficits when spatial orientation relies on allocentric representation, and are associated with age-related deficits in spatial attention.

Spatial navigation in normal aging and the prodromal stage of Alzheimer's disease: insights from imaging and behavioral studies.

Normal aging and mild Alzheimer's disease (AD) are associated with declines in navigational skills, including allocentric and egocentric representations, cognitive mapping, landmark processing, and spatial memory. These changes, however, are associated with different patterns of structural and functional alterations in the neural network of navigation. In AD, these changes occur in the hippocampus, parahippocampal gyrus, parietal lobe, retrosplenial cortex, prefrontal cortex, and caudate nucleus, whereas in aging, modifications occur mainly in the prefrontal cortex and the hippocampus. The navigation abilities of patients with mild cognitive impairment (MCI) have been found to show different performance patterns, depending on their cognitive profiles. Since patients with MCI do not uniformly develop dementia of the Alzheimer type, it is important to identify reliable early cognitive markers of conversion to AD dementia. In this review, we propose that navigation deficits may help distinguish patients at higher risk of developing AD dementia from individuals with normal cognitive aging and those with other neurodegenerative diseases.

Septohippocampal pathways contribute to system consolidation of a spatial memory: sequential implication of GABAergic and cholinergic neurons.

Studies of the neuropharmacological substrates of spatial memory formation have focused on the contribution of septohippocampal pathways. Although these pathways include, among others, cholinergic and GABAergic fibers innervating the hippocampus, research has essentially been oriented towards the role of their cholinergic component. Recently, a few studies investigated the role of GABAergic septohippocampal projections. These only focused on almost immediate or recent memory and yielded discrepant results. GABAergic lesions impaired learning or had no effects. Given the role of the hippocampus in memory consolidation and the potential modulatory influence of the septum on hippocampal function, it is relevant to study the role of the septohippocampal interface in memory stabilization. We performed investigations with relatively selective lesions of GABAergic (using oxerin-saporin) or/and cholinergic (using 192 IgG-saporin) medial septum/vertical limb of the diagonal band of Broca (MS/vDBB) neurons in rats, and assessed acquisition of a spatial memory and its subsequent recall in the water maze. Following a 6-day training phase during which all groups improved performance to comparable levels, retention was tested 1, 5, or 25 days later. At the 1-day delay, all groups performed above chance and did not differ significantly among each other. At the 5-day delay, only rats with GABAergic or combined lesions exhibited a retention deficit. At the 25-day delay, all three lesion groups performed at chance level; in these groups, performance was significantly lower than that found in sham-operated rats. Immunochemical and histochemical verifications of the lesion extent/selectivity showed extensive GABAergic damage after intraseptal orexin-saporin infusions or cholinergic damage after 192 IgG-saporin infusions, with relatively limited damage to the other neurotransmitter system. Our data show that GABAergic and cholinergic septohippocampal neurons both contribute to memory stabilization, and could do so in a sequential way: GABAergic processes could be engaged at an earlier stage than cholinergic ones during system consolidation of a spatial memory.