The risk of criminal behavior in the elderly and patients with neurodegenerative disease.

Behavioral changes are commonly observed in patients with dementia and can lead to criminal offenses, even without a history of criminal or antisocial behavior. Due to the growth of the aging population, this poses a rising problem to deal with for the criminal justice system and in general for society. Criminal behavior may include minor crimes such as theft or traffic violations, but also serious crimes such as physical abuse, sexual offense, or murder. In the assessment of criminal behavior among elderly (first-time) offenders, it is important to be aware of possible neurodegenerative diseases at the time of the crime. This book chapter provides an overview on criminal behavior in the elderly and specifically discusses existing literature on patients suffering from a neurodegenerative disease, including Alzheimer disease, vascular dementia, frontotemporal dementia, Parkinson disease, and Huntington disease. Each section is introduced by a true case to illustrate how the presence of a neurodegenerative disease may affect the criminal judgment. The chapter ends with a summary, multifactorial model of crime risk, future perspectives, and concluding remarks.

Amyloid-driven disruption of default mode network connectivity in cognitively healthy individuals.

Cortical accumulation of amyloid beta is one of the first events of Alzheimer's disease pathophysiology, and has been suggested to follow a consistent spatiotemporal ordering, starting in the posterior cingulate cortex, precuneus and medio-orbitofrontal cortex. These regions overlap with those of the default mode network, a brain network also involved in memory functions. Aberrant default mode network functional connectivity and higher network sparsity have been reported in prodromal and clinical Alzheimer's disease. We investigated the association between amyloid burden and default mode network connectivity in the preclinical stage of Alzheimer's disease and its association with longitudinal memory decline. We included 173 participants, in which amyloid burden was assessed both in CSF by the amyloid beta 42/40 ratio, capturing the soluble part of amyloid pathology, and in dynamic PET scans calculating the non-displaceable binding potential in early-stage regions. The default mode network was identified with resting-state functional MRI. Then, we calculated functional connectivity in the default mode network, derived from independent component analysis, and eigenvector centrality, a graph measure recursively defining important nodes on the base of their connection with other important nodes. Memory was tested at baseline, 2- and 4-year follow-up. We demonstrated that higher amyloid burden as measured by both CSF amyloid beta 42/40 ratio and non-displaceable binding potential in the posterior cingulate cortex was associated with lower functional connectivity in the default mode network. The association between amyloid burden (CSF and non-displaceable binding potential in the posterior cingulate cortex) and aberrant default mode network connectivity was confirmed at the voxel level with both functional connectivity and eigenvector centrality measures, and it was driven by voxel clusters localized in the precuneus, cingulate, angular and left middle temporal gyri. Moreover, we demonstrated that functional connectivity in the default mode network predicts longitudinal memory decline synergistically with regional amyloid burden, as measured by non-displaceable binding potential in the posterior cingulate cortex. Taken together, these results suggest that early amyloid beta deposition is associated with aberrant default mode network connectivity in cognitively healthy individuals and that default mode network connectivity markers can be used to identify subjects at risk of memory decline.

GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients.

Background: Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered in patients responsive to either anticonvulsants or ß-adrenergic blockers. Methods: In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using 1H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls. Results: There were no group differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. There was no correlation with tremor severity. Discussion: Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+/Cr, Glx/Cr, NAA/Cr, and GABA+/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.

Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson's disease.

BACKGROUND: Notwithstanding the large improvement in motor function in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role. OBJECTIVE: We studied whether apathy in DBS-treated PD patients could be a stimulation effect. METHODS: In 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy. RESULTS: Average apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex. CONCLUSIONS: The present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.

The dynamics of resting-state alpha oscillations predict individual differences in creativity.

The neuronal mechanisms underlying creativity are poorly understood. Arguably, the brain's ability to switch states would contribute to achieving novel ideas, and thus to creativity. Faster brain-state switching is reflected in the temporal dynamics of functional brain activity. Stronger autocorrelations in brain activity measures can make a brain stay in a certain state for longer periods, whereas low temporal autocorrelations reflect faster state switching. We established the brain's inherent tendency to switch or stay in a resting, no-task condition using 128 channel electroencephalography (EEG). We assessed temporal autocorrelations of the amplitude modulation of the dominant alpha oscillations (8-13 Hz). Creativity was measured by a self-rating, an examiner-rating and the alternative uses task in 40 healthy young adults, which was scored on dimensions of verbal fluency, originality, elaboration, usefulness, and flexibility. For each dimension, the total number of subject-reported alternative uses that matched the criterion was noted (the quantity measure), as well as the proportion of uses that matched the dimensional criterion. A principal components analysis confirmed the two-component structure of quantity and quality. Partial correlation analysis was used controlling for gender and age, and a cluster permutation test was performed to correct for multiple testing. A significant cluster over right central/temporal brain areas was found with a negative correlation between creativity and temporal autocorrelations were observed (p = 0.028). To our knowledge, this is the first demonstration that individual variation in the dynamically changing activity in the brain may offer a neuronal explanation for individual variation in creative ideation.

Motor effects of deep brain stimulation correlate with increased functional connectivity in Parkinson's disease: An MEG study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established symptomatic treatment in Parkinson's disease, yet its mechanism of action is not fully understood. Locally in the STN, stimulation lowers beta band power, in parallel with symptom relief. Therefore, beta band oscillations are sometimes referred to as "anti-kinetic". However, in recent studies functional interactions have been observed beyond the STN, which we hypothesized to reflect clinical effects of DBS. Resting-state, whole-brain magnetoencephalography (MEG) recordings and assessments on motor function were obtained in 18 Parkinson's disease patients with bilateral STN-DBS, on and off stimulation. For each brain region, we estimated source-space spectral power and functional connectivity with the rest of the brain. Stimulation led to an increase in average peak frequency and a suppression of absolute band power (delta to low-beta band) in the sensorimotor cortices. Significant changes (decreases and increases) in low-beta band functional connectivity were observed upon stimulation. Improvement in bradykinesia/rigidity was significantly related to increases in alpha2 and low-beta band functional connectivity (of sensorimotor regions, the cortex as a whole, and subcortical regions). By contrast, tremor improvement did not correlate with changes in functional connectivity. Our results highlight the distributed effects of DBS on the resting-state brain and suggest that DBS-related improvements in rigidity and bradykinesia, but not tremor, may be mediated by an increase in alpha2 and low-beta functional connectivity. Beyond the local effects of DBS in and around the STN, functional connectivity changes in these frequency bands might therefore be considered as "pro-kinetic".

Distance to white matter tracts is associated with deep brain stimulation motor outcome in Parkinson's disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in patients with Parkinson's disease (PD). However, the underlying mechanism of tremor suppression is not well understood. Stimulation of white matter tracts, such as the dentatorubrothalamic tract (DRT), might be involved. Also, side effects, including dysarthria, might result from (unwanted) stimulation of white matter tracts in proximity to the STN. The aim of this study was to establish an association between stimulation effect on tremor and dysarthria and stimulation location relative to relevant white matter tracts. METHODS: In 35 PD patients in whom a bilateral STN DBS system was implanted, the authors established clinical outcome measures per electrode contact. The distance from each stimulation location to the center of the DRT, corticopontocerebellar tract, pyramidal tract (PT), and medial lemniscus was determined using diffusion-weighted MRI data. Clinical outcome measures were subsequently related to the distances to the white matter tracts. RESULTS: Patients with activated contacts closer to the DRT showed increased tremor improvement. Proximity of activated contacts to the PT was associated with dysarthria. CONCLUSIONS: Proximity to specific white matter tracts is associated with tremor outcome and side effects in DBS. This knowledge can help to optimize both electrode placement and postsurgical electrode contact selection. Presurgical white matter tract visualization may improve targeting and DBS outcome. These findings are of interest not only for treatment in PD, but potentially also for other (movement) disorders.