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Gliomas are a rare form of primary brain tumor, and the rate of morbidity and mortality is very high (Ho et al., 2014). Glioma patients often suffer from cognitive deficits, particularly in Executive Functioning (EF), which can decrease their quality of life (Caramanna et al., 2021; van Kessel et al., 2017; Weyer-Jamora et al., 2021). EF refers to a set of cognitive processes that are important in the cognitive control of behaviors such as attention, decision-making and working memory. EF deficits exist before surgery, and although studies have shown that tumor resection may be helpful in alleviating such problems, research has demonstrated varying trajectories in EF changes in patients that have undergone tumor resection, with some noting improving as well as deteriorating EF after surgery (Lemaitre et al., 2021; Ng et al., 2019; Noll et al., 2021; Sinha et al., 2020; Talacchi et al., 2011). Research has shown that gliomas are often localized in the frontal regions of the brain, residing in the white matter under the frontal cortices (Larjavaara et al., 2007, Wang et al., 2020). These brain regions have been shown to play an important role in the regulation of EF. Importantly, gliomas seem to directly integrate into their neural environment. The area in the vicinity of the tumor, the peritumoral area, has been shown to be hyperactive (Venkatesh et al., 2019, Numan et al., 2021). Investigations into the relationship between gliomas and neuronal activity in rodents, have revealed a direct link between the two, whereby synaptic and electric integration of gliomas into the neuronal networks occurs, which in turn promotes glioma progression (Buckingham et al., 2011; Campbell et al., 2012; Gibson et al., 2014; Venkatesh et al., 2015; Venkatesh et al., 2017; Venkatesh et al., 2019). Studies in rodents have further revealed that increased neuronal activity promotes glioma proliferation and growth (Gibson et al., 2014; Venkatesh et al., 2015). Various molecular mechanisms underlying this phenomenon have been researched, with some studies focusing on neuroligin-3 (NLGN3), whereby stimulation of neurons causes the cleavage and secretion of NLGN3, stimulating glioma growth (Venkatesh et al., 2015; Venkatesh et al., 2017). Other studies have shown similar mechanisms to occur through the secretion of brain derived neurotrophic factor (BDNF), glutamate and dopamine, all of which seem to promote tumor growth (Xiong et al., 2013; Dolma et al., 2016; Ishiuchi et al., 2002; Ishiuchi et al., 2007). Conversely, gliomas are also able to stimulate neuronal activity by forming synapses with healthy neurons through glutamate release (Buckingham et al., 2011; Campbell et al., 2012). Overall, such studies have shown an intricate bidirectional relationship between neurons and gliomas which impacts tumor growth. Further studies, in glioma patients, have also linked tumor progression and brain activity, as measured with magnetoencephalography (MEG), which may contribute to the progression of the disease. In patients, it has been shown that activity, as measured with magnetoencephalography (MEG), is pathologically heightened in comparison to healthy controls (HCs), not only around the tumor but throughout the entire brain (Numan et al., 2022; Zimmermann et al., 2023) Lower levels of oscillatory brain activity were correlated with lower levels of NLGN3 and with longer progression free survival (PFS) in glioma patients (Derks et al., 2018). Similarly, higher levels of broadband power, a proxy for neural activity, postoperatively, predicted shorter PFS and overall survival (OS) in this patient group and were shown to serve as an additional prognostic marker (Belgers et al., 2020). Further supporting the concept of glioma induced neuronal circuits remodeling, are studies that have observed altered electrophysiological properties throughout the brain of patients with glioma, when comparing to HCs. Distinct electrophysiological patterns have been detected, characterized by an increase in slow wavelengths such as higher delta band activity in comparison to HCs (Aabedi et al., 2022; Baayen et al., 2003; Bosma et al., 2008; De Jongh et al., 2003; Oshino et al., 2007). Such alterations have also been correlated with differences in cognition, such as language (Wolthuis et al., 2022). Moreover, recent studies using magnetoencephalography (MEG) demonstrated differences in network clustering (Derks et al., 2021) and connectivity in the brain as compared to HCs (Bartolomei et al., 2006a; Bartolomei et al., 2006b). These findings in turn have been associated with cognitive functioning (Bosma et al., 2008; Bosma et al., 2009; van Dellen et al., 2012; Derks et al., 2019). A recent study by van Lingen et al., (2023) investigated the link between alterations in multilayer network topology in the frontoparietal network (FPN), a network that plays an important role in facilitating EF, and changes in EF in glioma patients from the pre-operative state to a one-year follow up (FU). Results showed that lower set shifting correlated with a decrease in integration. Although studies, such as the previously mentioned one, have investigated how gliomas may affect cognitive functioning in patients, most of the current research has focused on linking alterations in neuronal networks and EF. However, neuronal activity has yet to be investigated with regard to its relationship to cognitive functioning in glioma patients. This is of particular interest due to the previously illustrated findings that demonstrated the integration of the tumor into its neural surroundings and the finding that activity is heightened throughout the brain in these patients in comparison to controls (Numan et al., 2021; Zimmermann et al., 2023). Additionally, it is unknown how activity changes from pre- to post-tumor resection in such patients. This study will therefore aim to bridge these gaps of knowledge by building upon previous work conducted by van Lingen et al., (2023). In addition to analyzing the relationship between activity and EF in patients, this study aims to explore the same in healthy individuals. Patient studies have found that greater brain activity in the default mode network (DMN) is associated with better cognitive flexibility (Sambataro et al., 2010). Furthermore, Zou et al. (2012) discovered that intrinsic resting-state brain activity was significantly correlated with working memory task performance. In addition to such research, brain stimulation, through techniques such as transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (TRNS), have been shown to enhance long-term memory and other cognitive functions (Grover et al., 2022; Qi et al., 2021; Snowball et al., 2023). Although these findings suggest that activity may be related to cognitive performance, the association between EF and activity in the FPN in healthy individuals is unknown. This study therefore intends to investigate the relationship between activity in the FPN and EF in glioma patients and HCs. As brain activity has been shown to impact various aspects of glioma pathology, the question remains how this may relate to cognition.

Cognitive control is built upon the interactions of multiple brain regions. It is currently unclear whether the involved regions are temporally separable in relation to different cognitive processes and how these regions are temporally associated in relation to different task performances. Here, using stop‐signal task data acquired from 119 healthy participants, we showed that concurrent and poststop cognitive controls were associated with temporally distinct but interrelated neural mechanisms. Specifically, concurrent cognitive control activated regions in the cingulo‐opercular network (including the dorsal anterior cingulate cortex [dACC], insula, and thalamus), together with superior temporal gyrus, secondary motor areas, and visual cortex; while regions in the fronto‐parietal network (including the lateral prefrontal cortex [lPFC] and inferior parietal lobule) and cerebellum were only activated during poststop cognitive control. The associations of activities between concurrent and poststop regions were dependent on task performance, with the most notable difference in the cerebellum. Importantly, while concurrent and poststop signals were significantly correlated during successful cognitive control, concurrent activations during erroneous trials were only correlated with posterror activations in the fronto‐parietal network but not cerebellum. Instead, the cerebellar activation during posterror cognitive control was likely to be driven secondarily by posterror activation in the lPFC. Further, a dynamic causal modeling analysis demonstrated that postsuccess cognitive control was associated with inhibitory connectivity from the lPFC to cerebellum, while excitatory connectivity from the lPFC to cerebellum was present during posterror cognitive control. Overall, these findings suggest dissociable but temporally related neural mechanisms underlying concurrent, postsuccess, and posterror cognitive control processes in healthy individuals., Concurrent cognitive control activated regions in the cingulo‐opercular network and sensory cortices, while poststop cognitive control activated regions in the fronto‐parietal network and cerebellum. During correct trials, concurrent and poststop activations were significantly correlated; while during erroneous trials, concurrent activations were only correlated with posterror activations in the fronto‐parietal network but not cerebellum. Postsuccess cognitive control was associated with inhibitory connectivity from the prefrontal cortex to cerebellum, while excitatory connectivity from the prefrontal cortex to cerebellum was present during posterror cognitive control.

International audience; The current standard model of language production involves a sensorimotor dorsal stream connecting areas in the temporo-parietal junction with those in the inferior frontal gyrus and lateral premotor cortex. These regions have been linked to various aspects of word production such as phonological processing or articulatory programming, primarily through neuropsychological and functional imaging group studies. Most if not all the theoretical descriptions of this model imply that the same network should be identifiable across individual speakers. We tested this hypothesis by quantifying the variability of activation observed across individuals within each dorsal stream anatomical region. This estimate was based on electrical activity recorded directly from the cerebral cortex with millisecond accuracy in awake epileptic patients clinically implanted with intracerebral depth electrodes for pre-surgical diagnosis. Each region's activity was quantified using two different metrics-intracerebral evoked related potentials and high gamma activity-at the level of the group, the individual, and the recording contact. The two metrics show simultaneous activation of parietal and frontal regions during a picture naming task, in line with models that posit interactive processing during word retrieval. They also reveal different levels of between-patient variability across brain regions, except in core auditory and motor regions. The independence and non-uniformity of cortical activity estimated through the two metrics push the current model towards sub-second and sub-region explorations focused on individualized language speech production. Several hypotheses are considered for this within-region heterogeneity.

The fronto‐parietal network (FPN) is crucial for cognitively demanding tasks as it selectively represents task‐relevant information and controls other brain regions. To implement these functions, it has been argued that it is a flexible hub that reconfigures its functional connectivity with other networks. This was supported by a study in which a set of demanding tasks were presented, that varied in their sensory features, comparison rules, and response mappings, and the FPN showed greater reconfiguration of functional connectivity between tasks than any other network. However, this task set was designed to engage the FPN, and therefore it remains an open question whether the FPN is in a flexible hub in general or only for such task sets. Using two freely available datasets (Experiment 1, N = 15, Experiment 2, N = 644), we examined dynamic functional connectivity during naturalistic cognition, while participants watched a movie. Many differences in the flexibility were found across networks but the FPN was not the most flexible hub in the brain, during either movie for any of two measures, using a regression model or a correlation model and across five timescales. We, therefore, conclude that the FPN does not have the trait of being a flexible hub, although it may adopt this state for particular task sets., The fronto‐parietal network (FPN) is crucial for cognitively demanding tasks as it selectively represents task‐relevant information and controls other brain regions. It has been argued that it is a flexible hub that reconfigures its functional connectivity with other networks. Using two freely available datasets (Experiment 1, N = 15, Experiment 2, N = 644), we examined dynamic functional connectivity during naturalistic cognition, while participants watched a movie. Many differences in the flexibility were found across networks but the FPN was not the most flexible hub in the brain. We, therefore, conclude that the FPN does not have the trait of being a flexible hub, although it may adopt this state for particular task sets.

In healthy participants, the strength of task-evoked network reconfigurations is associated with cognitive performance across several cognitive domains. It is, however, unclear whether the capacity for network reconfiguration also plays a role in cognitive deficits in brain tumor patients. In the current study, we examined whether the level of reconfiguration of the fronto-parietal (‘FPN’) and default mode network (‘DMN’) during task execution is correlated with cognitive performance in patients with different types of brain tumors. For this purpose, we combined data from a resting state and task-fMRI paradigm in patients with a glioma or meningioma. Cognitive performance was measured using the in-scanner working memory task, as well as an out-of-scanner cognitive flexibility task. Task-evoked changes in functional connectivity strength (defined as the mean of the absolute values of all connections) and in functional connectivity patterns within and between the FPN and DMN did not differ significantly across meningioma and fast (HGG) and slowly growing glioma (LGG) patients. Across these brain tumor patients, a significant and positive correlation was found between the level of task-evoked reconfiguration of the FPN and cognitive performance. This suggests that the capacity for FPN reconfiguration also plays a role in cognitive deficits in brain tumor patients, as was previously found for normal cognitive performance in healthy controls.

Balanced time perspective refers to the ability to flexibly switch between different temporal foci in an adaptive manner according to the current context. Functional connectivity within the default mode network (DMN) has been suggested to support balanced time perspective. The coupling between the DMN and fronto-parietal network (FPN) may drive many important expressions of internally directed cognition. However, it remains unclear whether balanced time perspective is supported by the interaction between the FPN and DMN. To examine these issues, we recruited 91 participants (52 males with mean age of 19.6, and 39 females with mean age of 20.0) to undergo resting-state brain imaging scan and to complete a questionnaire measuring balanced time perspective. Seed-based voxel-wise functional connectivity analyses implicated midline DMN regions including the anterior medial prefrontal cortex (amPFC) and posterior cingulate cortex (PCC) along with the anterior cingulate cortex (ACC), precuneus, and cerebellum in supporting a balanced time perspective. More importantly, functional connectivity between the right amPFC and right dorsal lateral prefrontal cortex (DLPFC) in the FPN was found to associate with balanced time perspective. Our findings suggest the importance of coordinated brain activity in supporting a balanced time perspective.

Investigating human consciousness based on brain activity alone is a key challenge in cognitive neuroscience. One of its central facets, the ability to form autobiographical memories, has been investigated through several fMRI studies that have revealed a pattern of activity across a network of frontal, parietal, and medial temporal lobe regions when participants view personal photographs, as opposed to when they view photographs from someone else’s life. Here, our goal was to attempt to decode when participants were re-experiencing an entire event, captured on video from a first-person perspective, relative to a very similar event experienced by someone else. Participants were asked to sit passively in a wheelchair while a researcher pushed them around a local mall. A small wearable camera was mounted on each participant, in order to capture autobiographical videos of the visit from a first-person perspective. One week later, participants were scanned while they passively viewed different categories of videos; some were autobiographical, while others were not. A machine-learning model was able to successfully classify the video categories above chance, both within and across participants, suggesting that there is a shared mechanism differentiating autobiographical experiences from non-autobiographical ones. Moreover, the classifier brain maps revealed that the fronto-parietal network, mid-temporal regions and extrastriate cortex were critical for differentiating between autobiographical and non-autobiographical memories. We argue that this novel paradigm captures the true nature of autobiographical memories, and is well suited to patients (e.g., with brain injuries) who may be unable to respond reliably to traditional experimental stimuli.

The ability to flexibly adapt thoughts and actions in a goal-directed manner appears to rely on cognitive control mechanisms that are strongly impacted by individual differences. A powerful research strategy for investigating the nature of individual variation is to study monozygotic (identical) twins. Evidence of twin effects have been observed in prior behavioral and neuroimaging studies, yet within the domain of cognitive control, it remains to be demonstrated that the neural underpinnings of such effects are specific and reliable. Here, we utilize a multi-task, within-subjects event-related neuroimaging design with functional magnetic resonance imaging to investigate twin effects through multivariate pattern similarity analyses. We focus on fronto-parietal brain regions exhibiting consistently increased activation associated with cognitive control demands across four task domains: selective attention, context processing, multi-tasking, and working memory. Healthy young adult monozygotic twin pairs exhibited increased similarity of within- and cross-task activation patterns in these fronto-parietal regions, relative to unrelated pairs. Twin activation pattern similarity effects were clearest under high control demands, were not present in a set of task-unrelated parcels or due to anatomic similarity, and were primarily observed during the within-trial timepoints in which the control demands peaked. Together, these results indicate that twin similarity in the neural representation of cognitive control may be domain-general but also functionally and temporally specific in relation to the level of control demand. The findings suggest a genetic and/or environmental basis for individual variation in cognitive control function, and highlight the potential of twin-based neuroimaging designs for exploring heritability questions within this domain.

Numerous studies have reported the beneficial effects of acute exercise on executive functions. Less is known, however, about the effects of exercise on working memory as one subcomponent of executive functions and about its effects on older adults. We investigated the effects of acute moderate-intensity exercise on working memory performance, the respective cortical hemodynamic activation patterns, and the development and persistence of such effects in healthy older adults. Forty-four participants (M: 69.18 years &plusmn, 3.92, 21 females) performed a letter 2-back task before and at three time points after (post 15 min, post 30 min, and post 45 min) either listening to an audiobook or exercising (15 min, 50% VO2-peak). Functional near-infrared spectroscopy (fNIRS) was used to assess cortical hemodynamic activation and brain-behavior correlations in the fronto-parietal working memory network. Overall, we found no group differences for working memory performance. However, only within the experimental group, 2-back performance was enhanced 15 min and 45 min post-exercise. Furthermore, 15 min post-exercise frontal activation predicted working memory performance, regardless of group. In sum, our results indicate slight beneficial effects of acute moderate-intensity exercise on working memory performance in healthy older adults. Findings are discussed in light of the cognitive aging process and moderators affecting the exercise-cognition relationship.

Background: The rs405509 polymorphism ofthe apolipoprotein E (APOE) promoter is related to Alzheimer’sdisease (AD). The T/T allele of rs405509 is known to decrease the transcription of the APOE gene and lead to impairments in specific brain structural networks with aging; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects brain functional connectivity (FC) in aging. Methods: We investigated the effect of the rs405509 genotype (T/T vs. G-allele) on age-related brain FC using functional magnetic resonance imaging. Forty-five elderly TT carriers and 45 elderly G-allele carriers were scanned during a working memory (WM) task. Results: We found that TT carriers showed an accelerated age-related increase in functional activation in the left postcentral gyrus compared with G-allele carriers. Furthermore, the FC between the left postcentral gyrus and some key regions during WM performance, including the right caudal and superior frontal sulcus (SFS), was differentially modulated by age across rs405509 genotype groups. Conclusions: These results demonstrate that the rs405509 T/T allele of APOE causes an age-related brain functional decline in nondemented elderly people, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.

Resting‐state functional MRI (rs‐fMRI) allows mapping temporally coherent brain networks, and intra‐ and inter‐network alterations have been described in different diseases. This prospective study investigated hemispheric resting‐state functional connectivity (RSFC) differences in the default‐mode network (DMN) and fronto‐parietal network (FPN) between patients with left‐ and right‐hemispheric gliomas (LH PAT, RH PAT), addressing asymmetry effects the tumor might have on network‐specific intrinsic functional connectivity under consideration of the prognostically relevant isocitrate‐dehydrogenase (IDH) mutation status. Twenty‐seven patients (16 LH PAT, 12 IDH‐wildtype) and 27 healthy controls underwent anatomical and rs‐fMRI as well as neuropsychological assessment. Independent component analyses were performed to identify the DMN and FPN. Hemispheric DMN‐ and FPN‐RSFC were computed, compared across groups, and correlated with cognitive performance. Patient groups did not differ in tumor volume, grade or location. RH PAT showed higher contra‐tumoral DMN‐RSFC than controls and LH PAT. With regard to the FPN, contra‐tumoral RSFC was increased in both patient groups as compared to controls. Higher contra‐tumoral RSFC was associated with worse cognitive performance in patients, which, however, seemed to apply mainly to IDH‐wildtype patients. The benefit of RSFC alterations for cognitive performance varied depending on the affected hemisphere, cognitive demand, and seemed to be altered by IDH‐mutation status. At the time of study initiation, a clinical trial registration was not mandatory at our faculty, but it can be applied for if requested., This prospective study investigated hemispheric resting‐state functional connectivity (RSFC) differences in the default‐mode network (DMN) and fronto‐parietal network (FPN) between patients with left‐ and right‐hemispheric gliomas and healthy controls (LH PAT, RH PAT, HC), addressing asymmetry effects the tumor might have on network‐specific intrinsic functional connectivity under consideration of the prognostically relevant isocitrate‐dehydrogenase mutation status. Hemispheric RSFC in glioma patients varied depending on tumor hemisphere and investigated network, indicating a dissociation between tumor‐related DMN‐ and FPN‐RSFC changes. Hemispheric RSFC increases were not necessarily found to be beneficial for performance in terms of better performance measures in patients, but to vary depending on tumor side and cognitive demand, which seemed to be further altered by IDH‐mutation status.

Previous studies have shown age‐related impairments in the ability to suppress salient distractors. One possibility is that this is mediated by age‐related impairments in the recruitment of the left intraparietal sulcus (Left IPS), which has been shown to mediate the suppression of salient distractors in healthy, young participants. Alternatively, this effect may be due to a shift in engagement from proactive control to reactive control, possibly to compensate for age‐related impairments in proactive control. Another possibility is that this is due to changes in the functional specificity of brain regions that mediate salience suppression, expressed in changes in spontaneous connectivity of these regions. We assessed these possibilities by having participants engage in a proactive distractor suppression task while in an fMRI scanner. Although we did not find any age‐related differences in behavior, the young (N = 15) and older (N = 15) cohorts engaged qualitatively distinctive brain networks to complete the task. Younger participants engaged the predicted proactive control network, including the Left IPS. On the other hand, older participants simultaneously engaged both a proactive and a reactive network, but this was not a consequence of reduced network specificity as resting state functional connectivity was largely comparable in both age groups. Furthermore, improved behavioral performance for older adults was associated with increased resting state functional connectivity between these two networks. Overall, the results of this study suggest that age‐related differences in the recruitment of a left lateralized ventral fronto‐parietal network likely reflect the specific recruitment of reactive control mechanisms for distractor inhibition., Older participants engage a qualitatively distinct left fronto‐parietal network for proactive inhibition. The results of this study suggest that age‐related differences in the recruitment of a left lateralized ventral fronto‐parietal network likely reflect the specific recruitment of reactive control mechanisms for proactive distractor inhibition.

In real life, humans make decisions by taking into account multiple independent factors, such as delay and probability. Cognitive psychology suggests that cognitive control mechanisms play a key role when facing such complex task conditions. However, in value-based decision-making, it still remains unclear to what extent cognitive control mechanisms become essential when the task condition is complex. In this study, we investigated decision-making behaviors and underlying neural mechanisms using a multifactor gambling task where participants simultaneously considered probability and delay. Decision-making behavior in the multifactor task was modulated by both probability and delay. The behavioral effect of probability was stronger than delay, consistent with previous studies. Furthermore, in a subset of conditions that recruited fronto-parietal activations, reaction times were paradoxically elongated despite lower probabilistic uncertainty. Notably, such a reaction time elongation did not occur in control tasks involving single factors. Meta-analysis of brain activations suggested an association between the paradoxical increase of reaction time and strategy switching. Together, these results suggest a novel aspect of complex value-based decision-makings that is strongly influenced by fronto-parietal cognitive control.Highlights•A value-based decision task with concurrent delay and probabilistic uncertainty•Stronger behavioral effect of probability than delay•Paradoxically long reaction time despite low probabilistic uncertainty•The task activated fronto-parietal cognitive control network•Reaction time elongation coincided with activation similar to strategy switching

Emotion regulation by means of cognitive reappraisal has been widely studied with functional magnetic resonance imaging (fMRI). To date, several meta-analyses of studies using cognitive reappraisal tasks in healthy volunteers have been carried out, but no meta-analyses have yet been performed on the fMRI data of clinical populations with identified alterations in emotion regulation capacity. We provide a comprehensive meta-analysis of cognitive reappraisal fMRI studies in populations of patients with mood or anxiety disorders, yielding a pooled sample of 247 patients and 262 controls from thirteen independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from six of these studies. Our primary results demonstrated that patients with mood and anxiety disorders recruited the regulatory fronto-parietal network involved in cognitive reappraisal to a lesser extent in comparison to healthy controls. Conversely, they presented increased activation in regions that may be associated with the emotional experience (i.e., insula, cerebellum, precentral and inferior occipital gyri) and in regions whose activation may be the consequence of compensatory mechanisms (i.e., supramarginal gyri and superior parietal lobule). Moreover, activations in the left ventrolateral prefrontal cortex and the left superior temporal gyrus were associated with reinterpretation emotion regulation strategies, whereas medial frontal and parietal activations were associated with the deployment of distancing strategies. The regions revealed by this meta-analysis conform to a pattern of dysfunctional brain activation during cognitive reappraisal common to mood and anxiety disorders. As such, this neural pattern may reflect a transdiagnostic feature of these disorders.

Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10-12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility.

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10–12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design, response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10–12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus, of the default mode network (DMN) with left precuneus, of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens, and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity.

Grasping movements are known to activate the fronto-parietal brain networks both in human and non-human primates. However, it is unclear if these activations represent properties of the objects or hand postures or both at different stages of the movement. We manipulated the intrinsic properties of the objects and the grasping types in order to create twelve unique combinations of grasping movements and we investigated, in healthy adult humans, the low-frequency time-domain EEG representation of grasping over different stages of the movement. Next, we implemented two multiclass decoders for the grasp type and objects' properties and evaluated them over time. Furthermore, we investigated the similarity between these grasping EEG representations and categorical models that encode properties of the movement and intrinsic properties of the objects. We found that properties of the grasping movement (grasp types, number of fingers) and intrinsic object properties (shape and size) as represented in EEG are encoded in different brain areas throughout the movement stages. Both object properties and grasp types can be decoded significantly above chance level using low-frequency EEG activity during the planning and execution of the movement. Moreover, we found that this preferential time-wise encoding allows the decoding of object properties already from the observation stage, while the grasp type can also be accurately decoded at the object release stage. These findings contribute to the understanding of the grasping representation based on noninvasive EEG brain signals, and its evolution over the course of movement in relation to categorical models that describe the grasped object's properties or that encode properties of the grasping movement. Moreover, our multiclass grasping decoders are informative for the design and implementation of noninvasive motor control strategies.

Background Both major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are characterized by alterations in intrinsic functional connectivity. Here we investigated changes in intrinsic functional connectivity across these disorders as a function of cognitive behavioral therapy (CBT), an effective treatment in both disorders. Methods 53 unmedicated right-handed participants were included in a longitudinal study. Patients were diagnosed with PTSD (n = 18) and MDD (n = 17) with a structured diagnostic interview and treated with 12 sessions of manualized CBT over a 12-week period. Patients received an MRI scan (Siemens 3 T Trio) before and after treatment. Longitudinal functional principal components analysis (LFPCA) was performed on functional connectivity of the bilateral amygdala with the fronto-parietal network. A matched healthy control group (n = 18) was also scanned twice for comparison. Results LFPCA identified four eigenimages or principal components (PCs) that contributed significantly to the longitudinal change in connectivity. The second PC differentiated CBT-treated patients from controls in having significantly increased connectivity of the amygdala with the fronto-parietal network following CBT. Limitations Analysis of CBT-induced amygdala connectivity changes was restricted to the a priori determined fronto-parietal network. Future studies are needed to determine the generalizability of these findings, given the small and predominantly female sample. Conclusion We found evidence for the hypothesis that CBT treatment is associated with changes in connectivity between the amygdala and the fronto-parietal network. CBT may work by strengthening connections between the amygdala and brain regions that are involved in cognitive control, potentially providing enhanced top-down control of affective processes that are dysregulated in both MDD and PTSD., Highlights • CBT treatment effects found in functional connectivity for combined MDD and PTSD patients. • Novel longitudinal dimension reduction method characterizes direction of changes. • Study shows CBT increases amygdala connectivity with the fronto-parietal network. • CBT mechanism may be to enhance cognitive control region connectivity. • A post-hoc whole brain voxel-wise analysis independently confirmed the findings.

The fronto-parietal network is involved in top-down and bottom-up processes necessary to achieve cognitive control. We investigated the role of asymmetric enhancement of the left dorsolateral prefrontal cortex (lDLPFC) and right posterior parietal cortex (rPPC) in cognitive control under conditions of emotional conflict arising from emotional distractors. The effects of anodal tDCS over the lDLPFC/cathodal over the rPPC and the effects of anodal tDCS over the rPPC/cathodal over the lDLPFC were compared to sham tDCS in a double-blind design. The findings showed that anodal stimulation over the lDLPFC reduced interference from emotional distractors, but only when participants had already gained experience with the task. In contrast, having already performed the task only eliminated facilitation effects for positive stimuli. Importantly, anodal stimulation of the rPPC did not affect distractors&rsquo, interference. Therefore, the present findings indicate that the lDLPFC plays a crucial role in implementing top-down control to resolve emotional conflict, but that experience with the task is necessary to reveal this role.

Background: Previous evidence suggests that postural control processing may be more related to spatial working memory (SWM) than to nonspatial working memory (NWM). Methodological discrepancies between spatial and nonspatial cognitive tasks have made direct comparisons between the two systems difficult. Methods: To explore the neural mechanisms of SWM and NWM relative to that of postural control, participants were subjected a cognitive-posture dual-task paradigm, consisting of a 3-back letter working memory (WM) task, using physically identical stimuli with spatial and nonspatial components memorized in different sessions, and a standing balance task with a tandem stance. Additionally, there were two control sessions: a single-postural control session wherein participants pressed mouse buttons at random while standing; and a single-cognitive task control session wherein subjects completed a WM task while seated. The subjects underwent functional near-infrared spectral imaging (fNIRS) during task performance, wherein oxygenated hemoglobin concentration ([HbO]) was measured in frontal and parietal regions. Results: Postural control reduced discernment in the SWM task significantly, but did not affect NWM task performance. fNIRS showed that postural control had a significant tendency to decrease the [HbO] in the frontal-parietal network of the left hemisphere when participants completed the SWM task. No posture-associated differences in [HbO] were observed in NWM-related areas during NWM task performance. Behavioral and fNIRS data demonstrated that postural control had a selective interaction with SWM. Specifically, postural control reduced SWM discrimination and SWM-related brain activity (frontal-parietal network), but not NWM discrimination or NWM-related brain activity. Furthermore, the multiple linear regression analysis showed that SWM, but not NWM, was an important predictor of postural control. These results suggest that postural control may share more cognitive resources with SWM than with NWM.

Past attempts to characterize the neural mechanisms of affective priming have conceptualized it in terms of classic cognitive conflict, but have not examined the neural oscillatory mechanisms of subliminal affective priming. Using behavioral and electroencephalogram (EEG) time frequency (TF) analysis, the current study examines the oscillatory dynamics of unconsciously triggered conflict in an emotional facial expressions version of the masked affective priming task. The results demonstrate that the power dynamics of conflict are characterized by increased midfrontal theta activity and suppressed parieto-occipital alpha activity. Across-subject and within-trial correlation analyses further confirmed this pattern. Phase synchrony and Granger causality analyses (GCAs) revealed that the fronto-parietal network was involved in unconscious conflict detection and resolution. Our findings support a response conflict account of affective priming, and reveal the role of the fronto-parietal network in unconscious conflict control.

Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n=18) and controls (CON group; n=19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p=0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p&nbsp

Impaired mobility is a major concern for older adults and has significant consequences. While the widely accepted belief is that improved physical function underlies the effectiveness of targeted exercise training in improving mobility and reducing falls, recent evidence suggests cognitive and neural benefits gained through exercise may also play an important role in promoting mobility. However, the underlying neural mechanisms of this relationship are currently unclear. Thus, we hypothesize that six months of progressive aerobic exercise training would alter frontoparietal network (FPN) connectivity during a motor task among older adults with mild subcortical ischemic vascular cognitive impairment (SIVCI)—and exercise-induced changes in FPN connectivity would correlate with changes in mobility. We focused on the FPN as it is involved in top-down attentional control as well as motor planning and motor execution. Participants were randomized either to usual-care (CON), which included monthly educational materials about VCI and healthy diet; or thrice-weekly aerobic training (AT), which was walking outdoors with progressive intensity. Functional magnetic resonance imaging was acquired at baseline and trial completion, where the participants were instructed to perform bilateral finger tapping task. At trial completion, compared with AT, CON showed significantly increased FPN connectivity strength during right finger tapping (p

Background The study aimed to isolate and localize mutually independent cognitive processes evoked during a word recognition task involving food‐related and food‐neutral words using independent component analysis (ICA) for continuously recorded EEG data. Recognition memory (old/new effect) involves cognitive subcomponents—familiarity and recollection—which may be temporally and spatially dissociated in the brain. Food words may evoke additional attentional salience which may interact with the old/new effect. Methods Sixteen satiated female participants undertook a word recognition task consisting of an encoding phase (learning of presented words, 40 food‐related and 40 food neutral) and a test phase (recognition of previously learned words and new words). Simultaneously recorded 64‐channel EEG data were decomposed into mutually independent components using the Infomax algorithm in EEGLAB. The components were localized using single dipole fitting using a four‐shell BESA head model. The resulting (nonartefactual) components with

Highlights • LLD patients present lower functional connectivity in the right FPN. • LLD patients present impaired white matter integrity in tracts to the right FPN. • FPN alterations were negatively correlated with anxiety severity in LLD patients. • The right IFG might be a crucial hub underlying the neuropathology of LLD., The present study investigated functional connectivity and white matter integrity of the fronto-parietal network (FPN) to reveal the neural mechanisms that underlie late-life depression (LLD). Fifty patients with LLD and 40 non-depressed controls were included in the study. A multi-parametric approach was used by applying independent component analysis (ICA) to estimate functional connectivity of the FPN and by applying tract­based spatial statistics to examine white-matter integrity in tracts to the FPN. Patients with LLD exhibited functional abnormalities in the right inferior frontal gyrus, middle frontal gyrus, and inferior parietal gyrus and lower white matter fractional anisotropy in the right inferior fronto-occipital fasciculus, anterior thalamic radiation, and uncinate fasciculus. Alterations of functional connectivity and white matter fractional anisotropy in these regions were negatively correlated with the severity of symptomatic anxiety in LLD patients. The right inferior frontal gyrus might be a crucial hub in transferring information between these abnormal regions. Significant correlations were found between anxiety symptoms and brain alterations, suggesting that impairments in the FPN network might be involved in symptomatic anxiety in elderly individuals with depression.

Objective To evaluate the utility of an oral fMRI-adapted version of the Symbol Digit Modalities Test (SDMT) to assess information processing speed (IPS) using three different interstimulus intervals (ISI). Methods Nineteen right-handed healthy controls performed the adapted version of the SDMT, consisting of a block design that had a total of 6 control/activation block pairs with 3 different ISIs (1.5, 2 and 2.5 s) presented in two different runs: in ascending and descending orders. The brain activation patterns during different ISIs were assessed by effective functional connectivity analysis based on independent component analysis. Results As expected, all conditions yielded activations in the fronto-parietal networks (FPNs) related to attention processes. Shorter ISIs (1.5 and 2 s) not only yielded greater patterns of connectivity within fronto-parietal and occipital regions such as the FPN and fronto-occipital network (FON), but also recruited more functional networks overall. Task performance at the shortest ISI was negatively correlated with connectivity at the FPN and activity of the pre-supplementary motor area extending to the cingulate gyrus. Conclusion Increasing IPS demands due to shorter ISIs resulted in an increased level and number of functional networks required, increased connectivity within the FPN and FON, and enhancement of the prefrontal cortex. IPS does not arise from activity of a single b area but from affective information transfer among distant cortical regions of the frontal and parietal cortices. This adapted version of the SDMT may be useful for studying alterations of IPS in clinical and nonclinical populations.

Highlights • sLORETA analyses performed on 14 healthy adults at rest and during an arithmetic task. • Theta and alpha directed connectivity revealed ACC and left IPL as hubs during task. • Information flow between left IFG and STG suggested a feedback loop., Objectives The aim of this paper is to investigate cortical electric neuronal activity as an indicator of brain function, in a mental arithmetic task that requires sustained attention, as compared to the resting state condition. The two questions of interest are the cortical localization of different oscillatory activities, and the directional effective flow of oscillatory activity between regions of interest, in the task condition compared to resting state. In particular, theta and alpha activity are of interest here, due to their important role in attention processing. Methods We adapted mental arithmetic as an attention ask in this study. Eyes closed 61-channel EEG was recorded in 14 participants during resting and in a mental arithmetic task (“serial sevens subtraction”). Functional localization and connectivity analyses were based on cortical signals of electric neuronal activity estimated with sLORETA (standardized low resolution electromagnetic tomography). Functional localization was based on the comparison of the cortical distributions of the generators of oscillatory activity between task and resting conditions. Assessment of effective connectivity was based on the iCoh (isolated effective coherence) method, which provides an appropriate frequency decomposition of the directional flow of oscillatory activity between brain regions. Nine regions of interest comprising nodes from the dorsal and ventral attention networks were selected for the connectivity analysis. Results Cortical spectral density distribution comparing task minus rest showed significant activity increase in medial prefrontal areas and decreased activity in left parietal lobe for the theta band, and decreased activity in parietal-occipital regions for the alpha1 band. At a global level, connections among right hemispheric nodes were predominantly decreased during the task condition, while connections among left hemispheric nodes were predominantly increased. At more detailed level, decreased flow from right inferior frontal gyrus to anterior cingulate cortex for theta, and low and high alpha oscillations, and increased feedback (bidirectional flow) between left superior temporal gyrus and left inferior frontal gyrus, were observed during the arithmetic task. Conclusions Task related medial prefrontal increase in theta oscillations possibly corresponds to frontal midline theta, while parietal decreased alpha1 activity indicates the active role of this region in the numerical task. Task related decrease of intracortical right hemispheric connectivity support the notion that these nodes need to disengage from one another in order to not interfere with the ongoing numerical processing. The bidirectional feedback between left frontal-temporal-parietal regions in the arithmetic task is very likely to be related to attention network working memory function. Significance The methods of analysis and the results presented here will hopefully contribute to clarify the roles of the different EEG oscillations during sustained attention, both in terms of their functional localization and in terms of how they integrate brain function by supporting information flow between different cortical regions. The methodology presented here might be clinically relevant in evaluating abnormal attention function.

Attention facilitates the processing of task-relevant visual information and suppresses interference from task-irrelevant information. Modulations of neural activity in visual cortex depend on attention, and likely result from signals originating in fronto-parietal and cingulo-opercular regions of cortex. Here, we tested the hypothesis that attentional facilitation of visual processing is accomplished in part by changes in how brain networks involved in attentional control interact with sectors of V1 that represent different retinal eccentricities. We measured the strength of background connectivity between fronto-parietal and cingulo-opercular regions with different eccentricity sectors in V1 using functional MRI data that were collected while participants performed tasks involving attention to either a centrally presented visual stimulus or a simultaneously presented auditory stimulus. We found that when the visual stimulus was attended, background connectivity between V1 and the left frontal eye fields (FEF), left intraparietal sulcus (IPS), and right IPS varied strongly across different eccentricity sectors in V1 so that foveal sectors were more strongly connected than peripheral sectors. This retinotopic gradient was weaker when the visual stimulus was ignored, indicating that it was driven by attentional effects. Greater task-driven differences between foveal and peripheral sectors in background connectivity to these regions were associated with better performance on the visual task and faster response times on correct trials. These findings are consistent with the notion that attention drives the configuration of task-specific functional pathways that enable the prioritized processing of task-relevant visual information, and show that the prioritization of visual information by attentional processes may be encoded in the retinotopic gradient of connectivty between V1 and fronto-parietal regions.

The etiology of anorexia nervosa (AN) is poorly understood. Results from functional brain imaging studies investigating the neural profile of AN using cognitive and emotional task paradigms are difficult to reconcile. Task-related imaging studies often require a high level of compliance and can only partially explore the distributed nature and complexity of brain function. In this study, resting state functional connectivity imaging was used to investigate well-characterized brain networks potentially relevant to understand the neural mechanisms underlying the symptomatology and etiology of AN. Resting state functional magnetic resonance imaging data was obtained from 35 unmedicated female acute AN patients and 35 closely matched healthy controls female participants (HC) and decomposed using spatial group independent component analyses (ICA). Using validated templates, we identified components covering the fronto-parietal “control” network, the default mode network (DMN), the salience network, the visual and the sensory-motor network. Group comparison revealed an increased functional connectivity between the angular gyrus and the other parts of the fronto-parietal network in patients with AN in comparison to HC. Connectivity of the angular gyrus was positively associated with self-reported persistence in HC. In the DMN, AN patients also showed an increased functional connectivity strength in the anterior insula in comparison to HC. Anterior insula connectivity was associated with self-reported problems with interoceptive awareness. This study, with one of the largest sample to date, shows that acute AN is associated with abnormal brain connectivity in two major resting state networks (RSN). The finding of an increased functional connectivity in the fronto-parietal network adds novel support for the notion of AN as a disorder of excessive cognitive control, whereas the elevated functional connectivity of the anterior insula with the DMN may reflect the high levels of self- and body-focused ruminations when AN patients are at rest.

Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec “on” alternating with 22 sec of baseline (device was “off”). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment.

1\. Titel 2\. Inhaltsverzeichnis 3\. Abbildungsverzeichnis 4\. Einleitung 5\. Vorstellung der für die Untersuchung relevanten Gehirnareale 6\. Zielsetzungen 7\. Entwicklung des Paradigmas 8\. Methode und Probanden 9\. Ergebnisse 10\. Diskussion 11\. Zusammenfassung 12\. Literaturverzeichnis 13\. Abkürzungsverzeichnis 14\. Anhang 15\. Danksagung 16\. Lebenslauf, Die funktionelle Kernspintomographie (fMRT) ist eine nicht invasive Untersuchungsmethode, die präoperativ ermöglicht, aktivierte Gehirnareale zu bestimmen. Für das Experiment wurde ein neuartiges, visuelles Paradigma entwickelt, welches 19 Versuchspersonen durch eine spezielle Optik präsentiert wurde. Das so genannte "Tunnel-Paradigma" vermittelt visuell den Eindruck von Eigenbewegung im Raum, ohne dass eine aktive Bewegung durchgeführt werden muss. Die Erstellung der funktionellen Bilder erfolgte durch das Computerprogramm Brain Voyager Version 4.2 (R. Goebel, Maastricht). Die funktionellen Daten wurden anhand der Korrelationsanalyse mit einem Schwellenwert von r > 0,6 ausgewertet. Bei allen Probanden konnten zwei verschiedene signifikante Aktivierungsareale ermittelt werden, die dem frontalen prämotorischen Kortex und dem posterioren parietalen Kortex zugeordnet wurden. Diese Aktivierungen werden als zwei neue Landmarken angesehen, die anhand ihrer Lokalisation indirekt ermöglichen, den Sulcus centralis zu bestimmen. Die Landmarken können als zusätzliche Information zur Bestimmung der Zentralregion in der präoperativen Diagnostik eingesetzt werden. Dabei kann das visuelle Paradigma auch bei Patienten mit motorischen Einschränkungen, bedingt durch Paresen oder gestörte Bewegungsabläufe, benutzt werden. Die mittels der fMRT erweiterten Erkenntnisse über funktionell bedeutsame Hirnareale können eine sichere Operationsplanung ermöglichen und postoperative neurologische Defizite reduzieren. Die gewonnenen Daten unterstützen die Annahme, dass es bei Menschen ein neuronales Netzwerk gibt, welches wie aus Studien bei Macaquen bekannt ist, frontale prämotorische und posteriore parietale Regionen miteinander verbindet, um eine Bewegungsverarbeitung zu ermöglichen., Functional magnet resonance tomography (fMRI) is a non-invasive method for detecting activated areas of the human brain prior to neurosurgery. In this thesis a new exclusively developed visual task "tunnel" was presented to 19 healthy participants. This task was called "tunnel" as it simulates an impression of movement in space without any active movement of the participants. Thus it is helpful for patients with neurological deficits, such as paresis. The MR images were analysed using the software programme "Brain Voyager Version 4.2" (R.Goebbel, Maastricht). All functional data was computed to a correlation-analysis at a threshold r > 0.6. The results can be summarised as followed: All 19 subjects showed two specific activated regions. The first activation was located on the frontal cortex according to the premotor cortex, the second activation was localised on the posterior parietal cortex. These activations can be seen as two new landmarks which can be used for indirectly localising the sulcus centralis due to their localisation. These new landmarks can be used to achieve additional pre-operative information on the localisation of the sulcus centralis for detecting the motor cortex. Thus, the new landmark can improve the pre-operative planning and thereby reduce post-operative neurological deficits. The results suggest the thesis that the neuronal network of the human brain has a comparative structure to the fronto-parietal network of the macaquen brain, which allows a planning and processing of visual guided movements.

Coding of reaching in the cerebral cortex is based on the operation of distributed populations of parietal and frontal neurons, whose main functional characteristics reside in their combinatorial power, i.e., in the capacity for combining different information related to the spatial aspects of reaching. The tangential distribution of reach-related neurons endowed with different functional properties changes gradually in the cortex and defines, in the parieto-frontal network, trends of functional properties. These visual-to-somatic gradients imply the existence of cortical regions of functional overlaps, i.e., of combinatorial domains, where the integration of different reach-related signals occurs. Studies of early coding of reaching in the mesial parietal areas show how somatomotor information, such as that related to arm posture and movement, influences neuronal activity in the very early stages of the visuomotor transformation underlying the composition of the motor command and is not added “downstream” in the frontal cortex. This influence is probably due to re-entrant signals traveling through fronto-parietal-association connections. Together with the gradient architecture of the network and the reciprocity of cortico-cortical connections, this implies that coding of reaching cannot be regarded as a top-down, serial sequence of coordinate transformation, each performed by a given cortical area, but as a recursive process, where different signals are progressively matched and further elaborated locally, due to intrinsic cortical connections. This model of reaching is also supported by psychophysical studies stressing the parallel processing of the different relevant parameters and the “hybrid” nature of the reference frame where they are combined. The theoretical frame presented here can also offer a background for a new interpretation of a well-known visuomotor disorder, due to superior parietal lesions, i.e., optic ataxia. More than a disconnection syndrome, this can now be interpreted as the consequence of the breakdown of the operations occurring in the combinatorial domains of the superior parietal segment of the parieto-frontal network.

Background: Healthy older adults show a decrease in motor performance and motor learning capacity as well as in working memory (WM) performance. WM has been suggested to be involved in motor learning processes, such as sequence learning. Correlational evidence has shown the involvement of the fron-toparietal network (FPN), a network underlying WM processes, in motor sequence learning. However, causal evidence is currently lacking. Non-invasive brain stimulation (NIBS) studies have focused so far predominantly on motor-related areas to enhance motor sequence learning while areas associated with more cognitive aspects of motor learning have not yet been addressed.Hypothesis: In this study, we aim to provide causal evidence for the involvement of WM processes and the underlying FPN in the successful performance of a motor sequence learning task by using theta transcranial alternating current stimulation (tACS) targeting the FPN during a motor sequence learning task.Methods: In a cohort of 20 healthy older adults, we applied bifocal tACS in the theta range to the FPN during a sequence learning task. With the use of a double-blind, cross-over design, we tested the efficacy of active compared to sham stimulation. Two versions of the motor task were used: one with high and one with low WM load, to explore the efficacy of stimulation on tasks differing in WM demand. Addi-tionally, the effects of stimulation on WM performance were addressed using an N-back task. The tACS frequency was personalized by means of EEG measuring the individual theta peak frequency during the N-back task.Results: The application of personalized theta tACS to the FPN improved performance during the motor sequence learning task with high WM load (p < .001), but not with low WM load. Active stimulation significantly improved both speed (p < .001), and accuracy (p = .03) during the task with high WM load. In addition, the stimulation paradigm improved performance on the N-back task for the 2-back task (p = .013), but not for 1-back and 3-back.Conclusion: The performance during a motor sequence learning task can be enhanced by means of personalized bifocal theta tACS to the FPN when WM load is high, indicating that the efficacy of this stimulation paradigm is dependent on the cognitive demand during the learning task. These data provide further causal evidence for the critical involvement of WM processes and the FPN during the execution of a motor sequence learning task in healthy older. These findings open new exciting possibilities to counteract the age-related decline in motor performance, learning capacity and WM performance.(c) 2022 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).