Interhemispheric connectivity and hemispheric specialization in schizophrenia patients and their unaffected siblings

Chang, Xiao; Collin, Guusje; Mandl, René C.W.; Cahn, Wiepke; Kahn, René S.

doi:10.1016/j.nicl.2019.101656

Cited by 17 publications

(16 citation statements)

References 84 publications

(114 reference statements)

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“…In addition to dysfunctional regional interhemispheric connectivity, dysfunctional interhemispheric connectivity within larger networks such as the sensorimotor and default mode networks have also been found and linked with neurocognitive deficits and auditory verbal hallucinations, respectively [39,40]. Decreased interhemispheric connectivity within regions and larger networks may lead to increased hemispheric autonomy and decreased interhemispheric cooperation [35]. Our findings are consistent with this notion; stimulation of the left BA9 revealed decreased contralateral activation and increased local ipsilateral activation in subjects with schizophrenia relative to controls.…”

Section: Discussionsupporting

confidence: 87%

“…Our results provide causal evidence for interhemispheric dysconnectivity within the prefrontal cortex in subjects with schizophrenia. Previous work suggests that interhemispheric dysconnectivity may be central to the etiology of schizophrenia [35]. Decreased resting state homotopic connectivity has been identified in several regions, including the occipital lobe, thalamus, cerebellum, precuneus, precentral gyrus, postcentral gyrus, superior temporal gyrus, middle occipital gyrus, and the fusiform gyrus [36e38].…”

Section: Discussionmentioning

confidence: 99%

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Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

et al. 2020

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Background: Prefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia. Objective: /Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity. Methods: We enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition. Results: Of the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p ¼ 0.0157; max z-score ¼ 4.7) and neighboring BA46 (p ¼ 0.019; max z-score ¼ 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p ¼ 0.02; max z-score ¼ 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r ¼ 0.83, p ¼ 0.004). Conclusions: Subjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

et al. 2020

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“…These studies will contribute to the elucidation of the fundamental cause of psychiatric and developmental disorders that show inter-hemispheric [28,29] or long-distance interregional loss of connectivity [30] and partial volume loss in the corpus callosum [31], and to the development of treatments for these disorders.…”

Section: Discussionmentioning

confidence: 99%

Disconnection between Rat’s Left and Right Hemisphere Impairs Short-Term Memory but Not Long-Term Memory

Sakaguchi

Sakurai

2021

Symmetry

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Split-brain experiments, which have been actively conducted since the twentieth century, have provided a great deal of insight into functional asymmetry and inter-hemispheric interactions. However, how communication between the left and right hemispheres directly contributes to memory formation is still poorly understood. To address this issue, we cut the rat commissural fibers prior to performing behavioral tests, which consisted of two short-term and two long-term memory tasks. The result showed that cutting the commissural fibers impairs short-term memory but not long-term memory. This suggests that the left-right hemispheric interaction through the commissural fibers contributes to the appropriate formation of short-term memory, but not that of long-term memory. Our findings would help to elucidate dynamic memory formation between the two hemispheres and contribute to the development of therapeutics for some neurological diseases which cause a reduction in the inter-hemispheric interaction.

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“…However, our work suggests a couple of potential directions. First, symptoms of schizophrenia have been linked to reduced interhemispheric functional connectivity between other PFC regions (e.g., VLPFC and medial PFC; Bleich-Cohen et al 2012;Mwansisya et al 2013;Chang et al 2019). Moreover, glutamatergic theories of schizophrenia suggest that symptoms of schizophrenia may partially due to reduced NMDA (N-methyl-d-aspartic acid) receptor activity, which is a type of glutamatergic receptor activity, specifically in the PFC (Carlsson et al 2001;Donald and Joseph 2001;Moghaddam and Javitt 2012).…”

Section: Implications For Clinical Syndromesmentioning

confidence: 99%

Association of γ-aminobutyric acid and glutamate/glutamine in the lateral prefrontal cortex with patterns of intrinsic functional connectivity in adults

et al. 2020

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This study examined how levels of neurotransmitters in the lateral prefrontal cortex (LPFC), a region underlying higherorder cognition, are related to the brain's intrinsic functional organization. Using magnetic resonance spectroscopy (MRS), GABA+ and Glx (glutamate + glutamine) levels in the left dorsal (DLPFC) and left ventral (VLPFC) lateral prefrontal cortex were obtained in a sample of 64 female adults (mean age = 48.5). We measured intrinsic connectivity via resting-state fMRI in three ways: (a) via seed-based connectivity for each of the two spectroscopy voxels; (b) via the spatial configurations of 17 intrinsic networks defined by a well-known template; and (c) via examination of the temporal interrelationships between these intrinsic networks. The results showed that different neurotransmitter indexes (Glx-specific, GABA+-specific, Glx-GABA+ average and Glx-GABA+ ratio) were associated with distinct patterns of intrinsic connectivity. Neurotransmitter levels in the left LPFC are mainly associated with connectivity of right hemisphere prefrontal (e.g., DLPFC) or striatal (e.g., putamen) regions, two areas of the brain connected to LPFC via large white matter tracts. While the directions of these associations were mixed, in most cases, higher Glx levels are related to reduced connectivity. Prefrontal neurotransmitter levels are also associated with the degree of connectivity between non-prefrontal regions. These results suggest robust relationships between the brain's intrinsic functional organization and local neurotransmitters in the LPFC which may be constrained by white matter neuroanatomy.

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Interhemispheric connectivity and hemispheric specialization in schizophrenia patients and their unaffected siblings

Cited by 17 publications

References 84 publications

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study

Disconnection between Rat’s Left and Right Hemisphere Impairs Short-Term Memory but Not Long-Term Memory

Association of γ-aminobutyric acid and glutamate/glutamine in the lateral prefrontal cortex with patterns of intrinsic functional connectivity in adults

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