Laterality of motor symptom onset in Parkinson’s disease (PD) is well-known and under-appreciated. It is still unclear though if this laterality might have an influence on other symptoms. Specifically, REM sleep behavior disorder has been shown to be a factor that has a high probability to be lined to PD. In this study we analyzed the longitudinal effect of REM symptomatology on brain lateralization in PD.

We used the baseline and 3-year visit data of 116 participants (67 without REM (PD-non-REM), 49 with REM (PD-REM)) aged 37-81 years from the Parkinson’s Progression Markers Initiative (PPMI) dataset. Statistical 3T MRI data (cortical thicknesses, areas, foldings of cortical Desikan atlas and volumes of subcortical regions) were obtained via FreeSurfer 7.1.1. Lateralization was computed using the formula: (left-right)/(lef +right). Mixed ANOVAs were performed on each region of interest.

Our findings showed an increased right asymmetry of the paracentral lobule area and of the pars orbitalis area and volume in PD-REM. There was a reduced right asymmetry of the parietal inferior volume at baseline in PD-REM, whereas REM symptomatology had a stable effect at the 3 years visit. At baseline, there was an increased left asymmetry of the thickness of the caudal anterior cingulate, pars orbitalis and pars triangularis regions in PD-REM. After 3 years, there was an increased right asymmetry in those regions. The precentral, frontal superior and transversal temporal gyri showed inverse results: an increased right asymmetry of the thickness at baseline and an increased left asymmetry after 3 years. Finally, REM symptomatology is associated with more significant increases of the left asymmetry of the frontal superior gyrus volume and of the right asymmetry of the supramarginal gyrus volume after 3 years than at baseline.

These results provide evidence of the modulating effect of the disease progression on the relationship between REM symptoms and brain lateralization in PD.

Lateralization and localization of neuropathology helps determine the extent to which eloquent cortex and diseased brain tissue share loci, important information for neurosurgical decision-making, and predicting neurocognitive outcomes. Emerging data suggest that lateralization and localization can inform specific neurorehabilitation approaches following acquired brain injury (ABI). In recent years, computerized cognitive remediation (CCR) of attention and working memory (WM) has been included among treatment guidelines to enhance cognition in post-acute recovery following ABI. Although CCR has shown promise for improving attention and executive functioning in ABI, it is unknown how treatment response may be predicted by locus of ABI. Even less is known about the effects of CCR following neurosurgery. The current study explores neurosurgical lateralization and localization as potential variables for predicting treatment response to CCR.

Adult patients with a variety of neurological diagnoses (N = 17; ∼47% women) completed a full course of Cogmed Working Memory Training (CWMT) s/p neurosurgical intervention. All participants engaged in 30 sessions of CWMT over eight weeks, as well as neuropsychological (NP) assessment at pre-training baseline, immediate post-training, and at 3-month follow-up. Objective and subjective indices of attention, working memory, executive functioning, and emotional well-being were evaluated at three time-points. Neurosurgical loci included left-hemisphere frontal, temporal, and temporoparietal lobes, as well as right-hemisphere frontal, frontotemporal, and temporal lobes.

NP data were reviewed and yielded a clinical impression of cognitive and affective functioning for a cohort of patients with heterogeneous diagnoses (e.g., brain tumor, epilepsy, NPH). Preliminary NP findings suggested that treatment response to CCR for WM was consistent with extant literature on brain-behavior relationships according to lateralization and localization of neurosurgical intervention.

Neurosurgical patients experience neurocognitive and affective dysfunction that may respond well to cognitive rehabilitation (CR) that includes CCR. Additionally, it is possible that lateralization and localization of surgical intervention may contribute to individual differences in treatment response. Further neurorehabilitation research is warranted to identify patients most likely to benefit from CCR and better tailor CR modalities to optimize recovery s/p neurological surgery.

Parkinson’s disease (PD) is typically characterized by unilateral onset of motor symptoms (i.e., tremors, rigidity) which is caused by dopaminergic degeneration of the substantia nigra that influences basal ganglia-prefrontal circuitry. Over time, motor symptoms become more bilateral, though continue to remain asymmetric. Many neuropsychological studies suggest that laterality of motor onset may be linked to hemispheric specific cognitive or mood changes. Namely, worse verbal/language performance may be present in individuals with right body (left hemisphere) onset and conversely for visuospatial performance, with depression symptoms relating more so to individuals with right body (left hemisphere) onset. To date, findings are often inconsistent, with some studies showing evidence for laterality effects and others not. The basis for this inconsistency is unclear, though one possibility relates to small sample sizes and varying methodologies. Thus, the goal of this study was to examine potential cognitive and mood laterality effects in a large clinical sample of individuals with PD.

Participants included a convenience sample of 600 nondemented individuals with idiopathic PD from the University of Florida Fixel Institute Movement Disorders Center. As a group, participants were around 60 years of age (Mean Age=63.9+9.4), well educated (Mean years=14.9+2.7), predominantly male (70%), and white non-Hispanic (93%). Side of initial motor symptom onset was based on self-report: Right (N=337) and Left (N=263). Approximately 79% were tremor predominant. All received mood and neurocognitive measures as part of standard clinical care, including indices of executive function (Stroop Color-Word, Trails B, Letter Fluency), recent verbal memory (delayed recall: Hopkin’s Verbal Learning Test, WMS-III Logical Memory), language (Boston Naming Test, Animal fluency), visuospatial skills (Judgment of Line Orientation, Facial Recognition Test). Evaluation of emotion symptoms included: depression (Beck Depression Inventory-II), apathy (Apathy Scale), and anxiety (State-Trait Anxiety Inventory). Analyses used raw scores from these measures. Due to non-normality of most measures’ distributions, laterality effects were examined using bootstrapped multivariate methods (multivariate analysis of variance [MANOVA]). Separate MANOVA’s were run for each cognitive domain (i.e., EF, language, etc.) and mood measures.

The right and left sided onset groups did not significantly differ in demographic (age, education, sex) or disease characteristics (duration, PD subtype). Results of the MANOVA’s with cognitive variables were all nonsignificant broadly (all with F’s ranging from .33 to .94) and at the single test level. Similarly, the left and right onset groups did not significantly differ (a=0.05) across standard scales of depression (F=0.031), anxiety (Trait F=0.463; State F=3.29), and apathy (F=0.74).

We found no evidence that laterality of initial motor symptoms influenced cognitive or mood symptoms in a large cohort of 600 individuals with PD. These findings raise questions about importance of motor onset laterality for cognitive and emotion related changes in PD. Future studies should move beyond self-report and behavioral motor scales for determining hemispheric contributions. In PD, use of refined metrics for determining the extent of asymmetric dopaminergic degeneration (e.g., DAT scan) at the hemispheric level coupled with sensitive neuropsychological measures may provide clearer understanding of potential neural circuitry relationships.

Our objective is to investigate whether handedness is associated with performance on verbal and visual neuropsychological tests in people with severe mental disorders. A recent study, applying a continuous scale of hand preference, reports that handedness is not associated with test performance in people with schizophrenia disorders. Conversely, in a recent large meta-analysis where handedness was applied as a dichotomous variable, right-handers had better performance in spatial ability (but not verbal ability) compared to left-handers, irrespective of gender or health status. We hypothesize that a dichotomous classification of handedness will reveal an advantage of right-handedness on tests of visuospatial functions—but not verbal functions—in people with severe mental disorders. We expect that gender will not be associated with the neuropsychological test results.

Data from a sample of 385 patients with severe mental disorders, mainly within the schizophrenia spectrum, were analyzed. All participants had Norwegian as their first language. Their mean age was 24.8 years (SD=6.2) and 153 (39.7%) were women. Handedness was evaluated by observation of preferred hand in writing and drawing during neuropsychological assessment. Chi-square tests were used to compare proportions of cases with reported frequencies of handedness in the general population and comparable clinical samples. Raw scores on Semantic Fluency and Line Orientation from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were analyzed using Mann-Whitney U tests, and possible effects of gender with two-way ANOVA. Frequencies of low scores were analyzed using frequency analyses.

Overall prevalence of left-handers was 10.4% compared to 10.6% in the general population (χ2=.018, p=.893). Observed prevalence for women was 9.2% compared to expected prevalence of 9.5% (χ2=.026, p=.873) and for men 10.7% and 11.6%, respectively (χ2=.039, p=.844). There was a significant difference in Line Orientation scores (Mdright-handers=18, Mdleft-handers=17; U=5268.0, p=.013) but not Semantic Fluency scores (Mdright-handers=17, Mdleft-handers=18.5; U=7568.5, p=.315). Right-handed men had higher scores on Line Orientation but there was no handedness by gender interaction (F(1)=1.69, p=.194). For Semantic Fluency, left-handed men had higher scores and a gender by handedness interaction was found (F(1)=7.21, p=.008). Using scores corresponding to <5th percentile, 15% of left-handers and 8% of right-handers had scores <5th percentile on Line Orientation, as opposed to 15% and 14% on Semantic Fluency.

Right-handers had significantly better performance on a test measuring visuospatial function, irrespective of gender. Left-handers had about twice the number of scores in the impaired range (i.e., <5th percentile) compared to right-handers. Left-handed men had better performance on a test of verbal functions, which was unexpected. A recent study reported no right-hand associated advantage on visuospatial tests in people with schizophrenia disorders when measuring handedness on a continuous scale. This suggests that the classification of handedness as either a dichotomous or as a continuous variable is important in studies of handedness and cognitive functions.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive functional neuroimaging method that takes advantage of the optical properties of hemoglobin to provide an indirect measure of brain activation via task-related relative changes in oxygenated hemoglobin (HbO). Its advantage over fMRI is that fNIRS is portable and can be used while walking and talking. In this study, we used fNIRS to measure brain activity in prefrontal and motor region of interests (ROIs) during single- and dual-task walking, with the goal of identifying neural correlates.

Nineteen healthy young adults [mean age=25.4 (SD=4.6) years; 14 female] engaged in five tasks: standing single-task cognition (serial-3 subtraction); single-task walking at a self-selected comfortable speed on a 24.5m oval-shaped course (overground walking) and on a treadmill; and dual-task cognition+walking on the same overground course and treadmill (8 trials/condition: 20 seconds standing rest, 30 seconds task). Performance on the cognitive task was quantified as the number of correct subtractions, number of incorrect subtractions, number of self-corrected errors, and percent accuracy over the 8 trials. Walking speed (m/sec) was recorded for all walking conditions. fNIRS data were collected on a system consisting of 16 sources, 15 detectors, and 8 short-separation detectors in the following ROIs: right and left lateral frontal (RLF, LLF), right and left medial frontal (RMF, LMF), right and left medial superior frontal (RMSF, LMSF), and right and left motor (RM, LM). Lateral and medial refer to ROIs’ relative positions on lateral prefrontal cortex. fNIRS data were analyzed in Homer3 using a spline motion correction and the iterative weighted least squares method in the general linear model. Correlations between the cognitive/speed variables and ROI HbO data were applied using a Bonferroni adjustment for multiple comparisons.

Subjects with missing cognitive data were excluded from analyses, resulting in sample sizes of 18 for the single-task cognition, dual-task overground walking, and dual-task treadmill walking conditions. During dual-task overground walking, there was a significant positive correlation between walking speed and relative change in HbO in RMSF [r(18)=.51, p<.05] and RM [r(18)=.53, p<.05)]. There was a significant negative correlation between total number of correct subtractions and relative change in HbO in LMSF ([r(18)=-.75, p<.05] and LM [r(18)=-.52, p<.05] during dual-task overground walking. No other significant correlations were identified.

These results indicate that there is lateralization of the cognitive and motor components of overground dual-task walking. The right hemisphere appears to be more active the faster people walk during the dual-task. By contrast, the left hemisphere appears to be less active when people are working faster on the cognitive task (i.e., serial-3 subtraction). The latter results suggest that automaticity of the cognitive task (i.e., more total correct subtractions) is related to decreased brain activity in the left hemisphere. Future research will investigate whether there is a change in cognitive automaticity over trials and if there are changes in lateralization patterns in neurodegenerative disorders that are known to differentially affect the hemispheres (e.g., Parkinson’s disease).

Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.

Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.

Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.

These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.

As sinistrality could be linked to a failure of hemisphere specialization in schizophrenia that would translate into language disorders, sinistrality was found out in disorganized and positive schizophrenic patients characterized by language disorders.

Seventy-three schizophrenic patients (DSM IV) and 81 controls were evaluated with the Edinburgh Handedness Inventory (EHI). Patients were evaluated and classified into five subtypes (deficit, positive, disorganized, mixed and residual) with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome.

Disorganized patients had a significantly more severe sinistrality in comparison to the deficit, residual and mixed subtypes and controls. A negative correlation was found between the disorganization and the EHI scores (r = – 0.34; P < 0.01). A significantly more severe sinistrality was also observed in the positive subtype in comparison to controls, but there was no correlation between hallucinatory and EHI scores (r = 0.06).

The findings provided further evidence that the defects in the normal process of lateralization observed in schizophrenia affects primarily disorganized patients.

Asymmetry in brain structure and function is implicated in the pathogenesis of psychiatric disorders. Although right hemisphere abnormality has been documented in obsessive–compulsive disorder (OCD), cerebral asymmetry is rarely examined. Therefore, in this study, we examined anomalous cerebral asymmetry in OCD patients using the line bisection task.

A total of 30 patients with OCD and 30 matched healthy controls were examined using a reliable and valid two-hand line bisection (LBS) task. The comparative profiles of LBS scores were analysed using analysis of covariance.

Patients with OCD bisected significantly less number of lines to the left and had significant rightward deviation than controls, indicating right hemisphere dysfunction. The correlations observed in this study suggest that those with impaired laterality had more severe illness at baseline.

The findings of this study indicate abnormal cerebral lateralisation and right hemisphere dysfunction in OCD patients.

Facial emotion perception (FEP) is a critical human skill for successful social interaction, and a substantial body of literature suggests that explicit FEP is disrupted in major depressive disorder (MDD). Prior research suggests that weakness in FEP may be an important phenomenon underlying patterns of emotion-processing challenges in MDD and the disproportionate frequency of MDD in women.

Women with (n = 24) and without (n = 22) MDD, equivalent in age and education, completed a FEP task during functional magnetic resonance imaging.

The MDD group exhibited greater extents of frontal, parietal and subcortical activation compared with the control group during FEP. Activation in the inferior frontal gyrus (IFG) appeared shifted from a left >right pattern observed in healthy women to a bilateral pattern in MDD women. The ratio of left to right suprathreshold IFG voxels in healthy controls was nearly 3:1, whereas in the MDD group, there was a greater percentage of suprathreshold IFG voxels bilaterally, with no leftward bias. In MDD, relatively greater activation in right IFG compared with left IFG (ratio score) was present and predicted FEP accuracy (r = 0.56, p < 0.004), with an inverse relationship observed between FEP and subgenual cingulate activation (r = − 0.46, p = 0.02).

This study links, for the first time, disrupted IFG activation laterality and increased subgenual cingulate activation with deficient FEP in women with MDD, providing an avenue for imaging-to-assessment translational applications in MDD.