Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

Evaluation of Error Production in Animal Fluency and Its Relationship to Frontal Tracts in Normal Aging and Mild Alzheimer’s Disease: A Combined LDA and Time-Course Analysis Investigation

Semantic verbal fluency (VF), assessed by animal category, is a task widely used for early detection of dementia. A feature not regularly assessed is the occurrence of errors such as perseverations and intrusions. So far, no investigation has analyzed the how and when of error occurrence during semantic VF in aging populations, together with their possible neural correlates. The present study aims to address the issue using a combined methodology based on latent Dirichlet allocation (LDA) analysis for word classification together with a time-course analysis identifying exact time of errors’ occurrence. LDA is a modeling technique that discloses hidden semantic structures based on a given corpus of documents. We evaluated a sample of 66 participants divided into a healthy young group (n = 24), healthy older adult group (n = 23), and group of patients with mild Alzheimer’s disease (AD) (n = 19). We performed DTI analyses to evaluate the white matter integrity of three frontal tracts purportedly underlying error commission: anterior thalamic radiation, frontal aslant tract, and uncinate fasciculus. Contrasts of DTI metrics were performed on the older groups who were further classified into high-error rate and low-error rate subgroups. Results demonstrated a unique deployment of error commission in the patient group characterized by high incidence of intrusions in the first 15 s and higher rate of perseverations toward the end of the trial. Healthy groups predominantly showed very low incidence of perseverations. The DTI analyses revealed that the patients with AD committing high-error rate presented significantly more degenerated frontal tracts in the left hemisphere. Thus, our findings demonstrated that the appearance of intrusions, together with left hemisphere degeneration of frontal tracts, is a pathognomic trait of mild AD. Furthermore, our data suggest that the error commission of patients with AD arises from executive and working memory impairments related partly to deteriorated left frontal tracts.

Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research

Objective To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels. Methods The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction. Results In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012–0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132–0.926]). Conclusions Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Clustering and switching in verbal fluency: a comparison between control and individuals with brain damage

ABSTRACT Purpose The aim of this study is to analyze and compare the performance and strategies used by control subjects and patients with unilateral brain damage on phonemic and semantic Verbal Fluency tasks. Methods The sample consisted of 104 participants divided into four groups (26 with left hemisphere damage and aphasia- LHDa, 28 with left hemisphere damage and no aphasia- LHDna, 25 with right hemisphere damage- RHD and 25 neurologically healthy control subjects). All participants were administered the phonemic (“M” letter-based) and semantic (animals) verbal fluency tasks from the Montreal-Toulouse Language Assessment Battery (MTL-BR). Results Patients in the LHDa group showed the worst performance (fewer words produced, fewer clusters and switches) in both types of fluency task. RHD group showed fewer switching productions when compared with controls and LHDna had fewer words productions than controls in the first 30 seconds block. Conclusion Our findings suggest that the LHDa group obtained lower scores in most measures of SVF and PVF when compared to the other groups.

Assessing lexical-semantic naming deficits using an automated machine learning approach

After left hemisphere stroke, 20-50% of people experience language deficits, including difficulties in naming. Naming errors that are semantically related to the intended target (e.g., producing “violin” for picture HARP) indicate a potential impairment in accessing knowledge of word forms and their meanings. Understanding the cause of naming impairments is crucial to better modeling of language production as well as for tailoring individualized rehabilitation. However, evaluation of naming errors is typically by subjective and laborious dichotomous classification. As a result, these evaluations do not capture the degree of semantic similarity and are susceptible to lower inter-rater reliability because of subjectivity. We investigated whether a computational linguistic measure, word2vec (Mikolov, Chen, Corrado, & Dean, 2013) addressed these limitations by evaluating errors during object naming in a group of patients during the acute stage of a left-hemisphere stroke (N=105). Pearson correlations demonstrated excellent convergent validity of word2vec’s semantically related estimates of naming errors and independent tests of access to lexical-semantic knowledge (p’s < .0001). Further, multiple regression analysis showed word2vec’s semantically related estimates were significantly better than human error classification at predicting performance on tests of lexical-semantic knowledge (p < .001). Useful to both theorists and clinicians, word2vec provides an automated, continuous, and objective psychometric measure of access to lexical-semantic knowledge during naming.

Segmental Abnormalities of White Matter Microstructure in End-Stage Renal Disease Patients: An Automated Fiber Quantification Tractography Study

Background and Purpose: End-stage renal disease (ESRD) results in extensive white matter abnormalities, but the specific damage segment cannot be identified. This study aimed to determine the segmental abnormalities of white matter microstructure in ESRD and its relationship with cognitive and renal function indicators.Methods: Eighteen ESRD patients and 19 healthy controls (HCs) were prospectively recruited. All participants underwent DTI and clinical assessments. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along 16 main white matter tracts. We compared the DTI parameters between groups. Besides, we used partial correlation and multiple linear regression analyses to explore the associations between white matter integrity and cognitive performance as well as renal function indicators.Results: In the global tract level, compared to HCs, ESRD patients had greater MD, AD, and RD values and lower FA value in several fibers (P < 0.05, FDR correction). In the point-wise level, extensive damage existed in specific locations of different fiber tracts, particularly in the left hemisphere (P < 0.05, FDR correction). Among these tracts, the mean AD values of the left cingulum cingulate correlated negatively with MoCA score. Urea and UA level were independent predictors of the AD value of superior component of the left corticospinal. Besides, urea level was the independent predictors of mean MD value of left anterior thalamic radiation (ATR).Conclusion: White matter fiber tract damage in ESRD patients may be characterized by abnormalities in its specific location, especially in the left hemisphere. Aberrational specific located fibers were related to cognitive impairment and renal dysfunction.

Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left- hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. Poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. These results demonstrate that while left- lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

Aufhocker : Quand l’identité Alien d’un de nos corps-fantômes se porte sur le dos

"Within the framework of the most recent advances in the BRAINCUBUS model of neurocognitive anthropology, we will analyze the transcultural narrative motif of the Aufhocker (F472. Huckauf. A goblin which jumps on one’s back). From the Alps to the Himalayas, we will track down experiential encounters with numerous supernatural beings who jump on the backs of humans and are carried away with all their crushing heaviness. We recognize these supernatural beings as neurally real phantom-body connectomes, generated by the activation of the Temporo-Parietal Junction in the left hemisphere of the human brain."

Overlapping but Language-Specific Mechanisms in Morphosyntactic Processing in Highly Competent L2 Acquired at School Entry: fMRI Evidence From an Alternating Language Switching Task

Many bilingual individuals acquire their second language when entering primary school; however, very few studies have investigated morphosyntax processing in this population. Combining a whole-brain and region of interest (ROI)-based approach, we studied event-related fMRI during morphosyntactic processing, specifically person-number phi-features, in Turkish (L1) and Persian (L2) by highly proficient bilinguals who learned Persian at school entry. In a design with alternating language switching and pseudorandomized grammaticality conditions, two left-lateralized syntax-specific ROIs and 11 bilateral ROIs involved in executive functions (EF) were analyzed for the intensity of activation relative to a resting baseline. Our findings indicate a strong overlap of neural networks for L1 and L2, suggesting structural similarities of neuroanatomical organization. In all ROIs morphosyntactic processing invoked stronger activation in L1 than in L2. This may be a consequence of symmetrical switch costs in the alternating design used here, where the need for suppressing the non-required language is stronger for the dominant L1 when it is non-required as compared to the non-dominant L2, leading to a stronger rebound for L1 than L2 when the language is required. Both L1 and L2 revealed significant activation in syntax-specific areas in left hemisphere clusters and increased activation in EF-specific areas in right-hemisphere than left-hemisphere clusters, confirming syntax-specific functions of the left hemisphere, whereas the right hemisphere appears to subserve control functions required for switching languages. While previous reports indicate a leftward bias in planum temporale activation during auditory and linguistic processing, the present study shows the activation of the right planum temporale indicating its involvement in auditory attention. More pronounced grammaticality effect in left pars opercularis for L1 and in left pSTG for L2 indicate differences in the processing of morphosyntactic information in these brain regions. Nevertheless, the activation of pars opercularis and pSTG emphasize the centrality of these regions in the processing of person-number phi-features. Taken together, the present results confirm that morphosyntactic processing in bilinguals relates to composite, syntax-sensitive and EF-sensitive mechanisms in which some nodes of the language network are differentially involved.

Abnormal Cortical Activation Patterns Among Chinese-Speaking Schizophrenia Patients During Category and Letter Verbal Fluency Tasks Revealed by Multi-Channel Functional Near-Infrared Spectroscopy

Background: Functional near-infrared spectroscopy (fNIRS) has many advantages over other neuroimaging modalities for routine measurement of task-dependent cortical activation, but most fNIRS studies of schizophrenia have used letter fluency tasks (LFTs). Further, performances on category fluency tasks (CFTs) and LFTs may be distinct in Chinese patients due to the unique semantic features of Chinese written characters. To identify unique disease biomarkers measurable by fNIRS in Chinese schizophrenia patients, this study compared cortical oxygenated hemoglobin changes ([oxy-Hb]) during a Chinese LFT and CFT between patients and healthy controls.Methods: Inpatients of the Second Affiliated Hospital of Xinxiang Medical University were recruited from Match 2020 to July 2021. The Positive and Negative Symptom Scale (PANSS) was used to evaluate psychiatric symptoms. Dynamic changes in [oxy-Hb], an indicator of neural activity, were measured during CFT and LFT performance by 52-channel fNIRS.Results: Forty-seven schizophrenia inpatients and 29 healthy controls completed all tests. Schizophrenia patients showed significant cortical activation at 15 channels covering the left hemisphere and 17 channels over the right hemisphere during the CFT. During the LFT, activity was significantly increased at only six channels, all over the left hemisphere (FDR P < 0.05). In healthy controls, significant [oxy-Hb] increases were found at 24 channels over the left hemisphere and 19 channels over the right hemisphere during CFT. While during the LFT, the significant increases were found at 7 channels all over the left hemisphere (FDR P < 0.05). When years of education was included as a covariate, the schizophrenia group demonstrated no significant hypoactivation relative to healthy controls at any channel after FDR correction (FDR P < 0.05) during CFT while demonstrated significant hypoactivation at channel 11 during LFT (FDR P < 0.05). There were no significant associations between PANSS scores and [oxy-Hb] changes after FDR correction (FDR P < 0.05).Conclusions: Left lateralization during CFT was reduced among schizophrenia patients and may be related to the semantic deficit. The Chinese-CFT could be a more sensitive indicator of frontal-temporal dysfunction in schizophrenia.