Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study.

BACKGROUND: Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression. METHOD: We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis. RESULTS: ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years. CONCLUSIONS: Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.

Smaller size of high metabolic rate organs explains lower resting energy expenditure in Asian-Indian Than Chinese men.

BACKGROUND: In Singapore, the obesity prevalence is disproportionately higher in the Asian-Indians and Malays than the Chinese. Lower resting energy expenditure (REE) may be a contributory factor. OBJECTIVE: We explored the association between ethnicity and REE in Chinese, Asian-Indian and Malay men living in Singapore and determined the influence of body composition, mass/volume of high metabolic rate organs, represented by brain volume and trunk fat-free mass (FFM), and physical activity on ethnic differences. DESIGN: Two hundred and forty-four men from Singapore (n=100 Chinese, 70 Asian-Indians and 74 Malays), aged 21-40 years and body mass index of 18.5-30.0 kg m(-2), were recruited in this cross-sectional study. REE was assessed by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. Brain volume was measured by magnetic resonance imaging. Physical activity was assessed by the Singapore Prospective Study Program Physical Activity Questionnaire. RESULTS: REE was significantly lower in Asian-Indians compared with that in Chinese after adjusting for body weight. FFM (total, trunk and limb) and total fat mass were important predictors of REE across all ethnic groups. Brain volume was positively associated with REE only in Malays. Moderate and vigorous physical activity was positively associated with REE only in Asian-Indians and Malays. The difference in REE between Asian-Indians and Chinese was attenuated but remained statistically significant after adjustment for total FFM (59±20 kcal per day), fat mass (67±20 kcal per day) and brain volume (54±22 kcal per day). The association between REE and ethnicity was no longer statistically significant after total FFM was replaced by trunk FFM (which includes heart, liver, kidney and spleen) but not when it was replaced by limb FFM (skeletal muscle). CONCLUSIONS: We have demonstrated a lower REE in Asian-Indians compared with Chinese who may contribute to the higher rates of obesity in the former. This difference could be accounted for by differences in metabolically active organs.

Acute ophthalmoplegia with pupillary areflexia associated with anti-GQ1b antibody.

Raised anti-GQ1b antibody is associated with Miller Fisher syndrome, Guillain-Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff's brain stem encephalitis, acute ophthalmoparesis without ataxia and ataxic GBS without opthalmoplegia. We report a rare case of acute ophthalmoplegia associated with anti-GQ1b antibody that also had pupillary areflexia. A 35-year-old Chinese lady presented with external ophthalmoplegia, pupillary areflexia and no other abnormalities of cranial nerves, muscle tone, deep tendon reflexes, limb power or cerebellar dysfunction. Anti-GQ1b IgG antibody titre was significantly elevated, while neuroimaging of brain and orbital structures, nerve conduction study and cerebral spinal fluid examination were normal. Pupillary areflexia should be recognized as another feature that may be present in conditions associated with raised anti-GQ1b antibody.

Seeing how we think about words using BOLD contrast fMR imaging.

This review examines how blood oxygen level-dependent functional magnetic resonance imaging (fMRI) may be harnessed to study the brain when it engages in language processing tasks. This method makes clinical and scientific contributions to understanding language function. Issues such as the lateralisation of language function, brain plasticity in health, ageing and neurological disease, and as well as how 2 different languages are processed, may all be evaluated by fMRI.

Relative language proficiency modulates BOLD signal change when bilinguals perform semantic judgments. Blood oxygen level dependent.

The effect of relative language proficiency on the spatial distribution and magnitude of BOLD signal change was evaluated by studying two groups of right-handed English-Mandarin bilingual participants with contrasting language proficiencies as they made semantic judgments with words and characters. Greater language proficiency corresponded to shorter response times and greater accuracy in the semantic judgment task. Within the left prefrontal and parietal regions, the change in BOLD signal was smaller in a participant's more proficient language. The least proficient performance was associated with right, in addition to left, inferior frontal activation. The results highlight the importance of taking into consideration nature of task and relative language proficiency when drawing inferences from functional imaging studies of bilinguals.

Overlap and dissociation of semantic processing of Chinese characters, English words, and pictures: evidence from fMRI.

The functional anatomy of Chinese character processing was investigated using fMRI. Right-handed Mandarin-English bilingual participants made either semantic or perceptual size judgements with characters and pictures. Areas jointly activated by character and picture semantic tasks compared to size judgement tasks included the left prefrontal region (BA 9, 44, 45), left posterior temporal, left fusiform, and left parietal regions. Character processing produced greater activation than picture processing in the left mid and posterior temporal as well as left prefrontal regions. The lateral occipital regions were more active during picture semantic processing than character semantic processing. A similar pattern of activation and contrasts was observed when English words and pictures were compared in another set of bilingual participants. However, there was less contrast between word and picture semantic processing than between character and picture processing in the left prefrontal region. When character and word semantic processing were compared directly in a third group, the loci of activation peaks was similar in both languages but Chinese character semantic processing was associated with a larger MR signal change. The semantic processing of Chinese characters, English words, and pictures activates a common semantic system within which there are modality-specific differences. The semantic processing of Chinese characters more closely resembles English words than pictures.

Dorsolateral prefrontal cortex and the implicit association of concepts and attributes.

The Implicit Association Test (IAT) examines the differential association of two object categories (e.g. flower and insect) with attribute categories (e.g. pleasant and unpleasant). When items from congruent categories (e.g. flower + pleasant) share a response key, performance is faster and more accurate than when items from incongruent categories (e.g. insect + pleasant) share a key. Performing incongruent word classification engages inhibitory processes to overcome the prepotent tendency to map emotionally congruent items to the same response key. Using fMRI on subjects undergoing the IAT, we show that the left dorsolateral prefrontal cortex, and to a lesser extent the anterior cingulate cortex, mediate inhibitory processes where manipulation of word association is required.

Culture positive tuberculous meningitis: clinical indicators of poor prognosis.

Few studies have evaluated culture positive tuberculous meningitis (TBM) as a group. We evaluated certain clinical factors in culture positive TBM which could be associated with a poorer outcome. Out of 40 consecutive TBM patients seen over a period of 4 years in a tertiary referral hospital, 18 culture positive and non-human immunodeficiency virus (HIV) related cases were studied. The mean age was 37.9 +/- 14.9 years (range 9-63); five were males and 13 females. None had any associated active chronic medical illness. Patients (44.4%) started on antituberculous treatment within 24 h of admission. Treatment was initiated at a median time of 48 h upon admission in hospital. Univariate analysis revealed a significant correlation between hydrocephalus (P = 0.007) and poor morbidity and mortality. The other clinical factors were not statistically significant: age (P = 0.36): sex (P = 0.49); symptom duration (P = 0.69); BCG vaccination (P = 0.65); cerebral infarct (P = 0.63); extrameningeal spread (P = 1.00); steroids (P = 1.00); time to treatment (P = 0.94) and stage of disease (P = 0.11). Hydrocephalus was the only significant factor predisposing culture positive TBM patients to a poorer outcome. There was also a trend towards a poorer prognosis in those with advanced stage of the disease.

Processing of visually presented sentences in Mandarin and English studied with fMRI.

Comprehension of visually presented sentences in fluent bilinguals was studied with functional magnetic resonance imaging (fMRI) using a set of conceptually similar sentences in two orthographically and phonologically distinct languages, Mandarin and English. Responses were monitored during scanning. Sentence comprehension in each language was compared to fixation in nine subjects and Tamil-like pseudo-word strings in five subjects. Spatially congruent activations in the prefrontal, temporal, and superior parietal regions and in the anterior supplementary motor area were observed for both languages and in both experiments at the individual and group levels of analysis. Proficient bilinguals exposed to both languages early in life utilize common neuroanatomical regions during the conceptual and syntactic processing of written language irrespective of their differences in surface features.

Mandarin and English single word processing studied with functional magnetic resonance imaging.

The cortical organization of language in bilinguals remains disputed. We studied 24 right-handed fluent bilinguals: 15 exposed to both Mandarin and English before the age of 6 years; and nine exposed to Mandarin in early childhood but English only after the age of 12 years. Blood oxygen level-dependent contrast functional magnetic resonance imaging was performed while subjects performed cued word generation in each language. Fixation was the control task. In both languages, activations were present in the prefrontal, temporal, and parietal regions, and the supplementary motor area. Activations in the prefrontal region were compared by (1) locating peak activations and (2) counting the number of voxels that exceeded a statistical threshold. Although there were differences in the magnitude of activation between the pair of languages, no subject showed significant differences in peak-location or hemispheric asymmetry of activations in the prefrontal language areas. Early and late bilinguals showed a similar pattern of overlapping activations. There are no significant differences in the cortical areas activated for both Mandarin and English at the single word level, irrespective of age of acquisition of either language.

Auditory and visual word processing studied with fMRI.

Brain activations associated with semantic processing of visual and auditory words were investigated using functional magnetic resonance imaging (fMRI). For each form of word presentation, subjects performed two tasks: one semantic, and one nonsemantic. The semantic task was identical for both auditory and visual presentation: single words were presented and subjects determined whether the word was concrete or abstract. In the nonsemantic task for auditory words, subjects determined whether the word had one syllable or multiple syllables. In the nonsemantic task for visual words, subjects determined whether the word was presented in lower case or upper case. There was considerable overlap in where auditory and visual word semantic processing occurred. Visual and auditory semantic tasks both activated the left inferior frontal (BA 45), bilateral anterior prefrontal (BA 10, 46), and left premotor regions (BA 6) and anterior SMA (BA 6, 8). Left posterior temporal (middle temporal and fusiform gyrus) and predominantly right-sided cerebellar activations were observed during the auditory semantic task but were not above threshold during visual word presentation. The data, when averaged across subjects, did not show obligatory activation of left inferior frontal and temporal language areas during nonsemantic word tasks. Individual subjects showed differences in the activation of the inferior frontal region while performing the same task, even though they showed similar response latency and accuracy.

Right hemisphere language in a neurologically normal dextral: a fMRI study.

Dextrals with right cerebral hemisphere dominance for language are rare. Eight neurologically intact dextrals underwent BOLD-fMRI while being presented auditory and visual words. Fortuitously, in one subject, right hemisphere activations with visually presented words were seen in the inferior frontal, premotor regions together with predominantly left cerebellar activation. These were a mirror image of activations obtained from the seven other dextrals. Also mirrored was temporal activation from auditory words which extended more posteriorly on the right side than the left. These results showing mirror organization of language were replicated in another scanning session and also by using a second word task. Although rare, mirrored organization of language can occur in normal dextrals without penalizing language function.

MRI of the fornix and mamillary body in temporal lobe epilepsy.

We performed MRI on 27 patients with clinically proven temporal lobe epilepsy (TLE), all with prior EEG lateralisation, and 10 volunteers, studied to evaluate disparity in size arising from biological variation (group 1). Three-dimensional spoiled GRASS (3DSPGR) sequences provided 2-mm contiguous sections of the limbic system, enabling assessment of the hippocampus (HC), fornix (FN) and mamillary body (MB). Measurements of FN and MB width were made from a workstation. Any percentage difference in size was computed. In 19 cases there was unilateral abnormality in the HC (group 2); in 18 and 19 cases respectively there was a smaller FN and MB on the same side as the abnormal HC. This percentage difference in size was significantly greater than that in group 1 in the FN and MB in 17 and 17 cases respectively. Comparison of percentage difference computations for FN and MB between groups 1 and 2 showed high statistical significance (P < 0.0002). In 5 patients with clinical TLE the HC was normal on MRI (group 3). Unequal FN and MB sizes were found in 4, significant in 2. Comparison of percentage difference computations for FN and MB showed statistical significance (P < 0.0005 and P < 0.0003 respectively). There was no case of discordance between the sides of hippocampal abnormality and the smaller FN or MB or between the sides of smaller FN and MB. The strong concordance between the changes in the HC and those in the FN and MB suggests that this combination will play an important role in the assessment of TLE and limbic system abnormality.

Speech and the dominant superior frontal gyrus: correlation of ictal symptoms, EEG, and results of surgical resection.

Two patients with seizures characterized by speech arrest had astrocytoma in the superior frontal gyrus (SFG) of the left hemisphere. Preoperative video EEG monitoring of seizures using subdural electrode arrays showed that comprehension, crude vocalization, and limb and tongue movements were preserved during speech arrest. One patient had difficulty writing during seizures. Ictal EEG onset was localized to the SFG without involvement of Broca's area. Electrical stimulation of SFG electrodes reproduced the speech arrest and writing difficulty. Resection of this region reduced seizures but did not result in lasting speech deficit. Cessation of speech with electrical stimulation of the superior frontal gyrus occurs by interrupting control of muscles required for speaking, which occurs independently of simple 'negative' motor effects. We postulate that functional redundancy is the basis for resection of this region without producing significant speech deficits.

Hippocampal volumetry with magnetic resonance imaging: a cost-effective validated solution.

PURPOSE: The clinical utility of hippocampal volumetry is well documented, but the materials and techniques required to perform the procedure are not widely available outside major research centers. We describe a personal computer-based method of volumetric data analysis. METHODS: Using a 1.0-T scanner, we obtained 2-mm-thick tilted coronal MPRAGE magnetic resonance imaging (MRI) scans of 20 healthy volunteers aged 20-38 years. We used an inexpensive utility program to extract image information and an NIH Image for image analysis. The hippocampal formations were traced with a graphics tablet and landmarks described by Watson et al. (Neurology 1992;42:1743-50). Overlays of individual observers' tracings were used to fine tune the selection of landmarks and boundaries. Filled-in silhouette pairs generated from these "training tracings" were compared to determine how well observers could visually quantify area differences. RESULTS: Visual detection of asymmetry of silhouette pairs was sensitive, but the magnitude of asymmetry was underestimated. We achieved intraobserver coefficients of variation of right/left volume ratios between 0.82 and 3.16 and an interobserver range of volume ratios of 6%. In 20 healthy controls aged 20-38 years, the mean right and left hippocampal volumes were 2,911 mm3 and 2,836 mm3, respectively. The lower limits of normal were 2,217 mm3 for the right and 2,178 mm3 for the left. The mean right/left hippocampal ratio was 1.03, and the limits of normal (3 SD) for this were 0.95 to 1.10. CONCLUSIONS: Hippocampal volumetry can be performed reliably and economically. Our methodology makes it possible for different observers to generate consistent and comparable measurements.

Mesial temporal lobe epilepsy in Singapore.

Mesial temporal lobe epilepsy due to mesial temporal sclerosis is a distinctive syndrome and a surgically remediable form of epilepsy. We present 26 Singaporean cases of mesial temporal lobe epilepsy defined by clinical, electroencephalographic and MR features and validated by good surgical outcome (12 seizure free, 5 with two or fewer seizures) in all 17 patients who have so far undergone surgery and who have been followed up for at least 6 months. Sixty-five percent of patients experienced their first seizure in the setting of a febrile illness. Seventy-three percent of patients had seizure onset before the age of 10 years and the median interval between seizure onset and intractability of seizures was 3.75 years. 80.7% of patients had an aura and an equal number had at least one lateralizing sign during their seizures. Sixty-four percent of patients had predominantly unilateral anterior temporal interictal spikes. Eighty-eight percent of patients had seizures which were lateralised on scalp ictal EEG. MRI abnormalities were most frequently seen in the head and body of the hippocampal formation. Asymmetric hippocampal atrophy was more common than hippocampal T2 or T2* signal changes. There is much similarity in characteristics of mesial temporal lobe epilepsy in our population compared to what has been published regarding Caucasian subjects.

Fulminant Guillain-Barré syndrome with quadriplegia and total paresis of motor cranial nerves as a result of segmental demyelination.

Guillain-Barré syndrome (GBS) is a subacute demyelinating polyneuropathy with a monophasic course. Rarely, demyelination may be so severe as to produce electrically unexcitable nerves. We present a patient with fulminant onset of symptoms who was quadriplegic and had bilateral involvement of all motor cranial nerves. Serial EMGs indicated that segmental demyelination was responsible for these clinical findings.

Neuronal migration disorder presenting with epilepsy: a report of five illustrative cases.

Neuronal migration disorders are an uncommon but well-recognised cause of medically intractable epilepsy. The increasing availability of magnetic resonance imaging of the brain has made it possible to diagnose this condition ante-mortem. There are several types of migration disorders, each with different radiological and clinical features. A case each of focal cortical dysplasia, focal subcortical heterotopia, double cortex syndrome, periventricular nodular heterotopia and closed lip schizencephaly is presented to highlight the distinctive features of each entity.