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Home > Library > Annotated Journal Abstracts > 2014 Q2: Neuropsychiatry

Annotated Abstracts of Journal Articles
2014, 2nd Quarter


Annotations by Nicholas Kontos, MD
June 2014

  1. Systematic review of neuroimaging correlates of executive functioning: converging evidence from different clinical populations
  2. Distinguishing between patients with pure psychogenic nonepileptic seizures and those with comorbid epilepsy by means of clinical data
  3. Biological vulnerability to depression: linked structural and functional brain network findings

Also of interest:

PUBLICATION #1 — Neuropsychiatry
Systematic review of neuroimaging correlates of executive functioning: converging evidence from different clinical populations
Nowrangi MA, Lyketsos C, Rao V, Munro CA
J Neuropsychiatry Clin Neurosci 2014 Apr 1; 26(2):114-25

ANNOTATION (Nicholas Kontos)

The Finding:  Regions from far-flung areas of cerebral cortex and cerebellum—excluding the occipital lobes and, to a lesser degree, temporal lobes—participate in executive functioning as revealed by studies of a number of different demonstrably organic and idiopathic (neuro) psychiatric disorders.

Strengths and Weaknesses:  A coherent theory encompassing the nature and functional neuroanatomy of executive functioning should be revealed by (and hold up under) the study of disparate disorders where impairment in this domain is seen. This study attempts to take a step in this direction. Much like the aphasias, executive dysfunction appears to result from lesions in a variety of locations that participate in a distributed network with a (frontal) epicenter. A valuable and informative step towards elaborating our understanding of executive dysfunction, this study is limited by its (necessarily) limited analysis of highly disparate studies and by the somewhat arbitrary nature of its self-declared “systematic” approach.

Relevance: While a more complex understanding of executive (dys)function is a work in progress, it is time for neurologists and psychiatrists to begin thinking about it in a way that goes beyond “frontal-subcortical” anatomy.


Executive functioning (EF) is an important cognitive domain that is negatively affected in a number of neuropsychiatric conditions. Neuroimaging methods have led to insights into the anatomical and functional nature of EF. The authors conducted a systematic review of the recent cognitive and neuroimaging literature to investigate how the neuroimaging correlates of EF compare between different diagnostic groups. The authors found that the frontal, parietal, and cerebellar lobes were most frequently associated with EF when comparing results from different clinical populations; the occipital lobe was not correlated with EF in any group. These findings suggest that individual disease processes affect circuits within an identifiable distributed network rather than isolated regions.

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PUBLICATION #2 — Neuropsychiatry
Distinguishing between patients with pure psychogenic nonepileptic seizures and those with comorbid epilepsy by means of clinical data
Hoepner R, Labudda K, May TW, Schöndienst M, Bien CG, Brandt C
Epilepsy Behav 2014 Jun; 35:54-8

ANNOTATION (Nicholas Kontos)

The Finding:  Older age at onset of paroxysms (older than 15 y/o), shorter length of time between first paroxysm to admission, fewer EEG correlates, and higher number and polypharmacy of antiepileptic medications, all were found to be associated with the PNES-ES combination compared to patients with PNES alone.

Strengths and Weaknesses:  While the primary concern of psychiatrists and neurologists investigating “pseudoseizures” has typically been discriminating PNES from ES, the co-occurrence of both types of paroxysms is a subject of much research and lore. In addition to performing an interesting study, the authors present a brief but informative review of the literature on this subject—informative in terms of demonstrating the disappointingly wide range of findings in this area (e.g., 3-58% of patients with PNES have been found to have co-occurring ES). These sorts of trends, of course, are of limited utility in a given consultation. For example, the authors make much of another of their findings where subtracting the number of psychotropic drugs from the number of antiepileptic drugs taken by a patient, if >1, identified patients with PNES + ES (relative to PNES alone) with 92% sensitivity; this despite only 60% specificity of this finding. As is typical, the generalizability of the findings are limited here by the study being conducted in a specialty epilepsy center.

Relevance: This paper casts some light, both by review and by research, on an area where discussions are excessively based on received wisdom rather than data. An important, if underplayed, finding here is the iatrogenic burden of unwarranted polypharmacy seen in the PNES-ES patients. This ought to give pause to psychiatrists, who are often in the position of pharmacologically treating unsubstantiated “comorbidities.”


Patients with psychogenic nonepileptic seizures (PNESs) often have additional epileptic seizures (ESs). Distinguishing between those with ESs and those without ESs is difficult but mandatory. We hypothesize that these two patient groups differ in clinical data, which might be useful for establishing diagnosis. All patients with PNESs (n=114) from the Bethel Epilepsy Centre treated between 1/11/2010 and 1/11/2011 were included. Thirty-six percent had additional epilepsy. In contrast, 84 of the 114 patients with PNESs took antiepileptic drugs (AEDs) (AED treatment: patients with PNESs=44/73, patients with PNESs+ESs=40/41), most of them (65.5%) as polytherapy. Significant differences between both groups were as follows: patients with PNESs were older at disease onset, had a shorter duration from onset to inpatient visit, were less frequently on AEDs, were less frequently on antiepileptic polytherapy, and had a normal EEG compared with patients with PNESs+ESs. Multivariate stepwise logistic regression revealed age at seizure onset, number of AEDs, and difference between number of AEDs and psychiatric drugs as significant predictors of patients with ESs in PNESs (Nagelkerke's r2=0.59). Therefore, clinical data proved to be useful in the diagnostic process.

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PUBLICATION #3 — Neuropsychiatry
Biological vulnerability to depression: linked structural and functional brain network findings
Nixon NL, Liddle PF, Nixon E, Worwood G, Liotti M, Palaniyappan L
Br J Psychiatry 2014 Apr; 204:283-9

ANNOTATION (Nicholas Kontos)

The Finding:  Alterations in the brain’s default mode network appear to exist in the remitted state of major depressive disorder. The alterations found suggest an imbalance between processing/monitoring of self versus environmental stimuli emphasizing internal orientation.

Strengths and Weaknesses:  Rigorous screening of subjects took the important step of trying to identify and exclude personality disorders. This important and all-to-frequently omitted scientific step may, of course, simultaneously restrict the clinical applicability of the findings.

Relevance: The default mode network is not a new idea, but one of increasing interest in neuroscience. This paper provides an “in” for clinicians to begin to think about its importance in understanding psychopathology.


Background: Patients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD.

Aims: To test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities.

Method: A multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recovered-state patients with MDD with 20 matched healthy controls.

Results: The MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus).

Conclusions: This is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability.

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