Enhancing cognitive performance with repetitive transcranial magnetic stimulation at human individual alpha frequency

We applied rapid-rate repetitive transcranial magnetic stimulation (rTMS) at individual alpha frequency (IAF) to improve cognitive performance by influencing the dynamics of alpha desynchronization. Previous research indicates that a large upper alpha power in a reference interval preceding a task is related to both large suppression of upper alpha power during the task and good performance. Here, we tested the hypothesis that rTMS at individual upper alpha frequency (IAF + 1 Hz) can enhance alpha power in the reference interval, and can thus improve task performance. Repetitive TMS was delivered to the mesial frontal (Fz) and right parietal (P6) cortex, and as sham condition with 90 degrees-tilted coil (P6 position). The behavioural effect was assessed in a mental rotation task. Further control conditions were rTMS at a lower IAF (IAF - 3 Hz) and at 20 Hz. The results indicate that rTMS at IAF + 1 Hz can enhance task performance and, concomitantly, the extent of task-related alpha desynchronization. This provides further evidence for the functional relevance of oscillatory neuronal activity in the alpha band for the implementation of cognitive performance.     

Contribution of the primary motor cortex to motor imagery: a subthreshold TMS study

Motor imagery (MI) mostly activates the same brain regions as movement execution (ME) including the primary motor cortex (Brodmann area 4, BA4). However, whether BA4 is functionally relevant for MI remains controversial. The finding that MI tasks are impaired by BA4 virtual lesions induced by transcranial magnetic stimulation (TMS) supports this view, though previous studies do not permit to exclude that BA4 is also involved in other processes such as hand recognition. Additionally, previous works largely underestimated the possible negative consequences of TMS-induced muscle twitches on MI task performance. Here we investigated the role of BA4 in MI by interfering with the function of the left or right BA4 in healthy subjects performing a MI task in which they had to make laterality judgements on rotated hand drawings. We used a subthreshold repetitive TMS protocol and monitored electromyographic activity to exclude undesirable effects of hand muscle twitches. We found that BA4 virtual lesions selectively increased reaction times in laterality judgments on hand drawings, leaving unaffected a task of equal difficulty, involving judgments on letters. Interestingly, the effects of virtual lesions of left and right BA4 on MI task performance were the same irrespective of the laterality (left/right) of hand drawings. A second experiment allowed us to rule out the possibility that BA4 lesions affect visual or semantic processing of hand drawings. Altogether, these results indicate that BA4 contribution to MI tasks is specifically related to the mental simulation process and further emphasize the functional coupling between ME and MI.     

No evidence for a substantial involvement of primary motor hand area in handedness judgements: a transcranial magnetic stimulation study

Twelve right-handed volunteers were asked to judge the laterality of a hand stimulus by pressing a button with one of their toes. Judgements were based on two-dimensional drawings of the back or palm of a right or left hand at various orientations. Suprathreshold single-pulse transcranial magnetic stimulation (TMS) was given to the left primary motor hand area (M1-HAND) at 0, 200, 400, 600, 800 or 1000 ms after stimulus onset to probe the functional involvement of the dominant left M1 at various stages of handedness recognition. We found that mean reaction times and error rates increased with angle of rotation depending on the actual biomechanical constraints of the hand but suprathreshold TMS had no influence on task performance regardless of the timing of TMS. However, the excitability of the corticomotor output from the left M1-HAND was modulated during the reaction. Judging left hand drawings was associated with an attenuation of motor-evoked potentials 300-100 ms before the response, whereas judging right hand drawings facilitated the motor-evoked potentials only immediately before the response. These effects were the same for pictures of backs and palms and were independent of the angle of rotation. The failure of TMS to affect task performance suggests that there is no time window during which the M1-HAND makes a critical contribution to mental rotation of the hand. The modulation of motor-evoked potentials according to the laterality of the stimulus indicates a secondary effect of the task on corticomotor excitability that is not directly related to mental rotation itself.     

Judging the angles formed by visible and imaginary clock hands: a study of hemispatial effects in healthy volunteers

Healthy, right-handed volunteers (six male, six female) either saw or imagined the hands of a clock set a particular time. In both conditions, they then judged whether the angle between the clock hands was greater than or less than 90 degrees. Subjects pressed one of two response keys to indicate their decision, and hand of response (left/right) was counterbalanced within and between subjects. The subjects had significantly longer reaction times and made significantly more errors when the imaginary angles formed by the clock hands were located in left hemispace (e.g. 8:30) than right hemispace (e.g. 4:30). With visible hands, there was no reaction time difference between visual hemifields, although significantly more errors were made when the angle formed by the hands fell within the left visual field. In the perceptual task (visible hands), reaction times and error rates increased monotonically as the distance between the hands approximated more closely to 90 degrees. This psychophysical relationship was not found in the representational task (imaginary hands). Rather, there was a significant positive correlation between reaction times/error rates and the magnitude of the number indicative of the position of the minute hand. The latter finding is consistent with the hypothesis that the lateral asymmetry in the representational task (reaction times and error rates are higher in left hemispace) is due to the time taken to mentally rotate the imaginary minute hand in a clockwise direction. No such operation is required in the perceptual condition where the hands are clearly visible.     

Neurobiological correlates of social conformity and independence during mental rotation.

BACKGROUND: When individual judgment conflicts with a group, the individual will often conform his judgment to that of the group. Conformity might arise at an executive level of decision making, or it might arise because the social setting alters the individual's perception of the world. METHODS: We used functional magnetic resonance imaging and a task of mental rotation in the context of peer pressure to investigate the neural basis of individualistic and conforming behavior in the face of wrong information. RESULTS: Conformity was associated with functional changes in an occipital-parietal network, especially when the wrong information originated from other people. Independence was associated with increased amygdala and caudate activity, findings consistent with the assumptions of social norm theory about the behavioral saliency of standing alone. CONCLUSIONS: These findings provide the first biological evidence for the involvement of perceptual and emotional processes during social conformity.     

早期帕金森病患者视觉空间翻转能力受损

目的探讨早期帕金森病(Parkinson disease,PD)患者视觉空间翻转能力的损害情况。方法对29例PD患者及29名健康对照者进行空间翻转测试检查,检查图片包括人体左手、右手、左足、右足以及被黑框挡住左灯或右灯的轿车车头图片,所有图片均有6个角度,要求受试者进行左右判断,以正确率作为比较两组成绩的指标。结果在对客体(车)进行翻转测试时,PD组成绩(89.7%±9.3%)与对照组成绩(91.5%±7.2%)差异无统计学意义(t=0.803,P=0.426),在对自体(手)进行翻转时,PD组成绩(82.5%±11.5%)明显差于对照组(91.5%±6.6%)(t=3.681,P=0.001);以左侧肢体起病者在对自体(手)进行翻转时的成绩(80.7%±16.4%)与对照组(91.5%±6.6%)比较无统计学差异(t=-1.817,P=0.109),以右侧肢体起病者对自体(手)进行翻转时的成绩(83.5%±9.6%)明显差于对照组(91.5%±6.6%)(t=-2.979,P=0.007);PD患者的空间翻转能力与MoCA评分呈正相关。结论早期PD患者存在视觉空间翻转能力受损,并且这种损害存在分离现象,即对自体的空间翻转能力受损,对客体的空间翻转能力相对保留;以右侧肢体起病者更易出现自体的空间翻转能力损害;PD患者的空间翻转能力与总体认知状况相关。     

Synesthetic colors induced by graphemes that have not been consciously perceived

Grapheme–color synesthetes experience colors when they see printed letters of the alphabet. Currently, we tested four “projector” synesthetes, whose colors evoked by graphemes have sensory support or quale and appear to be restricted spatially to the letters like real colors. We use three different kinds of puzzle pictures that contained hidden letters, which require 30 s or more for nonsynesthetes to identify. Grapheme–color projector synesthetes recognize them three times faster and report that the colors were evoked before conscious letter recognition, clueing them as to what the letters were. Subjectively, the synesthetic subjects reported that they also saw mirror-reversed letters in the same colors as nonreversed letters which enabled them to read mirror-reversed text at thrice the normal speed. We conclude that in some synesthetes colors are evoked preconsciously early in sensory processing.     

Sex differences in associations between spatial ability and corpus callosum morphology

Rotating mental representations of objects is accompanied by widespread bilateral brain activations. Thus, interhemispheric communication channels may play a relevant part when engaging in mental rotation tasks. Indeed, links between mental rotation and dimensions of the corpus callosum—the brain's main commissure system—have been reported. However, existing findings are sparse and inconsistent across studies. Here we set out to further characterize the nature of any such links, including their exact location across the corpus callosum. For this purpose, we applied an advanced image analysis approach assessing callosal thickness at 100 equidistant points in a sample of 38 healthy adults (19 men, 19 women), aged between 22 and 45 years. We detected a sex interaction, with significant structure–performance relationships in women, but not in men. Specifically, better mental rotation performance was linked to a thicker female corpus callosum within regions of the callosal splenium, posterior midbody, and anterior third. These findings may suggest sex differences in problem solving strategies where in women, more than in men, stronger interhemispheric connectivity—especially between occipitoparietal, frontal, and prefrontal regions—is associated with improved task performance. © 2018 Wiley Periodicals, Inc.     

Neural basis of stereotype-induced shifts in women's mental rotation performance

Recent negative focus on women's academic abilities has fueleddisputes over gender disparities in the sciences. The controversyderives, in part, from women's relatively poorer performancein aptitude tests, many of which require skills of spatial reasoning.We used functional magnetic imaging to examine the neural structureunderlying shifts in women's performance of a spatial reasoningtask induced by positive and negative stereotypes. Three groupsof participants performed a task involving imagined rotationsof the self. Prior to scanning, the positive stereotype groupwas exposed to a false but plausible stereotype of women's superiorperspective-taking abilities; the negative stereotype groupwas exposed to the pervasive stereotype that men outperformwomen on spatial tasks; and the control group received neutralinformation. The significantly poorer performance we found inthe negative stereotype group corresponded to increased activationin brain regions associated with increased emotional load. Incontrast, the significantly improved performance we found inthe positive stereotype group was associated with increasedactivation in visual processing areas and, to a lesser degree,complex working memory processes. These findings suggest thatstereotype messages affect the brain selectively, with positivemessages producing relatively more efficient neural strategiesthan negative messages.     

Unraveling the cerebral dynamics of mental imagery

Evidence from functional brain imaging studies suggests that mental imagery processes, like other higher cognitive functions, simultaneously activate different neuronal networks involving multiple cortical areas. The question of whether these different areas are truly simultaneously active or whether they are temporally distinct and might reflect different steps of information processing cannot be answered by these imaging methods. We applied spatiotemporal analysis techniques to multichannel event-related potential (ERP) recordings in order to elucidate the topography and chronology of brain processes involved in mental rotation. We measured 41-electrode ERPs in 12 healthy subjects who had to evaluate whether rotated letters were in a normal or mirror-reflected position. These figures were presented in the left, right, or central visual fields and were randomly rotated by 0°, 50°, 100°, or 150°. Behaviorally, we replicated the observation that reaction time increases with greater angles of rotation. Electrophysiologically, we identified a set of dominant electric potential distributions, each of them stable for a certain time period. Only one of these time segments (appearing between 400–600 msec) increased significantly in duration with greater angles of rotation mirroring reaction time. We suggest that the rotation of mental images is carried out during this time segment. A general linear inverse solution applied to this segment showed occipito-parietal cerebral activity that was lateralized to the right hemisphere. Hum. Brain Mapping 5:410–421, 1997. © 1997 Wiley-Liss, Inc.     

Functional subdivisions within the human intraparietal sulcus are involved in visuospatial transformation in a non‐context‐dependent manner

Object‐based visuospatial transformation is important for the ability to interact with the world and the people and objects within it. In this preliminary investigation, we hypothesized that object‐based visuospatial transformation is a unitary process invoked regardless of current context and is localized to the intraparietal sulcus. Participants (n = 14) performed both antisaccade and mental rotation tasks while scanned using fMRI. A statistical conjunction confirmed that both tasks activated the intraparietal sulcus. Statistical parametric anatomical mapping determined that the statistical conjunction was localized to intraparietal sulcus subregions hIP2 and hIP3. A Gaussian naïve Bayes classifier confirmed that the conjunction in region hIP3 was indistinguishable between tasks. The results provide evidence that object‐based visuospatial transformation is a domain‐general process that is invoked regardless of current context. Our results are consistent with the modular model of the posterior parietal cortex and the distinct cytoarchitectonic, structural, and functional connectivity profiles of the subregions in the intraparietal sulcus. Hum Brain Mapp 39:354–368, 2018. © 2017 Wiley Periodicals, Inc.     

Mental rotation test performance in four cross-cultural samples (n = 3367): overall sex differences and the role of academic program in performance

Two meta-analyses (Linn and Petersen, 1985; Voyer et al., 1995) discuss variables that affect mental rotation performance but they do not mention a potentially important variable, the Academic Program in which students are enrolled. Sex differences in brain size have been related to sex differences in spatial performance (e.g., Falk et al., 1999) and thus it is important to know whether mental rotation performance shows a significant interaction between Sex and Academic Program. To put our understanding of the Academic Program effect on a firmer empirical footing, we conducted a large scale multicultural study, with samples from Canada, Germany and Japan, using identical test procedures in all studies. Significant main effects for Sex and Academic Program were found in all four studies, with large effect sizes for Sex and medium to large effect sizes for Academic Program (based on Cohen's d). No significant interactions between these variables were found in the four samples. Our demonstration of a reliable Academic Program effect has clear and important pragmatic implications for a broad range of work on spatial ability and its interpretation.     

Impaired passive maintenance and spared manipulation of internal representations in patients with schizophrenia

Working memory (WM) impairment is a core feature of schizophrenia (SZ), but the integrity of the various components of WM is unclear. After encoding, mental representations must be maintained in WM during the delay period. In addition to maintenance, manipulation of internal representation can occur in WM. It has been argued that manipulation of items in WM is more impaired than simple maintenance in SZ, but direct empirical data to support this claim have been mixed. Discrepant findings among studies might be explained by task parameters, specifically the degree to which the manipulation task places demands on encoding and maintenance processes. The present study set out to examine these components of WM in patients with SZ (n = 20) and demographically matched healthy controls (n = 19) using a spatial delayed response task (DRT) to measure maintenance processes and 2 mental rotation tasks (allocentric and egocentric) with no delay period or restriction on encoding time to measure manipulation processes. Consistent with previous findings, patients were impaired on the spatial DRT. However, patients performed equally well on the egocentric mental rotation task and were more accurate than controls on the allocentric mental rotation task as the required degree of rotation increased. These results indicated impaired maintenance and spared manipulation of representations in WM and suggest a pocket of cognitive function that might be enhanced in SZ.     

The involvement of primary motor cortex in mental rotation revealed by transcranial magnetic stimulation

We used single‐pulse transcranial magnetic stimulation of the left primary hand motor cortex and motor evoked potentials of the contralateral right abductor pollicis brevis to probe motor cortex excitability during a standard mental rotation task. Based on previous findings we tested the following hypotheses. (i) Is the hand motor cortex activated more strongly during mental rotation than during reading aloud or reading silently? The latter tasks have been shown to increase motor cortex excitability substantially in recent studies. (ii) Is the recruitment of the motor cortex for mental rotation specific for the judgement of rotated but not for nonrotated Shepard & Metzler figures? Surprisingly, motor cortex activation was higher during mental rotation than during verbal tasks. Moreover, we found strong motor cortex excitability during the mental rotation task but significantly weaker excitability during judgements of nonrotated figures. Hence, this study shows that the primary hand motor area is generally involved in mental rotation processes. These findings are discussed in the context of current theories of mental rotation, and a likely mechanism for the global excitability increase in the primary motor cortex during mental rotation is proposed.     

Mental rotation of body parts and sensory temporal discrimination in fixed dystonia

Fixed dystonia is an uncommon but severely disabling condition typically affecting young women following a minor peripheral injury. There is no evidence of any structural lesions of the central nervous system nor any clear peripheral nerve or root damage. Electrophysiological techniques such as short intracortical inhibition, cortical silent period and a plasticity inducing protocol have revealed similarities but also differences compared to classical mobile dystonia. To further explore the pathophysiology of fixed dystonia we compared mental rotation of body parts and sensory temporal discrimination in 11 patients with fixed dystonia, 11 patients with classical mobile dystonia and 10 healthy controls. In the mental rotation task subjects were presented with realistic photos of left or right hands, feet and the head of a young women with a black patch covering the left or the right eye in six different orientations. Subjects had to verbally report the laterality of the presented stimuli. To assess sensory temporal discrimination subjects were asked to discriminate whether pairs of visual, tactile (electrical), or visuo‐tactile stimuli were simultaneous or sequential (temporal discrimination threshold) and in the latter case which stimulus preceded the other (temporal order judgement). In accordance with previous studies patients with mobile dystonia were abnormal in mental rotation and temporal discrimination, whereas patients with fixed dystonia were only impaired in mental rotation. Possible explanations for this deficit may include the influence of the abnormal body posture itself, a shared predisposing pathophysiology for mobile and fixed dystonia, or a body image disturbance. These findings add information to the developing pathophysiological picture of fixed dystonia. © 2010 Movement Disorder Society     

Disturbed spatial cognitive processing of body-related stimuli in a case of a lesion to the right fusiform gyrus

The fusiform gyrus (FG) is well known as one of the main neural sites of human face and body processing. We report the case of a young male patient with epilepsy and a circumscribed lesion in the right FG who presented with isolated impairments in spatial cognitive processing of body-related stimuli. However, he did not show any clinical signs of prosopagnosia. In particular, handling/processing of body and face stimuli was impaired, when stimuli were presented in unconventional views and orientations, thus requiring additional spatial cognitive operations. In this case study, we discuss the patient’s selective impairment from the view of current empirical and theoretical work on the segregation of functions in the FG.     

Sensory functions in dystonia: Insights from behavioral studies

The pathophysiology of primary dystonia is thought to involve dysfunction of the basal ganglia cortico‐striatal‐thalamo‐cortical motor circuits. In the past, emphasis was placed on the role of the basal ganglia in controlling movements; in more recent times, however, it has also become clear that they play an important part in sensory as well as cognitive functions. Here, we review evidence for dysfunction of sensory processing in patients with dystonia, and speculate that this may lead to abnormalities in a crucial role of the basal ganglia that links sensory information to appropriate motor output. Sensory function, particularly in the somatosensory domain, has been shown to be compromised in patients with primary dystonia, both in adult onset focal dystonia and in genetically characterized DYT1 dystonia. Given that nonaffected DYT1 gene carriers may show similar abnormalities to clinically affected individuals, sensory deficits could constitute a subclinical endophenotypic trait of disease that precedes overt clinical manifestations. Whether they can trigger primary dystonia or are an epiphenomenon is an issue warranting further study, but the fact that a number of different neurorehabilitative approaches explicitly manipulate somatosensory inputs to improve motor function suggests there may be a causal link between them. We believe that in future, randomized, blind and controlled studies in large patient populations should address this issue, providing efficient strategies to aid functional recovery, particularly in focal hand dystonia, where the available medical treatments offer little benefit. © 2009 Movement Disorder Society     

The ratio of the 2nd to 4th finger length predicts spatial ability in men but not women

On average men score higher on time-constrained tests of spatial ability than women. Both brain and behaviour are influenced by prenatal and adult exposure to gonadal steroid hormones. In humans the ratio of the 2ndto 4thfinger length (2D:4D) is a sexually dimorphic character that is lower in men than women and negatively correlated with testosterone levels. We report three independent studies from Sweden/London, Hungary and Liverpool confirming that 2D:4D is generally larger in women than men, that men obtain higher MRT scores than women, and demonstrating that 2D:4D is negatively correlated with MRT score in men but not women. We argue that this negative correlation between 2D:4D and spatial ability reflects the association between 2D:4D and prenatal, rather than adult, exposure to testosterone and conclude that testosterone exposure influences brain development leading to better performance on male-favouring spatial tasks.     

Distinct neural responses to conscious versus unconscious monetary reward cues

Human reward pursuit is often assumed to involve conscious processing of reward information. However, recent research revealed that reward cues enhance cognitive performance even when perceived without awareness. Building on this discovery, the present functional MRI study tested two hypotheses using a rewarded mental‐rotation task. First, we examined whether subliminal rewards engage the ventral striatum (VS), an area implicated in reward anticipation. Second, we examined differences in neural responses to supraliminal versus subliminal rewards. Results indicated that supraliminal, but not subliminal, high‐value reward cues engaged brain areas involved in reward processing (VS) and task performance (supplementary motor area, motor cortex, and superior temporal gyrus). This pattern of findings is striking given that subliminal rewards improved performance to the same extent as supraliminal rewards. So, the neural substrates of conscious versus unconscious reward pursuit are vastly different—but despite their differences, conscious and unconscious reward pursuit may still produce the same behavioral outcomes. Hum Brain Mapp 35:5578–5586, 2014. © 2014 Wiley Periodicals, Inc .     

The norepinephrine system affects specific neurophysiological subprocesses in the modulation of inhibitory control by working memory demands

Inhibitory control processes are known to be modulated by working memory demands. However, the neurobiological mechanisms behind these modulations are inconclusive. One important system to consider in this regard is the locus coeruleus (LC) norepinephrine (NE) system. In the current study the role of the LC‐NE system by means of pupil diameter recordings that are integrated with neurophysiological (EEG) and source localization data were examined. A combined mental‐rotation Go/Nogo task was used. The results show that increases in working memory load complicate response inhibition processes. On a neurophysiological level these effects were reflected by specific modulations in event‐related potentials (ERPs) reflecting motor inhibition processes (i.e., Nogo‐P3). Attentional selection processes (reflected by the P1 and N1) as well as pre‐motor inhibition or conflict monitoring processes (reflected by the Nogo‐N2) were not affected. Activity of the LC‐NE systems, as indexed by the pupil diameter data, predicted neurophysiological processes selectively in the Nogo‐P3 time range. Source localization analyses suggest that this modulation occurs in the right middle and inferior frontal gyrus. The study provides evidence that the LC‐NE system is an important neurobiological system modulating the effects of working memory load on response inhibition processes. More specifically, it modulates a subset of dissociable cognitive processes that are related to prefrontal cortical regions. Hum Brain Mapp 38:68–81, 2017. © 2016 Wiley Periodicals, Inc.