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Rajeev Krishnadas

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YNICL Journal 2024 Journal Article

Entrainment of neural oscillations during language processing in Early-Stage schizophrenia

  • Tineke Grent-’t-Jong
  • Pradeep Dheerendra
  • Paolo Fusar-Poli
  • Joachim Gross
  • Andrew I. Gumley
  • Rajeev Krishnadas
  • Lars F. Muckli
  • Peter J. Uhlhaas

BACKGROUND: Impairments in language processing in schizophrenia (ScZ) are a central aspect of the disorder but the underlying pathophysiology mechanisms are unclear. In the current study, we tested the hypothesis that neural oscillations are impaired during speech tracking in early-stage ScZ and in participants at clinical high-risk for psychosis (CHR-P). METHOD: Magnetoencephalography (MEG) was used in combination with source reconstructed time-series to examine delta and theta-band entrainment during continuous speech. Participants were presented with a 5-minute audio recording during which they either attened to the story or word level. MEG-data were obtained from n = 22 CHR-P participants, n = 23 early-stage ScZ-patients, and n = 44 healthy controls (HC). Data were analysed with a Mutual Information (MI) approach to compute statistical dependence between the MEG and auditory signal, thus estimating individual speech-tracking ability. MEG-activity was reconstructed in a language network (bilateral inferior frontal cortex [F3T; Broca's], superior temporal areas [STS3, STS4; Wernicke's areas], and primary auditory cortex [bilateral HES; Heschl's gyrus]). MEG-data were correlated with clinical symptoms. RESULTS: Theta-band entrainment in left Heschl's gyrus, averaged across groups, was significantly lower in the STORY compared to WORD condition (p = 0.022), and averaged over conditions, significantly lower in CHR-Ps (p = 0.045), but intact in early ScZ patients (p = 0.303), compared to controls. Correlation analyses between MEG data and symptom indicated that lower theta-band tracking in CHR-Ps was linked to the severity of perceptual abnormalities (p = 0.018). CONCLUSION: Our results show that CHR-P participants involve impairments in theta-band entrainment during speech tracking in left primary auditory cortex while higher-order speech processing areas were intact. Moreover, the severity of aberrant perceptual experiences in CHR-P participants correlated with deficits in theta-band entrainment. Together, these findings highlight the possibility that neural oscillations during language processing could reveal fundamental abnormalities in speech processing which may constitute candidate biomarkers for early detection and diagnosis of ScZ.

YNICL Journal 2022 Journal Article

Hippocampal structural alterations in early-stage psychosis: Specificity and relationship to clinical outcomes

  • Gina Brunner
  • Ruchika Gajwani
  • Joachim Gross
  • Andrew I. Gumley
  • Rajeev Krishnadas
  • Stephen M. Lawrie
  • Matthias Schwannauer
  • Frauke Schultze-Lutter

Hippocampal dysfunctions are a core feature of schizophrenia, but conflicting evidence exists whether volumetric and morphological changes are present in early-stage psychosis and to what extent these deficits are related to clinical trajectories. In this study, we recruited individuals at clinical high risk for psychosis (CHR-P) (n = 108), patients with a first episode of psychosis (FEP) (n = 37), healthy controls (HC) (n = 70) as well as a psychiatric control group with substance abuse and affective disorders (CHR-N: n = 38). MRI-data at baseline were obtained and volumetric as well as vertex analyses of the hippocampus were carried out. Moreover, volumetric changes were examined in the amygdala, caudate, nucleus accumbens, pallidum, putamen and thalamus. In addition, we obtained follow-up functional and symptomatic assessments in CHR-P individuals to examine the question whether anatomical deficits at baseline predicted clinical trajectories. Our results show that the hippocampus is the only structure showing significant volumetric decrease in early-stage psychosis, with FEPs showing significantly smaller hippocampal volumes bilaterally alongside widespread shape changes in the vertex analysis. For the CHR-P group, volumetric decreases were confined to the left hippocampus. However, hippocampal alterations in the CHR-P group were not robustly associated with clinical outcomes, including the persistence of attenuated psychotic symptoms and functional trajectories. Accordingly, our findings highlight that dysfunctions in hippocampal anatomy are an important feature of early-stage psychosis which may, however, not be related to clinical outcomes in CHR-P participants.

YNICL Journal 2021 Journal Article

Long range temporal correlations (LRTCs) in MEG-data during emerging psychosis: Relationship to symptoms, medication-status and clinical trajectory

  • Gabriela Cruz
  • Tineke Grent-'t-Jong
  • Rajeev Krishnadas
  • J. Matias Palva
  • Satu Palva
  • Peter J. Uhlhaas

Long-Range Temporal Correlations (LRTCs) index the capacity of the brain to optimally process information. Previous research has shown that patients with chronic schizophrenia present altered LRTCs at alpha and beta oscillations. However, it is currently unclear at which stage of schizophrenia aberrant LRTCs emerge. To address this question, we investigated LRTCs in resting-state magnetoencephalographic (MEG) recordings obtained from patients with affective disorders and substance abuse (clinically at low-risk of psychosis, CHR-N), patients at clinical high-risk of psychosis (CHR-P) (n = 115), as well as patients with a first episode (FEP) (n = 25). Matched healthy controls (n = 47) served as comparison group. LRTCs were obtained for frequencies from 4 to 40 Hz and correlated with clinical and neuropsychological data. In addition, we examined the relationship between LRTCs and transition to psychosis in CHR-P participants, and the relationship between LRTC and antipsychotic medication in FEP participants. Our results show that participants from the clinical groups have similar LRTCs to controls. In addition, LRTCs did not correlate with clinical and neurocognitive variables across participants nor did LRTCs predict transition to psychosis. Therefore, impaired LRTCs do not reflect a feature in the clinical trajectory of psychosis. Nevertheless, reduced LRTCs in the beta-band over posterior sensors of medicated FEP participants indicate that altered LRTCs may appear at the onset of the illness. Future studies are needed to elucidate the role of anti-psychotic medication in altered LRTCs.

YNICL Journal 2013 Journal Article

Cardio-metabolic risk factors and cortical thickness in a neurologically healthy male population: Results from the psychological, social and biological determinants of ill health (pSoBid) study

  • Rajeev Krishnadas
  • John McLean
  • David G. Batty
  • Harry Burns
  • Kevin A. Deans
  • Ian Ford
  • Alex McConnachie
  • Agnes McGinty

INTRODUCTION: Cardio-metabolic risk factors have been associated with poor physical and mental health. Epidemiological studies have shown peripheral risk markers to be associated with poor cognitive functioning in normal healthy population and in disease. The aim of the study was to explore the relationship between cardio-metabolic risk factors and cortical thickness in a neurologically healthy middle aged population-based sample. METHODS: T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness in 40 adult males (average age = 50.96 years), selected from the pSoBid study. The relationship between cardio-vascular risk markers and cortical thickness across the whole brain, was examined using the general linear model. The relationship with various covariates of interest was explored. RESULTS: Lipid fractions with greater triglyceride content (TAG, VLDL and LDL) were associated with greater cortical thickness pertaining to a number of regions in the brain. Greater C reactive protein (CRP) and intercellular adhesion molecule (ICAM-1) levels were associated with cortical thinning pertaining to perisylvian regions in the left hemisphere. Smoking status and education status were significant covariates in the model. CONCLUSIONS: This exploratory study adds to a small body of existing literature increasingly showing a relationship between cardio-metabolic risk markers and regional cortical thickness involving a number of regions in the brain in a neurologically normal middle aged sample. A focused investigation of factors determining the inter-individual variations in regional cortical thickness in the adult brain could provide further clarity in our understanding of the relationship between cardio-metabolic factors and cortical structures.

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