Right hemisphere dominance for language in a woman with schizophrenia and a porencephalic cyst of the left hemisphere

<p>A large left hemisphere porencephalic cyst was incidentally found in a 48-year-old woman (MS) with a Diagnostic and Statistical Manual (DSM)-5 diagnosis of schizophrenia. The encephaloclastic characteristics of the cyst indicated that it was acquired between the 22nd and 24th gestational weeks, after the major waves of neuronal migration had tapered off. The cyst destroyed the left temporal and occipital lobes, and the inferior parietal lobule. Surprisingly, MS had no evidence of aphasia, alexia, agraphia, or ideational apraxia; in contrast, cognitive functions dependent on the integrity of the right hemisphere were severely impaired. To test the hypothesis that the development of language in MS took place at the expense of functions that are normally carried out by the right hemisphere, we investigated MS’s correlates of oral comprehension with fMRI as a proxy for auditory comprehension and other cognitive functions strongly lateralized to the posterior left hemisphere, such as ideational praxis and reading. Comprehension of spoken language engaged the homologous of Wernicke’s area in the right <i>planum temporale</i>. Porencephaly may represent a natural model of neuroplasticity supervening at predictable epochs of prenatal development.</p

Clusters of voxels significantly different (<i>p</i><0.05, FWE corrected for multiple comparisons across space using TFCE (Threshold-Free Cluster Enhancement) from healthy controls (CTL) are shown in red for FA (A) and in blue for MD (B) measures in the white matter of bvFTD and CBS patients.

<p>Each panel shows the significant voxel clusters superimposed on the mean FA map in the axial slices. MNI coordinates are shown. Images are displayed in radiological convention (right brain on left side).</p

Mean MD and FA values, statistical significance of group comparisons (α = 0.05, two-tailed), effect sizes (<i>η</i>²)^a and statistical power (1−β)^b.

<p>ROI: regions of interest; DTI: diffusion tensor imaging; NC: normal controls; bvFTD: behavioral variant fronto-temporal dementia; CBS: corticobasal syndrome; Genu (CC_genu) and splenium (CC_spl) of the corpus callosum; bilateral posterior limb of internal capsule (IC); bilateral corona radiata (Cor_RAD); bilateral frontal (UF_front) and temporal (UF_temp) sectors of the uncinate fasciculus; anterior and mid-cingulate bundle (CB_ant and CBmid); Fractional anisotropy (FA); mean diffusivity (MD); <i>η</i>²: effect size; MD in mm³/s.</p

Clusters of voxels that differ significantly (<i>p</i><0.05, corrected for multiple comparisons across space (FWE) using TFCE (Threshold-Free Cluster Enhancement) between CBS and bvFTD patients for measures of MD in blue and FA in red in the axial slices (A and B), and selected coronal and sagittal slices (C and D).

<p>MNI coordinates shown in the axial slices.</p

Clinical characteristics of remitted MDD group (N = 21).

*<p>All co-morbid disorders were fully remitted at time of study. None of the co-morbid disorders was a likely primary cause of the depressive episodes. SSRI = selective serotonin reuptake inhibitor, SNRI = serotonin norepinephrine reuptake inhibitor. MDD subtype classification was based on adapting the SCID-I for DSMIV-TR to allow lifetime assessment of the subtypes. All medication-free participants had stopped medication well before the required washout phase.</p

Data_Sheet_1_Emotion Regulation Using Virtual Environments and Real-Time fMRI Neurofeedback.docx

<p>Neurofeedback (NFB) enables the voluntary regulation of brain activity, with promising applications to enhance and recover emotion and cognitive processes, and their underlying neurobiology. It remains unclear whether NFB can be used to aid and sustain complex emotions, with ecological validity implications. We provide a technical proof of concept of a novel real-time functional magnetic resonance imaging (rtfMRI) NFB procedure. Using rtfMRI-NFB, we enabled participants to voluntarily enhance their own neural activity while they experienced complex emotions. The rtfMRI-NFB software (FRIEND Engine) was adapted to provide a virtual environment as brain computer interface (BCI) and musical excerpts to induce two emotions (tenderness and anguish), aided by participants' preferred personalized strategies to maximize the intensity of these emotions. Eight participants from two experimental sites performed rtfMRI-NFB on two consecutive days in a counterbalanced design. On one day, rtfMRI-NFB was delivered to participants using a region of interest (ROI) method, while on the other day using a support vector machine (SVM) classifier. Our multimodal VR/NFB approach was technically feasible and robust as a method for real-time measurement of the neural correlates of complex emotional states and their voluntary modulation. Guided by the color changes of the virtual environment BCI during rtfMRI-NFB, participants successfully increased in real time, the activity of the septo-hypothalamic area and the amygdala during the ROI based rtfMRI-NFB, and successfully evoked distributed patterns of brain activity classified as tenderness and anguish during SVM-based rtfMRI-NFB. Offline fMRI analyses confirmed that during tenderness rtfMRI-NFB conditions, participants recruited the septo-hypothalamic area and other regions ascribed to social affiliative emotions (medial frontal / temporal pole and precuneus). During anguish rtfMRI-NFB conditions, participants recruited the amygdala and other dorsolateral prefrontal and additional regions associated with negative affect. These findings were robust and were demonstrable at the individual subject level, and were reflected in self-reported emotion intensity during rtfMRI-NFB, being observed with both ROI and SVM methods and across the two sites. Our multimodal VR/rtfMRI-NFB protocol provides an engaging tool for brain-based interventions to enhance emotional states in healthy subjects and may find applications in clinical conditions associated with anxiety, stress and impaired empathy among others.</p

Group comparison on demographic and basic clinical variables.

<p>CC = contingency coefficient, * = significant at p = .05 threshold, 2-tailed, control: N = 18, remitted MDD: N = 21, U = Mann-Whitney-U. A similar table has been reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086900#pone.0086900-Green3" target="_blank">[31]</a>.</p

Summary of significant correlations between DTI (either FA or MD) and clinical measures.

<p>Cognitive (MDS-2) and psycho-pathological (NPI) abnormalities were related to focal WM damage in the posterior cingulate bundle, the uncinate fasciculus, and genu of the corpus callosum. (No laterality of findings implied by the depictions of the cerebral hemispheres).</p

Clinical Features of Controls, bvFTD and CBS.

<p>*Apathy-D-AMB: apathy-disinhibition-aberrant motor behavior.</p><p>**CBS ≠ FTD (Mann-Whitney <i>U</i> Test, <i>p</i><0.05, two-tailed).</p>§<p>CBS ≠ Controls (Mann-Whitney <i>U</i> Test, <i>p</i><0.05, two-tailed).</p

Clusters of voxels that differ significantly (<i>p</i><0.05, FWE corrected for multiple comparisons across space using TFCE (Threshold-Free Cluster Enhancement) between normal controls (CTL) and CBS patients (upper row) and between normal controls and bvFTD patients (bottom row) for measures of FA in selected axial slices.

<p>MNI coordinates are shown. UF =  uncinate fasciculus; ILF =  inferior longitudinal fasciculus; AC =  anterior commissure; CingAnt  =  anterior cingulate; CTT/MLF =  central tegmental tract/medial longitudinal fasciculus; IFOF/ILF =  inferior fronto-occipital fasciculus/inferior longitudinal fasciculus; CR =  corona radiata.</p