Tomás Ortiz

Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on functional connectivity patterns. Networks were calculated from resting-state magnetoencephalographic recordings from 15 brain injured patients and 14 healthy controls by means of wavelet coherence in standard frequency bands. We compared the parameters defining the network, such as number and strength of interactions as well as their topology, in controls and patients for two conditions: following a traumatic brain injury and after a rehabilitation treatment. A loss of delta- and theta-based connectivity and conversely an increase in alpha- and beta-band-based connectivity were found. Furthermore, connectivity parameters approached controls in all frequency bands, especially in slow-wave bands. A correlation between network reorganization and cognitive recovery was found: the reduction of delta-band-based connections and the increment of those based on alpha band correlated with Verbal Fluency scores, as well as Perceptual Organization and Working Memory Indexes, respectively. Additionally, changes in connectivity values based on theta and beta bands correlated with the Patient Competency Rating Scale. The current study provides new evidence of the neurophysiological mechanisms underlying neuronal plasticity processes after brain injury, and suggests that these changes are related with observed changes at the behavioural level.

Spanish language mapping using MEG: a validation study.

The purpose of the present study was to compare magnetoencephalography (MEG) data with the results of the intracarotid amytal procedure (IAP). Twenty-one native Spanish-speaking patients with intractable epilepsy underwent MEG language mapping. A subset of 8 patients also underwent an IAP. With the exception of 2 patients who showed right hemisphere dominance, all other patients showed left hemisphere dominance for language on the MEG recording. The IAP findings were consistent with MEG results in 7 patients. The eighth patient who, according to the MEG data, had probable right hemisphere dominance for language did not show clear hemispheric specialization for language on the IAP and suffered a transient global aphasia following a right temporal lobotomy. These results suggests that MEG-based language mapping can play an important role in presurgical clinical evaluation.

Hypofunction of Right Temporoparietal Cortex During Emotional Arousal in Depression

CONTEXT Neuropsychological models of depression highlight temporoparietal hypofunction associated with low emotional arousal in major depressive disorder (MDD). These models were derived from indirect measures such as neuropsychological tests and electroencephalography alpha band power. OBJECTIVE To determine if high-arousing stimuli directly modulated activity in attention and arousal-related sensory brain regions in patients with MDD. DESIGN Between-group comparison (patients with MDD vs healthy control subjects) of neuromagnetic oscillatory activity driven by flickering emotional and neutral pictures (steady-state visual evoked fields [ssVEFs]). SETTING Center of magnetoencephalography at a public university and public ambulatory mental health service. PARTICIPANTS Fifteen female low-anxious patients with MDD and 15 female controls. The groups were matched with respect to age and handedness. INTERVENTION Magnetoencephalographic recordings and self-report ratings. MAIN OUTCOME MEASURES Modulation of current source strengths obtained by frequency domain minimum norm source localization of ssVEFs. RESULTS Controls and patients with MDD showed enhanced current source strengths at ssVEF frequency in occipital and parietal cortex for high-arousing emotional pictures (P < .05 for permutation statistics). While this arousal modulation in controls was pronounced in the right temporoparietal cortex, weak arousal modulation characterized that brain region in patients with MDD (F(1,28) = 7.2, P < .05 for interaction group by quadraticcontrast). CONCLUSIONS Although emotional pictures engaged the dorsal visual stream to a greater extent than neutral pictures in both study groups, only controls showed strong arousal modulation in the right temporoparietal cortex. Because the right temporoparietal cortex is associated with the arousal dimension of emotion, subjects with depression may have difficulties in activating arousal-related brain areas, whereas basic stimulus processing related to activation of the dorsal visual stream is intact.

Neural mechanisms of evoked oscillations: Stability and interaction with transient events

There is increasing evidence that early event‐related potentials are a result of phase alignment of ongoing background oscillations of the electroencephalogram rather than additive amplitude modulation. Steady state visual‐evoked potentials (ssVEPs) can be recorded using an intensity modulated stimulus, resulting in an evoked brain response at a known frequency, i.e. the stimulation frequency. Given this property, the ssVEP is ideally suited for examining the relationship between single‐trial fluctuations in phase/amplitude and the evoked brain potential resulting from averaging across trials. To address this issue, the current study investigated the contribution of single trial power and intertrial phase locking to ssVEP generation by presenting a peripheral flicker. Further, transient stimuli were presented during flicker and at three increasing latency lags following flicker offset to examine (1) to what extent a stimulus can disturb the ssVEP oscillation and (2) how phase alignment during P1‐N1‐P2 time windows is affected during presence of evoked oscillations. The former assessment evaluates the stability of ssVEPs and the latter the phase alignment processes to transient stimuli under experimentally induced background oscillations. We observed that ssVEPs are a result of phase alignment rather than single trial amplitude modulation. In addition, ssVEP oscillations were not disturbed by transient stimuli. Finally, phase alignment in P1‐N1‐P2 time windows was distorted during and shortly after steady state stimulation. We conclude that ssVEPs represent strongly phase locked oscillations sharing the same generation mechanisms as early evoked potentials. Hum Brain Mapp, 2007.

Effects of cholinergic drugs and cognitive training on dementia: 2-year follow-up.

Several studies have shown that pharmacological and cognitive treatments for Alzheimers’s disease improve cognitive function for short periods, but fewer studies have evaluated the efficacy of those treatments for longer (2-year) periods. An initial sample of 68 subjects with mild Alzheimer’s disease underwent clinical and cognitive evaluation. After evaluation, subjects were assigned to four different groups and participated in a 2-year follow-up study. Group 1 (n = 14) received combined drug and cognitive stimulation, group 2 (n = 20) received only drug treatment, group 3 (n = 14) received only cognitive stimulation, and group 4 (n = 30) received no treatment at all. Results confirmed previous investigation, cognitive and combined stimulation improved patients’ performance throughout the 1st year; however, all groups deteriorated gradually throughout the 2nd year of treatment. According to this evidence, it can be concluded that we cannot stop cognitive deterioration after 2 years of treatment, although deterioration is greater and its progress faster in patients not receiving any treatment at all.

Complexity analysis of spontaneous brain activity in attention-deficit/hyperactivity disorder: diagnostic implications.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is defined as the most common neurobehavioral disorder of childhood, but an objective diagnostic test is not available yet to date. Neurophychological, neuroimaging, and neurophysiological research offer ample evidence of brain and behavioral dysfunctions in ADHD, but these findings have not been useful as a diagnostic test. METHODS Whole-head magnetoencephalographic recordings were obtained from 14 diagnosed ADHD patients and 14 healthy children during resting conditions. Lempel-Ziv complexity (LZC) values were obtained for each channel and child and averaged in five sensor groups: anterior, central, left lateral, right lateral, and posterior. RESULTS Lempel-Ziv complexity scores were significantly higher in control subjects, with the maximum value in anterior region. Combining age and anterior complexity values allowed the correct classification of ADHD patients and control subjects with a 93% sensitivity and 79% specificity. Control subjects showed an age-related monotonic increase of LZC scores in all sensor groups, while children with ADHD exhibited a nonsignificant tendency toward decreased LZC scores. The age-related divergence resulted in a 100% specificity in children older than 9 years. CONCLUSIONS Results support the role of a frontal hypoactivity in the diagnosis of ADHD. Moreover, the age-related divergence of complexity scores between ADHD patients and control subjects might reflect distinctive developmental trajectories. This interpretation of our results is in agreement with recent investigations reporting a delay of cortical maturation in the prefrontal cortex.

Effects of cholinergic drugs and cognitive training on dementia

A study was performed on patients with Alzheimer’s disease (AD) in order to evaluate the efficacy of a combined treatment (donepezil plus cognitive training) in both cognitive processes and affective states. Eighty-six subjects, 25 men and 61 women, with an average age of 75.58 years, were studied. Almost all the subjects had a basic educational level. Donezepil was administered at a dose of 10 mg daily along with cognitive treatment involving images of everyday life and reminiscent music; the sessions took place on Monday to Friday and lasted three quarters of an hour. The study lasted 12 months. Subjects underwent test-retest with the following tests: Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog); the Geriatric Depression Scale (GDS) and the overall deterioration scale (FAST). The results showed that subjects receiving the combined treatment had a better response than those who did not receive any cognitive training. These subjects’ MMSE score decreased by 3.24 on average. The affective symptomatology of those receiving only drug treatment improved whereas the cognitive processes did not.

Spatio-temporal patterns of brain magnetic activity during a memory task in Alzheimer's disease.

The brain magnetic activity patterns in a high load probe-letter (targets and distractors) memory task were examined in patients with Alzheimerss disease (AD) and elderly controls. Control subjects showed a higher number of activity sources over the temporal and parietal cortex between 400 and 700 ms after stimulus onset. However, AD patients showed a higher number of sources over the frontal motor areas, including Brocas and the insula. The number of activity sources on the left parietal areas in response to the target stimuli predicted the AD score oncognitive (MMSE, CAMCOG) and functional staging (FAST) scales. These results suggest that a high information load reveals a deficient functioning of phonological store and reduced task-related activity in temporal and parietal areas, manifesting in a rapid information trace decay. The increased levels of activity in motor areas may reflect a compensatory strategy in an attempt to facilitate rehearsal speed.

Complexity analysis of spontaneous brain activity: effects of depression and antidepressant treatment:

Magnetoencephalography (MEG) allows the real-time recording of neural activity and oscillatory activity in distributed neural networks. We applied a non-linear complexity analysis to resting-state neural activity as measured using whole-head MEG. Recordings were obtained from 20 unmedicated patients with major depressive disorder and 19 matched healthy controls. Subsequently, after 6 months of pharmacological treatment with the antidepressant mirtazapine 30 mg/day, patients received a second MEG scan. A measure of the complexity of neural signals, the Lempel–Ziv Complexity (LZC), was derived from the MEG time series. We found that depressed patients showed higher pre-treatment complexity values compared with controls, and that complexity values decreased after 6 months of effective pharmacological treatment, although this effect was statistically significant only in younger patients. The main treatment effect was to recover the tendency observed in controls of a positive correlation between age and complexity values. Importantly, the reduction of complexity with treatment correlated with the degree of clinical symptom remission. We suggest that LZC, a formal measure of neural activity complexity, is sensitive to the dynamic physiological changes observed in depression and may potentially offer an objective marker of depression and its remission after treatment.

Recruitment of Occipital Cortex during Sensory Substitution Training Linked to Subjective Experience of Seeing in People with Blindness

Over three months of intensive training with a tactile stimulation device, 18 blind and 10 blindfolded seeing subjects improved in their ability to identify geometric figures by touch. Seven blind subjects spontaneously reported ‘visual qualia’, the subjective sensation of seeing flashes of light congruent with tactile stimuli. In the latter subjects tactile stimulation evoked activation of occipital cortex on electroencephalography (EEG). None of the blind subjects who failed to experience visual qualia, despite identical tactile stimulation training, showed EEG recruitment of occipital cortex. None of the blindfolded seeing humans reported visual-like sensations during tactile stimulation. These findings support the notion that the conscious experience of seeing is linked to the activation of occipital brain regions in people with blindness. Moreover, the findings indicate that provision of visual information can be achieved through non-visual sensory modalities which may help to minimize the disability of blind individuals, affording them some degree of object recognition and navigation aid.