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Background: Research in functional asymmetry of Major Depressive Disorder (MDD) under different tasks is crucial for clinical diagnose., Methods: Fifty individuals with MDD and twenty healthy controls (HCS) were recruited for hemodynamic data collection under four fNIRS tasks (Emotional picture, Verbal fluency, Fingering and Negative emotional picture description task). Integral values and functional connectivity strength were employed to probe neural activation and functional connectivity in frontal and temporal lobes in MDD. Following, asymmetry characteristic of the frontal cortex between MDD and HCS under four tasks were carefully analyzed and compared., Results: Individuals with MDD demonstrated heightened connectivity between the frontal and right temporal lobes and reduced connectivity between the frontal and left temporal lobes compared to HCS in all tasks. Additionally, MDD exhibited attenuated activation in the left frontal lobes and exaggerated activation in the right frontal lobes, diverging from HCS. Furthermore, the disparities in left-right asymmetry characteristic of frontal cortex activation between MDD and HCS were more pronounced during the combined task., Limitations: Further research is required to grasp the neurophysiological mechanisms governing left-right asymmetry across various tasks and the influence of task-induced brain fatigue on cerebral cortex hemodynamics in MDD., Conclusion: The left-right asymmetry feature provides valuable neurophysiological insights for diagnosing MDD clinically. Variations in activation patterns and functional connectivity features between MDD and HCS are closely tied to the task chosen. Thus, in clinical practice, carefully selecting appropriate fNIRS tasks and relevant features can significantly improve the diagnostic accuracy of MDD., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The medial temporal lobe (MTL) is known to be critical for healthy memory function, but patients with MTL damage can, under certain circumstances, demonstrate successful learning of novel information encountered outside the laboratory. Here, we describe a patient, D.C., with extensive but focal bilateral MTL damage centering primarily on his hippocampus, whose memory for real-world experiences was assessed. Tests of remote memory indicated at least some capacity to retrieve specific details. To test his anterograde memory, he was taken on a tour of the NIH Clinical Center, with unique events occurring at each of ten specific locations. His memory for these events was tested after 1 h, and again after fifteen months. Initially, D.C. could not recall having participated in the tour, even when cued with photographs of specific places he had visited. However, he achieved 90% accuracy on a forced choice recognition test of old and new objects he encountered on the tour, and his recognition of these objects remained intact over a year later when he was tested once again. Subsequent recognition memory tests using novel picture stimuli in a standard laboratory-style computer task resulted in chance-level performance across multiple test formats and stimulus categories. These findings suggest a potentially privileged role for natural learning for long-term retention in a patient with severely damaged medial temporal lobes., (Published by Elsevier Ltd.)

People with similar levels of autistic traits are reported to exhibit better interactions than those with larger differences in autistic traits. However, whether this "similarity effect" exists at the neural level remains unclear. To address this gap, the present study employed functional near-infrared spectroscopy (fNIRS) hyperscanning technology to assess inter-brain synchronization (IBS) during naturalistic conversations among dyads with three types of autistic trait combinations (20 high-high, 22 high-low, and 18 low-low dyads). The results revealed that the high-high dyads exhibited significantly lower IBS in the right temporoparietal junction (rTPJ) region compared to the low-low dyads, with no significant differences observed between the high-low group and the other two groups. Moreover, though dyadic differences in conversation satisfaction were positively correlated with dyadic autistic trait differences, IBS only showed a significant negative correlation with the dyadic average autistic trait scores and no significant correlation with the dyadic difference scores of autistic traits. These findings suggest that dyads with high autistic traits may have shared feelings about conversations, but cannot produce IBS through successful mutual prediction and understanding., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although the role of the medial temporal lobe (MTL) and the hippocampus in episodic memory is well established, there is emerging evidence that these regions play a broader role in cognition, specifically in temporal processing. However, despite strong evidence that the hippocampus plays a critical role in sequential processing, the involvement of the MTL in timing per se is poorly understood. In the present study, we investigated whether patients with MTL damage exhibit differential performance on a temporal distance memory task. Critically, we manipulated context shifts, or boundaries, which have been shown to interfere with associative binding, leading to increases in subjective temporal distance. We predicted that patients with MTL damage would show impaired binding across boundaries and thus fail to show temporal expansion. Consistent with this hypothesis, unilateral patients failed to show a temporal expansion effect, and bilateral patients actually exhibited the reverse effect, suggesting a critical role for the MTL in binding temporal information across boundaries. Furthermore, patients were impaired overall on both the temporal distance memory task and recognition memory, but not on an independent, short-timescale temporal perception task. Interestingly, temporal distance performance could be independently predicted by performance on recognition memory and the short temporal perception task. Together, these data suggest that distinct mnemonic and temporal processes may influence long interval temporal memory and that damage to the MTL may impair the ability to integrate episodic and temporal information in memory., (© 2024 Massachusetts Institute of Technology.)

Unitization - the fusion of objects into a single unit through an action/consequence sequence - can mitigate relational memory impairments, but the circumstances under which unitization is effective are unclear. Using transverse patterning (TP), we compared unitization (and its component processes of fusion, motion, and action/consequence) with extended practice on relational learning and transfer in older adults and neuropsychological cases with lesions (to varying extents) in the medial prefrontal cortex (mPFC) or hippocampus/medial temporal lobe (HC/MTL). The latter included a person with bilateral HC lesions primarily within the dentate gyrus. For older adults, TP accuracy increased, and transfer benefits were observed, with extended practice and unitization. Broadly, the lesion cases did not benefit from either extended practice or unitization, suggesting the mPFC and dentate gyrus play important roles in relational memory and in unitization. The results suggest that personalized strategy interventions must align with the cognitive and neural profiles of the user.

To date, it is largely unknown how frequency range of neural oscillations measured with EEG is related to functional connectivity. To address this question, we investigated frequency-dependent directed functional connectivity among the structures of mesial and anterior temporal network including amygdala, hippocampus, temporal pole and parahippocampal gyrus in the living human brain. Intracranial EEG recording was obtained from 19 consecutive epilepsy patients with normal anterior mesial temporal MR imaging undergoing intracranial presurgical epilepsy diagnostics with multiple depth electrodes. We assessed intratemporal bidirectional functional connectivity using several causality measures such as Granger causality (GC), directed transfer function (DTF) and partial directed coherence (PDC) in a frequency-specific way. In order to verify the obtained results, we compared the spontaneous functional networks with intratemporal effective connectivity evaluated by means of SPES (single pulse electrical stimulation) method. The overlap with the evoked network was found for the functional connectivity assessed by the GC method, most prominent in the higher frequency bands (alpha, beta and low gamma), yet vanishing in the lower frequencies. Functional connectivity assessed by means of DTF and PCD obtained a similar directionality pattern with the exception of connectivity between hippocampus and parahippocampal gyrus which showed opposite directionality of predominant information flow. Whereas previous connectivity studies reported significant divergence between spontaneous and evoked networks, our data show the role of frequency bands for the consistency of functional and evoked intratemporal directed connectivity. This has implications for the suitability of functional connectivity methods in characterizing local brain circuits., (© 2024. The Author(s).)

The cerebellum is critical for sensorimotor learning. The specific contribution that it makes, however, remains unclear. Inspired by the classic finding that for declarative memories, medial temporal lobe (MTL) structures provide a gateway to the formation of long-term memory but are not required for short-term memory, we hypothesized that for sensorimotor memories, the cerebellum may play an analogous role. Here, we studied the sensorimotor learning of individuals with severe ataxia from cerebellar degeneration. We dissected the memories they formed during sensorimotor learning into a short-term temporally-volatile component, that decays rapidly with a time constant of just 15 to 20 s and thus cannot lead to long-term retention, and a longer-term temporally-persistent component that is stable for 60 s or more and leads to long-term retention. Remarkably, we find that these individuals display dramatically reduced levels of temporally-persistent sensorimotor memory, despite spared and even elevated levels of temporally-volatile sensorimotor memory. In particular, we find both impairment that systematically worsens with memory window duration over shorter memory windows (<12 s) and near-complete impairment of memory maintenance over longer memory windows (>25 s). This dissociation uncovers a unique role for the cerebellum as a gateway for the formation of long-term but not short-term sensorimotor memories, mirroring the role of the MTL for declarative memories. It thus reveals the existence of distinct neural substrates for short-term and long-term sensorimotor memory, and it explains both the trial-to-trial differences identified in this study and long-standing study-to-study differences in the effects of cerebellar damage on sensorimotor learning ability., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Anhedonia is a core symptom of depression that is closely related to prognosis and treatment outcomes. However, accurate and efficient treatments for anhedonia are lacking, mandating a deeper understanding of the underlying mechanisms., Methods: A total of 303 patients diagnosed with depression and anhedonia were assessed by the Snaith-Hamilton Pleasure Scale (SHAPS) and magnetic resonance imaging (MRI). The patients were categorized into a low-anhedonia group and a high-anhedonia group using the K-means algorithm. A data-driven approach was used to explore the differences in brain structure and function with different degrees of anhedonia based on MATLAB. A random forest model was used exploratorily to test the predictive ability of differences in brain structure and function on anhedonia in depression., Results: Structural and functional differences were apparent in several brain regions of patients with depression and high-level anhedonia, including in the temporal lobe, paracingulate gyrus, superior frontal gyrus, inferior occipital gyrus, right insular gyrus, and superior parietal lobule. And changes in these brain regions were significantly correlated with scores of SHAPS., Conclusions: These brain regions may be useful as biomarkers that provide a more objective assessment of anhedonia in depression, laying the foundation for precision medicine in this treatment-resistant, relatively poor prognosis group., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Previous studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism., Methods: Fifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay., Results: Activation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD., Conclusions: MDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD., Limitations: The sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system., Competing Interests: Declaration of competing interest The authors have no conflicts of interest in connection with this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Temporal lobe epilepsy (TLE) frequently involves an intricate, extensive epileptic frontal-temporal network. This study aimed to investigate the interactions between temporal and frontal regions and the dynamic patterns of the frontal-temporal network in TLE patients with different disease durations. The magnetoencephalography data of 36 postoperative seizure-free patients with long-term follow-up of at least 1 year, and 21 age- and sex-matched healthy subjects were included in this study. Patients were initially divided into LONG-TERM (n = 18, DURATION >10 years) and SHORT-TERM (n = 18, DURATION ≤10 years) groups based on 10-year disease duration. For reliability, supplementary analyses were conducted with alternative cutoffs, creating three groups: 0 < DURATION ≤7 years (n = 11), 7 < DURATION ≤14 years (n = 11), and DURATION >14 years (n = 14). This study examined the intraregional phase-amplitude coupling (PAC) between theta phase and alpha amplitude across the whole brain. The interregional directed phase transfer entropy (dPTE) between frontal and temporal regions in the alpha and theta bands, and the interregional cross-frequency directionality (CFD) between temporal and frontal regions from the theta phase to the alpha amplitude were further computed and compared among groups. Partial correlation analysis was conducted to investigate correlations between intraregional PAC, interregional dPTE connectivity, interregional CFD, and disease duration. Whole-brain intraregional PAC analyses revealed enhanced theta phase-alpha amplitude coupling within the ipsilateral temporal and frontal regions in TLE patients, and the ipsilateral temporal PAC was positively correlated with disease duration (r = 0.38, p <.05). Interregional dPTE analyses demonstrated a gradual increase in frontal-to-temporal connectivity within the alpha band, while the direction of theta-band connectivity reversed from frontal-to-temporal to temporal-to-frontal as the disease duration increased. Interregional CFD analyses revealed that the inhibitory effect of frontal regions on temporal regions gradually increased with prolonged disease duration (r = -0.36, p <.05). This study clarified the intrinsic reciprocal connectivity between temporal and frontal regions with TLE duration. We propose a dynamically reorganized triple-stage network that transitions from balanced networks to constrained networks and further develops into imbalanced networks as the disease duration increases., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To determine the intracranial ictal onset and early spread patterns in pediatric patients with Temporal lobe epilepsy and its possible association with histopathology, temporal structure involved, mesial structural pathology, and possible implication in postsurgical outcome., Methods: A descriptive, retrospective, cross-sectional study was carried out in a group of children from Children's Wisconsin between 2016 and 2022., Results: This study showed a strong association between ictal onset patterns and underlying histology (p < 0.05). Low-Frequency High Amplitude periodic spikes were seen only in patients with HS (20.6 %). A strong statistically significant association was found between different ictal onset patterns and the temporal lobe structure involved in the ictal onset (p < 0.001). Seizures with ictal onset consisting of Slow Potential Shift with superimposed Low Voltage Fast Activity arise from the Inferior Temporal Lobe or Middle Temporal Gyrus in a more significant proportion of seizures than those that originated from mesial temporal structures (Difference of proportion; p < 0.05). Low Voltage Fast Activity periodic spikes as an ictal pattern were seen in a patient with seizures arising outside the mesial temporal structure. The most frequent early spread pattern observed was Low Voltage Fast Activity (89.4 %); this pattern did not depend on the type of mesial structure pathology. Ictal onset patterns were associated with postsurgical outcomes (p < 0.001). The ictal onset pattern depends on the histopathology in the ictal onset zone and the temporal lobe structure involved in the ictal onset (p = 0.001)., Conclusions: Intracranial ictal onset patterns in TEMPORAL LOBE EPILEPSY depend on underlying histology and the temporal lobe structure involved in its onset., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Understanding the neurobiology of semantic knowledge is a major goal of cognitive neuroscience. Taxonomic and thematic semantic knowledge are represented differently within the brain's conceptual networks, but the specific neural mechanisms remain unclear. Some neurobiological models propose that the anterior temporal lobe is an important hub for taxonomic knowledge, whereas the TPJ is especially involved in the representation of thematic knowledge. However, recent studies have provided divergent evidence. In this context, we investigated the neural correlates of taxonomic and thematic confrontation naming errors in 79 people with aphasia. We used three complementary lesion-symptom mapping (LSM) methods to investigate how structure and function in both spared and impaired brain regions relate to taxonomic and thematic naming errors. Voxel-based LSM mapped brain damage, activation-based LSM mapped BOLD signal in surviving tissue, and network-based LSM mapped white matter subnetwork integrity to error type. Voxel- and network-based lesion symptom mapping provided converging evidence that damage/disruption of the left mid-to-anterior temporal lobe was associated with a greater proportion of thematic naming errors. Activation-based lesion symptom mapping revealed that higher BOLD signal in the left anterior temporal lobe during an in-house naming task was associated with a greater proportion of taxonomic errors on the Philadelphia Naming Test administered outside of the scanner. A lower BOLD signal in the bilateral angular gyrus, precuneus, and right inferior frontal cortex was associated with a greater proportion of taxonomic errors. These findings provide novel evidence that damage to the anterior temporal lobe is especially related to thematic naming errors., (© 2024 Massachusetts Institute of Technology.)

Studies have revealed that somatization symptoms are associated with emotional memory in adolescents with depressive disorders. This study investigated somatization symptoms and emotional memory among adolescents with depressive disorders using low-frequency amplitude fluctuations (ALFF). Participants were categorized into the somatization symptoms (FSS) group, non-FSS group and healthy control group (HC). The correctness of negative picture re-recognition was higher in the FFS and HC group than in the non-FSS group. The right superior occipital gyrus and right inferior temporal gyrus were significantly larger in the FSS group than those in the non-FSS and HC groups. Additionally, the ALFF in the superior occipital and inferior temporal gyrus were positively correlated with CSI score. Furthermore, the ALFF values in the temporal region positively correlated with correct negative image re-recognition. The negative image re-recognition rate was positively correlated with the ALFF in the left and right middle occipital gyri. These findings indicated that somatization symptoms in adolescent depression are associated with the superior occipital gyrus and inferior temporal gyrus. Notably, somatization symptoms play a role in memory bias within depressive disorders, with middle occipital and inferior temporal gyri potentially serving as significant brain regions., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Older adults have difficulties to detect the intentions, thoughts, and feelings of others, indicating an age-associated decline of socio-cognitive abilities that are known as "mentalizing". These deficits in mental state recognition are driven by neurofunctional alterations in brain regions that are implicated in mentalizing, such as the right temporo-parietal junction (rTPJ) and the dorso-medial prefrontal cortex (dmPFC). We tested whether focal transcranial current stimulation (tDCS) of the rTPJ and dmPFC has the potential to eliminate mentalizing deficits in older adults. Mentalizing deficits were assessed with a novel mindreading task that required the recognition of mental states in child faces. Older adults (n = 60) performed worse than younger adults (n = 30) on the mindreading task, indicating age-dependent deficits in mental state recognition. These mentalizing deficits were ameliorated in older adults who received sham-controlled andodal tDCS over the rTPJ (n = 30) but remained unchanged in older adults who received sham-controlled andodal tDCS over the dmPFC (n = 30). We, thus, showed for the first time that anodal tDCS over the rTPJ has the potential to remediate age-dependent mentalizing deficits in a region-specific way. This provides a rationale for exploring stimulation-based interventions targeting mentalizing deficits in older age., (© 2024. The Author(s).)

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects., (© 2024. The Author(s).)

Despite promising advancements, closed-loop neurostimulation for drug-resistant epilepsy (DRE) still relies on manual tuning and produces variable outcomes, while automated predictable algorithms remain an aspiration. As a fundamental step towards addressing this gap, here we study predictive dynamical models of human intracranial EEG (iEEG) response under parametrically rich neurostimulation. Using data from n = 13 DRE patients, we find that stimulation-triggered switched-linear models with ~300 ms of causal historical dependence best explain evoked iEEG dynamics. These models are highly consistent across different stimulation amplitudes and frequencies, allowing for learning a generalizable model from abundant STIM OFF and limited STIM ON data. Further, evoked iEEG in nearly all subjects exhibited a distance-dependent pattern, whereby stimulation directly impacts the actuation site and nearby regions (≲ 20 mm), affects medium-distance regions (20 ~ 100 mm) through network interactions, and hardly reaches more distal areas (≳ 100 mm). Peak network interaction occurs at 60 ~ 80 mm from the stimulation site. Due to their predictive accuracy and mechanistic interpretability, these models hold significant potential for model-based seizure forecasting and closed-loop neurostimulation design., (© 2024. The Author(s).)

Brain resection is curative for a subset of patients with drug resistant epilepsy but up to half will fail to achieve sustained seizure freedom in the long term. There is a critical need for accurate prediction tools to identify patients likely to have recurrent postoperative seizures. Results from preclinical models and intracranial EEG in humans suggest that the window of time immediately before and after a seizure ("peri-ictal") represents a unique brain state with implications for clinical outcome prediction. Using a dataset of 294 patients who underwent temporal lobe resection for seizures, we show that machine learning classifiers can make accurate predictions of postoperative seizure outcome using 5 min of peri-ictal scalp EEG data that is part of universal presurgical evaluation (AUC 0.98, out-of-group testing accuracy > 90%). This is the first approach to seizure outcome prediction that employs a routine non-invasive preoperative study (scalp EEG) with accuracy range likely to translate into a clinical tool. Decision curve analysis (DCA) shows that compared to the prevalent clinical-variable based nomogram, use of the EEG-augmented approach could decrease the rate of unsuccessful brain resections by 20%., (© 2024. The Author(s).)

Background: Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions., Methods: A general linear model was used for analysis of brain activation following task-state fNIRS from 131 patients with SCZ, 132 patients with MDD and 130 healthy controls (HCs). Subsequently, seventy-seven time-frequency analysis methods were used to construct new features of fNIRS, followed by the implementation of five machine learning algorithms to develop a differential diagnosis model for the three groups. This model was evaluated by comparing it to both a diagnostic model relying on traditional fNIRS features and assessments made by two psychiatrists., Results: Brain activation analysis revealed significantly lower activation in Broca's area, the dorsolateral prefrontal cortex, and the middle temporal gyrus for both the SCZ and MDD groups compared to HCs. Additionally, the SCZ group exhibited notably lower activation in the superior temporal gyrus and the subcentral gyrus compared to the MDD group. When distinguishing among the three groups using independent validation datasets, the models utilizing new fNIRS features achieved an accuracy of 85.90 % (AUC = 0.95). In contrast, models based on traditional fNIRS features reached an accuracy of 52.56 % (AUC = 0.66). The accuracies of the two psychiatrists were 42.00 % (AUC = 0.60) and 38.00 % (AUC = 0.50), respectively., Conclusion: This investigation brings to light the shared and distinct neurobiological abnormalities present in SCZ and MDD, offering potential enhancements for extant diagnostic systems., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: While it is well-established that humans possess an innate need for social belonging, the neural mechanisms underlying motivation for connection are still largely unknown. We propose that inclusion motivation - measured through the effort that individuals are willing to invest to be included in social interactions - may serve as one of the basic building blocks of social behavior and may change in lonely individuals., Methods: Following the screening of 303 participants, we scanned 30 low- and 28 high-loneliness individuals with functional magnetic resonance imaging while they performed the Active Inclusion Task (AIT). The AIT assesses the participants' levels of effort invested in influencing their inclusion during classic Cyberball conditions of fair play and exclusion., Results: High- compared to low-loneliness individuals showed higher urgency for inclusion, specifically during fair play, which correlated with higher activity in the right thalamus. Furthermore, in high-loneliness individuals, we found increased functional connectivity between the thalamus and the temporoparietal junction, putamen, and insula., Limitations: Participants interacted with computerized avatars, reducing ecological validity. Additionally, although increasing inclusion in the task required action, the physical demand was not high. Additional limitations are discussed., Conclusions: Inclusion motivation in loneliness is heightened during fair but not exclusionary interactions, and is linked to activity in brain regions implicated in appetitive behavior and social cognition. The findings indicate that lonely individuals may view threat in inclusionary interactions, prompting them to take action to regain connection. This suggests that inclusion motivation may help explain social difficulties in loneliness., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Background and Aims: Gambling activity evolves along a continuum from recreational to Gambling Disorder (GD) and a particular challenge is to identify whether there are some neurophysiological particularities already present in gamblers at an early stage. Our main goal was to determine whether, in the gamblers' population, neural responses generated during uncertain decisions were different depending on problematic gambling risk defined by the Canadian Problem Gambling Index (CPGI). We tested the following hypothesis, that the Problem Gambling group would show a different brain activity related to outcomes processing than people with low risk., Methods: For this purpose, we established a relatively homogeneous population of Online Poker Players divided into two groups according to the CPGI (Low Risk and Problem Gambling). By means of high-density EEG, we compared the spatio-temporal dynamics generated during the completion of the Iowa Gambling Task., Results: One specific topographic map was observed between 150-175 ms after a negative outcome for both groups, whereas it was displayed in the win condition only for the Problem Gambling group. We found that the Global Field Power of this map was negatively correlated with participants' adherence to a strategy. Source localization identified Anterior Cingulate Cortex and Temporal regions as generators of this map., Discussion and Conclusions: Reward hypersensitivity EEG responses identified in the early outcome process could constitute a potential biomarker of problematic gambling.

The human auditory system includes discrete cortical patches and selective regions for processing voice information, including emotional prosody. Although behavioral evidence indicates individuals with autism spectrum disorder (ASD) have difficulties in recognizing emotional prosody, it remains understudied whether and how localized voice patches (VPs) and other voice-sensitive regions are functionally altered in processing prosody. This fMRI study investigated neural responses to prosodic voices in 25 adult males with ASD and 33 controls using voices of anger, sadness, and happiness with varying degrees of emotion. We used a functional region-of-interest analysis with an independent voice localizer to identify multiple VPs from combined ASD and control data. We observed a general response reduction to prosodic voices in specific VPs of left posterior temporal VP (TVP) and right middle TVP. Reduced cortical responses in right middle TVP were consistently correlated with the severity of autistic symptoms for all examined emotional prosodies. Moreover, representation similarity analysis revealed the reduced effect of emotional intensity in multivoxel activation patterns in left anterior superior temporal cortex only for sad prosody. These results indicate reduced response magnitudes to voice prosodies in specific TVPs and altered emotion intensity-dependent multivoxel activation patterns in adult ASDs, potentially underlying their socio-communicative difficulties., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Functional MRI (fMRI) is gaining importance in the preoperative assessment of language for presurgical planning. However, inconsistencies with the Wada test might arise. This current case report describes a very rare case of an epileptic patient who exhibited bilateral distribution (right > left) in the inferior frontal gyrus (laterality index [LI] = -0.433) and completely right dominance in the superior temporal gyrus (LI = -1). However, the Wada test revealed a dissociation: his motor speech was located in the left hemisphere, while he could understand vocal instructions with his right hemisphere. A clinical implication is that the LIs obtained by fMRI should be cautiously used to determine Broca's area in atypical patients; for example, even when complete right dominance is found in the temporal cortex in right-handed patients. Theoretically, as the spatially separated functions of motor speech and language comprehension (by the combined results of fMRI and Wada) can be further temporally separated (by the intracarotid amobarbital procedure) in this case report, these findings might provide direct support to Broca's initial conclusions that Broca's area is associated with acquired motor speech impairment, but not language comprehension per se . Moreover, this current finding supports the idea that once produced, motor speech can be independent from language comprehension., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Background: Non-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI., Method: Thirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest., Results: MDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI., Conclusion: In MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Despite the benefits of anterior temporal lobectomy with amygdalohippocampectomy in patients with temporal lobe epilepsy (TLE), approximately up to 5% may have hemiparesis as its postoperative complication. This paper aims to describe which step/s of the anterior temporal lobectomy with amygdalohippocampectomy have the highest probability of having the greatest decrease in motor evoked potential (MEP) amplitude., Methods: This study used a cross-sectional design of obtaining data from TLE patients who underwent anterior temporal lobectomy with amygdalohippocampectomy with transcranial MEP monitoring. Each of the following steps were evaluated for reduction in MEP amplitude: 1) dural opening, 2) opening the inferior horn, 2) vertical temporal lobe resection 3) subpial dissection, 4) temporal lobe stem resection, 5) lateral temporal lobe resection, 6) hippocampal resection, 7) amygdala resection, 8) uncus resection, and 9) dural closure., Results: Nineteen patients were included in the study. Based on the Friedman Test, 1 or more steps had significantly different average MEP amplitude reductions (Friedman = 50.7, P = 0.0001). When compared with baseline (100%, cutoff P = 0.005), hippocampal resection (z = -3.81, P < 0.0001), T1 subpial dissection (z = -3.2, P = 0.0010), uncus resection (z = -3.48, P = 0.0002), temporal stem resection (z = -3.26, P = 0.001), lateral temporal lobe resection (z = -3.13, P = 0.002), and amygdalectomy (-z = -3.37, P = 0.0005) were significantly lower. Of these, hippocampal resection, uncus resection, and amygdalectomy were deemed highly significant., Conclusions: MEP amplitude tends to decrease during amygdala, hippocampal, and uncal resection because of surgical manipulation of anterior choroidal arteries, which can potentially cause hemiparesis. Careful attention should be paid to changes in MEP during these steps., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Phonemic paraphasia, a common characteristic of conduction aphasia, has traditionally been attributed to phonological representation dysfunction. An alternative hypothesis posits that phonemic paraphasia arises from difficulty converting phonemes into their corresponding articulatory maneuvers. However, detailed case studies supporting this theory have been lacking. In this report, we present the case of a 61-year-old right-handed man with right temporo-parietal infarction who exhibited crossed aphasia characterized by typical conduction aphasia symptoms (eg, relatively fluent speech with intact comprehension, frequent phonemic paraphasia, and pronounced difficulties in oral repetition) in the absence of distorted articulation, syllable segmentation, and prosody impairment. Despite the frequent occurrence of phonemic paraphasia and articulatory challenges, our patient's phonological representations remained relatively intact. His phonemic paraphasia was often self-corrected to produce correct responses, a feature known as conduit d'approche. During the oral repetition of individual mora (ie, the smallest unit of speech in Japanese), we observed that the patient consistently traced the corresponding Hiragana phonetic symbol accurately, despite his difficulties in articulation. We substantiated this phenomenon through objective assessment and posit that it resulted from an unusual separation of language functions in crossed aphasia-specifically, a disconnection between phonological representations in the right temporo-parietal cortex and speech articulation engrams in the left hemisphere. In this case of conduction aphasia, articulatory-based phonemic paraphasia may be viewed as an inability to convert phonemes into the appropriate articulatory maneuvers rather than as phonological representation dysfunction or apraxia of speech., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Temporal encephaloceles are a cause of drug-resistant temporal lobe epilepsy; however, their relationship with epileptogenesis is unclear, and optimal surgical resection is uncertain. EEG source localization (ESL) may guide surgical decision-making., Methods: We reviewed patients at Mayo Clinic Rochester with drug-resistant temporal lobe epilepsy and temporal encephaloceles, who underwent limited resection and had 1-year outcomes. EEG source localization was performed using standard density scalp EEG of ictal and interictal activity. Distance from dipole and standardized low-resolution brain electromagnetic tomography (sLORETA) solutions to the encephalocele were measured. Concordance of ESL with encephalocele and surgical resection was compared with 1-year surgical outcomes., Results: Seventeen patients met criteria. The mean distances from ESL results to encephalocele center for dipole and sLORETA analyses were 23 mm (SD 9) and 22 mm (SD 11), respectively. Ten patients (55.6%) had Engel I outcomes at 1 year. Dipole-encephalocele distance and sLORETA-encephalocele distance were significantly longer in patients with Engel I outcome and patients whose encephalocele was contained by sLORETA had worse outcome as well; however, multiple logistic regression analysis found that only containment of encephalocele by the sLORETA current density was significant ( P < 0.05), odds ratio 0.12 (95% confidence interval [0.021, 0.71])., Conclusions: EEG source localization of scalp EEG localizes near encephaloceles, however, typically not in the encephalocele itself; this may be due to scalp EEG sampling propagated activity or alternatively that the seizure onset zone extends beyond the herniated cortex. Surprisingly, we observed increased ESL to encephalocele distances in patients with excellent surgical outcomes. Larger cohort studies including intracranial EEG data are needed to further explore this finding., Competing Interests: J.J. Van Gompel disclosures: named inventor for intellectual property licensed to Cadence Neuroscience Inc, which is co-owned by Mayo Clinic. Investigator for the Medtronic EPAS trial, SLATE trial, and Mayo Clinic Medtronic NIH Public Private Partnership (UH3-NS95495), also with consulting contract-Stock Ownership and Consulting Contract with Neuro-One Inc. Site Primary Investigator in the Polyganics ENCASE II trial. Site Primary Investigator in the NXDC Gleolan Men301 trial-site Primary Investigator in the Insightec MRgUS EP001 trail. B.H. Brinkmann disclosures: named inventor for intellectual property licensed to Cadence Neuroscience Inc, which is co-owned by Mayo Clinic, and for intellectual property licensed to Seer Medical. Research support from UNNEG Medical A/S. Investigator for the Mayo Clinic Medtronic NIH Public Private Partnership (UH3-NS95495, devices provided at no charge by Medtronic). The other authors have no funding or conflicts of interest to disclose, (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Background: Cognitive impairment is common in major depressive disorder (MDD) and potentially linked to inflammation-induced alterations in brain function. However, the relationship between inflammation, dynamic brain activity, and cognitive impairment in MDD remains unclear., Methods: Fifty-seven first-episode, drug-naïve MDD patients and sixty healthy controls underwent fMRI scanning. Dynamic amplitude of low-frequency fluctuations (dALFF) and dynamic functional connectivity (dFC) were measured using the sliding window method. Plasma IL - 6 levels and cognitive function were assessed using enzyme-linked immunosorbent assay (ELISA) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively., Results: MDD patients exhibited decreased dALFF in the bilateral inferior temporal gyrus (ITG), right inferior frontal gyrus, opercular part (IFGoperc), and bilateral middle occipital gyrus (MOG). Regions of dALFF associated with IL-6 included right ITG (r = -0.400/p = 0.003), left ITG (r = -0.381/p = 0.004), right IFGoperc (r = -0.342/p = 0.011), and right MOG (r = -0.327/p = 0.016). Furthermore, IL-6-related abnormal dALFF (including right ITG: r = 0.309/p = 0.023, left ITG: r = 0.276/p = 0.044) was associated with attention impairment. These associations were absent entirely in MDD patients without suicidal ideation. Additionally, IL-6 levels were correlated with dFC of specific brain regions., Limitations: Small sample size and cross-sectional study design., Conclusions: Inflammation-related dALFF was associated with attention impairment in MDD patients, with variations observed among MDD subgroups. These findings contribute to the understanding of the intricate relationship between inflammation, dynamic brain activity and cognitive impairments in MDD., Competing Interests: Declaration of competing interest All the authors declared that there is no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The anxiolytic effect of oxytocin (OXT) on psychosocial stress has been well documented, but the effectiveness under the interference of other factors still requires in-depth research. Previous studies have shown that nicotine addiction interacts with OXT on psychosocial stress on the behavioral level. However, the underlying neural mechanism of interaction between OXT and nicotine addiction on psychosocial stress has not been examined, and we conducted two experiments to reveal it. Firstly, after intranasal administration of randomized OXT or placebo (saline), a group of healthy participants (n = 27) and a group of smokers (n = 26) completed the Montreal Imaging Stress Task (MIST) in an MRI scanner. Secondly, a group of smokers (n = 22) was recruited to complete a transcranial direct current stimulation (tDCS) experiment, in which anodal tDCS was applied on subjects' anterior right superior temporal gyrus (rSTG). In both experiment, subjective stress ratings, salivary cortisol samples and the amount of daily cigarette consumption were obtained from each participant. Analysis of variance were applied on both behavioral and neural data to examine the effects of OXT and nicotine addiction, and correlation analysis were used to examine relationships between neural and behavioral data. In first fMRI experiment, analysis of variance (ANOVA) revealed an interaction of OXT and nicotine addiction on subjective stress. In smokers, OXT failed to suppress the elevation of subjective stress and craving ratings after psychosocial stress. A voxel-wise ANOVA of fMRI data identified an interaction between OXT and nicotine addiction in anterior rSTG, and its functional connectivity with right middle frontal gyrus. Correlations between this functional connectivity and subjective psychosocial stress were also found abnormal in smokers. In second tDCS experiment, we found that under tDCS, OXT successfully suppressed the elevation of subjective stress and craving ratings after stress. In summary, we found that nicotine addiction blocked OXT's anxiolytic on psychosocial stress, which was related to abnormalities in anterior rSTG. By applying anodal tDCS on anterior rSTG, OXT's anxiolytic effect was restored in smokers. These findings will support further development on oxytocin's intervention of psychosocial stress in nicotine addiction, and provides essential information for indicating OXT's effectiveness., (© 2024. The Author(s).)

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe (TL) seizures induced by penicillin injection in the hippocampus (HPC) of two nonhuman primates. The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then compared the 3-second segments recorded in pre-ictal, onset, offset and post-ictal periods based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This study constitutes the first demonstration of TL seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the onset and offset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests:Robert E. Gross serves as a consultant to Medtronic, which manufactures products related to the research described in this manuscript and receives compensation for these services. He also receives support for unrelated research. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policiesThis does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Connolly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Suicide is the second leading cause of death in youth, and depression is a strong proximal predictor of adolescent suicide. It is important to identify psychological factors that may protect against suicide ideation in depressed adolescents. Self-compassion may be such a factor. Converging evidence indicates the inverse association between self-compassion and suicide ideation, but the neural mechanisms underlying their link remain unknown. Because self-referential caudate activity is associated with both self-compassion and suicide ideation, its functional connectivity might explain their relationship. In this study, we examined the relationship between self-compassion and caudate functional connectivity during self-appraisals, a typical self-referential paradigm, and their associations with suicide ideation in both depressed and healthy youth. In the scanner, 79 depressed youth and 36 healthy controls evaluated, from various perspectives, whether phrases they heard were self-descriptive. Self-compassion and suicide ideation were rated with self-report and interview-based measures. We found that self-compassion was associated with stronger left caudate functional connectivity with bilateral posterior superior temporal sulcus/temporoparietal junction, the left middle temporal gyrus (MTG), and the left middle occipital gyrus during positive versus negative self-appraisals. Stronger left caudate connectivity with the left MTG explained the association between higher self-compassion and lower suicide ideation, even controlling for non-suicide ideation depression severity, anxiety severity, and non-suicidal self-injurious behavior. The findings suggest that the left caudate to MTG connectivity during positive versus negative self-referential processing could be a biomarker to be targeted by neural stimulation interventions for reducing suicide ideation in depressed youth, combined with self-compassion interventions., (© 2024. The Author(s).)

Background: Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network., Methods: Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus., Results: We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with inter-regional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation., Limitation: Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language., Conclusion: As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis., Competing Interests: Competing interests:: Maria Francisca Alonso-Sánchez is a member of the steering committee of the Discourse in Psychosis consortium. Rui He reports support meeting or travel support from the European Research Council and the Department of Science and Technology of Guangdong Province. Lena Palaniyappan reports speaker or consultant fees from Janssen Canada and Otsuka Canada, SPMM Course Limited, and the Canadian Psychiatric Association, book royalties from Oxford University Press, and investigator-initiated educational grants from Janssen Canada, Sunovion, and Otsuka Canada. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Introduction: Neuro-navigated repetitive transcranial magnetic stimulation (rTMS) of the left angular gyrus has been broadly investigated for the treatment of amnestic mild cognitive impairment (aMCI). Although abnormalities in two hippocampal networks, the anterior-temporal (AT) and posterior-medial (PM) networks, are consistent with aMCI and are potential therapeutic targets for rTMS, the underlying mechanisms of the therapeutic effects of rTMS on hippocampal network connections remain unknown. Here, we assessed the impact of left angular gyrus rTMS on activity in these networks and explored whether the treatment response was due to the distance between the clinically applied target (the group average optimal site) and the personalized target in patients with aMCI., Methods: Sixty subjects clinically diagnosed with aMCI participated in this study after 20 sessions of sham-controlled rTMS targeting the left angular gyrus. Resting-state functional magnetic resonance imaging and neuropsychological assessments were performed before and after rTMS. Functional connectivity alterations in the PM and AT networks were assessed using seed-based functional connectivity analysis and two-factor repeated measures analysis of variance (ANOVA). We then computed the correlations between the functional connectivity changes and clinical rating scales. Finally, we examined whether the Euclidean distance between the clinically applied and personalized targets predicted the subsequent treatment response., Results: Compared with the sham group, the active rTMS group showed rTMS-induced deactivation of functional connectivity within the medial temporal lobe-AT network, with a negative correlation with episodic memory score changes. Moreover, the active rTMS lowers the interdependency of changes in the PM and AT networks. Finally, the Euclidean distance between the clinically applied and personalized target distances could predict subsequent network lever responses in the active rTMS group., Conclusions: Neuro-navigated rTMS selectively modulates widespread functional connectivity abnormalities in the PM and AT hippocampal networks in aMCI patients, and the modulation of hippocampal-AT network connectivity can efficiently reverse memory deficits. The results also highlight the necessity of personalized targets for fMRI., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE., Methods: Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation., Results: Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes., Significance: Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Reduced cerebral blood flow (CBF) in the temporoparietal region and gray matter volumes (GMVs) in the temporal lobe were previously reported in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the temporal relationship between reductions in CBF and GMVs requires further investigation. This study sought to determine if reduced CBF is associated with reduced GMVs, or vice versa. Data came from 148 volunteers of the Cardiovascular Health Study Cognition Study (CHS-CS), including 58 normal controls (NC), 50 MCI, and 40 AD who had perfusion and structural MRIs during 2002-2003 (Time 2). Sixty-three of the 148 volunteers had follow-up perfusion and structural MRIs (Time 3). Forty out of the 63 volunteers received prior structural MRIs during 1997-1999 (Time 1). The relationships between GMVs and subsequent CBF changes, and between CBF and subsequent GMV changes were investigated. At Time 2, we observed smaller GMVs (p<0.05) in the temporal pole region in AD compared to NC and MCI. We also found associations between: (1) temporal pole GMVs at Time 2 and subsequent declines in CBF in this region (p=0.0014) and in the temporoparietal region (p=0.0032); (2) hippocampal GMVs at Time 2 and subsequent declines in CBF in the temporoparietal region (p=0.012); and (3) temporal pole CBF at Time 2 and subsequent changes in GMV in this region (p = 0.011). Therefore, hypoperfusion in the temporal pole may be an early event driving its atrophy. Perfusion declines in the temporoparietal and temporal pole follow atrophy in this temporal pole region.

Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates among individuals with schizophrenia (SZ). In our previous work (Wang et al., 2023), we conducted the first feasibility study of using functional near-infrared spectroscopy (fNIRS) with our developed EE stimuli to examine cortical hemodynamics in SZ. To better understand the neural mechanisms underlying EE environmental factors in SZ, we extended our investigation by employing functional connectivity (FC) analysis with a graph theory approach to fNIRS signals. Relative to healthy controls (N=40), individuals with SZ (N=37) exhibited altered connectivity across the medial prefrontal cortex (mPFC), left ventrolateral prefrontal cortex (vlPFC), and left superior temporal gyrus (STG) while exposed to EE environments. Notably, while individuals with SZ were exposed to high-EE environments, (i) reduced connectivity was observed in these brain regions and (ii) the left vlPFC-STG coupling was found to be associated with the negative symptom severity. Taken together, our FC findings suggest individuals with SZ experience a more extensive disruption in neural functioning and coordination, particularly indicating an increased susceptibility to high-EE environments. This further supports the potential utility of integrating fNIRS with the created EE stimuli for assessing EE environmental influences, paving the way for more targeted therapeutic interventions., Competing Interests: Declaration of competing interest Dr. Roger McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs., Methods: In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group). During NFB, participants were instructed to upregulate their STG activity by attending to pre-recorded sentences spoken in their own voice and downregulate it by ignoring unfamiliar voices. Before and after NFB, participants completed a self-reference task where they evaluated if trait adjectives referred to themselves (self condition), Abraham Lincoln (other condition), or whether adjectives had a positive valence (semantic condition). FMRI activation analyses of self-reference task data tested between-group changes after NFB (self>semantic, post>pre-NFB, experimental>control). Analyses were pre-masked within a self-reference network., Results: Activation analyses revealed significantly (p < 0.001) greater activation increase in the experimental, compared to the control group, after NFB within anterior regions of the self-reference network (mPFC, ACC, superior frontal cortex)., Conclusions: STG-NFB was associated with activity increase in the mPFC, ACC, and superior frontal cortex during self-reference. Modulating the STG is associated with activation changes in other, not-directly targeted, regions subserving higher-level cognitive processes associated with self-referential processes and AHs psychopathology in SZ., Clinicaltrials: GOV: Rt-fMRI Neurofeedback and AH in Schizophrenia; https://clinicaltrials.gov/study/NCT03504579., Competing Interests: Declaration of competing interest All authors declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence, or be perceived to influence, their work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Doll play may provide opportunities for children to rehearse social interactions, even when playing alone. Previous research has found that the posterior superior temporal sulcus (pSTS) was more engaged when children played with dolls alone, compared to playing with tablet games alone. Children's use of internal state language (ISL) about others was also associated with pSTS activity. As differences in social cognition are frequently observed in autistic people, we were interested in the brain and language correlates of doll play in children with varying levels of autistic traits. We investigated children's (N = 57, mean age = 6.72, SD = 1.53) use of ISL and their pSTS brain activity using functional near-infrared spectroscopy (fNIRS) as they played with dolls and tablet games, both alone and with a social partner. We also investigated whether there were any effects of autistic traits using the parent-report Autism Spectrum Quotient-Children's Version (AQ-Child). We found that the left pSTS was engaged more as children played with dolls or a tablet with a partner, and when playing with dolls alone, compared to when playing with a tablet alone. Relations between language and neural correlates of social processing were distinct based on the degree of autistic traits. For children with fewer autistic traits, greater pSTS activity was associated with using ISL about others. For children with more autistic traits, greater pSTS activity was associated with experimenter talk during solo play. These divergent pathways highlight the importance of embracing neurodiversity in children's play patterns to best support their development through play., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Tongue coating affects cognition, and cognitive decline at early stage also showed relations to functional and structural remodeling of superior temporal sulcus (STS) in amnestic mild cognitive impairment (aMCI). The potential correlation between disparate cognitive manifestations in aMCI patients with different tongue coatings, and corresponding mechanisms of STS remodeling remains uncharted. In this case-control study, aMCI patients were divided into thin coating (n = 18) and thick coating (n = 21) groups. All participants underwent neuropsychological evaluations and multimodal magnetic resonance imaging. Group comparisons were conducted in clinical assessments and neuroimaging measures of banks of the STS (bankssts). Generalized linear models were constructed to explore relationships between neuroimaging measures and cognition. aMCI patients in the thick coating group exhibited significantly poorer immediate and delayed recall and slower information processing speed (IPS) (P < 0.05), and decreased functional connectivity (FC) of bilateral bankssts with frontoparietal cortices (P < 0.05, AlphaSim corrected) compared to the thin coating group. It was found notable correlations between cognition encompassing recall and IPS, and FC of bilateral bankssts with frontoparietal cortices (P < 0.05, Bonferroni's correction), as well as interaction effects of group × regional homogeneity (ReHo) of right bankssts on the first immediate recall (P < 0.05, Bonferroni's correction). aMCI patients with thick coating exhibited poor cognitive performance, which might be attributed to decreased FC seeding from bankssts. Our findings strengthen the understanding of brain reorganization of STS via which tongue coating status impacts cognition in patients with aMCI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP., Methods: We enrolled 28 drug-naïve FEP and 34 age and sex-matched healthy controls. Clinical symptoms, neurocognition, psychosocial functioning, auditory duration MMN, and T1 structural magnetic resonance imaging data were collected. We measured CT in the superior temporal gyrus (STG), a primary MMN-generating region., Results: We found a significant negative correlation between MMN amplitude and bilateral CT of STG (CT&#95;STG) in FEP (left: r = -.709, P < .001; right: r = -.612, P = .008). Multiple mediation models revealed that a thinner left STG cortex affected functioning through both direct (24.66%) and indirect effects (75.34%). In contrast, the effects of the right CT&#95;STG on functioning were mainly mediated through MMN and neurocognitive pathways., Conclusions: Bilateral CT&#95;STG showed significant association with MMN, and MMN plays a mediating role between CT and cognition. Both MMN alone and its interaction with cognition mediated the effects of structural alterations on psychosocial function. The decline in overall function in FEP may stem from decreased CT&#95;STG, leading to subsequent MMN deficits and neurocognitive dysfunction. These findings underline the crucial role of MMN in elucidating how subtle structural alterations can impact neurocognition and psychosocial function in FEP., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual-Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini-Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia., (© 2024. The Author(s).)

The cerebellum has been involved in social abilities and autism. Given that the cerebellum is connected to the cortex via the cerebello-thalamo-cortical loop, the connectivity between the cerebellum and cortical regions involved in social interactions, that is, the right temporo-parietal junction (rTPJ) has been studied in individuals with autism, who suffer from prototypical deficits in social abilities. However, existing studies with small samples of categorical, case-control comparisons have yielded inconsistent results due to the inherent heterogeneity of autism, suggesting that investigating how clinical dimensions are related to cerebellar-rTPJ functional connectivity might be more relevant. Therefore, our objective was to study the functional connectivity between the cerebellum and rTPJ, focusing on its association with social abilities from a dimensional perspective in a transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) and functional MRI (fMRI) scans obtained during naturalistic films watching from a large transdiagnostic dataset, the Healthy Brain Network (HBN), and examined the association between cerebellum-rTPJ functional connectivity and social abilities measured with the social responsiveness scale (SRS). We conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), and predictive support vector regression (SVR). We included 1404 subjects in the structural analysis (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) and 414 subjects in the functional analysis (age: 11.260 ± 3.318 years, range: 6.020-21.820, 161 females). Our CCA model revealed a significant association between cerebellum-rTPJ functional connectivity, full-scale IQ (FSIQ) and SRS scores. However, this effect was primarily driven by FSIQ as suggested by SVR and univariate seed-to-voxel analysis. We also demonstrated the specificity of the rTPJ and the influence of structural anatomy in this association. Our results suggest that there is a complex relationship between cerebellum-rTPJ connectivity, social performance and IQ. This relationship is specific to the cerebellum-rTPJ connectivity, and is largely related to structural anatomy in these two regions. PRACTITIONER POINTS: We analyzed cerebellum-right temporoparietal junction (rTPJ) connectivity in a pediatric transdiagnostic sample. We found a complex relationship between cerebellum and rTPJ connectivity, social performance and IQ. Cerebellum and rTPJ functional connectivity is related to structural anatomy in these two regions., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: Suicide attempters show increased activation in the right superior temporal gyrus (rSTG). Here, we investigated the rSTG functional connectivity (FC) to identify a functional network involved in suicidality and its associations with psychological suicidality risk and resilience factors., Methods: The resting state functional magnetic resonance imaging data of 151 healthy individuals from the Human Connectome Project Young Adult database were used to explore the FC of the rSTG with itself and with the rest of the brain. The correlation between the rSTG FC and loneliness and purpose in life scores was assessed with the NIH Toolbox. The effect of sex was also investigated., Results: The rSTG had a positive FC with bilateral cortical and subcortical regions, including frontal, temporal, parietal, occipital, limbic, and cerebellar regions, and a negative FC with the medulla oblongata. The FC of the rSTG with itself and with the left central operculum were associated with loneliness scores. The within rSTG FC was also negatively correlated with purpose in life scores, although at a trend level. We did not find any effect of sex on FC and its associations with psychological factors., Limitations: The cross-sectional design, the limited age range, and the lack of measures of suicidality limit the generalizability of our findings., Conclusions: The rSTG functional network is associated with loneliness and purpose in life. Together with the existing literature on suicide, this supports the idea that the neural activity of rSTG may contribute to suicidality by modulating risk and resilience factors associated with suicidality., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lesions in the language-dominant ventral occipitotemporal cortex (vOTC) can result in selective impairment of either reading or naming, resulting in alexia or anomia. Yet, functional imaging studies that show differential activation for naming and reading do not reveal activity exclusively tuned to one of these inputs. To resolve this dissonance in the functional architecture of the vOTC, we used focused stimulation to the vOTC in 49 adult patients during reading and naming, and generated a population-level, probabilistic map to evaluate if reading and naming are clearly dissociable within individuals. Language mapping (50 Hz, 2829 stimulations) was performed during passage reading (216 positive sites) and visual naming (304 positive sites). Within the vOTC, we isolated sites that selectively disrupted reading (24 sites in 11 patients) or naming (27 sites in 12 patients), and those that disrupted both processes (75 sites in 21 patients). The anteromedial vOTC had a higher probability of producing naming disruption, while posterolateral regions resulted in greater reading-specific disruption. Between them lay a multi-modal region where stimulation disrupted both reading and naming. This work provides a comprehensive view of vOTC organization-the existence of a heteromodal cortex critical to both reading and naming, along with a causally dissociable unimodal naming cortex, and a reading-specific visual word form area in the vOTC. Their distinct roles as associative regions may thus relate to their connectivity within the broader language network that is disrupted by stimulation, more than to highly selective tuning properties. Our work also implies that pre-surgical mapping of both reading and naming is essential for patients requiring vOTC resections, as these functions are not co-localized, and such mapping may prevent the occurrence of unexpected deficits., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The necessity of the human hippocampus and surrounding medial temporal lobe structures to semantic memory remains contentious. Impaired semantic memory following hippocampal lesions could arise either due to partially intertwined episodic memories and/or retrograde/anterograde effects. In this study, we tested amnesic individuals with lesions in hippocampus and surrounding medial temporal lobe (n = 7) and age-matched controls (n = 14) on their ability to precisely recall the dates of famous public events that occurred either before (i.e., pre-lifetime) or after participants' birth date (lifetime). We show that deficits in dating precision are greatest for recent lifetime events, consistent with the notion that recent event memory may be particularly intertwined with episodic memory. At the same time, individuals with medial temporal lobe lesions showed more subtle impairments in their ability to date pre-birth and remote lifetime events precisely. Together, these findings suggest that the hippocampus and surrounding medial temporal lobe structures are important for representational precision of semantic memories regardless of their remoteness., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: We investigated how well a visual associative learning task discriminates Alzheimer's disease (AD) dementia from other types of dementia and how it relates to AD pathology., Methods: 3,599 patients (63.9 ± 8.9 years old, 41% female) from the Amsterdam Dementia Cohort completed two sets of the Visual Association Test (VAT) in a single test session and underwent magnetic resonance imaging. We performed receiver operating curve analysis to investigate the VAT's discriminatory ability between AD dementia and other diagnoses and compared it to that of other episodic memory tests. We tested associations between VAT performance and medial temporal lobe atrophy (MTA), and amyloid status ( n = 2,769, 77%)., Results: Patients with AD dementia performed worse on the VAT than all other patients. The VAT discriminated well between AD and other types of dementia (area under the curve range 0.70-0.86), better than other episodic memory tests. Six-hundred forty patients (17.8%) learned all associations on VAT-A, but not on VAT-B, and they were more likely to have higher MTA scores (odds ratios range 1.63 (MTA 0.5) through 5.13 for MTA ≥ 3, all p < .001) and to be amyloid positive (odds ratio = 3.38, 95%CI = [2.71, 4.22], p < .001) than patients who learned all associations on both sets., Conclusions: Performance on the VAT, especially on a second set administered immediately after the first, discriminates AD from other types of dementia and is associated with MTA and amyloid positivity. The VAT might be a useful, simple tool to assess early episodic memory deficits in the presence of AD pathology.

Introduction: Hypokinetic dysarthria (HD) is a common motor speech symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated short-term effects of transcranial direct current stimulation (tDCS) on HD in PD using acoustic analysis of speech. Based on our previous studies we focused on stimulation of the right superior temporal gyrus (STG) - an auditory feedback area., Methods: In 14 PD patients with HD, we applied anodal, cathodal and sham tDCS to the right STG using a cross-over design. A protocol consisting of speech tasks was performed prior to and immediately after each stimulation session. Linear mixed models were used for the evaluation of the effects of each stimulation condition on the relative change of acoustic parameters. We also performed a simulation of the mean electric field induced by tDCS., Results: Linear mixed model showed a statistically significant effect of the stimulation condition on the relative change of median duration of silences longer than 50 ms (p = 0.015). The relative change after the anodal stimulation (mean = -5.9) was significantly lower as compared to the relative change after the sham stimulation (mean = 12.8), p = 0.014. We also found a correlation between the mean electric field magnitude in the right STG and improvement of articulation precision after anodal tDCS (R = 0.637; p = 0.019)., Conclusions: The exploratory study showed that anodal tDCS applied over the auditory feedback area may lead to shorter pauses in a speech of PD patients., (© 2024. The Author(s).)

Objective: The aim of this study was to explore the relation of language functional MRI (fMRI)-guided tractography with postsurgical naming decline in people with temporal lobe epilepsy (TLE)., Methods: Twenty patients with unilateral TLE (9 left) were studied with auditory and picture naming functional MRI tasks. Activation maxima in the left posterobasal temporal lobe were used as seed regions for whole-brain fibre tractography. Clinical naming performance was assessed preoperatively, 4 months, and 12 months following temporal lobe resection. Volumes of white matter language tracts in both hemispheres as well as tract volume laterality indices were explored as moderators of postoperative naming decline using Pearson correlations and multiple linear regression with other clinical variables., Results: Larger volumes of white matter language tracts derived from auditory and picture naming maxima in the hemisphere of subsequent surgery as well as stronger lateralization of picture naming tract volumes to the side of surgery correlated with greater language decline, which was independent of fMRI lateralization status. Multiple regression for picture naming tract volumes was associated with a significant decline of naming function with 100% sensitivity and 93% specificity at both short-term and long-term follow-up., Interpretation: Naming fMRI-guided white matter language tract volumes relate to postoperative naming decline after temporal lobe resection in people with TLE. This can assist stratification of surgical outcome and minimize risk of postoperative language deficits in TLE., (© 2024. The Author(s).)