The directional effect of target position on spatial selective auditory attention

Spatial selective auditory attention plays a crucial role in listening in a mixture of competing speech sounds. Previous neuroimaging studies have reported alpha band neural activity modulated by auditory attention, along with the alpha lateralization corresponding to attentional focus. A greater cortical representation of the attended speech envelope compared to the ignored speech envelope was also found, a phenomenon known as \u27neural speech tracking’. However, little is known about the neural activities when attentional focus is directed on speech sounds from behind the listener, even though understanding speech from behind is a common and essential aspect of daily life. The objectives of this study are to investigate the impact of four distinct target positions (left, right, front, and particularly, behind) on spatial selective auditory attention by concurrently assessing 1) spatial selective speech identification, 2) oscillatory alpha-band power, and 3) neural speech tracking. Fifteen young adults with normal hearing (NH) were enrolled in this study (M = 21.40, ages 18-29; 10 females). The selective speech identification task indicated that the target position presented at back was the most challenging condition, followed by the front condition, with the lateral condition being the least demanding. The normalized alpha power was modulated by target position and the power was significantly lateralized to either the left or right side, not the front and back. The parieto-occipital alpha power in front-back configuration was significantly lower than the results for left-right listening configuration and the normalized alpha power in the back condition was significantly higher than in the front condition. The speech tracking function of to-be-attended speech envelope was affected by the direction of ix target stream. The behavioral outcome (selective speech identification) was correlated with parieto-occipital alpha power and neural speech tracking correlation coefficient as neural correlates of auditory attention, but there was no significant correlation between alpha power and neural speech tracking. The results suggest that in addition to existing mechanism theories, it might be necessary to consider how our brain responds depending on the location of the sound in order to interpret the neural correlates and behavioral consequences in a meaningful way as well as a potential application of neural speech tracking in studies on spatial selective hearing

Neural signatures of task-related fluctuations in auditory attention change with age

Listening in everyday life requires attention to be deployed dynamically – when listening is expected to be difficult and when relevant information is expected to occur – to conserve mental resources. Conserving mental resources may be particularly important for older adults who often experience difficulties understanding speech. We use electro- and magnetoencephalography to investigate the neural and behavioral mechanics of dynamic attention regulation during listening and the effects that aging may have on these. We show that neural alpha oscillatory activity indicates when in time attention is deployed (Experiment 1) and that deployment depends on listening difficulty (Experiment 2). Older adults also show successful attention regulation, although younger adults appear to utilize timing information a bit differently compared to older adults. We further show that the recruited brain regions differ between age groups. Superior parietal cortex is involved in attention regulation in younger adults, whereas posterior temporal cortex is more involved in older adults (Experiment 3). This difference in the sources of alpha activity across age groups was only observed when a task was performed, and not for alpha activity during resting-state recordings (Experiment S1). In sum, our study suggests that older adults employ different neural control strategies compared to younger adults to regulate attention in time under listening challenges

The Relationships Among Age, Physical Activity, and Working Memory

As our population ages, determining exogenous factors that may offset cognitive decline become increasingly important. The primary goal of the present study was to determine whether older individuals who engage in regular physical activity demonstrate superior working memory performance relative to older sedentary individuals. Forty young (20 active, 20 sedentary) and forty older (20 active, 20 sedentary) individuals engaged in cognitive measures of information processing speed, inhibitory function, and verbal and visuospatial working memory. Age differences in recall were found for verbal and visuospatial span tasks, as well as for recall reaction time on verbal and visuospatial n-back tasks, and age-related performance decrements were exacerbated in the most difficult task conditions. All participants performed less accurately and took longer to respond to stimuli as the verbal and visuospatial n-back tasks became more difficult. A second objective was to examine the effects of age and physical activity on frontal midline theta and hemispheric alpha, as a function of verbal and visuospatial n-back task difficulty. Frontal midline theta recorded at Fz increased for all participants as taskload increased for the verbal, but not visuospatial n-back task. However, as the visuospatial task became more difficult, the younger group showed a greater increase in frontal midline theta than the older group. Neither age, physical activity, nor taskload had an effect on frontal and parietal alpha asymmetry as analyzed from recordings at F3, F4, P3, and P4. The third objective was to evaluate the degree to which physical activity was related to information processing speed and inhibitory function in older adults, as these two constructs are associated with working memory. Cognitive processing speed, attention accuracy, and attention reaction time were all influenced by age. The hypothesized interaction between age and physical activity was not observed for any of the behavioral nor physiological measurements. Several possible explanations for why the main predictions were not supported are discussed, including the idea that it may be physical fitness, rather than physical activity, which contributes to healthy adult brain aging

The implications of state-dependent tDCS effects in aging:Behavioural response is determined by baseline performance

Young adults typically display a processing advantage towards the left side of space (“pseudoneglect”), possibly as a result of right parietal dominance for spatial attention. This bias is ameliorated with age, with older adults displaying either no strongly lateralised bias, or a slight bias towards the right. This may represent an age-related reduction of right hemispheric dominance and/or increased left hemispheric involvement. Here, we applied anodal transcranial direct current stimulation (atDCS) to the right posterior parietal cortex (PPC; R-atDCS), the left PPC (L-atDCS) and a Sham protocol in young and older adults during a titrated lateralised visual detection task. We aimed to facilitate visual detection sensitivity in the contralateral visual field with both R-atDCS and L-atDCS relative to Sham. We found no differences in the effects of stimulation between young and older adults. Instead the effects of atDCS were state-dependent (i.e. related to task performance at baseline). Relative to Sham, poor task performers were impaired in both visual fields by anodal stimulation of the left posterior parietal cortex (PPC). Conversely, good performers maintained sensitivity in both visual fields in response to R-atDCS, although this effect was small. We highlight the importance of considering baseline task ability when designing tDCS experiments, particularly in older adults

사람에서 점멸광자극을 이용한 성공적인 감마뇌파동조 유도의 결정 요인

학위논문(박사) -- 서울대학교대학원 : 자연과학대학 뇌인지과학과, 2023. 2. 김기웅.Background and Objectives: Although gamma entrainment using flickering light stimulus (FLS) of 40Hz was effective in reducing pathologies and enhancing cognitive function in mouse models of Alzheimers disease (AD), its efficacy was controversial in AD patients. The conflicting results in AD patients may be attributable to a couple of key factors. First, the optimal parameters of FLS for gamma entrainment may be different between diurnal humans and nocturnal mice. Second, the response to optimal FLS may be different between AD patients due to inter-individual difference in the microstructural integrity of white matter (WM) tracts. This study aimed to find the optimal parameters (color, luminal intensity and flickering frequency) of FLS for entraining gamma rhythms in diurnal humans and to examine the effect of fractional anisotropy (FA) of WM tracts on the entrainment and propagation of gamma rhythms. Methods: We first investigated the optimal color (white, red, green, and blue), luminal intensity (10 cd/m2, 100 cd/m2, 400 cd/m2, and 700 cd/m2), and frequency (32 - 50 Hz) of FLS for entraining gamma rhythms in visual cortex using event-related desynchronization/event-related synchronization (ERD/ERS) and for propagating gamma rhythm entrained in visual cortex to other brain regions using spectral Granger Causality (sGC) in 16 cognitively normal young adults (24.0 ± 3.7 yrs) and 35 cognitively normal older adults (70.0 ± 2.4 yrs). We also examined the adverse effects of FLS in both younger and older adults. Then we examined the effect of the FA of posterior thalamic radiations on the ERS of gamma rhythms entrained in visual cortex and that of and middle and superior longitudinal fasciculi on the sGC of the connectivity from visual cortex to temporal and frontal regions in 26 cognitively normal older adults using analysis of variance and linear regression analyses. Results: The FLSs using the lights of longer wavelengths such as white (p < 0.05) and red (p < 0.01) entrained and propagated gamma rhythms better than those of shorter wavelengths such as green and blue. The FLSs using stronger lights such as 700 cd/m2 (p < 0.001) and 400 cd/m2 (p < 0.01) entrained and propagated gamma rhythms better than weaker lights of 100 cd/m2 and 10 cd/m2. The FLSs flickering at 34-38 Hz were best for entraining and propagating gamma rhythm in younger adults (entrainment at Pz: p < 0.05, propagation: p < 0.05) while those flickering at 32-34 Hz were best for older adults (entrainment at Pz: p < 0.05, propagation: p < 0.001). In older adults, white FLSs of 700 cd/m2 flickering at 32–34 Hz entrained the gamma rhythms most strongly at visual cortex (p < 0.05) and propagated them most widely to other brain regions (p < 0.05). The FLSs of 700 cd/m2 flickering at 32 Hz entrained gamma rhythms worse in the visual cortex of the older adults whose FA of left posterior thalamic radiation was low than in those whose FA of left posterior thalamic radiation was not low (p 0.05), and their severity of adverse effects was milder than that in younger adults. Conclusion: In diurnal human, optimal flickering frequency for gamma entrainment was about 20% lower than that in nocturnal mice. Although the FLSs of stronger luminal intensity and the longer wavelength may entrain gamma rhythms better, they may result in more and severe adverse effects. In older adults, white or red FLSs of 700 cd/m2 flickering at 32-34 Hz may be optimal for entraining and propagating gamma rhythms. Since gamma rhythms were not properly entrained by optimal FLS in the older adults whose microstructural integrity of the white matter tracts was impaired, the integrity of the white matter tracts involved in the entrainment and propagation of gamma rhythm should be measured and considered in determining the indication of gamma entrainment using visual stimulation.연구배경 및 목적: 40Hz 점멸광자극 (flickering light stimulation, FLS)을 사용한 감마뇌파동조는 알츠하이머병 (Alzheimers disease, AD) 모델 쥐에서 병리를 감소시키고 인지 기능을 향상시키는 데 효과적이었지만 알츠하이머병 환자에서는 그 효능에 대해 논란이 있다. 알츠하이머병 환자의 상충되는 결과는 몇 가지 주요 요인에 기인할 수 있다. 첫째, 감마뇌파동조를 위한 FLS의 최적 매개변수는 일주 동물인 인간과 야행성 동물인 쥐 간에 다를 수 있다. 둘째, 최적의 FLS에 대한 반응은 백질 (white matter, WM) 섬유 다발 미세 구조적 무결성의 개인 간 차이로 인해 알츠하이머병 환자 간에 다를 수 있다. 이 연구는 일주 동물인 인간에서 감마뇌파를 동반하기 위한 FLS의 최적 매개변수 (색상, 밝기 및 점멸 주파수)를 찾고 감마뇌파의 동반 및 전파에 대한 백질 섬유 다발의 확산비등방성 (fractional anisotropy, FA)의 영향을 조사하는 것을 목표로 했다. 연구방법: 인지기능이 정상인 젊은 성인 16명과 노인 35명을 대상으로, 시각피질에 감마뇌파동조를 유도하고, 동조 된 시각피질의 감마뇌파를 다른 뇌 영역으로의 전파시킬 수 있는 FLS의 최적 색상 (백색, 적색, 녹색 및 청색), 밝기 (10 cd/m2, 100 cd/m2, 400 cd/m2 및 700 cd/m2) 및 점멸 주파수 (32-50 Hz)를 사건 관련 비 동기화/사건 관련 동기화 (event-related desynchronization/event-related synchronization, ERD/ERS)와 스펙트럼 그랜저 인과성 (spectral Granger Causality, sGC) 분석을 이용하여 조사했다. 아울러 젊은 성인과 노인에서 FLS의 부작용을 조사했다. 이어서 감마뇌파가 FLS에 의해 시각피질에 적절하게 동조 된 인지기능이 정상인 노인 26명을 대상으로, 시각피질에서 동조 된 감마뇌파의 ERS와 시각피질과 측두 및 전두 영역들 간 연결성인 sGC에 후방시상방사와 중간 및 상부 세로다발들의 확산비등방성이 미치는 영향을 회귀분석과 분산분석을 이용하여 조사했다. 연구결과: 사람에서는 백색 (p < 0.05) 및 적색 (p < 0.01)과 같은 장파장 FLS가 녹색 및 청색과 같은 단파장 FLS보다 감마뇌파동조를 더 강하게 유발하고, 동조 된 감마뇌파를 더 넓은 뇌 영역으로 전파시켰다. 또 700 cd/m2 (p < 0.001) 및 400 cd/m2 (p < 0.01)와 같은 강한 휘도 FLS는 100 cd/m2 및 10 cd/m2와 같은 약한 휘도 FLS보다 감마뇌파동조를 더 강하게 유발하고, 동조 된 감마뇌파를 더 넓은 뇌 영역으로 전파시켰다. 34-38 Hz에서 점멸하는 FLS는 젊은 성인에서 감마뇌파를 동반하고 전파하는 데 가장 효과적이었고 (Pz에서 동반: p < 0.05, 전파: p < 0.05) 32-34 Hz에서 점멸하는 FLS는 노인에게 가장 효과적이었다 (Pz에서 동반: p < 0.05, 전파: p < 0.001). 노인에서 32-34 Hz에서 점멸하는 700 cd/m2의 백색 FLS는 시각 피질에서 가장 강하게 감마뇌파를 동반하고 (p < 0.05) 다른 뇌 영역으로 가장 널리 전파했다 (p < 0.05). 32 Hz에서 점멸하는 700 cd/m2의 FLS는 좌후시상방사선의 FA가 낮지 않은 노인보다 낮은 노인에서 감마뇌파가 시각피질에 덜 동반된다 (p 0.05), 부작용의 심각성은 젊은 성인보다 경미했다. 결론: 주행성인 인간에서 감마 동조를 위한 최적의 점멸 주파수는 야행성 쥐보다 약 20% 낮았다. 더 강한 휘도와 더 긴 파장의 FLS가 감마뇌파를 더 잘 동조 시킬 수 있지만 더 크고 심각한 부작용을 초래할 수 있다. 노인의 경우 32-34 Hz에서 점멸하는 700 cd/m2의 백색 또는 적색 FLS가 감마뇌파를 동조하고 전파하는 데 최적일 수 있다. 감마뇌파는 백질 섬유 다발의 미세 구조적 무결성이 손상된 노인에서는 최적의 FLS에 의해 적절하게 동조 되지 않았기 때문에, 감마뇌파의 동조 및 전파와 관련된 백질 영역의 무결성은 시각적 자극을 사용하여 감마뇌파동조 적용을 결정할 때 측정되고 고려되어야 한다.1. Introduction 1 1.1. Background 1 1.2. Purpose 4 2. Methods 6 2.1. Study design 6 2.1.1. Study 1. Investigation on the optimal parameters of FLS for gamma entrainment in humans 6 2.1.2. Study 2. Investigation on the effect of WM microstructural integrity on the gamma entrainment by FLS in humans 7 2.2. Participants 7 2.2.1. Study 1. Investigation on the optimal parameters of FLS for gamma entrainment in humans 7 2.2.2. Study 2. Investigation on the effect of WM microstructural integrity on the gamma entrainment by FLS in humans 8 2.2.3. Clinical evaluation of the participants 8 2.3. Research ethics 9 2.4. FLS 9 2.5. Recording, preprocessing and analysis of EEG 10 2.6. Acquisition, preprocessing and analysis of DTI 13 2.7. Statistical analyses 14 3. Results 16 3.1. Effects of the rsEEG spectral band power on cognitive function 16 3.2. Entrainment and propagation of the gamma rhythms by FLS 16 3.3. Effects of the FLS color on gamma entrainment and propagation 17 3.4. Effects of the FLS intensity on gamma entrainment and propagation 18 3.5. Effects of the FLS frequency on gamma entrainment and propagation 18 3.6. Effects of the microstructural integrity of WM tracts on the gamma entrainment and propagation 20 3.7. Adverse effects 21 4. Discussions 23 5. Conclusions 35 Bibliography 66 국문초록 81박

Learning under uncertainty in the young and older human brain: Common and distinct mechanisms of different attentional and intentional systems

The human brain is able to infer the probability of future events by combining information of past observations with current sensory input. Naturally, we are surrounded by more stimuli than we can pay attention to, so selection of relevant input is crucial. The present thesis aimed at identifying common and distinct neural correlates engaged in predictive processing in spatial attention (selection of attended locations) and motor intention (selection of prepared motor responses). Secondly, age-related influences on probabilistic inference in spatial-attention, feature-based attention (selection of attended color) and motor intention, and the impact of task difficulty were considered. Orienting attention during goal-directed behavior can be supported by visual cues, whereas reorienting to unexpected events following misguiding information is linked to behavioral costs and updating of predictions. These processes can be investigated with a cueing paradigm in which differences in reaction time (RT) between valid and invalidly cued trials increase with higher cue validity (%CV) (Posner, 1980). Bayesian models can describe the experience-dependent learning effects of inferring %CV, following novel events (Vossel et al., 2014c; Vossel, Mathys, Stephan & Friston, 2015). The principle aim of the first experiment was to identify and compare the neural correlates involved in inferring probabilities in the spatial attentional and motor intentional domain. Cues indicated either the possible location or prepared the motor response associated with the target. Instead of a fixed probability context, participants were exposed to a volatile environment, in which the validity of the cue information changed unpredictably over time. Combining functional magnetic resonance imaging (fMRI) data with behavioral estimates derived from a Bayesian learning model (Mathys, Daunizeau, Friston & Stephan, 2011) unveiled domain-specific predictability-dependent responses within the right temporoparietal junction (TPJ) for spatial attention and the left angular gyrus (ANG) and anterior cingulate (ACC) in the motor intention task. The blood oxygen level dependent (BOLD) amplitude particularly increased in accord with violations of cue predictability in high cue validity contexts (i.e. when invalid trials were least expected). Valid trials however, induced no (TPJ and ANG) or decreased modulation (ACC). A further aim was to examine possible commonalities in the neural signatures of predictability-dependent processing. Connectivity analysis uncovered common coupling of all three seed regions involved in predictability-dependent processing with the right anterior hippocampus. Since cognitive functions undergo substantial changes in healthy ageing, a second behavioral study was conducted to test whether age differentially influences probabilistic inference in different attentional subsystems, and how task difficulty impacts on learning performance. Thus, following up on the first experiment, similar tasks and the same computational model was used to assess updating behavior in healthy aging. Older and younger adults performed two separate experiments with different difficulty levels. Each experiment included three versions of a cueing task, entailing predictive spatial- (i.e. location), feature- (i.e. color of target) and motor intention cues (i.e. prepare response). Results of the easier version demonstrated a preserved ability of older adults to generate predictions and profit from all cue types. Interestingly, increased task demand uncovered a reduced ability to use motor intention cues to update predictions in older compared to younger adults. In conclusion, the results provide evidence for a segregated functional anatomy of probabilistic inference in spatial attention and motor intention. Nonetheless a common connectivity profile with the hippocampus also points at commonalities. Finally age seems to differentially impact the efficiency of learning behavior in the motor intention system, supporting the notion of independence of the attentional- and intentional subsystems

Anticipatory attention is a stable state induced by transient control mechanisms

Anticipatory attention is a neurocognitive state in which attention control regions bias neural activity in sensory cortical areas to facilitate the selective processing of incoming targets. Previous electroencephalographic (EEG) studies have identified event-related potential (ERP) signatures of anticipatory attention, and implicated alpha band (8–12 Hz) EEG oscillatory activity in the selective control of neural excitability in visual cortex. However, the degree to which ERP and alpha band measures reflect related or distinct underlying neural processes remains to be further understood. To investigate this question, we analyzed EEG data from 20 human participants performing a cued object-based attention task. We used support vector machine (SVM) decoding analysis to compare the attentional time courses of ERP signals and alpha band power. We found that ERP signals encoding attentional instructions are dynamic and precede stable attention-related changes in alpha power, suggesting that ERP and alpha power reflect distinct neural processes. We proposed that the ERP patterns reflect transient attentional orienting signals originating in higher order control areas, whereas the patterns of synchronized oscillatory neural activity in the alpha band reflect a sustained attentional state. These findings support the hypothesis that anticipatory attention involves transient top-down control signals that establish more stable neural states in visual cortex, enabling selective sensory processing

Perception and cognition in Parkinson's disease: a neural network perspective

Parkinson’s disease (PD) is a neurodegenerative disorder commonly presenting with perceptual and cognitive dysfunction. Whereas previous work in PD suggests that abnormal basal ganglia activity has profound effects on integrated functioning of widespread cortical networks, the relation of specific network functions to the perceptual and cognitive impairments is still poorly understood. Here, I present a series of fMRI investigations of network-level functioning in non-demented individuals with PD with the aim of elucidating these associations. Study 1 examined the neural correlates of optic flow processing in 23 individuals with PD and 17 age-matched control participants (MC). An optic flow network comprising visual motion areas V6, V3A, MT+ and visuo-vestibular areas PIVC and CSv is known to be important for parsing egomotion depth cues in humans. The hypothesis was that individuals with PD would show less activation in these regions than MC when processing optic flow. While MC participants showed robust activation in this network, PD participants showed diminished activity within MT+ and CSv. Diminished CSv activity also correlated with greater disease severity. Study 2 investigated intrinsic network organization in PD with a focus on the functional coupling among three neurocognitive networks: the default-mode network (DMN), the salience network (SN), and the central executive network (CEN). Twenty-four individuals with PD and 20 MC participants were scanned at rest. The hypothesis was that PD participants would demonstrate dysfunctional SN coupling with the DMN and CEN. Relative to MC, in PD the CEN was less positively coupled with the SN and less anti-correlated with the DMN. Study 3 investigated the association between functional coupling and cognition in the same group that participated in Study 2. As hypothesized, anti-correlated functional coupling between the SN and DMN was related to successful performance on tests of executive function, psychomotor speed, and memory retrieval in MC but not in PD, suggesting that dysfunction within these networks could underlie early cognitive deficits in PD. Together, the results from the three studies suggest that dysfunctional activity in cortical networks important for visual motion processing and neurocognitive efficiency may underlie aspects of perceptual and cognitive impairment in PD.2017-12-06T00:00:00

Impact of chronic pain in emotional and cognitive behaviour in the rat : the effects of age and lateralization

Tese de doutoramento em Ciências da Saúde - Especialidade de Ciências Biológicas e BiomédicasMultiple areas along the neuroaxis mediate pain modulation and perception. Dysfunction at any of these stations can have devastating consequences that result in pain chronification and in the surfacing of emotional and cognitive disturbances. In the past decade, it was demonstrated that these comorbidities frequently associated with chronic pain also manifest in the animal model, paving the way for further research on the underling pathophysiology. However, conflicting observations have been published probably as a result of experimental heterogeneity. This prompted us to further characterize emotional and cognitive behaviour alterations in a rodent model of chronic neuropathic pain – the spared nerve injury (SNI). In the first set of experiments, the effect of chronic neuropathic pain was studied in the context of ageing. We observed an age-related increase of anxiety-like behaviour in the elevated-plus maze (EPM), which was further augmented in young and old males, but not mid-aged SNI animals. On the contrary, only SNI mid-aged animals had a depressive-like phenotype in the forced-swimming test (FST) when compared to age-matched controls. SNI mid-aged animals had also an impaired ability to perform a reversal learning task when compared with the respective age-matched controls. In this task, the SNI lesion affected neither young nor old groups, although in the last, controls themselves had a poorer performance. In fact, in this cognitive domain ageing was a major determinant of incapacity. Ageing was also demonstrated to have a mild negative influence in the performance of a spatial working memory (WM) but not in a long-term spatial memory – Morris water maze (MWM). The SNI lesion had no observable effect in both WM and MWM. In the second set of experiments, the effect of pain lateralization was accessed in young rats. Left-sided (but not right-sided) SNI was shown to be anxiogenic in the EPM. On the contrary, right-sided (but not left-sided) SNI was detrimental in all prefrontal cortex (PFC)-dependent cognitive paradigms, namely WM, reversal learning (in the attentional-set shifting task; ASST) and response inhibition (impulsivity). Neither right- nor left-side SNI affected the performance in the MWM.These observations indicate that both the age of the animal at the pain onset as well as the location of pain are determinant in the behavioural outcome on emotional and cognitive paradigms. Additionally, our behavioural observations suggest that the PFC has a major role in the observed emotional and cognitive shifts occurring after SNI installation.A modulação e percepção da dor dependem da contribuição de várias áreas ao longo do neuro-eixo. A disfunção deste eixo pode resultar em consequências devastadoras que incluem a cronificação da dor e a manifestação de perturbações emocionais e cognitivas. Na última década, demonstrou-se que estas comorbilidades associadas a estados de dor crónica também se manifestavam no modelo animal, o que abriu novas perspectivas de investigação sobre os mecanismos subjacentes. No entanto, dados contraditórios têm vindo a ser publicados quanto à natureza destas manifestações. Este cenário esteve na base dos estudos desta tese, que pretenderam aprofundar a caracterização das alterações do comportamento emocional e cognitivo num modelo de dor crónica neuropática – o modelo SNI (spared nerve injury). No primeiro conjunto de experiências, o efeito da dor crónica foi estudado no contexto do envelhecimento. Com o envelhecimento observamos um aumento do comportamento do tipo ansioso no paradigma elevated-plus maze (EPM) e que este efeito era potenciado nos animais novos e velhos submetidos à lesão neuropática SNI. Pelo contrário, apenas o grupo de meiaidade submetido ao SNI apresentava um comportamento do tipo depressivo no teste do forced-swimming (FST) quando comparado com o respectivo controlo da mesma idade. O mesmo grupo SNI de meia-idade mostrou também uma capacidade reduzida de aprendizagem reversa, o que não se verificava nos grupos de animais mais novos ou mais velhos embora, nestes últimos, os próprios controlos tenham tido um mau desempenho. De facto, neste paradigma o aumento da idade revelou-se um factor determinante de insucesso. O envelhecimento estava também associado a uma deterioração do desempenho numa tarefa de memória de trabalho (WM; working memory) não havendo no entanto qualquer influência na tarefa de memória de longo prazo (MWM; Morris water maze). A lesão SNI não teve qualquer influência no desempenho destes paradigmas pelos animais dos diferentes grupos etários. No segundo conjunto de estudos, avaliou-se o efeito da lateralidade da dor em animais jovens. A lesão SNI esquerda, (mas não a direita), resultou no aumento do comportamento do tipoansioso no EPM. Pelo contrário, a lesão SNI direita, (mas não a esquerda), induziu um pior desempenho nos paradigmas de comportamento cognitivo, nomeadamente em todos aqueles com um componente prefrontal (prefrontal cortex; PFC): WM, aprendizagem reversa (no contexto de um paradigma de attentional-set shifting task; ASST) e controlo da resposta impulsiva. A lesão SNI, independentemente do lado onde era instalada, não teve qualquer efeito na execução do MWM. Os nossos dados indicam que, quer a idade do individuo aquando da instalação da neuropatia, quer o lado do corpo onde esta se localiza, influenciam o desempenho em paradigmas de comportamento emocional e cognitivo. Resulta também das nossas observações que o PFC tem um papel determinante nas alterações comportamentais observadas após a instalação da neuropati