Cerebral Functional Organization Research Articles

Brain state identification and neuromodulation to promote recovery of consciousness.

Experimental and clinical studies of consciousness identify brain states (i.e. quasi-stable functional cerebral organization) in a non-systematic manner and largely independent of the research into brain state modulation. In this narrative review, we synthesize advances in the identification of brain states associated with consciousness in animal models and physiological (sleep), pharmacological (anaesthesia) and pathological (disorders of consciousness) states of altered consciousness in humans. We show that in reduced consciousness the frequencies in which the brain operates are slowed down and that the pattern of functional communication is sparser, less efficient, and less complex. The results also highlight damaged resting-state networks, in particular the default mode network, decreased connectivity in long-range connections and especially in the thalamocortical loops. Next, we show that therapeutic approaches to treat disorders of consciousness, through pharmacology (e.g. amantadine, zolpidem), and (non-) invasive brain stimulation (e.g. transcranial direct current stimulation, deep brain stimulation) have shown partial effectiveness in promoting consciousness recovery. Although some features of conscious brain states may improve in response to neuromodulation, targeting often remains non-specific and does not always lead to (behavioural) improvements. The fields of brain state identification and neuromodulation of brain states in relation to consciousness are showing fascinating developments that, when integrated, might propel the development of new and better-targeted techniques for disorders of consciousness. We here propose a therapeutic framework for the identification and modulation of brain states to facilitate the interaction between the two fields. We propose that brain states should be identified in a predictive setting, followed by theoretical and empirical testing (i.e. in animal models, under anaesthesia and in patients with a disorder of consciousness) of neuromodulation techniques to promote consciousness in line with such predictions. This framework further helps to identify where challenges and opportunities lay for the maturation of brain state research in the context of states of consciousness. It will become apparent that one angle of opportunity is provided through the addition of computational modelling. Finally, it aids in recognizing possibilities and obstacles for the clinical translation of these diagnostic techniques and neuromodulation treatment options across both the multimodal and multi-species approaches outlined throughout the review.

S-06-4: IMPACT OF ANTI-HYPERTENSIVE THERAPY ON CEREBRAL FUNCTIONAL NETWORKS AND CONNECTIVITY

It is well known that hypertension is the main modifiable risk factor leading to cognitive impairment and various forms of dementia. Leveraging functional MRI it has been possible to characterize hypertensives brain functional connectivity, a main feature of cerebral activation and health measurable by resting-state functional MRI. This characterization let us analyze how pathological conditions influence the cognitive processes and the spontaneous organization of brain activity, and have shown that hypertensive patients even before showing signs of vascular dementia have alterations in cerebral connections compared to normotensive patients. Our current question is whether different classes of antihypertensives, differentiated in mechanism of action and potential to cross the blood brain barrier may have different impact on cerebral functional organization. 42 hypertensives with controlled hypertension (SBP< 140mmHg e DBP< 90mmHg) were subjected to resting-state functional MRI. Functional connectivity was elaborated by CONN, according to an analysis pipeline to build functional connectivity networks matrices calculating the cross-correlation of BOLD signal among different brain regions. The obtained network of connections has been analyzed by general linear model, to implement regression models that highlight the connections in the brains modulated by the specific classes of antihypertensives analyzed. The application of regression models with age, sex, BMI, alcohol, smoke, SBP and DBP levels, heart rate as covariates shown that treatment with diuretics modulate a large connectivity network among Salience Network, Default Mode Network and Language Network (Fig. A). Ace-inhibitors treatment is associated with a significant modulation of a connection between Default Mode Network and the FrontoParietal Network (Fig. B), while ARBs are associated to the modulation of connections between Cerebellar and Language Networks (Fig. C). Finally, beta-blockers are associated with connections centered in Dorsal Attention Network and projected to Language and FrontoParietal Networks (Fig. D). Globally, the most relevant functional modulation of the brain is imposed by the use of diuretics, with a possible explanation in the fact that lowering global volume of circulating blood may have a significant impact on cerebral circulation. By this analysis, we will be able to take into account the central and cognitive impact of different antihypertensive drugs on the choice of best personalized treatment of hypertension.

Lateralization of word and face processing in developmental dyslexia and developmental prosopagnosia

In right-handed adults, face processing is lateralized to the right hemisphere and visual word processing to the left hemisphere. According to the many-to-many account (MTMA) of functional cerebral organization this lateralization pattern is partly dependent on the acquisition of literacy. Hence, the MTMA predicts that: (i) processing of both words and faces should show no or at least less lateralization in individuals with developmental dyslexia compared with controls, and (ii) lateralization in word processing should be normal in individuals with developmental prosopagnosia whereas lateralization in face processing should be absent. To test these hypotheses, 21 right-handed adults with developmental dyslexia and 21 right-handed adults with developmental prosopagnosia performed a divided visual field paradigm with delayed matching of faces, words and cars. Contrary to the predictions, we find that lateralization effects in face processing are within the normal range for both developmental dyslexics and prosopagnosics. Moreover, the group with developmental dyslexia showed right hemisphere lateralization for word processing. We argue that these findings are incompatible with the specific predictions of the MTMA.

Comparison of Interests and Special Abilities of Left- and Right-handers

Cerebral lateralization is associated with differences in brain organization and handedness is seen as its main marker. In order to verify the hypothesis that differences in brain organization tend to be associated with different patterns of interests and abilities, 379 normal left-handed subjects (221 women, aged 18 – 72 years) and 366 normal right-handed subjects (256 women, aged 18 – 72 years) were interviewed about their interests and special abilities. The following interests and special abilities were studied: singing, playing an instrument, dancing, painting, acting, foreign language skills, sports skills, and writing poetry.The results in the left-handers group showed that there is a significantly higher percentage of subjects with a pronounced interest in playing an instrument. In the group of right-handers, the study demonstrated a significantly higher percentage of subjects specifically interested in learning foreign languages. With respect to the abilities, a significantly higher incidence of participants with vocal, instrumental, sports, and foreign language skills was found in the left-handers’ group. Differences in functional cerebral organization between left- and right-handers were suggested as possible explanation for the relationship of handedness with special abilities.

Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity

Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

Longitudinal Changes in the Cerebral Cortex Functional Organization of Healthy Elderly.

Healthy aging is accompanied by disruptions in the functional modular organization of the human brain. Cross-sectional studies have shown age-related reductions in the functional segregation and distinctiveness of brain networks. However, less is known about the longitudinal changes in brain functional modular organization and their associations with aging-related cognitive decline. We examined age- and aging-related changes in functional architecture of the cerebral cortex using a dataset comprising a cross-sectional healthy young cohort of 57 individuals (mean ± SD age, 23.71 ± 3.61 years, 22 males) and a longitudinal healthy elderly cohort of 72 individuals (mean ± baseline age, 68.22 ± 5.80 years, 39 males) with 2-3 time points (18-24 months apart) of task-free fMRI data. We found both cross-sectional (elderly vs young) and longitudinal (in elderly) global decreases in network segregation (decreased local efficiency), integration (decreased global efficiency), and module distinctiveness (increased participation coefficient and decreased system segregation). At the modular level, whereas cross-sectional analyses revealed higher participation coefficient across all modules in the elderly compared with young participants, longitudinal analyses revealed focal longitudinal participation coefficient increases in three higher-order cognitive modules: control network, default mode network, and salience/ventral attention network. Cross-sectionally, elderly participants also showed worse attention performance with lower local efficiency and higher mean participation coefficient, and worse global cognitive performance with higher participation coefficient in the dorsal attention/control network. These findings suggest that healthy aging is associated with whole-brain connectome-wide changes in the functional modular organization of the brain, accompanied by loss of functional segregation, particularly in higher-order cognitive networks.SIGNIFICANCE STATEMENT Cross-sectional studies have demonstrated age-related reductions in the functional segregation and distinctiveness of brain networks. However, longitudinal aging-related changes in brain functional modular architecture and their links to cognitive decline remain relatively understudied. Using graph theoretical and community detection approaches to study task-free functional network changes in a cross-sectional young and longitudinal healthy elderly cohort, we showed that aging was associated with global declines in network segregation, integration, and module distinctiveness, and specific declines in distinctiveness of higher-order cognitive networks. Further, such functional network deterioration was associated with poorer cognitive performance cross-sectionally. Our findings suggest that healthy aging is associated with system-level changes in brain functional modular organization, accompanied by functional segregation loss particularly in higher-order networks specialized for cognition.

Hemispheric lateralization of resting-state functional connectivity of the ventral striatum: an exploratory study

Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The ventral striatum (VS) is critical to motivated behavior, with extant studies suggesting functional hemispheric asymmetry. The current work investigated differences in rsFC between the left (L) and right (R) VS and explored gender differences in the extent of functional lateralization. In 106 adults, we computed a laterality index (fcLI) to query whether a target region shows greater or less connectivity to the L vs R VS. A total of 45 target regions with hemispheric masks were examined from the Automated Anatomic Labeling atlas. One-sample t test was performed to explore significant laterality in the whole sample and in men and women separately. Two-sample t test was performed to examine gender differences in fcLI. At a corrected threshold (p < 0.05/45 = 0.0011), the dorsomedial prefrontal cortex (dmPFC) and posterior cingulate cortex (pCC) showed L lateralization and the intraparietal sulcus (IPS) and supramarginal gyrus (SMG) showed R lateralization in VS connectivity. Except for the pCC, these findings were replicated in a different data set (n = 97) from the Human Connectome Project. Furthermore, the fcLI of VS-pCC was negatively correlated with a novelty seeking trait in women but not in men. Together, the findings may suggest a more important role of the L VS in linking saliency response to self control and other internally directed processes. Right lateralization of VS connectivity to the SMG and IPS may support attention and action directed to external behavioral contingencies.

Inferring Individual-Level Variations in the Functional Parcellation of the Cerebral Cortex.

Functional parcellation of the cerebral cortex is variable across different subjects or between cognitive states. Ignoring individual-or state-dependent variations in the functional parcellation may lead to inaccurate representations of individual functional connectivity, limiting the precision of interpretations of differences in individual connectivity profiles. However, it is difficult to infer the individual-level variations due to the relatively low robustness of methods for parcellation of individual subjects. We propose a method called "joint K-means" to robustly parcellate the cerebral cortex using functional magnetic resonance imaging (fMRI) data for contrasts between two states or subjects that intended to characterize variance in individual functional parcellations. The key idea of the proposed method is to jointly infer parcellations in contrasted datasets by iterative descent, while constraining the similarity of the two pathways in searches for local minima to reduce spurious variations. Parcellations of resting-state fMRI datasets from the Human Connectome Project show that the similarity of parcellations for an individual subject studied on two sessions is greater than that between different subjects. Differences in parcellations between subjects are nonuniformly distributed across the cerebral cortex, with clusters of higher variance in the prefrontal, lateral temporal, and occipito-parietal cortices. This pattern is reproducible across sessions, between groups, and using different numbers of parcels. The individual-level variations inferred by the proposed method are plausible and consistent with the previously reported functional connectivity variability. The proposed method is a promising tool for investigating relationships between the cerebral functional organization and behavioral differences.

Hemispheric Lateralization of Resting-State Functional Connectivity of the Anterior Insula: Association with Age, Gender, and a Novelty-Seeking Trait.

Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The imaging literature has described lateralization of insula activations during cognitive and affective processing. Evidence appears to support a role of the right-hemispheric insula in attentional orientation to salient stimulus, interoception, and physiological arousal, and a role of the left-hemispheric insula in cognitive and affective control, as well as perspective taking. In this study, in a large data set of healthy adults, we examined lateralization of the rsFC of the anterior insula (AI) by computing a laterality index (LI) of connectivity with 54 regions from the Automated Anatomic Labeling atlas. At a corrected threshold (p < 0.001), the AI is left lateralized in connectivity with the dorsomedial prefrontal cortex, superior frontal gyrus, inferior frontal cortex, and posterior orbital gyrus and right lateralized in connectivity with the postcentral gyrus, supramarginal gyrus, and superior parietal lobule. In gender differences, women, but not men, showed right-lateralized connectivity to the thalamus. Furthermore, in a subgroup of participants assessed by the tridimensional personality questionnaire, novelty seeking is correlated with the extent of left lateralization of AI connectivity to the pallidum and putamen in men and with the extent of right lateralization of AI connectivity to the parahippocampal gyrus in women. These findings support hemispheric functional differentiation of the AI.

Aberrant interhemispheric functional and structural connectivity in heroin-dependent individuals.

Models of heroin addiction emphasize the role of disrupted frontostriatal circuitry supporting cognitive control processes. However, heroin addiction-related alterations in functional and structural interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. The corpus callosum (CC), which connects homologous regions of the cortex, is the major conduit for information transfer between the cerebral hemispheres and represents a structural connectivity index between hemispheres. We compared interhemispheric voxel-mirrored homotopic connectivity (VMHC) and CC volume between 45 heroin dependent-individuals (HDIs) and 35 non-addict individuals. We observed significant reduction of VMHC in a number of regions, particularly the striatum/limbic system regions, and significant decrease in splenium and genu sub-regions of CC in HDI. Importantly, within HDI, VMHC in the dorsal lateral prefrontal cortex (DLPFC) correlated with genu CC volume, VMHC in the putamen, VMHC in the DLPFC and genu CC volume and splenium CC volume were negatively correlated with heroin duration and impulsivity traits. Further analyses demonstrated that impairment of VMHC of bilateral DLPFC partially mediated the association between genu CC volumes decreased and increased impulsivity in HDI. Our results reveal a substantial impairment of interhemispheric coordination in the HDI. Further, interhemispheric connectivity correlated with the duration of heroin abuse and higher impulsivity behavior in HDI. Our findings provide insight into a heroin addicts' related pathophysiology and reinforce an integrative view of the interhemispheric cerebral functional and structural organization.

Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology.

Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic etiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential to cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs.

Brain Reactivity Differentiates Subjects with High and Low Dream Recall Frequencies during Both Sleep and Wakefulness

The neurophysiological correlates of dreaming remain unclear. According to the "arousal-retrieval" model, dream encoding depends on intrasleep wakefulness. Consistent with this model, subjects with high and low dream recall frequency (DRF) report differences in intrasleep awakenings. This suggests a possible neurophysiological trait difference between the 2 groups. To test this hypothesis, we compared the brain reactivity (evoked potentials) of subjects with high (HR, N = 18) and low (LR, N = 18) DRF during wakefulness and sleep. During data acquisition, the subjects were presented with sounds to be ignored (first names randomly presented among pure tones) while they were watching a silent movie or sleeping. Brain responses to first names dramatically differed between the 2 groups during both sleep and wakefulness. During wakefulness, the attention-orienting brain response (P3a) and a late parietal response were larger in HR than in LR. During sleep, we also observed between-group differences at the latency of the P3a during N2 and at later latencies during all sleep stages. Our results demonstrate differences in the brain reactivity of HR and LR during both sleep and wakefulness. These results suggest that the ability to recall dreaming is associated with a particular cerebral functional organization, regardless of the state of vigilance.

A “concrete view” of aging: Event related potentials reveal age-related changes in basic integrative processes in language

Normal aging is accompanied by changes in both structural and functional cerebral organization. Although verbal knowledge seems to be relatively stable across the lifespan, there are age-related changes in the rapid use of that knowledge during on-line language processing. In particular, aging has been linked to reduce effectiveness in preparing for upcoming words and building an integrated sentence-level representation. The current study assessed whether such age-related changes extend even to much simpler language units, such as modification relations between a centrally presented adjective and a lateralized noun. Adjectives were used to elicit concrete and abstract meanings of the same, polysemous lexical items (e.g., “green book” vs. “interesting book”). Consistent with findings that lexical information is preserved with age, older adults, like younger adults, exhibited concreteness effects at the adjectives, with more negative responses to concrete adjectives over posterior (300–500 ms; N400) and frontal (300–900 ms) channels. However, at the noun, younger adults exhibited concreteness-based predictability effects linked to left hemisphere processing and imagery effects linked to right hemisphere processing, contingent on whether the adjectives and nouns formed a cohesive conceptual unit. In contrast, older adults showed neither effect, suggesting that they were less able to rapidly link the adjective–noun meaning to form an integrated conceptual representation. Age-related changes in language processing may thus be more pervasive than previously realized.

TMS over the left angular gyrus impairs the ability to discriminate left from right

The underlying cognitive and neural mechanisms of the ability to discriminate left from right are hardly explored. Clinical studies from patients with impairments of left–right discrimination (LRD) and neuroimaging data suggest that the left angular gyrus is particularly involved in LRD. Moreover, it is argued that the often reported sex difference in LRD, with women being more susceptible to left–right errors than men, is the result of a stronger lateralization in men than women. Offline repetitive transcranial magnetic stimulation (rTMS) was used to test whether the left angular gyrus is involved in LRD and whether men have a stronger lateralization in LRD than women. Twenty-four participants (12 men, 12 women) completed a behavioral LRD task in three different conditions: after rTMS of the left and right angular gyrus and after ‘sham’ rTMS (control). The results revealed that after rTMS of the left angular gyrus, LRD accuracy rates were significantly reduced compared to the control condition. After rTMS of the right angular gyrus no difference to the control condition was observed. In addition, there was no overall sex difference in the LRD task and men and women were similarly affected by stimulation over the left and right angular gyrus, suggesting that the functional cerebral organization of LRD does not differ in men and women with similar LRD skills. Taken together, the findings suggest that the left angular gyrus is critically involved in LRD. It is argued that the left angular gyrus integrates spatial information with the meaning of the words ‘left’ and ‘right’, thereby assigning the labels ‘left’ and ‘right’ to a certain state or direction, etc.

Neuropsychologie bei Epilepsie

In order to understand cognitive impairment associated with epilepsy, it is essential to appreciate that independent static and dynamic factors affect brain function in this disease. Whereas morphological lesions or structural changes are associated with more or less irreversible deficits, epileptic activity, seizures, and the treatment of epilepsy can cause dynamic and principally reversible impairment. The relative contribution of these factors differs depending on the type of epilepsy, the age at lesion/epilepsy onset, the localization and lateralization of epilepsy and individual demographic patient characteristics. Altered brain structure and function can result in epilepsy, but epilepsy can also alter the functional cerebral organization of the brain. Thus epilepsy-related cognitive impairment must be integrated within a developmental neuropsychological framework. The aetiology of epilepsy is strongly related to the age of onset. From a neuropsychological point of view, it makes a big difference for cognitive outcome as to whether epilepsy hits the maturing versus mature or aging brain. Dependent on this, epilepsy can result in retardation, loss of acquired functions, or accelerated mental decline. It will be demonstrated that cognitive impairments in epilepsy mostly exist from the beginning of epilepsy, that early onset lesions/epilepsy interfere with mental development, and that a progressive aetiology, severe seizures, and lesions secondary to epilepsy may accelerate mental decline. It will furthermore be discussed that uncontrolled epilepsy and epileptic activity may reversibly and irreversibly contribute to cognitive impairment. The same is demonstrated with regard to the pharmacological treatment of epilepsy. Finally, the cognitive risks and benefits of epilepsy surgery and the advantages of selective surgery will be addressed. The consequences for the neuropsychological assessment are discussed in part two of this review.

Age of seizure onset, functional reorganization, and neuropsychological outcome in temporal lobectomy

Patients with early onset seizure disorder tend to have less cognitive decline following surgical resection than patients with late onset seizure disorder. Differential opportunity for presurgical cerebral functional reorganization has been proposed to account for this “age of onset” effect. However, the relationships between age of seizure onset, functional organization, and neuropsychological outcome remain incompletely understood. To shed additional light on these issues, we investigated 66 patients with anterior temporal lobectomies (37 left; 29 right), all of whom completed comprehensive neuropsychological assessment prior to and following surgical resection. The sample was divided into two groups: 34 patients with early onset (EO) epilepsy and 32 patients with late onset (LO) epilepsy. We found the typical age of onset effect: post-surgically, EO patients demonstrated relatively better outcome in multiple neuropsychological domains, especially verbal memory, compared to LO patients. Based on presurgical Wada testing, 23 patients were classified as having traditional cerebral functional organization (TFO) and 35 were classified as having nontraditional cerebral functional organization (NTFO). The NTFO group had an earlier age of seizure onset than the TFO group, and NTFO was more frequent in EO patients (70%) than LO patients (50%). NTFO patients demonstrated relatively better post-surgical outcome in several neuropsychological domains, compared to TFO patients. Our findings are consistent with the notion that functional reorganization may be an explanatory factor for the better neuropsychological outcome of EO epilepsy patients following anterior temporal lobectomy.

Diffusion tensor imaging of brain development

Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral organization and maturation. Diffusion tensor imaging (DTI), a recent magnetic resonance (MR) modality which assesses water diffusion in biological tissues at a microstructural level, has revealed a powerful technique to explore the structural basis of normal brain development. In fact, the tissue organization can be probed non-invasively, and the age-related changes of diffusion parameters (mean diffusivity, anisotropy) reveal crucial maturational processes, such as white matter myelination. Nevertheless, the developing human brain presents several challenges for DTI applications compared with the adult brain. DTI may further be used to detect brain injury well before conventional MRI, as water diffusion changes are an early indicator of cellular injury. This is particularly critical in infants in the context of administration of neuroprotective therapies. Changes in diffusion characteristics further provide early evidence of both focal and diffuse white matter injury in association with periventricular leukomalacia in the preterm infant. Finally, with the development of 3D fiber tractography, the maturation of white matter connectivity can be followed throughout infant development into adulthood with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.

Shift-back of right into left hemisphere language dominance after control of epileptic seizures: Evidence for epilepsy driven functional cerebral organization

Atypical, i.e. right hemisphere language dominance is frequently observed in early onset left hemisphere epilepsies. In left mesial temporal lobe epilepsy, where eloquent cortex is not directly involved, it is a matter of debate, to which degree atypical language dominance is driven not only by morphological lesions but also by epileptic dysfunction, and whether atypical dominance is hardwired or not. Taking this as the background this study evaluated the hypothesis that epilepsy driven atypical dominancy might be reversible when seizures are successfully controlled. This was evaluated in patients with left mesial temporal lobe epilepsy, who were atypically language dominant by means of language fMRI before surgery, and became seizure free after left selective amygdalo-hippocampectomy. Three out of 53 consecutive atypically dominant patients with chronic epilepsy fulfilled these criteria. Postoperative follow-up language fMRI indicated reversal of right into left dominance in one patient going along with unexpected losses in verbal memory performance. The two other patients experienced unchanged or even enhancement of the pre-existing dominance pattern, going along with consistent postoperative performance changes in cognition. The data thus provide supporting evidence that atypical language dominance can indeed be functionally driven and moreover that in at least some patients, right hemispheric language can shift-back to the left hemisphere when the driving factor, i.e. seizures, becomes successfully controlled. The results have clinical implications for outcome prediction after brain surgery in atypically dominant patients with epilepsy. However, further research in larger groups of atypically dominant patients is required to identify the conditions under which atypical dominance becomes hardwired and when not.

Transcallosal inhibition across the menstrual cycle: A TMS study

Objective To determine if there are steroid-dependent changes in transcallosal transfer during the menstrual cycle in normal women. Methods We tested 13 normally cycling women during the menstrual, follicular and midluteal phases. Blood levels of estradiol (E) and progesterone (P) were determined by radioimmunoassay. Ipsilateral tonic voluntary muscle activity suppression, called ipsilateral silent period (iSP), was evoked by applying transcranial magnetic stimulation (TMS) over the left motor cortex and by measuring the EMG of the ipsilateral first dorsal interosseus (FDI) muscle. Both iSP-duration and transcallosal conduction times were measured and related to cycle phase and steroid levels. Results Duration of iSPs varied over the cycle with largest differences between follicular and midluteal phases. During the midluteal phase high levels of P were significantly related to short iSPs. This relation also applied to E levels and iSPs during the follicular phase. Conclusions Our study shows for the first time that the transcallosal transfer is modulated by E and P and changes over the menstrual cycle. Significance It is suggested that gonadal steroid hormones affect the interhemispheric interaction and change the functional cerebral organization sex dependently via its neuromodulatory properties on GABAergic and glutamatergic neurons.

Real-life spatial skills, handedness, and family history of handedness

According to Annett (1985), pronounced left hemisphere lateralization for language abilities in women, as in female absolute right-handers, limits their right hemisphere capacity and spatial abilities. This study examines the degree of handedness and the family history of non-right-handedness with respect to real-life spatial abilities in women. Twenty-four women had, first, to learn a new route and, second, to orient themselves within a labyrinth. In the former task, the number of errors and completion time were evaluated; in the latter task, degree of error for orienting was recorded. The results show that, contrary to Annett’s prediction, right-handers with and without a family history of non-right-handedness did not differ on these measures. In addition, and unexpectedly, absolute right-handers were found to surpass non-absolute ones in the spatial orientation task. These findings do not support Annett’s hypothesis and are discussed in relation to functional cerebral organization.